Appendices for U.S. Medical Eligibility Criteria for Contraceptive Use, 2016

Appendix A

Summary of Changes from U.S. Medical Eligibility Criteria for Contraceptive Use, 2010

The classification additions, deletions, and modifications from the 2010 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) are summarized in the following tables ( Box A1) ( Tables A1 and A2). For conditions for which classifications changed for one or more contraceptive methods or the condition description underwent a major modification, the changes or modifications are in bold italics (Tables A1 and A2). Conditions that do not appear in this table remain unchanged from the 2010 U.S. MEC.

TABLE A1. Summary of changes in classifications from U.S. Medical Eligibility Criteria for Contraceptive Use, 2010*

Condition	Cu-IUD		LNG-IUD		Implants	DMPA		POP	CHCs	Clarification
Breastfeeding
a. <21 days postpartum	—		—		2	2		2	4	Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
b. 21 to <30 days postpartum
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	—		—		2	2		2	3	Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
										CHCs: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
ii. Without other risk factors for VTE	—		—		2	2		2	3	Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
c. 30–42 days postpartum
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	—		—		1	1		1	3	Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
										CHCs: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
ii. Without other risk factors for VTE	—		—		1	1		1	2	Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
d. >42 days postpartum	—		—		1	1		1	2	Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
Postpartum (nonbreastfeeding women)
a. <21 days postpartum	—		—		1	1		1	4	—
b. 21–42 days postpartum
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	—		—		1	1	1		3	CHCs: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
ii. Without other risk factors for VTE	—		—		1	1	1		2	—
c. >42 days postpartum	—		—		1	1	1		1	—
Postpartum (including cesarean delivery)
a. <10 minutes after delivery of the placenta										IUDs: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower. Breastfeeding: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
i. Breastfeeding	1		2		—	—	—		—
ii. Nonbreastfeeding	1		1		—	—	—		—
b. 10 minutes after delivery of the placenta to <4 weeks (breastfeeding or nonbreastfeeding)	2		2		—	—	—		—	IUDs: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
										Breastfeeding: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
c. =4 weeks (breastfeeding or nonbreastfeeding)	1		1		—	—	—		—	IUDs: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
										Breastfeeding: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
d. Postpartum sepsis	4		4		—	—	—		—	—
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels)	1		2		2	3	2		3/4	Implants, DMPA, POP: When multiple major risk factors exist, risk for cardiovascular disease might increase substantially. Certain POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs. The effects of DMPA might persist for some time after discontinuation.
										CHCs: When a woman has multiple major risk factors, any of which alone would substantially increase her risk for cardiovascular disease, use of CHCs might increase her risk to an unacceptable level. However, a simple addition of categories for multiple risk factors is not intended; for example, a combination of two category 2 risk factors might not necessarily warrant a higher category.
										Implants, DMPA, POP, CHCs: The recommendations apply to known preexisting medical conditions or characteristics. Few if any screening tests are needed before initiation of contraception. See the U.S. Selected Practice Recommendations for Contraceptive Use (http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usspr.htm)
Superficial venous disorders
a. Varicose veins	1		1		1	1	1		1	—
b. Superficial venous thrombosis (acute or history)	1		1		1	1	1		3	CHCs: Superficial venous thrombosis might be associated with an increased risk for VTE. If a woman has risk factors for concurrent DVT (e.g., known thrombophilia or cancer) or has current or history of DVT, see recommendations for DVT/PE. Superficial venous thrombosis associated with a peripheral intravenous catheter is less likely to be associated with additional thrombosis and use of CHCs may be considered.
Headaches
a. Nonmigraine (mild or severe)	1		1		1	1		1	1	CHCs: Classification depends on accurate diagnosis of those severe headaches that are migraines and those headaches that are not, as well as diagnosis of ever experiencing aura. Aura is a specific focal neurologic symptom. For more information about headache classification see The International Headache Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdfpdf iconexternal icon). Any new headaches or marked changes in headaches should be evaluated.
b. Migraine										CHCs: Classification depends on accurate diagnosis of those severe headaches that are migraines and those headaches that are not, as well as diagnosis of ever experiencing aura. Aura is a specific focal neurologic symptom. For more information about headache classification see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdfpdf iconexternal icon). Any new headaches or marked changes in headaches should be evaluated. CHCs: Classification is for women without any other risk factors for stroke (e.g., age, hypertension, and smoking).
i. Without aura (This category of migraine includes menstrual migraine.)	1		1		1	1		1	2
ii. With aura	1		1		1	1		1	4
Multiple sclerosis
a. With prolonged immobility	1		1		1	2		1	3	—
b. Without prolonged immobility	1		1		1	2		1	1	—
Gestational trophoblastic disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).										For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
a. Suspected gestational trophoblastic disease (immediate postevacuation)										For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
i. Uterine size first trimester	1		1		1	1		1	1
ii. Uterine size second trimester	2		2		1	1		1	1
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring)	Initiation	Continuation	Initiation	Continuation
i. Undetectable/nonpregnant ß-hCG levels	1	1	1	1	1	1		1	1	For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
ii. Decreasing ß-hCG levels	2	1	2	1	1	1		1	1	For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance. IUD: For women at higher risk for disease progression, the benefits of effective contraception must be weighed against the potential need for early IUD removal.
iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease	2	1	2	1	1	1		1	1	For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease	4	2	4	2	1	1		1	1	For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
Sexually transmitted diseases	Initiation	Continuation	Initiation	Continuation
a. Current purulent cervicitis or chlamydial infection or gonococcal infection	4	2	4	2	1	1		1	1	IUD continuation: Treat the STD using appropriate antibiotics. The IUD usually does not need to be removed if the woman wants to continue using it. Continued use of an IUD depends on the woman’s informed choice and her current risk factors for STDs and PID.
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis)	2	2	2	2	1	1		1	1	—
c. Other factors related to STDs	2	2	2	2	1	1		1	1	IUD initiation: Most women do not require additional STD screening at the time of IUD insertion. If a woman with risk factors for STDs has not been screened for gonorrhea and chlamydia according to CDC STD treatment guidelines (2), screening may be performed at the time of IUD insertion and insertion should not be delayed.
High risk for HIV	Initiation	Continuation	Initiation	Continuation						DMPA: Some studies suggest that women using progestin-only injectable contraception might be at increased risk for HIV acquisition; other studies do not show this association. CDC reviewed all available evidence and agreed that the data were not sufficiently conclusive to change current guidance. However, because of the inconclusive nature of the body of evidence on possible increased risk for HIV acquisition, women using progestin-only injectable contraception should be strongly advised to also always use condoms (male or female) and take other HIV preventive measures. Expansion of contraceptive method mix and further research on the relationship between hormonal contraception and HIV infection are essential. These recommendations will be continually reviewed in light of new evidence.
	2	2	2	2	1	1		1	1
HIV infection For women with HIV infection who are not clinically well or not receiving ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	—	—	—	—	1	1		1	1	Implants, DMPA, POP, CHCs: Drug interactions might exist between hormonal contraceptives and ARV drugs; see Drug Interactions section.
a. Clinically well receiving ARV therapy	1	1	1	1	—	—		—	—	—
b. Not clinically well or not receiving ARV therapy	2	1	2	1	—	—		—	—	—
Cystic fibrosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		1		1	2		1	1	Persons with cystic fibrosis are at increased risk for diabetes, liver disease, gallbladder disease, and VTE (particularly related to use of central venous catheters) and are frequently prescribed antibiotics. Categories assigned to such conditions in U.S. MEC should be the same for women with cystic fibrosis who have these conditions. For cystic fibrosis, classifications are based on the assumption that no other conditions are present; these classifications must be modified in the presence of such conditions.
										Implants, DMPA, POP, CHCs: Certain drugs to treat cystic fibrosis (e.g., lumacaftor) might reduce effectiveness of hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives.
Antiretroviral therapy	Initiation	Continuation	Initiation	Continuation						IUD: No known interaction exists between ARV therapy and IUD use. However, IUD insertion is classified as category 2 if the woman is not clinically well or not receiving ARV therapy. Otherwise, both insertion and continuation are classified as category 1 (see HIV Infection section).
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
i. Abacavir (ABC)	1/2	1	1/2	1	1	1		1	1	—
ii. Tenofovir (TDF)	1/2	1	1/2	1	1	1		1	1	—
iii. Zidovudine (AZT)	1/2	1	1/2	1	1	1		1	1	—
iv. Lamivudine (3TC)	1/2	1	1/2	1	1	1		1	1	—
v. Didanosine (DDI)	1/2	1	1/2	1	1	1		1	1	—
vi. Emtricitabine (FTC)	1/2	1	1/2	1	1	1		1	1	—
vii. Stavudine (D4T)	1/2	1	1/2	1	1	1		1	1	—
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
i. Efavirenz (EFV)	1/2	1	1/2	1	2	1		2	2	Implants, DMPA, POP, CHCs: Evidence suggests drug interactions between efavirenz and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
ii. Etravirine (ETR)	1/2	1	1/2	1	1	1		1	1	—
iii. Nevirapine (NVP)	1/2	1	1/2	1	1	1		1	1	—
iv. Rilpivirine (RPV)	1/2	1	1/2	1	1	1		1	1	—
c. Ritonavir-boosted protease inhibitors
i. Ritonavir-boosted atazanavir (ATV/r)	1/2	1	1/2	1	2	1		2	2	Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
										CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
ii. Ritonavir-boosted darunavir (DRV/r)	1/2	1	1/2	1	2	1		2	2	Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
										CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
iii. Ritonavir-boosted fosamprenavir (FPV/r)	1/2	1	1/2	1	2	1		2	2	Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
										CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
iv. Ritonavir-boosted lopinavir (LPV/r)	1/2	1	1/2	1	1	1		1	1	—
v. Ritonavir-boosted saquinavir (SQV/r)	1/2	1	1/2	1	2	1		2	2	Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
										CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
vi. Ritonavir-boosted tipranavir (TPV/r)	1/2	1	1/2	1	2	1		2	2	Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
										CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
d. Protease inhibitors without ritonavir
i. Atazanavir (ATV)	1/2	1	1/2	1	1	1		1	2	CHCs: Theoretical concern exists that increased levels of ethinyl estradiol because of interactions with ATV might increase the risk for adverse events.
ii. Fosamprenavir (FPV)	1/2	1	1/2	1	2	2		2	3	Implants, DMPA, POP: Theoretical concern exists that interactions between FPV and hormonal contraceptives leading to decreased levels of FPV might diminish effectiveness of the antiretroviral drug. The drug interaction likely involves CYP3A4 pathways; POCs have less effect on CYP3A4 enzymes than CHCs.
										CHCs: Concern exists that interactions between FPV and hormonal contraceptives leading to decreased levels of FPV might diminish effectiveness of the antiretroviral drug.
iii. Indinavir (IDV)	1/2	1	1/2	1	1	1		1	1	—
iv. Nelfinavir (NFV)	1/2	1	1/2	1	2	1		2	2	Implants, DMPA, POP: Theoretically, drug interactions might occur between certain protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA. Concern exists that interactions between NFV and POCs might decrease NFV levels.
										CHCs: Evidence suggests drug interactions between certain protease inhibitors and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
e. CCR5 co-receptor antagonists
i. Maraviroc (MVC)	1/2	1	1/2	1	1	1		1	1	—
f. HIV integrase strand transfer inhibitors
i. Raltegravir (RAL)	1/2	1	1/2	1	1	1		1	1	—
ii. Dolutegravir (DTG)	1/2	1	1/2	1	1	1		1	1	—
iii. Elvitegravir (EVG)	1/2	1	1/2	1	1	1		1	1	—
g. Fusion inhibitors
i. Enfuvirtide	1/2	1	1/2	1	1	1		1	1	—
Psychotropic medications
a. SSRIs	1		1		1	1		1	1	—
St. John’s wort	1		1		2	1		2	2	—

Abbreviations: ARV = antiretroviral; BMI = body mass index; CHC = combined hormonal contraceptive; COC = combined oral contraceptive; Cu-IUD = copper-containing intrauterine device; DMPA = depot medroxyprogesterone acetate; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; LDL = low-density lipoprotein; LNG-IUD = levonorgestrel-releasing intrauterine device; PE = pulmonary embolism; PID = pelvic inflammatory disease; POC = progestin-only contraceptive; POP = progestin-only pill; SSRI = selective serotonin uptake inhibitor; STD = sexually transmitted disease; VTE = venous thromboembolism.

* For conditions for which classification changed for one or more contraceptive methods or the condition description underwent a major modification, the changes or modifications are in bold italics.

