This document will not include any discussion of the unlabeled use of a product or a product under investigational use, with the exception that some of the recommendations in this document might be inconsistent with package labeling.# Introduction
Approximately 45% of all pregnancies that occur in the United States are unintended (1), with associated increased risks for adverse maternal and infant health outcomes (2) and increased health care costs (3). Women, men, and couples have increasing numbers of safe and effective choices for contraceptive methods, including long-acting reversible contraception methods such as intrauterine devices (IUDs) and implants, to reduce the risk for an unintended pregnancy. However, with these expanded options comes the need for evidence-based guidance to help health care providers offer quality family planning care to their patients, including choosing the most appropriate contraceptive method for individual circumstances and using that method correctly, consistently, and continuously to maximize effectiveness.
In 2010, CDC published the first U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC), which provided recommendations on safe use of contraceptive methods for women with various medical conditions and other characteristics (and was adapted from global guidance developed by the World Health Organization ) (4,5). U.S. MEC is a companion document to the U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR), which provides guidance on how to use contraceptive methods safely and effectively once they are deemed to be medically appropriate (6). WHO intended for the global guidance to be used by local or national policy makers, family planning program managers, and the scientific community as a reference when they develop family planning guidance at the country or program level. During 2008-2010, CDC participated in a formal process to adapt the global guidance for appropriateness for use in the United States, which included rigorous identification and critical appraisal of the scientific evidence through systematic reviews, and input from national experts on how to translate that evidence into recommendations for U.S. health care providers (5). At that time, CDC committed to keeping this guidance up to date and based on the best available evidence, with full review every few years (5).
This document updates CDC's U.S. MEC 2010 (5), based on new evidence and input from experts. A summary of changes from U.S. MEC 2010 is provided (Appendix A). Notable updates include the following:
- addition of recommendations for women with cystic fibrosis, women with multiple sclerosis, and women receiving certain psychotropic drugs or St. John's wort - revisions to the recommendations for emergency contraception, including the addition of ulipristal acetate - revisions to the recommendations for postpartum women; women who are breastfeeding; women with known dyslipidemias, migraine headaches, superficial venous disease, gestational trophoblastic disease, sexually transmitted diseases (STDs), and human immunodeficiency virus (HIV); and women who are receiving antiretroviral therapy The goal of these recommendations is to remove unnecessary medical barriers to accessing and using contraception, thereby decreasing the number of unintended pregnancies. These recommendations are meant to serve as a source of clinical guidance for health care providers; health care providers should always consider the individual clinical circumstances of each person seeking family planning services. This report is not intended to be a substitute for professional medical advice for individual patients, who should seek advice from their health care providers when considering family planning options.