TABLE A2. Summary of changes for emergency contraception from U.S. Medical Eligibility Criteria for Contraceptive Use, 2010*

Condition	Category				Clarification
	Cu-IUD	UPA	LNG	COC
Pregnancy	4	NA	NA	NA	IUD: The IUD is not indicated during pregnancy and should not be used because of the risk for serious pelvic infection and septic spontaneous abortion.
					ECPs: Although this method is not indicated for a woman with a known or suspected pregnancy, no harm to the woman, the course of her pregnancy, or the fetus if ECPs are inadvertently used is known to exist.
Breastfeeding	1	1	1	1	UPA: Breastfeeding is not recommended for 24 hours after taking UPA because it is excreted in breast milk with highest concentrations in the first 24 hours, and maximum maternal serum levels are reached 1-3 hours after administration. Mean UPA concentrations in breast milk decrease markedly from 0 to 24–48 hours and then slowly decrease over 5 days (3). Breast milk should be expressed and discarded for 24 hours after taking UPA.
Past ectopic pregnancy	1	1	1	1	—
History of bariatric surgery This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy)	1	1	1	1	—
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion)	1	1	1	1	—
History of severe cardiovascular disease (ischemic heart disease, cerebrovascular attack, or other thromboembolic conditions) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1	2	2	2	—
Rheumatoid arthritis
a. Receiving immunosuppressive therapy	2	1	1	1	—
b. Not receiving immunosuppressive therapy	1	1	1	1	—
Migraine	1	1	1	2	—
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease)	1	1	1	1	—
Severe liver disease (including jaundice) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1	2	2	2	—
Solid organ transplantation This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Complicated: graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy	3	1	1	1	—
b. Uncomplicated	2	1	1	1	—
Repeated ECP use	1	1	1	1	ECPs: Recurrent ECP use is an indication that the woman requires further counseling about other contraceptive options. Frequently repeated ECP use might be harmful for women with conditions classified as 2, 3, or 4 for CHC or POC use.
Sexual assault	2	1	1	1	IUD: Women who have experienced sexual assault are at increased risk for STDs. According to CDC STD treatment guidelines, routine presumptive treatment of chlamydia, gonorrhea, and trichomonas is recommended after sexual assault (2). Women with current purulent cervicitis or chlamydial infection or gonococcal infection should not undergo IUD insertion (category 4).
Obesity (BMI =30 kg/m2)	1	2	2	2	ECPs: ECPs might be less effective among women with BMI =30 kg/m2 than among women with BMI <25 kg/m2. Despite this, no safety concerns exist.
CYP3A4 inducers (e.g., bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John’s wort, topiramate, efavirenz, and lumacaftor)	1	2	2	2	ECPs: Strong CYP3A4 inducers might reduce the effectiveness of ECPs.

Abbreviations: BMI = body mass index; CHC = combined hormonal contraceptive; COC = combined oral contraceptive; Cu-IUD = copper-containing intrauterine device; ECP = emergency contraceptive pill; IUD = intrauterine device; LNG = levonorgestrel; NA = not applicable; POC = progestin-only contraceptive; STD = sexually transmitted disease; UPA = ulipristal acetate.

* For conditions for which classification changed for one or more contraceptive methods or the condition description underwent a major modification, the changes or modifications are in bold italics.

References

1. US Department of Health and Human Services. Healthy people 2020: maternal, infant, and child health objectives. Washington, DC: US Department of Health and Human Services; 2015. http://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-child-health/objectivesexternal icon
2. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-03). PubMedexternal icon
3. Watson Pharmaceuticals. Ella [Prescribing information]. Morristown, NJ; 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022474s000lbl.pdfpdf iconexternal icon

Appendix B

Classifications for Intrauterine Devices

Classifications for intrauterine devices (IUDs) are for the copper-containing IUD and levonorgestrel-releasing IUD (containing a total of either 13.5 mg or 52 mg levonorgestrel) ( Box B1) ( Table B1). IUDs do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

TABLE B1. Classifications for intrauterine devices, including the copper-containing intrauterine device and levonorgestrel-releasing intrauterine device

Condition	Category						Clarifications/Evidence/Comments
	Cu-IUD			LNG-IUD
Personal Characteristics and Reproductive History
Pregnancy	4				4		Clarification: The IUD is not indicated during pregnancy and should not be used because of the risk for serious pelvic infection and septic spontaneous abortion.
Age
a. Menarche to <20 years	2				2		Comment: Concern exists both about the risk for expulsion from nulliparity and for STDs from sexual behavior in younger age groups.
b. =20 years	1				1		—
Parity
a. Nulliparous	2				2		Evidence: Data conflict about whether IUD use is associated with infertility among nulliparous women, although well-conducted studies suggest no increased risk (1–9).
b. Parous	1				1		—
Postpartum (including cesarean delivery)
a. <10 minutes after delivery of the placenta							Clarification: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower. Clarification (breastfeeding): Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (10). Evidence: Studies suggest that immediate postplacental (<10 minutes) and early postpartum (10 minutes up until 72 hours) placement of Cu-IUDs and LNG-IUDs is associated with increased risk for expulsion compared with interval placement (i.e., not related to pregnancy). Early postpartum placement has similar or increased risk for expulsion compared with immediate postplacental placement. Although immediate postplacental placement at the time of cesarean delivery might have increased risk for expulsion compared with interval placement, risk appears lower than that for placement at the time of vaginal delivery. Evidence for infection, perforation, and removals for pain or bleeding are limited; however, these events are rare (11–62). Evidence (breastfeeding): Two randomized controlled trials found conflicting results on breastfeeding outcomes when LNG-IUDs were initiated immediately postpartum compared with 6–8 weeks postpartum. Initiation of LNG-IUDs immediately postpartum had no other harmful effect on infant health, growth, or development (63,64). Breastfeeding women using IUDs do not have an increased risk for certain IUD-related adverse events including expulsion, infection, pain, or bleeding compared with nonbreastfeeding women. The risk for perforation is increased independently among breastfeeding women and among women =36 weeks postpartum, compared with non-postpartum women; however, the absolute risk for perforation remains low (11–62,65). Comment (breastfeeding): Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
i. Breastfeeding	1				2
ii. Nonbreastfeeding	1				1
b. 10 minutes after delivery of the placenta to <4 weeks (breastfeeding or nonbreastfeeding)	2				2		Clarification: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
							Clarification (breastfeeding): Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (10).
							Evidence: Studies suggest that immediate postplacental (<10 minutes) and early postpartum (10 minutes up until 72 hours) placement of Cu-IUDs and LNG-IUDs is associated with increased risk for expulsion compared with interval placement (i.e., not related to pregnancy). Early postpartum placement has similar or increased risk for expulsion compared with immediate postplacental placement. Although immediate postplacental placement at the time of cesarean delivery might have increased risk for expulsion compared with interval placement, risk appears lower than that for placement at the time of vaginal delivery. Evidence for infection, perforation, and removals for pain or bleeding are limited; however, these events are rare (11–62).
							Evidence (breastfeeding): Two randomized controlled trials found conflicting results on breastfeeding outcomes when LNG-IUDs were initiated immediately postpartum compared with 6–8 weeks postpartum. Initiation of LNG-IUDs immediately postpartum had no other harmful effect on infant health, growth, or development (63,64). Breastfeeding women using IUDs do not have an increased risk for certain IUD-related adverse events including expulsion, infection, pain, or bleeding compared with nonbreastfeeding women. The risk for perforation is increased independently among breastfeeding women and among women =36 weeks postpartum, compared with non-postpartum women; however, the absolute risk for perforation remains low (11–62,65).
							Comment (breastfeeding): Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
c. =4 weeks (breastfeeding or nonbreastfeeding)	1				1		Clarification: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
							Clarification (breastfeeding): Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (10).
							Evidence (breastfeeding): Initiation of LNG-IUDs at 4 weeks postpartum or later demonstrated no detrimental effect on breastfeeding outcomes and no harmful effect on infant health, growth, or development (63,64). Breastfeeding women using IUDs do not have an increased risk for certain IUD-related adverse events including expulsion, infection, pain, or bleeding compared with nonbreastfeeding women. The risk for perforation is increased independently among breastfeeding women and among women =36 weeks postpartum, compared with non-postpartum women; however, the absolute risk for perforation remains low (11–62,65).
							Comment (breastfeeding): Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
d. Postpartum sepsis	4				4		Comment: Theoretical concern exists that postpartum insertion of an IUD in a women with recent chorioamnionitis or current endometritis might be associated with increased complications.
Postabortion
a. First trimester	1				1		Clarification: IUDs can be inserted immediately after spontaneous or induced abortion. Evidence: Risk for complications from immediate versus delayed insertion of an IUD after abortion did not differ. Expulsion was greater when an IUD was inserted after a second trimester abortion than when inserted after a first trimester abortion. Safety or expulsion for postabortion insertion of an LNG-IUD did not differ from that of a Cu-IUD (66).
b. Second trimester	2				2
c. Immediate postseptic abortion	4				4		Comment: Insertion of an IUD might substantially worsen the condition.
Past ectopic pregnancy	1				1		Comment: The absolute risk for ectopic pregnancy is extremely low because of the high effectiveness of IUDs. However, when a woman becomes pregnant during IUD use, the relative likelihood of ectopic pregnancy increases substantially.
History of pelvic surgery (see Postpartum [Including Cesarean Delivery] section)	1				1		—
Smoking
a. Age <35 years	1				1		—
b. Age =35 years
i. <15 cigarettes per day	1				1		—
ii. =15 cigarettes per day	1				1		—
Obesity
a. BMI =30 kg/m2	1				1		—
b. Menarche to <18 years and BMI =30 kg/m2	1				1		—
History of bariatric surgery This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy)	1				1		—
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion)	1				1		—
Cardiovascular Disease
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels)	1				2		—
Hypertension Systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Adequately controlled hypertension	1				1		Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
b. Elevated blood pressure levels (properly taken measurements)							Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. Comment: Theoretical concern exists about the effect of LNG on lipids. Use of Cu-IUDs has no restrictions.
i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg	1				1
ii. Systolic =160 mm Hg or diastolic =100 mm Hg	1				2
c. Vascular disease	1				2		Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
							Comment: Theoretical concern exists about the effect of LNG on lipids. Use of Cu-IUDs has no restrictions.
History of high blood pressure during pregnancy (when current blood pressure is measurable and normal)	1				1		—
Deep venous thrombosis/Pulmonary embolism
a. History of DVT/PE, not receiving anticoagulant therapy
i. Higher risk for recurrent DVT/PE (one or more risk factors)	1				2		—
• History of estrogen-associated DVT/PE • Pregnancy-associated DVT/PE • Idiopathic DVT/PE • Known thrombophilia, including antiphospholipid syndrome • Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer • History of recurrent DVT/PE
ii. Lower risk for recurrent DVT/PE (no risk factors)	1				2		—
b. Acute DVT/PE	2				2		Evidence: No direct evidence exists on the use of POCs among women with acute DVT/PE. Although findings on the risk for venous thrombosis with the use of POCs in otherwise healthy women are inconsistent, any small increased risk is substantially less than that with COCs (67–69).
c. DVT/PE and established anticoagulant therapy for at least 3 months							Evidence: No direct evidence exists on the use of POCs among women with acute DVT/PE. Although findings on the risk for venous thrombosis with the use of POCs in otherwise healthy women are inconsistent, any small increased risk is substantially less than that with COCs (67–69). Evidence: Limited evidence indicates that insertion of the LNG-IUD does not pose major bleeding risks in women receiving chronic anticoagulant therapy (70–73). Comment: The LNG-IUD might be a useful treatment for menorrhagia in women receiving long-term anticoagulation therapy.
i. Higher risk for recurrent DVT/PE (one or more risk factors)	2				2		—
• Known thrombophilia, including antiphospholipid syndrome • Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer • History of recurrent DVT/PE
ii. Lower risk for recurrent DVT/PE (no risk factors)	2				2		—
d. Family history (first-degree relatives)	1				1		—
e. Major surgery
i. With prolonged immobilization	1				2		—
ii. Without prolonged immobilization	1				1		—
f. Minor surgery without immobilization	1				1
Known thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; and protein S, protein C, and antithrombin deficiencies) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1				2		Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.
Superficial venous disorders
a. Varicose veins	1				1		—
b. Superficial venous thrombosis (acute or history)	1				1		—
Current and history of ischemic heart disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1				Initiation	Continuation	Comment: Theoretical concern exists about the effect of LNG on lipids. Use of Cu-IUDs has no restrictions.
					2	3
Stroke (history of cerebrovascular accident) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1				2		Comment: Theoretical concern exists about the effect of LNG on lipids. Use of Cu-IUDs has no restrictions.
Valvular heart disease Complicated valvular heart disease is a condition associated with increased risk for adverse health events as a result of pregnancy (Box 2).							Comment: According to the American Heart Association, administration of prophylactic antibiotics solely to prevent endocarditis is not recommended for patients who undergo genitourinary tract procedures, including insertion or removal of IUDs (74).
a. Uncomplicated	1				1
b. Complicated (pulmonary hypertension, risk for atrial fibrillation, or history of subacute bacterial endocarditis)	1				1
Peripartum cardiomyopathy This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).							Evidence: No direct evidence exists on the safety of IUDs among women with peripartum cardiomyopathy. Limited indirect evidence from noncomparative studies did not demonstrate any cases of arrhythmia or infective endocarditis in women with cardiac disease who used IUDs (75). Comment: IUD insertion might induce cardiac arrhythmias in healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (76)
i. <6 months	2				2
ii. =6 months	2				2
b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (76)	2				2
Rheumatic Diseases
Systemic lupus erythematosus This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	Initiation	Continuation
a. Positive (or unknown) antiphospholipid antibodies	1	1			3		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (73,77–94).
							Evidence: Antiphospholipid antibodies are associated with a higher risk for both arterial and venous thrombosis (95,96).
b. Severe thrombocytopenia	3	2			2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (73,77–94).
							Clarification: Severe thrombocytopenia increases the risk for bleeding. The category should be assessed according to the severity of thrombocytopenia and its clinical manifestations. In women with very severe thrombocytopenia who are at risk for spontaneous bleeding, consultation with a specialist and certain pretreatments might be warranted.
							Evidence: The LNG-IUD might be a useful treatment for menorrhagia in women with severe thrombocytopenia (73).
c. Immunosuppressive therapy	2	1			2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (73,77–94).
d. None of the above	1	1			2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (73,77–94).
Rheumatoid arthritis	Initiation	Continuation			Initiation	Continuation
a. Receiving immunosuppressive therapy	2	1			2	1	—
b. Not receiving immunosuppressive therapy	1				1		—
Neurologic Conditions
Headaches
a. Nonmigraine (mild or severe)	1				1		—
b. Migraine
i. Without aura (This category of migraine includes menstrual migraine.)	1				1		Evidence: No studies directly examined the risk for stroke among women with migraine using LNG-IUDs (97). Limited evidence demonstrated that women using LNG-IUDs do not have an increased risk for ischemic stroke compared with women not using hormonal contraceptives (98). Comment: Menstrual migraine is a subtype of migraine without aura. For more information see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdfpdf iconexternal icon).
ii. With aura	1				1
Epilepsy This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1				1		—
Multiple sclerosis
a. With prolonged immobility	1				1		—
b. Without prolonged immobility	1				1		—
Depressive Disorders
Depressive disorders	1				1		Clarification: If a woman is receiving psychotropic medications or St. John’s wort, see Drug Interactions section.
							Evidence: The frequency of psychiatric hospitalizations for women with bipolar disorder or depression did not significantly differ among women using DMPA, LNG-IUD, Cu-IUD, or sterilization (99).
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns					Initiation	Continuation
a. Irregular pattern without heavy bleeding	1				1	1	—
b. Heavy or prolonged bleeding (includes regular and irregular patterns)	2				1	2	Clarification: Unusually heavy bleeding should raise suspicion of a serious underlying condition.
							Evidence: Evidence from studies examining the treatment effects of the LNG-IUD among women with heavy or prolonged bleeding reported no increase in adverse effects and found the LNG-IUD to be beneficial in treating menorrhagia (100–107).
Unexplained vaginal bleeding (suspicious for serious condition) before evaluation	Initiation 4	Continuation 2			Initiation 4	Continuation 2	Clarification: If pregnancy or an underlying pathological condition (e.g., pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation. The IUD does not need to be removed before evaluation.
Endometriosis	2				1		Evidence: LNG-IUD use among women with endometriosis decreased dysmenorrhea, pelvic pain, and dyspareunia (108–112).
Benign ovarian tumors (including cysts)	1				1		—
Severe dysmenorrhea	2				1		Comment: Dysmenorrhea might intensify with Cu-IUD use. LNG-IUD use has been associated with reduction of dysmenorrhea.
Gestational trophoblastic disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Suspected gestational trophoblastic disease (immediate postevacuation)							Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance. Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113). Comment: The risk for expulsion immediately postevacuation for gestational trophoblastic disease is unknown. Expulsion is greater after IUD insertion immediately postevacuation for a spontaneous or induced abortion in the second trimester compared with IUD insertion after a first trimester abortion.
i. Uterine size first trimester	1				1
ii. Uterine size second trimester	2				2
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring)	Initiation	Continuation			Initiation	Continuation
i. Undetectable/nonpregnant ß-hCG levels	1	1			1	1	Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
							Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
							Comment: Once ß-hCG levels have decreased to nonpregnant levels, the risk for disease progression is likely to be very low.
ii. Decreasing ß-hCG levels	2	1			2	1	Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
							Clarification: For women at higher risk for disease progression, the benefits of effective contraception must be weighed against the potential need for early IUD removal.
							Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease	2	1			2	1	Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
							Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease	4	2			4	2	Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
							Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
							Comment: For women with suspected or confirmed intrauterine disease, an IUD should not be inserted because of theoretical risk for perforation, infection, and hemorrhage. For women who already have an IUD in place, individual circumstance along with the benefits of effective contraception must be weighed against theoretical risks of either removal or continuation of the IUD.
Cervical ectropion	1				1		—
Cervical intraepithelial neoplasia	1				2		Comment: Theoretical concern exists that LNG-IUDs might enhance progression of cervical intraepithelial neoplasia.
Cervical cancer (awaiting treatment)	Initiation		Continuation		Initiation	Continuation	Comment: Concern exists about the increased risk for infection and bleeding at insertion. The IUD most likely will need to be removed at the time of treatment but until then, the woman is at risk for pregnancy.
	4		2		4	2
Breast disease Breast cancer is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Undiagnosed mass	1				2		—
b. Benign breast disease	1				1		—
c. Family history of cancer	1				1		—
d. Breast cancer							Comment: Breast cancer is a hormonally sensitive tumor. Concerns about progression of the disease might be less with LNG-IUDs than with COCs or higher-dose POCs.
i. Current	1				4
ii. Past and no evidence of current disease for 5 years	1				3
Endometrial hyperplasia	1				1		Evidence: Among women with endometrial hyperplasia, no adverse health events occurred with LNG-IUD use; most women experienced disease regression (114).
Endometrial cancer This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	Initiation		Continuation		Initiation	Continuation	Comment: Concern exists about the increased risk for infection, perforation, and bleeding at insertion. The IUD most likely will need to be removed at the time of treatment, but until then, the woman is at risk for pregnancy.
	4		2		4	2
Ovarian cancer This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1				1		Comment: Women with ovarian cancer who undergo fertility-sparing treatment and need contraception may use an IUD.
Uterine fibroids	2				2		Evidence: Among women with uterine fibroids using an LNG-IUD, most experienced improvements in serum levels of hemoglobin, hematocrit, and ferritin and in menstrual blood loss (115). Rates of LNG-IUD expulsion were higher in women with uterine fibroids (11%) than in women without fibroids (0%–3%); these findings were either not statistically significant or significance testing was not conducted (115). Rates of expulsion found in noncomparative studies ranged from 0%–20% (115).
							Comment: Women with heavy or prolonged bleeding should be assigned the category for that condition.
Anatomical abnormalities
a. Distorted uterine cavity (any congenital or acquired uterine abnormality distorting the uterine cavity in a manner that is incompatible with IUD insertion)	4				4		Comment: An anatomical abnormality that distorts the uterine cavity might preclude proper IUD placement.
b. Other abnormalities (including cervical stenosis or cervical lacerations) not distorting the uterine cavity or interfering with IUD insertion	2				2		—
Pelvic inflammatory disease	Initiation		Continuation		Initiation	Continuation
a. Past PID							Comment: IUDs do not protect against STDs, including HIV, or PID. In women at low risk for STDs, IUD insertion poses little risk for PID.
i. With subsequent pregnancy	1		1		1	1
ii. Without subsequent pregnancy	2		2		2	2
b. Current PID	4		2		4	2	Clarification (continuation): Treat the PID using appropriate antibiotics. The IUD usually does not need to be removed if the woman wants to continue using it. Continued use of an IUD depends on the woman’s informed choice and her current risk factors for STDs and PID.
							Evidence: Among IUD users treated for PID, clinical course did not differ regardless of whether the IUD was removed or left in place (116).
Sexually transmitted diseases	Initiation		Continuation		Initiation	Continuation
a. Current purulent cervicitis or chlamydial infection or gonococcal infection	4		2		4	2	Clarification (continuation): Treat the STD using appropriate antibiotics. The IUD usually does not need to be removed if the woman wants to continue using it. Continued use of an IUD depends on the woman’s informed choice and her current risk factors for STDs and PID.
							Evidence: Among women who had an IUD inserted, the absolute risk for subsequent PID was low among women with STD at the time of insertion but greater than among women with no STD at the time of IUD insertion (117–123).
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis)	2		2		2	2	—
c. Other factors related to STDs	2		2		2	2	Clarification (initiation): Most women do not require additional STD screening at the time of IUD insertion. If a woman with risk factors for STDs has not been screened for gonorrhea and chlamydia according to CDC STD treatment guidelines (124), screening may be performed at the time of IUD insertion and insertion should not be delayed.
							Evidence: Women who undergo same-day STD screening and IUD insertion have low incidence rates of PID. Algorithms for predicting PID among women with risk factors for STDs have poor predictive value. Risk for PID among women with risk factors for STDs is low (125).
HIV
High risk for HIV	Initiation		Continuation		Initiation	Continuation	Evidence: Among women at risk for HIV, Cu-IUD use did not increase risk for HIV acquisition (126–136).
	2		2		2	2
HIV infection For women with HIV infection who are not clinically well or not receiving ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).							Evidence: Among IUD users, limited evidence shows a low risk for PID among HIV-infected women using IUDs and no higher risk for pelvic infectious complications in HIV-infected than in HIV-noninfected women or among women with varying degrees of HIV severity. IUD use did not adversely affect progression of HIV during 6–45 months of follow-up or when compared with hormonal contraceptive use among HIV-infected women. Furthermore, IUD use among HIV-infected women was not associated with increased risk for transmission to sex partners or with increased genital viral shedding (137).
a. Clinically well receiving ARV therapy	1		1		1	1
b. Not clinically well or not receiving ARV therapy	2		1		2	1
Other Infections
Schistosomiasis Schistosomiasis with fibrosis of the liver is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated	1				1		—
b. Fibrosis of the liver (if severe, see Cirrhosis section)	1				1		—
Tuberculosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	Initiation		Continuation		Initiation	Continuation
a. Nonpelvic	1		1		1	1	—
b. Pelvic	4		3		4	3	Comment: Insertion of an IUD might substantially worsen the condition.
Malaria	1				1		—
Endocrine Conditions
Diabetes Insulin-dependent diabetes; diabetes with nephropathy, retinopathy, or neuropathy; diabetes with other vascular disease; or diabetes of >20 years’ duration are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. History of gestational disease	1				1		—
b. Nonvascular disease							Evidence: Limited evidence on the use of the LNG-IUD among women with insulin-dependent or non–insulin-dependent diabetes suggests that these methods have little effect on short-term or long-term diabetes control (e.g., glycosylated hemoglobin levels), hemostatic markers, or lipid profile (138,139).
i. Non-insulin dependent	1				2
ii. Insulin dependent	1				2
c. Nephropathy, retinopathy, or neuropathy	1				2		—
d. Other vascular disease or diabetes of >20 years’ duration	1				2		—
Thyroid disorders
a. Simple goiter	1				1		—
b. Hyperthyroid	1				1		—
c. Hypothyroid	1				1		—
Gastrointestinal Conditions
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease)	1				1		Evidence: Although two case reports described three women with IBD who experienced exacerbation of disease 5 days–25 months after LNG-IUD insertion, no comparative studies have examined the safety of IUD use among women with IBD (140).
Gallbladder disease
a. Symptomatic
i. Treated by cholecystectomy	1				2		—
ii. Medically treated	1				2		—
iii. Current	1				2		—
b. Asymptomatic	1				2		—
History of cholestasis
a. Pregnancy related	1				1		—
b. Past COC related	1				2		Comment: Concern exists that history of COC related cholestasis might predict subsequent cholestasis with LNG use. Whether risk exists with use of LNG-IUD is unclear.
Viral hepatitis
a. Acute or flare	1				1		—
b. Carrier	1				1		—
c. Chronic	1				1		—
Cirrhosis Severe cirrhosis is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Mild (compensated)	1				1		—
b. Severe (decompensated)	1				3		—
Liver tumors Hepatocellular adenoma and malignant liver tumors are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Benign
i. Focal nodular hyperplasia	1				2		—
ii. Hepatocellular adenoma	1				3		Comment: No evidence is available about hormonal contraceptive use in women with hepatocellular adenoma. COC use in healthy women is associated with development and growth of hepatocellular adenoma; whether other hormonal contraceptives have similar effects is not known.
b. Malignant (hepatoma)	1				3		—
Respiratory Conditions
Cystic fibrosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1				1		Clarification: Persons with cystic fibrosis are at increased risk for diabetes, liver disease, gallbladder disease, and VTE (particularly related to use of central venous catheters) and are frequently prescribed antibiotics. Categories assigned to such conditions in U.S. MEC should be the same for women with cystic fibrosis who have these conditions. For cystic fibrosis, classifications are based on the assumption that no other conditions are present; these classifications must be modified in the presence of such conditions.
Anemias
Thalassemia	2				1		Comment: Concern exists about an increased risk for blood loss with Cu-IUDs.
Sickle cell disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	2				1		Comment: Concern exists about an increased risk for blood loss with Cu-IUDs.
Iron deficiency anemia	2				1		Comment: Concern exists about an increased risk for blood loss with Cu-IUDs.
Solid Organ Transplantation
Solid organ transplantation This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	Initiation	Continuation			Initiation	Continuation	Evidence: No comparative studies have examined IUD use among transplant patients. Four case reports of transplant patients using IUDs provided inconsistent results, including beneficial effects and contraceptive failures (141).
a. Complicated: graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy	3	2			3	2
b. Uncomplicated	2	2			2	2
Drug Interactions
Antiretroviral therapy	Initiation	Continuation			Initiation	Continuation	Clarification: No known interaction exists between ARV therapy and IUD use. However, IUD insertion is classified as category 2 if the woman is not clinically well or not receiving ARV therapy. Otherwise, both insertion and continuation are classified as category 1 (see HIV Infection section).
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
i. Abacavir (ABC)	1/2	1			1/2	1	—
ii. Tenofovir (TDF)	1/2	1			1/2	1	—
iii. Zidovudine (AZT)	1/2	1			1/2	1	—
iv. Lamivudine (3TC)	1/2	1			1/2	1	—
v. Didanosine (DDI)	1/2	1			1/2	1	—
vi. Emtricitabine (FTC)	1/2	1			1/2	1	—
vii. Stavudine (D4T)	1/2	1			1/2	1	—
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
i. Efavirenz (EFV)	1/2	1			1/2	1	—
ii. Etravirine (ETR)	1/2	1			1/2	1	—
iii. Nevirapine (NVP)	1/2	1			1/2	1	—
iv. Rilpivirine (RPV)	1/2	1			1/2	1	—
c. Ritonavir-boosted protease inhibitors
i. Ritonavir-boosted atazanavir (ATV/r)	1/2	1			1/2	1	—
ii. Ritonavir-boosted darunavir (DRV/r)	1/2	1			1/2	1	—
iii. Ritonavir-boosted fosamprenavir (FPV/r)	1/2	1			1/2	1	—
iv. Ritonavir-boosted lopinavir (LPV/r)	1/2	1			1/2	1	—
v. Ritonavir-boosted saquinavir (SQV/r)	1/2	1			1/2	1	—
vi. Ritonavir-boosted tipranavir (TPV/r)	1/2	1			1/2	1	—
d. Protease inhibitors without ritonavir
i. Atazanavir (ATV)	1/2	1			1/2	1	—
ii. Fosamprenavir (FPV)	1/2	1			1/2	1	—
iii. Indinavir (IDV)	1/2	1			1/2	1	—
iv. Nelfinavir (NFV)	1/2	1			1/2	1	—
e. CCR5 co-receptor antagonists
i. Maraviroc (MVC)	1/2	1			1/2	1	—
f. HIV integrase strand transfer inhibitors
i. Raltegravir (RAL)	1/2	1			1/2	1	—
ii. Dolutegravir (DTG)	1/2	1			1/2	1	—
iii. Elvitegravir (EVG)	1/2	1			1/2	1	—
g. Fusion inhibitors
i. Enfuvirtide	1/2	1			1/2	1	—
Anticonvulsant therapy
a. Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, and oxcarbazepine)	1				1		Evidence: Limited evidence suggests use of certain anticonvulsants does not interfere with the contraceptive effectiveness of the LNG-IUD (142).
b. Lamotrigine	1				1		Evidence: No drug interactions have been reported among women with epilepsy who are receiving lamotrigine and using the LNG-IUD (143).
Antimicrobial therapy
a. Broad-spectrum antibiotics	1				1		—
b. Antifungals	1				1		—
c. Antiparasitics	1				1		—
d. Rifampin or rifabutin therapy	1				1		Evidence: One cross-sectional survey found that rifabutin had no impact on the effectiveness of the LNG-IUD (142).
Psychotropic medications							Comment: For many common psychotropic agents, limited or no theoretical concern exists for clinically significant drug interactions when co-administered with hormonal contraceptives. However, either no or very limited data exist examining potential interactions for these classes of medications.
a. SSRIs	1				1		—
St. John’s wort	1				1		—