# Methods
Since publication of U.S. MEC 2010, CDC has monitored the literature for new evidence relevant to the recommendations through the WHO/CDC continuous identification of research evidence (CIRE) system. This system identifies new evidence as it is published and allows WHO and CDC to update systematic reviews and facilitate updates to recommendations as new evidence warrants. Automated searches are run in PubMed weekly, and the results are reviewed. Abstracts that meet specific criteria are added to the web-based CIRE system, which facilitates coordination and peer review of systematic reviews for both WHO and CDC (7). In 2014, CDC reviewed all of the existing recommendations in U.S. MEC 2010 for new evidence identified by CIRE that had the potential to lead to a changed recommendation. During August 27 -28, 2014, CDC held a meeting in Atlanta, Georgia, of 11 family planning experts and representatives from partner organizations to solicit their input on the scope of and process for updating both U.S. MEC 2010 and U.S. SPR 2013. The participants were experts in family planning and represented various types of health care providers, as well as health care provider organizations. A list of participants is provided at the end of this report. Meeting participants discussed topics to be addressed in the update of U.S. MEC based on new evidence published since 2010 (identified through the CIRE system), topics addressed at a 2014 WHO meeting to update global guidance, and suggestions CDC received from health care providers for the addition of recommendations for women with medical conditions not yet included in U.S. MEC (e.g., from provider feedback through e-mail, public inquiry, and questions received at conferences). CDC identified several topics to consider when updating the guidance, including revision of existing recommendations for certain medical conditions or characteristics (breastfeeding, postpartum, HIV, receiving antiretroviral therapy, obesity, dyslipidemia, increased risk for STDs, superficial venous thrombosis, gestational trophoblastic disease, and migraine headaches), addition of recommendations for new medical conditions (cystic fibrosis, multiple sclerosis, use of certain psychotropic drugs, and St. John's wort), and addition of recommendations for new contraceptive methods (ulipristal acetate for emergency contraception). CDC determined that all other recommendations in U.S. MEC 2010 were up to date and consistent with the existing body of evidence for that recommendation.
In preparation for a subsequent expert meeting held during August 2015, to review the scientific evidence for potential recommendations, CDC staff members and other invited authors listed at the end of this report conducted independent systematic reviews for each of the topics being considered. The purpose of these systematic reviews was to identify direct evidence about the safety of contraceptive method use by women with selected conditions (e.g., risk for disease progression or other adverse health effects in women with multiple sclerosis who use combined hormonal contraceptives ). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for reporting systematic reviews (8,9), and strength and quality of the evidence were assigned using the system of the U.S. Preventive Services Task Force (10). When direct evidence was limited or not available, indirect evidence (e.g., evidence on surrogate outcomes or among healthy women) and theoretical issues were considered and either added to direct evidence within a systematic review or separately compiled for presentation to the meeting participants. Completed systematic reviews were peer reviewed by two or three experts and then provided to participants before the expert meeting. Reviews are referenced and cited throughout this document; the full reviews appear in the published literature and contain the details of each review, including the systematic review question, literature search protocol, inclusion and exclusion criteria, evidence tables, and quality assessments. CDC staff continued to monitor new evidence identified through the CIRE system during the preparation for the August 2015 meeting.
During August 26-28, 2015, in Atlanta, Georgia, CDC held a meeting with 44 participants who were invited to provide their individual perspectives on the scientific evidence presented and potential recommendations. Twenty-nine of the participants represented a wide range of expertise in family planning provision and research, and included obstetricians/ gynecologists, pediatricians, family physicians, nurse practitioners, epidemiologists, and others with research and clinical practice expertise in contraceptive safety, effectiveness, and management; these individuals participated in the entire meeting. Fifteen participants with expertise relevant to specific topics on the meeting agenda provided information and participated in the discussion (e.g., an expert in cystic fibrosis was asked to provide general information about the condition and to assist in interpreting the evidence and any theoretical concerns on the use of contraceptive methods in women with the condition); these participants provided input only during the session for which their topics were discussed. Lists of participants and any potential conflicts of interest are provided at the end of this report. During the meeting, the evidence from the systematic review for each topic was presented, including direct evidence and any indirect evidence or theoretical concerns. Participants provided their perspectives on using the evidence to develop recommendations that would meet the needs of U.S. health care providers. After the meeting, CDC determined the recommendations in this report, taking into consideration the perspectives provided by the meeting participants. Feedback also was received from three external reviewers, composed of health care providers and researchers who had not participated in the update meetings. These reviewers were asked to provide comments on the accuracy, feasibility, and clarity of the recommendations. Areas of research that need additional investigation also were considered during the meeting (11).

# How to Use This Document
These recommendations are intended to help health care providers determine the safe use of contraceptive methods among women and men with various characteristics and medical conditions. Providers also can use the information in these recommendations when consulting with women, men, and couples about their selection of contraceptive methods. The tables in this document include recommendations for the use of contraceptive methods by women and men with particular characteristics or medical conditions. Each condition is defined as representing either an individual's characteristics (e.g., age or history of pregnancy) or a known preexisting medical or pathologic condition (e.g., diabetes or hypertension). The recommendations refer to contraceptive methods being used for contraceptive purposes; the recommendations do not consider the use of contraceptive methods for treatment of medical conditions because the eligibility criteria in these situations might differ. The conditions affecting eligibility for the use of each contraceptive method are classified into one of four categories (Box 1).