Abbreviations: ARV = antiretroviral; BMI = body mass index; COC = combined oral contraceptive; Cu-IUD = copper-containing IUD; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; IBD = inflammatory bowel disease; IUD = intrauterine device; LDL = low-density lipoprotein; LNG = levonorgestrel; LNG-IUD = levonorgestrel-releasing IUD; PE = pulmonary embolism; PID = pelvic inflammatory disease; POC = progestin-only contraceptive; SLE = systemic lupus erythematosus; SSRI = selective serotonin reuptake inhibitor; STD = sexually transmitted disease; VTE = venous thromboembolism.

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Appendix C

Classifications for Progestin-Only Contraceptives

Classifications for progestin-only contraceptives (POCs) include those for progestin-only implants, depot medroxyprogesterone acetate (DMPA; 150 mg intramuscularly or 104 mg subcutaneously), and progestin-only pills (POPs) ( Box C1) ( Table C1). POCs do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

TABLE C1. Classifications for progestin-only contraceptives, including implants, depot medroxyprogesterone acetate, and progestin-only pills

Condition	Category						Clarifications/Evidence/Comments
	Implants		DMPA		POPs
Personal Characteristics and Reproductive History
Pregnancy	NA		NA		NA		Clarification: Use of POCs is not required. No known harm to the woman, the course of her pregnancy, or the fetus occurs if POCs are inadvertently used during pregnancy. However, the relation between DMPA use during pregnancy and its effects on the fetus remains unclear.
Age							Evidence: Most studies have found that women lose BMD during DMPA use but recover BMD after discontinuation. Limited evidence shows a weak association with fracture. However, one large study suggests that women who choose DMPA might be at higher risk for fracture before initiation (1). It is unclear whether adult women with long durations of DMPA use can regain BMD to baseline levels before entering menopause and whether adolescents can reach peak bone mass after discontinuation of DMPA. The relationship between these changes in BMD during the reproductive years and future fracture risk is unknown. Studies generally find no effect of POCs other than DMPA on BMD (1–48).
a. Menarche to <18 years	1		2		1
b. 18–45 years	1		1		1
c. >45 years	1		2		1
Parity
a. Nulliparous	1		1		1		—
b. Parous	1		1		1		—
Breastfeeding
a. <21 days postpartum	2		2		2		Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (49).
							Evidence: Two small, randomized controlled trials found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at =6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (50,51).
							Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
b. 21 to <30 days postpartum							Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (49). Evidence: Two small, randomized controlled trials found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at =6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (50,51). Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	2		2		2
ii. Without other risk factors for VTE	2		2		2
c. 30–42 days postpartum							Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (49). Evidence: Two small, randomized controlled trials found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at =6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (50,51). Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	1		1		1
ii. Without other risk factors for VTE	1		1		1
d. >42 days postpartum	1		1		1		Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (49).
							Evidence: Overall, studies found that initiation of POPs, injectables, and implants at >6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (51).
							Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
Postpartum (nonbreastfeeding women)
a. <21 days postpartum	1		1		1		—
b. 21–42 days postpartum
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	1		1		1		—
ii. Without other risk factors for VTE	1		1		1		—
c. >42 days postpartum	1		1		1		—
Postabortion
a. First trimester	1		1		1		Clarification: POCs may be started immediately postabortion. Evidence: Limited evidence suggests that no adverse side effects occur when implants (Norplant) or progestin-only injectables (NET-EN) are initiated after first trimester abortion (52–55).
b. Second trimester	1		1		1		Clarification: POCs may be started immediately postabortion.
c. Immediate postseptic abortion	1		1		1		Clarification: POCs may be started immediately postabortion.
Past ectopic pregnancy	1		1		2		Comment: POP users have a higher absolute rate of ectopic pregnancy than do users of other POCs but still lower than women using no method.
History of pelvic surgery	1		1		1		—
Smoking
a. Age <35 years	1		1		1		—
b. Age =35 years
i. <15 cigarettes per day	1		1		1		—
ii. =15 cigarettes per day	1		1		1		—
Obesity							—
a. BMI =30 kg/m2	1		1		1		—
b. Menarche to <18 years and BMI =30 kg/m2	1		2		1		Evidence: Among adult women, generally no association has been found between baseline weight and weight gain among DMPA users compared with nonusers. Evidence is mixed for adolescent DMPA users, with some studies observing greater weight gain among obese compared with normal weight users but other studies showing no association; methodologic differences across studies might account for the differences in findings. Data on other POC methods and other adverse outcomes including weight gain are limited (56–73).
History of bariatric surgery This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy)	1		1		1		Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives among women who underwent laparoscopic placement of an adjustable gastric band (74).
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion)	1		1		3		Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives among women who underwent a biliopancreatic diversion; however, evidence from pharmacokinetic studies suggested conflicting results regarding oral contraceptive effectiveness among women who underwent a jejunoileal bypass (74).
							Comment: Bariatric surgical procedures involving a malabsorptive component have the potential to decrease oral contraceptive effectiveness, perhaps further decreased by postoperative complications such as long-term diarrhea, vomiting, or both.
Cardiovascular Disease
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels)	2		3		2		Clarification: When multiple major risk factors exist, risk for cardiovascular disease might increase substantially. Certain POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs. The effects of DMPA might persist for some time after discontinuation.
							Clarification: The recommendations apply to known preexisting medical conditions or characteristics. Few if any screening tests are needed before initiation of contraception. See the U.S. Selected Practice Recommendations for Contraceptive Use (http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usspr.htm).
Hypertension Systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Adequately controlled hypertension	1		2		1		Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
							Clarification: Women adequately treated for hypertension are at lower risk for acute myocardial infarction and stroke than are untreated women. Although no data exist, POC users with adequately controlled and monitored hypertension should be at lower risk for acute myocardial infarction and stroke than are untreated hypertensive POC users.
b. Elevated blood pressure levels (properly taken measurements)							Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. Evidence: Limited evidence suggests that among women with hypertension, those who used POPs or progestin-only injectables had a small increased risk for cardiovascular events compared with women who did not use these methods (75).
i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg	1		2		1
ii. Systolic =160 mm Hg or diastolic =100 mm Hg	2		3		2
c. Vascular disease	2		3		2		Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
							Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. However, little concern exists about these effects with regard to POPs. The effects of DMPA might persist for some time after discontinuation.
History of high blood pressure during pregnancy (when current blood pressure is measurable and normal)	1		1		1		—
Deep venous thrombosis/Pulmonary embolism
a. History of DVT/PE, not receiving anticoagulant therapy
i. Higher risk for recurrent DVT/PE (one or more risk factors)	2		2		2		—
• History of estrogen-associated DVT/PE • Pregnancy-associated DVT/PE • Idiopathic DVT/PE • Known thrombophilia, including antiphospholipid syndrome • Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer • History of recurrent DVT/PE
ii. Lower risk for recurrent DVT/PE (no risk factors)	2		2		2		—
b. Acute DVT/PE	2		2		2		Evidence: No direct evidence exists on use of POCs among women with acute DVT/PE. Although findings on the risk for venous thrombosis with use of POCs in otherwise healthy women is inconsistent, any small increased risk is substantially less than that with COCs (75–77).
c. DVT/PE and established anticoagulant therapy for at least 3 months							Evidence: No direct evidence exists on use of POCs among women with DVT/PE receiving anticoagulant therapy. Although findings on the risk for venous thrombosis with use of POCs is inconsistent in otherwise healthy women, any small increased risk is substantially less than that with COCs (75–77). Limited evidence indicates that intramuscular injections of DMPA in women receiving chronic anticoagulation therapy does not pose a significant risk for hematoma at the injection site or increase the risk for heavy or irregular vaginal bleeding (78).
i. Higher risk for recurrent DVT/PE (one or more risk factors)	2		2		2
• Known thrombophilia, including antiphospholipid syndrome • Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer • History of recurrent DVT/PE
ii. Lower risk for recurrent DVT/PE (no risk factors)	2		2		2
d. Family history (first-degree relatives)	1		1		1		—
e. Major surgery
i. With prolonged immobilization	2		2		2		—
ii. Without prolonged immobilization	1		1		1		—
f. Minor surgery without immobilization	1		1		1		—
Known thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; and protein S, protein C, and antithrombin deficiencies) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	2		2		2		Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.
Superficial venous disorders
a. Varicose veins	1		1		1		—
b. Superficial venous thrombosis (acute or history)	1		1		1		—
Current and history of ischemic heart disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	Initiation	Continuation			Initiation	Continuation	Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. However, little concern exists about these effects with regard to POPs. The effects of DMPA might persist for some time after discontinuation.
	2	3	3		2	3
Stroke (history of cerebrovascular accident) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	Initiation	Continuation			Initiation	Continuation	Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. However, little concern exists about these effects with regard to POPs. The effects of DMPA might persist for some time after discontinuation.
	2	3	3		2	3
Valvular heart disease Complicated valvular heart disease is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated	1		1		1		—
b. Complicated (pulmonary hypertension, risk for atrial fibrillation, or history of subacute bacterial endocarditis)	1		1		1		—
Peripartum cardiomyopathy This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).							Evidence: No direct evidence exists on the safety of POCs among women with peripartum cardiomyopathy. Limited indirect evidence from noncomparative studies of women with cardiac disease demonstrated few cases of hypertension, thromboembolism, and heart failure in women with cardiac disease using POPs and DMPA (79). Comment: Progestin-only implants might induce cardiac arrhythmias in healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (80)
i. <6 months	1		1		1
ii. =6 months	1		1		1
b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (80)	2		2		2
Rheumatic Diseases
Systemic lupus erythematosus This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).			Initiation	Continuation
a. Positive (or unknown) antiphospholipid antibodies	3		3	3	3		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (81–99).
							Evidence: Antiphospholipid antibodies are associated with a higher risk for both arterial and venous thrombosis (100,101).
b. Severe thrombocytopenia	2		3	2	2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (81–99).
							Comment: Severe thrombocytopenia increases the risk for bleeding. POCs might be useful in treating menorrhagia in women with severe thrombocytopenia. However, given the increased or erratic bleeding that might be seen on initiation of DMPA and its irreversibility for 11–13 weeks after administration, initiation of this method in women with severe thrombocytopenia should be done with caution.
c. Immunosuppressive therapy	2		2	2	2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (81–99).
d. None of the above	2		2	2	2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (81–99).
Rheumatoid arthritis
a. Receiving immunosuppressive therapy	1		2/3		1		Clarification (DMPA): DMPA use among women receiving long-term corticosteroid therapy with a history of, or with risk factors for, nontraumatic fractures is classified as category 3. Otherwise, DMPA use for women with rheumatoid arthritis is classified as category 2.
							Evidence: Limited evidence shows no consistent pattern of improvement or worsening of rheumatoid arthritis with use of oral contraceptives, progesterone, or estrogen (102).
b. Not receiving immunosuppressive therapy	1		2		1		Evidence: Limited evidence shows no consistent pattern of improvement or worsening of rheumatoid arthritis with use of oral contraceptives, progesterone, or estrogen (102).
Neurologic Conditions
Headaches
a. Nonmigraine (mild or severe)	1		1		1		—
b. Migraine							Evidence: No studies directly examined the risk for stroke among women with migraine using POCs (103). Limited evidence demonstrated that women using POPs, DMPA, or implants do not have an increased risk for ischemic stroke compared with nonusers (104). Comment: Menstrual migraine is a subtype of migraine without aura. For more information, see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdfpdf iconexternal icon).
i. Without aura (This category of migraine includes menstrual migraine.)	1		1		1
ii. With aura	1		1		1
Epilepsy This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		1		1		Clarification: If a woman is taking anticonvulsants, see Drug Interactions section. Certain anticonvulsants lower POC effectiveness.
Multiple sclerosis							Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with multiple sclerosis does not worsen the clinical course of disease (105). Comment: Women with multiple sclerosis might have compromised bone health from disease-related disability, immobility, and use of corticosteroids. Use of DMPA, which has been associated with small changes in BMD, might be of concern.
a. With prolonged immobility	1		2		1
b. Without prolonged immobility	1		2		1
Depressive Disorders
Depressive disorders	1		1		1		Clarification: If a woman is taking psychotropic medications or St. John’s wort, see Drug Interactions section.
							Evidence: The frequency of psychiatric hospitalizations for women with bipolar disorder or depression did not significantly differ among women using DMPA, LNG-IUD, Cu-IUD, or sterilization (106).
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns
a. Irregular pattern without heavy bleeding	2		2		2		Comment: Irregular menstrual bleeding patterns are common among healthy women. POC use frequently induces an irregular bleeding pattern. Implant use might induce irregular bleeding patterns, especially during the first 3–6 months, although these patterns might persist longer.
b. Heavy or prolonged bleeding (includes regular and irregular patterns)	2		2		2		Clarification: Unusually heavy bleeding should raise the suspicion of a serious underlying condition.
Unexplained vaginal bleeding (suspicious for serious condition) before evaluation	3		3		2		Clarification: If pregnancy or an underlying pathological condition (e.g., pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation.
							Comment: POCs might cause irregular bleeding patterns, which might mask symptoms of underlying pathologic conditions. The effects of DMPA might persist for some time after discontinuation.
Endometriosis	1		1		1		—
Benign ovarian tumors (including cysts)	1		1		1		—
Severe dysmenorrhea	1		1		1		—
Gestational trophoblastic disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).							Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
a. Suspected gestational trophoblastic disease (immediate postevacuation)
i. Uterine size first trimester	1		1		1
ii. Uterine size second trimester	1		1		1
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring)
i. Undetectable/nonpregnant ß–hCG levels	1		1		1
ii. Decreasing ß–hCG levels	1		1		1
iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease	1		1		1
iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease	1		1		1
Cervical ectropion	1		1		1		—
Cervical intraepithelial neoplasia	2		2		1		Evidence: Among women with persistent human papillomavirus infection, long-term DMPA use (=5 years) might increase the risk for carcinoma in situ and invasive carcinoma (107).
Cervical cancer (awaiting treatment)	2		2		1		Comment: Theoretical concern exists that POC use might affect prognosis of the existing disease. While awaiting treatment, women may use POCs. In general, treatment of this condition can render a woman sterile.
Breast disease Breast cancer is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Undiagnosed mass	2		2		2		Clarification: Evaluation should be pursued as early as possible.
b. Benign breast disease	1		1		1		—
c. Family history of cancer	1		1		1		—
d. Breast cancer							Comment: Breast cancer is a hormonally sensitive tumor, and the prognosis for women with current or recent breast cancer might worsen with POC use.
i. Current	4		4		4
ii. Past and no evidence of current disease for 5 years	3		3		3
Endometrial hyperplasia	1		1		1		—
Endometrial cancer This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		1		1		Comment: While awaiting treatment, women may use POCs. In general, treatment of this condition renders a woman sterile.
Ovarian cancer This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		1		1		Comment: While awaiting treatment, women may use POCs. In general, treatment of this condition can render a woman sterile.
Uterine fibroids	1		1		1		Comment: POCs do not appear to cause growth of uterine fibroids.
Pelvic inflammatory disease							Comment: Whether POCs, like COCs, reduce the risk for PID among women with STDs is unknown; however, they do not protect against HIV or lower genital tract STDs.
a. Past PID
i. With subsequent pregnancy	1		1		1
ii. Without subsequent pregnancy	1		1		1
b. Current PID	1		1		1
Sexually transmitted diseases
a. Current purulent cervicitis or chlamydial infection or gonococcal infection	1		1		1		—
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis)	1		1		1		—
c. Other factors related to STDs	1		1		1		—
HIV
High risk for HIV	1		1		1		Clarification (DMPA): Some studies suggest that women using progestin-only injectable contraception might be at increased risk for HIV acquisition; other studies do not show this association. CDC reviewed all available evidence and agreed that the data were not sufficiently conclusive to change current guidance. However, because of the inconclusive nature of the body of evidence on possible increased risk for HIV acquisition, women using progestin-only injectable contraception should be strongly advised to also always use condoms (male or female) and take other HIV preventive measures. Expansion of contraceptive method mix and further research on the relationship between hormonal contraception and HIV infection are essential. These recommendations will be continually reviewed in light of new evidence.
							Evidence: Overall, evidence does not support an association between oral contraceptives and risk for HIV acquisition, evidence is inconsistent regarding an association between DMPA and increased risk for HIV acquisition, and no studies have suggested an increased risk for HIV acquisition with etonogestrel implants although data are limited (108).
HIV infection For women with HIV infection who are not clinically well or not using ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		1		1		Clarification: Drug interactions might exist between hormonal contraceptives and ARV drugs; see Drug Interactions section.
							Evidence: Overall, evidence does not support an association between POC use and progression of HIV. Limited direct evidence on an association between POC use and transmission of HIV to noninfected partners, as well as studies measuring genital viral shedding as a proxy for infectivity, have had mixed results. Studies measuring whether hormonal contraceptive methods affect plasma HIV viral load generally have found no effect (109–111).
Other Infections
Schistosomiasis Schistosomiasis with fibrosis of the liver is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated	1		1		1		Evidence: Among women with uncomplicated schistosomiasis, limited evidence showed that DMPA use had no adverse effects on liver function (112).
b. Fibrosis of the liver (if severe, see Cirrhosis section)	1		1		1		—
Tuberculosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).							Clarification: If a woman is taking rifampin, see Drug Interactions section. Rifampin is likely to decrease the effectiveness of some POCs.
a. Nonpelvic	1		1		1
b. Pelvic	1		1		1
Malaria	1		1		1		—
Endocrine Conditions
Diabetes Insulin-dependent diabetes; diabetes with nephropathy, retinopathy, or neuropathy; diabetes with other vascular disease; or diabetes of >20 years’ duration are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. History of gestational disease	1		1		1		Evidence: POCs had no adverse effects on serum lipid levels in women with a history of gestational diabetes in two small studies (113,114). Limited evidence is inconsistent about the development of noninsulin-dependent diabetes among users of POCs with a history of gestational diabetes (115–118).
b. Nonvascular disease							Evidence: Among women with insulin-dependent or non–insulin-dependent diabetes, limited evidence on use of POCs (POPs, DMPA, and LNG implant) suggests that these methods have little effect on short-term or long-term diabetes control (e.g., glycosylated hemoglobin levels), hemostatic markers, or lipid profile (119–122).
i. Non-insulin dependent	2		2		2
ii. Insulin dependent	2		2		2
c. Nephropathy, retinopathy or neuropathy	2		3		2		Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. The effects of DMPA might persist for some time after discontinuation. Some POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs.
d. Other vascular disease or diabetes of >20 years’ duration	2		3		2		Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. The effects of DMPA might persist for some time after discontinuation. Some POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs.
Thyroid disorders
a. Simple goiter	1		1		1		—
b. Hyperthyroid	1		1		1		—
c. Hypothyroid	1		1		1		—
Gastrointestinal Conditions
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease)	1		2		2		Evidence: Risk for disease relapse among women with IBD using oral contraceptives (most studies did not specify formulation) did not increase significantly from that for nonusers (123).
							Comment: Absorption of POPs among women with IBD might be reduced if the woman has substantial malabsorption caused by severe disease or small bowel surgery. Women with IBD have a higher prevalence of osteoporosis and osteopenia than the general population. Use of DMPA, which has been associated with small changes in BMD, might be of concern.
Gallbladder disease
a. Symptomatic
i. Treated by cholecystectomy	2		2		2		—
ii. Medically treated	2		2		2		—
iii. Current	2		2		2		—
b. Asymptomatic	2		2		2		—
History of cholestasis
a. Pregnancy related	1		1		1		—
b. Past COC related	2		2		2		Comment: Theoretical concern exists that a history of COC-related cholestasis might predict subsequent cholestasis with POC use. However, this has not been documented.
Viral hepatitis
a. Acute or flare	1		1		1		—
b. Carrier	1		1		1		—
c. Chronic	1		1		1		—
Cirrhosis Severe cirrhosis is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Mild (compensated)	1		1		1		—
b. Severe (decompensated)	3		3		3		—
Liver tumors Hepatocellular adenoma and malignant liver tumors are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Benign
i. Focal nodular hyperplasia	2		2		2		Evidence: Limited direct evidence suggests that hormonal contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular hyperplasia (124).
ii. Hepatocellular adenoma	3		3		3		Comment: No evidence is available about hormonal contraceptive use among women with hepatocellular adenoma. COC use in healthy women is associated with development and growth of hepatocellular adenoma; whether other hormonal contraceptives have similar effects is not known.
b. Malignant (hepatoma)	3		3		3		—
Respiratory Conditions
Cystic fibrosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		2		1		Clarification: Persons with cystic fibrosis are at increased risk for diabetes, liver disease, gallbladder disease, and VTE (particularly related to use of central venous catheters) and are frequently prescribed antibiotics. Categories assigned to such conditions in U.S. MEC should be the same for women with cystic fibrosis who have these conditions. For cystic fibrosis, classifications are based on the assumption that no other conditions are present; these classifications must be modified in the presence of such conditions.
							Clarification: Certain drugs to treat cystic fibrosis (e.g., lumacaftor) might reduce effectiveness of hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives.
							Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with cystic fibrosis is not associated with worsening of disease severity. Very limited evidence suggests that cystic fibrosis does not impair the effectiveness of hormonal contraception (125).
							Comment: Women with cystic fibrosis have a higher prevalence of osteopenia, osteoporosis, and fragility fractures than the general population. Use of DMPA, which has been associated with small changes in BMD, might be of concern.
Anemias
Thalassemia	1		1		1		—
Sickle cell disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		1		1		Evidence: Among women with sickle cell disease, POC use did not have adverse effects on hematologic parameters and, in some studies, was beneficial with respect to clinical symptoms (126–133).
Iron deficiency anemia	1		1		1		Comment: Changes in the menstrual pattern associated with POC use have little effect on hemoglobin levels.
Solid Organ Transplantation
Solid organ transplantation This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Complicated: graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy	2		2		2		—
b. Uncomplicated	2		2		2		—
Drug Interactions
Antiretroviral therapy							Comment: These recommendations generally are for ARV agents used alone. However, most women receiving ARV therapy are using multiple drugs in combination. In general, whether interactions between ARVs and hormonal contraceptives differ when ARVs are given alone or in combination is unknown.
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
i. Abacavir (ABC)	1		1		1		Evidence: NRTIs do not appear to have significant risk for interactions with hormonal contraceptive methods (134–139).
ii. Tenofovir (TDF)	1		1		1
iii. Zidovudine (AZT)	1		1		1
iv. Lamivudine (3TC)	1		1		1
v. Didanosine (DDI)	1		1		1
vi. Emtricitabine (FTC)	1		1		1
vii. Stavudine (D4T)	1		1		1
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
i. Efavirenz (EFV)	2		1		2		Clarification: Evidence suggests drug interactions between EFV and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
							Evidence: One study found that women using etonogestrel implants with EFV had a higher pregnancy rate than women not using ARVs, although confidence intervals overlapped and absolute pregnancy rates were still lower than for other hormonal methods; another study found that etonogestrel levels were decreased and 5% of women had presumptive ovulation while using etonogestrel implants with EFV (140,141). Three studies of women using LNG implants showed increased pregnancy rates for women using EFV-containing ARV therapy compared with no ARV use, although absolute pregnancy rates were still lower than for other hormonal methods in one study (141–143); another study of LNG implant users found no difference in pregnancy rates with EFV compared with no EFV (144).No significant effects were found on pregnancy rates, DMPA levels, EFV levels, or HIV disease progression in women using DMPA and EFV compared with DMPA alone (141,144–148). No significant effects were found on HIV disease progression in women using LNG implants and EFV compared with no ARVs (143). No data have assessed effectiveness of contraceptive implants during later years of use when progestin concentrations are lower and risk for failure from drug interactions might be greater.
ii. Etravirine (ETR)	1		1		1		—
iii. Nevirapine (NVP)	1		1		1		Evidence: Five studies found no significant increase in pregnancy rates among women using implants and NVP compared with implants alone (141–144,149). Four studies found no significant increase in pregnancy rates among women using DMPA or other contraceptive injectables and NVP compared with DMPA or other contraceptive injectables alone (141,144,147,150). One study found no ovulations or changes in DMPA concentrations (145). No effect was found on HIV disease progression with use of NVP and DMPA or LNG implants (143,145,147–149,151). No data have assessed effectiveness of contraceptive implants during later years of use when progestin concentrations are lower and risk for failure from drug interactions might be greater.
iv. Rilpivirine (RPV)	1		1		1		—
c. Ritonavir-boosted protease inhibitors
i. Ritonavir-boosted atazanavir (ATV/r)	2		1		2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
							Evidence: One pharmacokinetic study demonstrated increased progestin concentrations with use of POPs and ATV/r compared with POPs alone (152).
ii. Ritonavir-boosted darunavir (DRV/r)	2		1		2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
iii. Ritonavir-boosted fosamprenavir (FPV/r)	2		1		2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
iv. Ritonavir-boosted lopinavir (LPV/r)	1		1		1		Evidence: One study demonstrated no pregnancies, no ovulations, no change in LPV/r level, and no change in HIV disease progression in women using DMPA (153); another study found a small increase in pregnancy rate in women using DMPA with LPV/r compared with no ARV therapy, however confidence intervals overlapped (141). Two studies found no increased risk for pregnancy in women using implants (141,142). Two studies found contraceptive hormones increased in women using LPV/r with DMPA or etonogestrel implants (140,153).
v. Ritonavir-boosted saquinavir (SQV/r)	2		1		2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
vi. Ritonavir-boosted tipranavir (TPV/r)	2		1		2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
d. Protease inhibitors without ritonavir
i. Atazanavir (ATV)	1		1		1		Comment: When ATV is administered with Cobicistat, theoretical concern exists for a drug interaction with hormonal contraceptives. Cobicistat is an inhibitor of CYP3A and CYP2D6 and could theoretically increase contraceptive hormone levels. However, its effects on CYP enzymes and drug levels might vary when combined with other ARVs.
ii. Fosamprenavir (FPV)	2		2		2		Clarification: Theoretical concern exists that interactions between FPV and hormonal contraceptives leading to decreased levels of FPV might diminish effectiveness of the ARV drug. The drug interaction likely involves CYP3A4 pathways; POCs have less effect on CYP3A4 enzymes than CHCs.
iii. Indinavir (IDV)	1		1		1		—
iv. Nelfinavir (NFV)	2		1		2		Clarification: Theoretically, drug interactions might occur between certain protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA. Concern exists that interactions between NFV and POCs might decrease NFV levels.
							Evidence: One study found no pregnancies, no ovulations, no change in DMPA concentrations and no change in HIV disease progression with use of DMPA and NFV compared with DMPA alone; NFV concentrations were decreased with concomitant DMPA use (145,147).
e. CCR5 co-receptor antagonists
i. Maraviroc (MVC)	1		1		1
f. HIV integrase strand transfer inhibitors
i. Raltegravir (RAL)	1		1		1		—
ii. Dolutegravir (DTG)	1		1		1		—
iii. Elvitegravir (EVG)	1		1		1		Comment: When EVG is administered with Cobicistat, theoretical concern exists for a drug interaction with hormonal contraceptives. Cobicistat is an inhibitor of CYP3A and CYP2D6 and could theoretically increase contraceptive hormone levels. However, its effects on CYP enzymes and drug levels may vary when combined with other ARVs.
g. Fusion inhibitors
i. Enfuvirtide	1		1		1		—
Anticonvulsant therapy							—
a. Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, and oxcarbazepine)	2		1		3		Clarification: Although the interaction of certain anticonvulsants with POPs and etonogestrel implants is not harmful to women, it is likely to reduce the effectiveness of POPs and etonogestrel implants. Whether increasing the hormone dose of POPs alleviates this concern remains unclear. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Use of DMPA is a category 1 because its effectiveness is not decreased by use of certain anticonvulsants.
							Evidence: Use of certain anticonvulsants might decrease the effectiveness of POCs (154–156).
b. Lamotrigine	1		1		1		Evidence: No drug interactions have been reported among women with epilepsy receiving lamotrigine and POCs (157).
Antimicrobial therapy
a. Broad-spectrum antibiotics	1		1		1		—
b. Antifungals	1		1		1		—
c. Antiparasitics	1		1		1		—
d. Rifampin or rifabutin therapy	2		1		3		Clarification: Although the interaction of rifampin or rifabutin with POPs and etonogestrel implants is not harmful to women, it is likely to reduce the effectiveness of POPs and etonogestrel implants. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Use of DMPA is a category 1 because its effectiveness is not decreased by use of rifampin or rifabutin. Whether increasing the hormone dose of POPs alleviates this concern remains unclear.
Psychotropic medications							Comment: For many common psychotropic agents, limited or no theoretical concern exits for clinically significant drug interactions when co-administered with hormonal contraceptives. However, either no or very limited data exist examining potential interactions for these classes of medications.
a. SSRIs	1		1		1		Evidence: No evidence specifically examined the use of POCs with SSRIs. Limited clinical and pharmacokinetic data do not demonstrate concern for SSRIs decreasing the effectiveness of oral contraceptives. Limited evidence suggests that for women taking SSRIs, the use of hormonal contraceptives was not associated with differences in effectiveness of the SSRI for treatment or in adverse events when compared with women not taking hormonal contraceptives (158).
							Comment: Drugs that are inhibitors of CYP3A4 or CYP2C9 theoretically have the potential to increase levels of contraceptive steroid, which might increase adverse events. Fluvoxamine is an SSRI known to be a moderate inhibitor of both 3A4 and 2C9; however, no clinical or pharmacokinetic studies were identified to explore potential drug-drug interactions.
St. John’s wort	2		1		2		Evidence: No evidence specifically examined the use of POCs with St John’s wort. Although clinical data are limited, studies with pharmacokinetic and pharmacodynamics outcomes raise concern that St. John’s wort might decrease effectiveness of hormonal contraceptives, including increased risk for breakthrough bleeding and ovulation and increased metabolism of estrogen and progestin. Any interactions might be dependent on the dose of St John’s wort, and the concentration of active ingredients across types of St. John’s wort preparations may vary (159).
							Comment: Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.

Abbreviations: ARV = antiretroviral; BMD = bone mineral density; BMI = body mass index; COC = combined oral contraceptive; DMPA = depot medroxyprogesterone acetate; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; IBD = inflammatory bowel disease; LDL = low-density lipoprotein; LNG = levonorgestrel; NA = not applicable; NET-EN = norethisterone enantate; PE = pulmonary embolism; PID = pelvic inflammatory disease; POC = progestin-only contraceptive; POP = progestin-only pill; SSRI = selective serotonin reuptake inhibitor; STD = sexually transmitted disease; VTE = venous thromboembolism.

References

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Appendix D

Classifications for Combined Hormonal Contraceptives

Combined hormonal contraceptives (CHCs) include low-dose (containing =35 µg ethinyl estradiol) combined oral contraceptives (COCs), the combined hormonal patch, and the combined vaginal ring ( Box D1) ( Table D1). Limited information is available about the safety of the combined hormonal patch and combined vaginal ring among women with specific medical conditions. Evidence indicates that the combined hormonal patch and the combined vaginal ring provide comparable safety and pharmacokinetic profiles to COCs with similar hormone formulations (1–33). Pending further studies, the evidence available for recommendations about COCs applies to the recommendations for the combined hormonal patch and vaginal ring. Therefore, the patch and ring should have the same categories as COCs, except where noted. Therefore, the assigned categories should be considered a preliminary best judgement, which will be reevaluated as new data become available.

COCs, the patch, and the ring do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited

TABLE D1. Classifications for combined hormonal contraceptives, including pill, patch, and ring

Condition	Category CHCs		Clarifications/Evidence/Comments
Personal Characteristics and Reproductive History
Pregnancy	NA		Clarification: Use of CHCs is not required. No known harm to the woman, the course of her pregnancy, or the fetus occurs if CHCs are inadvertently used during pregnancy.
Age			Evidence: Evidence is inconsistent about whether CHC use affects fracture risk (34–45), although three recent studies show no effect (34,35,45). CHC use might decrease BMD in adolescents, especially in those choosing very low-dose formulations (COCs containing <30 µg ethinyl estradiol) (46–59). CHC use has little to no effect on BMD in premenopausal women (60–74) and might preserve bone mass in those who are perimenopausal (75–83). BMD is a surrogate marker for fracture risk that might not be valid for premenopausal women and therefore might not accurately predict current or future (postmenopausal) fracture risk (84–86). Comment: The risk for cardiovascular disease increases with age and might increase with CHC use. In the absence of other adverse clinical conditions, CHCs can be used until menopause.
a. Menarche to <40 years	1
b. =40 years	2
Parity
a. Nulliparous	1		—
b. Parous	1		—
Breastfeeding
a. <21 days postpartum	4		Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
			Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
			Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (90–94).
			Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
b. 21 to <30 days postpartum
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	3		Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
			Clarification: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
			Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
			Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (90–94).
			Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
ii. Without other risk factors for VTE	3		Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
			Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
			Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (90–94).
			Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
c. 30–42 days postpartum
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	3		Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
			Clarification: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
			Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
			Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (90–94).
			Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
ii. Without other risk factors for VTE	2		Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
			Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
			Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (90–94).
			Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
d. >42 days postpartum	2		Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
			Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
			Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
Postpartum (nonbreastfeeding women)
a. <21 days postpartum	4		Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (90–94). Risk for pregnancy during the first 21 days postpartum is very low but increases after that point; ovulation before first menses is common (95).
b. 21–42 days postpartum
i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2 postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)	3		Clarification: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
			Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (90–94).
ii. Without other risk factors for VTE	2		Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (90–94).
c. >42 days postpartum	1		—
Postabortion			Clarification: CHCs may be started immediately postabortion. Evidence: Women who started taking COCs immediately after first trimester medical or surgical abortion did not experience more side effects or adverse vaginal bleeding outcomes or clinically significant changes in coagulation parameters than did women who used a placebo, an IUD, a nonhormonal contraceptive method, or delayed COC initiation (96–102). Limited evidence on women using the ring immediately after first trimester medical or surgical abortion found no serious adverse events and no infection related to use of the combined vaginal ring during 3 cycles of follow-up postabortion (103).
a. First trimester	1
b. Second trimester	1
c. Immediate postseptic abortion	1
Past ectopic pregnancy	1		Comment: The risk for future ectopic pregnancy is increased among women who have had an ectopic pregnancy in the past. CHCs protect against pregnancy in general, including ectopic gestation.
History of pelvic surgery	1		—
Smoking			Evidence: COC users who smoked were at increased risk for cardiovascular diseases, especially myocardial infarction, compared with those who did not smoke. Studies also showed an increased risk for myocardial infarction with increasing number of cigarettes smoked per day (104–116).
a. Age <35 years	2
b. Age =35 years
i. <15 cigarettes per day	3
ii. =15 cigarettes per day	4
Obesity			Evidence: Obese women who use COCs are more likely than obese women who do not use COCs to experience VTE. Research examining the interaction between COCs and BMI on VTE risk is limited, particularly for women in the highest BMI categories (BMI =35 kg/m2). Although the absolute risk for VTE in otherwise healthy women of reproductive age is small, obese women are at 2–3 times higher risk for VTE than normal weight women regardless of COC use. Limited evidence suggests that obese women who use COCs do not have a higher risk for acute myocardial infarction or stroke than do obese nonusers (117). Limited evidence suggests that effectiveness of some COC formulations might decrease with increasing BMI, however the observed reductions in effectiveness are minimal and evidence is conflicting (118–125). Effectiveness of the patch might be reduced in women >90 kg (126). Limited evidence suggests obese women are no more likely to gain weight during COC or vaginal ring use than normal weight or overweight women (117,127).
a. BMI =30 kg/m2	2
b. Menarche to <18 years and BMI =30 kg/m2	2
History of bariatric surgery This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy)	1		Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives among women who underwent laparoscopic placement of an adjustable gastric band (128).
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion)	COCs: 3 Patch and ring: 1		Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives among women who underwent a biliopancreatic diversion; however, evidence from pharmacokinetic studies reported conflicting results of oral contraceptive effectiveness among women who underwent a jejunoileal bypass (128).
			Comment: Bariatric surgical procedures involving a malabsorptive component have the potential to decrease oral contraceptive effectiveness, perhaps further decreased by postoperative complications, such as long-term diarrhea or vomiting.
Cardiovascular Disease
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels)	3/4		Clarification: When a woman has multiple major risk factors, any of which alone would substantially increase her risk for cardiovascular disease, use of CHCs might increase her risk to an unacceptable level. However, a simple addition of categories for multiple risk factors is not intended; for example, a combination of two category 2 risk factors might not necessarily warrant a higher category.
			Clarification: The recommendations apply to known preexisting medical conditions or characteristics. Few if any screening tests are needed before initiation of contraception. See the U.S. Selected Practice Recommendations for Contraceptive Use (http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usspr.htm).
Hypertension Systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Adequately controlled hypertension	3		Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
			Clarification: Women adequately treated for hypertension are at reduced risk for acute myocardial infarction and stroke compared with untreated women. Although no data exist, CHC users with adequately controlled and monitored hypertension should be at reduced risk for acute myocardial infarction and stroke compared with untreated hypertensive CHC users.
			Evidence: Among women with hypertension, COC users were at higher risk than nonusers for stroke, acute myocardial infarction, and peripheral arterial disease (104,106,113–116,129–143). Discontinuation of COCs in women with hypertension might improve blood pressure control (144).
b. Elevated blood pressure levels (properly taken measurements)			Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. Evidence: Among women with hypertension, COC users were at higher risk than nonusers for stroke, acute myocardial infarction, and peripheral arterial disease (104,106,113–116,129–143). Discontinuation of COCs in women with hypertension might improve blood pressure control (144).
i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg	3
ii. Systolic =160 mm Hg or diastolic =100 mm Hg	4
c. Vascular disease	4
History of high blood pressure during pregnancy (when current blood pressure is measurable and normal)	2		Evidence: Women with a history of high blood pressure in pregnancy who also used COCs had a higher risk for myocardial infarction and VTE than did COC users who did not have a history of high blood pressure during pregnancy. The absolute risks for acute myocardial infarction and VTE in this population remained small (115,130,142,143,145–151).
Deep venous thrombosis/Pulmonary embolism
a. History of DVT/PE, not receiving anticoagulant therapy
i. Higher risk for recurrent DVT/PE (one or more risk factors)	4		—
• History of estrogen-associated DVT/PE • Pregnancy-associated DVT/PE • Idiopathic DVT/PE • Known thrombophilia, including antiphospholipid syndrome • Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer • History of recurrent DVT/PE
ii. Lower risk for recurrent DVT/PE (no risk factors)	3		—
b. Acute DVT/PE	4		—
c. DVT/PE and established anticoagulant therapy for at least 3 months			Clarification: Women using anticoagulant therapy are at risk for gynecologic complications of therapy, such as hemorrhagic ovarian cysts and severe menorrhagia. Hormonal contraceptive methods can be of benefit in preventing or treating these complications. When a contraceptive method is used as a therapy, rather than solely to prevent pregnancy, the risk/benefit ratio might differ and should be considered on a case-by-case basis.
i. Higher risk for recurrent DVT/PE (one or more risk factors)	4
• Known thrombophilia, including antiphospholipid syndrome • Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer • History of recurrent DTV/PE
ii. Lower risk for recurrent DVT/PE (no risk factors)	3
d. Family history (first-degree relatives)	2		Comment: Some conditions that increase the risk for DTV/PE are heritable.
e. Major surgery
i. With prolonged immobilization	4		—
ii. Without prolonged immobilization	2		—
f. Minor surgery without immobilization	1		—
Known thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; and protein S, protein C, and antithrombin deficiencies) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	4		Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.
			Evidence: Among women with thrombogenic mutations, COC users had a twofold to twentyfold higher risk for thrombosis than did nonusers (152–175).
Superficial venous disorders
a. Varicose veins	1		Evidence: One study suggested that among women with varicose veins, the rate of VTE and superficial venous thrombosis was higher in oral contraceptive users compared with nonusers; however, statistical significance was not reported and the number of events was small (176).
b. Superficial venous thrombosis (acute or history)	3		Clarification: Superficial venous thrombosis might be associated with an increased risk for VTE. If a woman has risk factors for concurrent DVT (e.g., known thrombophilia or cancer) or has current or history of DVT, see recommendations for DVT/PE. Superficial venous thrombosis associated with a peripheral intravenous catheter is less likely to be associated with additional thrombosis and use of CHCs may be considered.
			Evidence: One study demonstrated that among women with superficial venous thrombosis, the risk for VTE was higher in oral contraceptive users compared with nonusers (176).
Current and history of ischemic heart disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	4		—
Stroke (history of cerebrovascular accident) This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	4		—
Valvular heart disease Complicated valvular heart disease is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated	2		—
b. Complicated (pulmonary hypertension, risk for atrial fibrillation, or history of subacute bacterial endocarditis)	4		Comment: Among women with valvular heart disease, CHC use may further increase the risk for arterial thrombosis; women with complicated valvular heart disease are at greatest risk.
Peripartum cardiomyopathy This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).			Evidence: No direct evidence exists about the safety of CHCs among women with peripartum cardiomyopathy. Limited indirect evidence from noncomparative studies of women with cardiac disease demonstrated few cases of hypertension and transient ischemic attack in women with cardiac disease using COCs. No cases of heart failure were reported (177). Comment: COCs might increase fluid retention in healthy women; fluid retention may worsen heart failure in women with peripartum cardiomyopathy. COCs might induce cardiac arrhythmias in healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (178)
i. <6 months	4
ii. =6 months	3
b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (178)	4
Rheumatic Diseases
Systemic lupus erythematosus This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Positive (or unknown) antiphospholipid antibodies	4		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (179–197).
			Evidence: Antiphospholipid antibodies are associated with a higher risk for both arterial and venous thrombosis (198,199).
b. Severe thrombocytopenia	2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (179–197).
c. Immunosuppressive therapy	2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (179–197).
d. None of the above	2		Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (179–197).
Rheumatoid arthritis			Evidence: Limited evidence shows no consistent pattern of improvement or worsening of rheumatoid arthritis with use of oral contraceptives, progesterone, or estrogen (200).
a. Receiving immunosuppressive therapy	2
b. Not receiving immunosuppressive therapy	2
Neurologic Conditions
Headaches
a. Nonmigraine (mild or severe)	1		Clarification: Classification depends on accurate diagnosis of those severe headaches that are migraines and those headaches that are not, as well as diagnosis of ever experiencing aura. Aura is a specific focal neurologic symptom. For more information about headache classification see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdfpdf iconexternal icon). Any new headaches or marked changes in headaches should be evaluated.
b. Migraine			Clarification: Classification depends on accurate diagnosis of those severe headaches that are migraines and those headaches that are not, as well as diagnosis of ever experiencing aura. Aura is a specific focal neurologic symptom. For more information about headache classification see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdfpdf iconexternal icon). Any new headaches or marked changes in headaches should be evaluated. Clarification: Classification is for women without any other risk factors for stroke (e.g., age, hypertension, and smoking). Evidence: Among women with migraine, oral contraceptive use is associated with about a threefold increased risk for ischemic stroke compared with nonuse, although most studies did not specify migraine type or oral contraceptive formulation. The only study to examine migraine type found that the risk for ischemic stroke among women with migraine with aura was increased to a similar level among both oral contraceptive users and nonusers, compared with women without migraine (201). The risk for ischemic stroke is increased among women using COCs, compared with women not using COCs (104,202). The risk for ischemic stroke is also increased among women with migraine with aura, compared with women without migraine (203–205). One older meta-analysis found that migraine without aura was associated with an increased risk for ischemic stroke, while two more recent meta-analyses did not find such an association (203–205). Comment: Menstrual migraine is a subtype of migraine without aura. For more information, see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdfpdf iconexternal icon).
i. Without aura (This category of migraine includes menstrual migraine.)	2
ii. With aura	4
Epilepsy This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		Clarification: If a woman is taking anticonvulsants, see Drug Interactions section. Certain anticonvulsants lower COC effectiveness. The extent to which patch or ring use is similar to COC use in this regard remains unclear.
Multiple sclerosis			Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with multiple sclerosis does not worsen the clinical course of disease (206). Comment: No data exist that evaluate the increased risk for VTE among women with multiple sclerosis using CHCs. However, women with multiple sclerosis are at higher risk than unaffected women for VTE.
a. With prolonged immobility	3
b. Without prolonged immobility	1
Depressive Disorders
Depressive disorders	1		Clarification: If a woman is receiving psychotropic medications or St. John’s wort, see Drug Interactions section.
			Evidence: COC use was not associated with increased depressive symptoms in women with depression or scoring above threshold levels on a validated depression screening instrument compared with baseline or with nonusers with depression. One small study of women with bipolar disorder found that oral contraceptives did not significantly change mood across the menstrual cycle (207).
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns
a. Irregular pattern without heavy bleeding	1		Comment: Irregular menstrual bleeding patterns are common among healthy women.
b. Heavy or prolonged bleeding (includes regular and irregular patterns)	1		Clarification: Unusually heavy bleeding should raise the suspicion of a serious underlying condition.
			Evidence: A Cochrane Collaboration Review identified one randomized controlled trial evaluating the effectiveness of COC use compared with naproxen and danazol in treating menorrhagia. Women with menorrhagia did not report worsening of the condition or any adverse events related to COC use (208).
Unexplained vaginal bleeding (suspicious for serious condition) before evaluation	2		Clarification: If pregnancy or an underlying pathological condition (e.g., pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation. Comment: No conditions that cause vaginal bleeding will be worsened in the short-term by use of CHCs.
Endometriosis	1		Evidence: A Cochrane Collaboration Review identified one randomized controlled trial evaluating the effectiveness of COC use compared with a gonadotropin-releasing hormone analog in treating the symptoms of endometriosis. Women with endometriosis did not report worsening of the condition or any adverse events related to COC use (209).
Benign ovarian tumors (including cysts)	1
Severe dysmenorrhea	1		Evidence: Risk for side effects with COC use was not higher among women with dysmenorrhea than among women not using COCs. Some COC users had a reduction in pain and bleeding (210,211).
Gestational trophoblastic disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).			Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance. Evidence: After molar pregnancy evacuation, the balance of evidence found COC use did not increase the risk for postmolar trophoblastic disease, and ß–hCG levels regressed more rapidly in some COC users than in nonusers (212). Limited evidence suggests that use of COCs during chemotherapy does not significantly affect the regression or treatment of postmolar trophoblastic disease compared with women who used a nonhormonal contraceptive method or DMPA during chemotherapy (212).
a. Suspected gestational trophoblastic disease (immediate postevacuation)
i. Uterine size first trimester	1
ii. Uterine size second trimester	1
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring)
i. Undetectable/nonpregnant ß-hCG levels	1
ii. Decreasing ß-hCG levels	1
iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease	1
iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease	1
Cervical ectropion	1		Comment: Cervical ectropion is not a risk factor for cervical cancer, and restriction of CHC use is unnecessary.
Cervical intraepithelial neoplasia	2		Evidence: Among women with persistent human papillomavirus infection, long-term COC use (=5 years) might increase the risk for carcinoma in situ and invasive carcinoma (213). Limited evidence on women with low-grade squamous intraepithelial lesions found use of the vaginal ring did not worsen the condition (9).
Cervical cancer (awaiting treatment)	2		Comment: Theoretical concern exists that CHC use might affect prognosis of the existing disease. While awaiting treatment, women may use CHCs. In general, treatment of this condition can render a woman sterile.
Breast disease Breast cancer is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Undiagnosed mass	2		Clarification: The woman should be evaluated as early as possible.
b. Benign breast disease	1		—
c. Family history of cancer	1		Evidence: Women with breast cancer susceptibility genes (e.g., BRCA1 and BRCA2) have a higher baseline risk for breast cancer than women without these genes. The baseline risk for breast cancer is also higher among women with a family history of breast cancer than among those who do not have such a history. However, evidence does not suggest that the increased risk for breast cancer among women with either a family history of breast cancer or breast cancer susceptibility genes is modified by the use of COCs (214–231).
d. Breast cancer			Comment: Breast cancer is a hormonally sensitive tumor, and the prognosis for women with current or recent breast cancer might worsen with CHC use.
i. Current	4
ii. Past and no evidence of current disease for 5 years	3
Endometrial hyperplasia	1		—
Endometrial cancer This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		Comment: COC use reduces the risk for endometrial cancer; whether patch or ring use reduces the risk for endometrial cancer is not known. While awaiting treatment, women may use CHCs. In general, treatment of this condition renders a woman sterile.
Ovarian cancer This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		Comment: COC use reduces the risk for ovarian cancer; whether patch or ring use reduces the risk for ovarian cancer is not known. While awaiting treatment, women may use CHCs. In general, treatment of this condition can render a woman sterile.
Uterine fibroids	1		Comment: COCs do not appear to cause growth of uterine fibroids, and patch and ring also are not expected to cause growth.
Pelvic inflammatory disease			Comment: COCs might reduce the risk for PID among women with STDs but do not protect against HIV or lower genital tract STDs. Whether use of patch or ring reduces the risk for PID among women with STDs is unknown; however, they do not protect against HIV or lower genital tract STDs.
a. Past PID
i. With subsequent pregnancy	1
ii. Without subsequent pregnancy	1
b. Current PID	1
Sexually transmitted diseases
a. Current purulent cervicitis or chlamydial infection or gonococcal infection	1		—
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis)	1		—
c. Other factors related to STDs	1		—
HIV
High risk for HIV	1		Evidence: Overall, evidence does not support an association between oral contraceptives and risk for HIV acquisition (232).
HIV infection For women with HIV infection who are not clinically well or not receiving ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		Clarification: Drug interactions might exist between hormonal contraceptives and ARV drugs; see Drug Interactions section.
			Evidence: Overall, evidence does not support an association between COC use and progression of HIV. Limited direct evidence does not support an association between COC use and transmission of HIV to noninfected partners; studies measuring genital viral shedding as a proxy for infectivity have had mixed results. Studies measuring whether hormonal contraceptive methods affect plasma HIV viral load generally have found no effect (233–235).
Other Infections
Schistosomiasis Schistosomiasis with fibrosis of the liver is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated	1		Evidence: Among women with uncomplicated schistosomiasis, COC use had no adverse effects on liver function (236–242).
b. Fibrosis of the liver (if severe, see Cirrhosis section)	1		—
Tuberculosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).			Clarification: If a woman is taking rifampin, see Drug Interactions section. Rifampin is likely to decrease COC effectiveness. The extent to which patch or ring use is similar to COC use in this regard remains unclear.
a. Nonpelvic	1
b. Pelvic	1
Malaria	1		—
Endocrine Conditions
Diabetes Insulin-dependent diabetes; diabetes with nephropathy, retinopathy, or neuropathy; diabetes with other vascular disease; or diabetes of >20 years’ duration are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. History of gestational disease	1		Evidence: The development of non–insulin-dependent diabetes in women with a history of gestational diabetes is not increased by use of COCs (243–250). Likewise, lipid levels appear to be unaffected by COC use (251–253).
b. Nonvascular disease			Evidence: Among women with insulin-dependent or non–insulin-dependent diabetes, COC use had limited effect on daily insulin requirements and no effect on long-term diabetes control (e.g., glycosylated hemoglobin levels) or progression to retinopathy. Changes in lipid profile and hemostatic markers were limited, and most changes remained within normal values (254–263).
i. Non-insulin dependent	2
ii. Insulin dependent	2
c. Nephropathy, retinopathy, or neuropathy	3/4		Clarification: The category should be assessed according to the severity of the condition.
d. Other vascular disease or diabetes of >20 years’ duration	3/4		Clarification: The category should be assessed according to the severity of the condition.
Thyroid disorders
a. Simple goiter	1		—
b. Hyperthyroid	1		—
c. Hypothyroid	1		—
Gastrointestinal Conditions
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease)	2/3		Clarification: For women with mild IBD and with no other risk factor for VTE, the benefits of CHC use generally outweigh the risks (category 2). However, for women with IBD who are at increased risk for VTE (e.g., those with active or extensive disease, surgery, immobilization, corticosteroid use, vitamin deficiencies, or fluid depletion), the risks of CHC use generally outweigh the benefits (category 3).
			Evidence: Risk for disease relapse was not significantly higher among women with IBD using oral contraceptives (most studies did not specify type) than among nonusers (264). Absorption of COCs among women with mild ulcerative colitis and no or small ileal resections was similar to the absorption among healthy women (264). Findings might not apply to women with Crohn’s disease or more extensive bowel resections. No data exist that evaluate the increased risk for VTE among women with IBD using CHCs. However, women with IBD are at higher risk than unaffected women for VTE (264).
Gallbladder disease			Comment: CHCs might cause a small increased risk for gallbladder disease. CHCs might worsen existing gallbladder disease.
a. Symptomatic
i. Treated by cholecystectomy	2
ii. Medically treated	3
iii. Current	3
b. Asymptomatic	2
History of cholestasis
a. Pregnancy related	2		Comment: History of pregnancy-related cholestasis might predict an increased risk for COC-related cholestasis.
b. Past COC related	3		Comment: History of COC-related cholestasis predicts an increased risk with subsequent COC use.
Viral hepatitis	Initiation	Continuation
a. Acute or flare	3/4	2	Clarification (initiation): The category should be assessed according to the severity of the condition.
			Evidence: Data suggest that in women with chronic hepatitis, COC use does not increase the rate or severity of cirrhotic fibrosis, nor does it increase the risk for hepatocellular carcinoma. For women who are carriers, COC use does not appear to trigger liver failure or severe dysfunction. Evidence is limited for COC use during active hepatitis (265).
b. Carrier	1	1	Evidence: Data suggest that in women with chronic hepatitis, COC use does not increase the rate or severity of cirrhotic fibrosis, nor does it increase the risk for hepatocellular carcinoma. For women who are carriers, COC use does not appear to trigger liver failure or severe dysfunction. Evidence is limited for COC use during active hepatitis (265).
c. Chronic	1	1	Evidence: Data suggest that in women with chronic hepatitis, COC use does not increase the rate or severity of cirrhotic fibrosis, nor does it increase the risk for hepatocellular carcinoma. For women who are carriers, COC use does not appear to trigger liver failure or severe dysfunction. Evidence is limited for COC use during active hepatitis (265).
Cirrhosis Severe cirrhosis is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Mild (compensated)	1		—
b. Severe (decompensated)	4		—
Liver tumors Hepatocellular adenoma and malignant liver tumors are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Benign
i. Focal nodular hyperplasia	2		Evidence: Limited direct evidence suggests that hormonal contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular hyperplasia (266).
ii. Hepatocellular adenoma	4		—
b. Malignant (hepatoma)	4		—
Respiratory Conditions
Cystic fibrosis This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	1		Clarification: Persons with cystic fibrosis are at increased risk for diabetes, liver disease, gallbladder disease, and VTE (particularly related to use of central venous catheters) and are frequently prescribed antibiotics. Categories assigned to such conditions in U.S. MEC should be the same for women with cystic fibrosis who have these conditions. For cystic fibrosis, classifications are based on the assumption that no other conditions are present; these classifications must be modified in the presence of such conditions.
			Clarification: Certain drugs to treat cystic fibrosis (e.g., lumacaftor) might reduce effectiveness of hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives.
			Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with cystic fibrosis is not associated with worsening of disease severity. Very limited evidence suggests that cystic fibrosis does not impair the effectiveness of hormonal contraception (267).
Anemias
Thalassemia	1		Comment: Anecdotal evidence from countries where thalassemia is prevalent indicates that COC use does not worsen the condition.
Sickle cell disease This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).	2		—
Iron deficiency anemia	1		Comment: CHC use might decrease menstrual blood loss.
Solid Organ Transplantation
Solid organ transplantation This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Complicated: graft failure (acute or chronic), rejection, cardiac allograft vasculopathy	4		Evidence: Limited evidence of COC and patch users indicated no overall changes in biochemical measures. However, one study reported discontinuations of COC use in two (8%) of 26 women as a result of serious medical complications, and in one case report, a woman developed cholestasis associated with high-dose COC use (268).
b. Uncomplicated	2		Clarification: Women with Budd-Chiari syndrome should not use CHCs because of the increased risk for thrombosis.
			Evidence: Limited evidence of COC and patch users indicated no overall changes in biochemical measures. However, one study reported discontinuations of COC use in two (8%) of 26 women as a result of serious medical complications, and in one case report, a woman developed cholestasis associated with high-dose COC use (268).
Drug Interactions
Antiretroviral therapy			Comment: These recommendations generally are for ARV agents used alone. However, most women receiving ARV therapy are using multiple drugs in combination. In general, whether interactions between ARVs and hormonal contraceptives differ when ARVs are given alone or in combination is unknown.
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
i. Abacavir (ABC)	1		Evidence: NRTIs do not appear to have significant risk for interactions with hormonal contraceptive methods (269–274).
ii. Tenofovir (TDF)	1
iii. Zidovudine (AZT)	1
iv. Lamivudine (3TC)	1
v. Didanosine (DDI)	1
vi. Emtricitabine (FTC)	1
vii. Stavudine (D4T)	1
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
i. Efavirenz (EFV)	2		Clarification: Evidence suggests drug interactions between EFV and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
			Evidence: Two studies suggested that pregnancy rates might be higher among women using COCs and EFV compared with COCs alone, although one study found no difference in pregnancy rates (275–277) Two studies found conflicting results on ovulations in women receiving COCs and EFV compared with EFV alone (278,279). Two pharmacokinetic studies demonstrated decreases in ethinyl estradiol and progestin concentrations in women receiving COCs and EFV compared with COCs alone (279,280). Pharmacokinetic studies demonstrated generally no changes in EFV concentrations with concomitant COC use (279,280).
ii. Etravirine (ETR)	1		Evidence: One study demonstrated no clinically relevant pharmacokinetic or pharmacodynamic changes in women using COCs and ETR compared with COCs alone (281).
iii. Nevirapine (NVP)	1		Evidence: Five studies found no significant differences in pregnancy rates among women using COCs and NVP compared with women using COCs alone (275–277,282,283). Three studies reported no ovulations among women receiving COCs and NVP (278,283,284). Two pharmacokinetic studies demonstrated decreased concentrations of ethinyl estradiol and progestin among women using COCs and NVP compared with COCs alone, and one study found no change in contraceptive hormone concentrations (278,284,285). Pharmacokinetic studies demonstrated generally no changes in NVP concentrations with concomitant COC use (278,285,286).
iv. Rilpivirine (RPV)	1		Evidence: One study demonstrated no clinical significant pharmacokinetic changes or adverse events in women using COCs and RPV compared with COCs alone (287).
c. Ritonavir-boosted protease inhibitors
i. Ritonavir-boosted atazanavir (ATV/r)	2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
			Evidence: One pharmacokinetic study demonstrated decreased estrogen but increased progestin concentrations in women using COCs and ATV/r compared with COCs alone (288).
ii. Ritonavir-boosted darunavir (DRV/r)	2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
			Evidence: One pharmacokinetic study demonstrated no change in follicle-stimulating hormone or luteinizing hormone but decreases in ethinyl estradiol and norethindrone in women using COCs with DRV/r compared with COCs alone (289).
iii. Ritonavir-boosted fosamprenavir (FPV/r)	2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
			Evidence: Information from the package label states that both ethinyl estradiol and norethindrone concentrations decreased with concurrent administration of COCs and FPV/r (290).
iv. Ritonavir-boosted lopinavir (LPV/r)	1		Evidence: One study demonstrated a non-significant increase in pregnancy rates among women using COCs and LPV/r compared with COCs alone (275). One study demonstrated no ovulations in women using the combined hormonal patch and LPV/r compared with combined hormonal patch alone; ethinyl estradiol concentrations for COC and patch users decreased but norelgestromin concentrations increased with use of the patch (291).
v. Ritonavir-boosted saquinavir (SQV/r)	2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
			Evidence: One pharmacokinetic study demonstrated no change in SQV concentrations in women using COC and SQV compared with COCs alone (292).
iv. Ritonavir-boosted tipranavir (TPV/r)	2		Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
			Evidence: Information from the package label states that ethinyl estradiol concentrations decrease but norethindrone concentrations increased with concurrent administration of COCs and TPV/r (293).
d. Protease inhibitors without ritonavir
i. Atazanavir (ATV)	2		Clarification: Theoretical concern exists that increased levels of ethinyl estradiol because of interactions with ATV might increase the risk for adverse events.
			Evidence: Information from the package label states that there are inconsistent changes in ethinyl estradiol concentrations and increases in progestin concentrations with concurrent administration of two different COCs and ATV (294).
			Comment: When ATV is administered with Cobicistat, theoretical concern exists for a drug interaction with hormonal contraceptives. Cobicistat is an inhibitor of CYP3A and CYP2D6 and could theoretically increase contraceptive hormone levels. However, its effects on CYP enzymes and drug levels may vary when combined with other ARVs.
ii. Fosamprenavir (FPV)	3		Clarification: Concern exists that interactions between FPV and hormonal contraceptives leading to decreased levels of FPV might diminish effectiveness of the ARV drug.
			Evidence: Information from the package label states that amprenavir concentrations decreased with concurrent administration of COCs and amprenavir. Norethindrone concentrations increased and ethinyl estradiol concentrations did not change (290).
iii. Indinavir (IDV)	1		Evidence: One small study found no pregnancies in women using COCs and IDV (277).
iv. Nelfinavir (NFV)	2		Clarification: Evidence suggests drug interactions between certain protease inhibitors and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
			Evidence: One small study suggested that women using COCs and NFV may have had higher pregnancy rates than those using COCs alone (277).
e. CCR5 co-receptor antagonists
i. Maraviroc (MVC)	1		Evidence: COC concentrations were not altered by co-administration with MVC (295).
f. HIV integrase strand transfer inhibitors
i. Raltegravir (RAL)	1		Evidence: One pharmacokinetic study demonstrated increased concentrations of norgestimate and no change in ethinyl estradiol among women using COCs and RAL compared with COCs alone (296).
ii. Dolutegravir (DTG)	1		Evidence: One study demonstrated no clinically relevant pharmacokinetic or pharmacodynamic changes in women using COCs and DTG compared with COCs alone (297).
iii. Elvitegravir (EVG)	1		Evidence: Information from the package label states that ethinyl estradiol concentrations decreased and norgestimate concentrations increased with concurrent administration of COCs and EVG (298).
			Comment: When ATV is administered with Cobicistat, theoretical concern exists for a drug interaction with hormonal contraceptives. Cobicistat is an inhibitor of CYP3A and CYP2D6 and could theoretically increase contraceptive hormone levels. However, its effects on CYP enzymes and drug levels may vary when combined with other ARVs.
g. Fusion inhibitors
i. Enfuvirtide	1		—
Anticonvulsant therapy
a. Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine)	3		Clarification: Although the interaction of certain anticonvulsants with CHCs is not harmful to women, it is likely to reduce the effectiveness of CHCs. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. When a COC is chosen, a preparation containing a minimum of 30 µg ethinyl estradiol should be used.
			Evidence: Use of certain anticonvulsants might decrease the effectiveness of COCs (299–302).
b. Lamotrigine	3		Clarification: The recommendation for lamotrigine applies only for situations where lamotrigine monotherapy is taken concurrently with COCs. Anticonvulsant treatment regimens that combine lamotrigine and non–enzyme-inducing antiepileptic drugs (e.g., sodium valproate) do not interact with COCs.
			Evidence: Pharmacokinetic studies show levels of lamotrigine decrease significantly during COC use (303–307). Some women who used both COCs and lamotrigine experienced increased seizure activity in one trial (303).
Antimicrobial therapy
a. Broad-spectrum antibiotics	1		Evidence: Most broad-spectrum antibiotics do not affect the contraceptive effectiveness of COCs (308–344), patch (345), or ring (346).
b. Antifungals	1		Evidence: Studies of antifungal agents have shown no clinically significant pharmacokinetic interactions with COCs (347–356), or ring (357).
c. Antiparasitics	1		Evidence: Studies of antiparasitic agents have shown no clinically significant pharmacokinetic interactions with COCs (236,358–362).
d. Rifampin or rifabutin therapy	3		Clarification: Although the interaction of rifampin or rifabutin therapy with CHCs is not harmful to women, it is likely to reduce the effectiveness of CHCs. Use of other contraceptives should be encouraged for women who are long-term users of either of these drugs. When a COC is chosen, a preparation containing a minimum of 30 µg ethinyl estradiol should be used.
			Evidence: The balance of the evidence suggests that rifampin reduces the effectiveness of COCs (363–378). Data on rifabutin are limited, but effects on metabolism of COCs are less than with rifampin, and small studies have not shown evidence of ovulation (365,372).
Psychotropic medications			Comment: For many common psychotropic agents, limited or no theoretical concern exists for clinically significant drug interactions when co-administered with hormonal contraceptives. However, either no or very limited data exist examining potential interactions for these classes of medications. For psychotropic agents that are CYP1A2 substrates, such as duloxetine, mirtazapine, ziprasidone, olanzapine, clomipramine, imipramine, and amitriptyline, co-administration with CHCs could theoretically yield increased concentrations of the psychotropic drug. For agents with narrow therapeutic windows, such as tricyclic antidepressants, increased drug concentrations might pose safety concerns that could necessitate closer monitoring.
a. SSRIs	1		Evidence: Limited clinical and pharmacokinetic data do not demonstrate concern for SSRIs decreasing the effectiveness of oral contraceptives. Limited evidence suggests that for women taking SSRIs, the use of hormonal contraceptives was not associated with differences in effectiveness of the SSRI for treatment or in adverse events when compared with women not taking hormonal contraceptives (379).
			Comment: Drugs that are inhibitors of CYP3A4 or CYP2C9 theoretically have the potential to increase levels of contraceptive steroids which might increase adverse events. Fluvoxamine is an SSRI known to be a moderate inhibitor of both CYP3A4 and CYP2C9; however, no clinical or pharmacokinetic studies were identified to explore potential drug-drug interactions.
St. John’s wort	2		Evidence: Although clinical data are limited, studies with pharmacokinetic and pharmacodynamics outcomes raise concern that St. John’s wort might decrease effectiveness of hormonal contraceptives, including increased risk for breakthrough bleeding and ovulation and increased metabolism of estrogen and progestins. Any interactions might be dependent on the dose of St John’s wort, and the concentration of active ingredients across types of St. John’s wort preparations may vary (380).