# Using the Categories in Practice
Health care providers can use the eligibility categories when assessing the safety of contraceptive method use for women and men with specific medical conditions or characteristics. Category 1 comprises conditions for which no restrictions exist for use of the contraceptive method. Classification of a method/condition as category 2 indicates the method generally can be used, although careful follow-up might be required. For a method/condition classified as category 3, use of that method usually is not recommended unless other more appropriate methods are not available or acceptable. The severity of the condition and the availability, practicality, and acceptability of alternative methods should be considered, and careful follow-up is required. Hence, provision of a contraceptive method to a woman with a condition classified as category 3 requires careful clinical judgement and access to clinical services. Category 4 comprises conditions that represent an unacceptable health risk if the method is used. For example, a smoker aged <35 years generally can use combined oral contraceptives (COCs) (category 2). However, for a woman BOX 1. Categories of medical eligibility criteria for contraceptive use 1 = A condition for which there is no restriction for the use of the contraceptive method. 2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks. 3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method. 4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
aged 35 years who smokes <15 cigarettes per day, the use of COCs usually is not recommended unless other methods are not available or acceptable to her (category 3). A woman aged 35 years who smokes 15 cigarettes per day should not use COCs because of unacceptable health risks, primarily the risk for myocardial infarction and stroke (category 4). The programmatic implications of these categories might depend on the circumstances of particular professional or service organizations. For example, in some settings, a category 3 might mean that a special consultation is warranted.
The recommendations address medical eligibility criteria for the initiation and continued use of all methods evaluated. The issue of continuation criteria is clinically relevant whenever a medical condition develops or worsens during use of a contraceptive method. When the categories differ for initiation and continuation, these differences are noted in the Initiation and Continuation columns. When initiation and continuation are not indicated, the category is the same for initiation and continuation of use.
On the basis of this classification system, the eligibility criteria for initiating and continuing use of a specific contraceptive method are presented in tables (Appendices A-K). In these tables, the first column indicates the condition. Several conditions are divided into subconditions to differentiate between varying types or severity of the condition. The second column classifies the condition for initiation or continuation (or both) into category 1, 2, 3, or 4. For certain conditions, the numeric classification does not adequately capture the recommendation; in these cases, the third column clarifies the numeric category. These clarifications were determined during the discussions of the scientific evidence and are considered a necessary element of the recommendation. The third column also summarizes the evidence for the recommendation if evidence exists. The recommendations for which no evidence is cited are based on expert opinion from either the WHO or U.S. expert meeting in which these recommendations were developed, and might be based on evidence from sources other than systematic reviews. For certain recommendations, additional comments appear in the third column and generally come from the WHO meeting or the U.S. meeting.

# Recommendations for Use of Contraceptive Methods
The classifications for whether women with certain medical conditions or characteristics can use specific contraceptive methods are provided for intrauterine contraception, including the copper-containing IUD and levonorgestrel-releasing IUDs (Appendix B); progestin-only contraceptives (POCs), including etonogestrel implants, depot medroxyprogesterone acetate injections, and progestin-only pills (Appendix C); CHCs, including low-dose (containing 35 g ethinyl estradiol) COCs, combined hormonal patch, and combined vaginal ring (Appendix D); barrier contraceptive methods, including male and female condoms, spermicides, diaphragm with spermicide, and cervical cap (Appendix E); fertility awarenessbased methods (Appendix F); lactational amenorrhea method (Appendix G); coitus interruptus (Appendix H); female and male sterilization (Appendix I); and emergency contraception, including emergency use of the copper-containing IUD and emergency contraceptive pills (Appendix J). A table at the end of this report summarizes the classifications for the hormonal and intrauterine methods (Appendix K).

# Contraceptive Method Choice
Many elements need to be considered by women, men, or couples at any given point in their lifetimes when choosing the most appropriate contraceptive method. These elements include safety, effectiveness, availability (including accessibility and affordability), and acceptability. The guidance in this report focuses primarily on the safety of a given contraceptive method for a person with a particular characteristic or medical condition. Therefore, the classification of category 1 means that the method can be used in that circumstance with no restrictions with regard to safety but does not necessarily imply that the method is the best choice for that person; other factors, such as effectiveness, availability, and acceptability, might play an important role in determining the most appropriate choice. Voluntary informed choice of contraceptive methods is an essential guiding principle, and contraceptive counseling, when applicable, might be an important contributor to the successful use of contraceptive methods.
In choosing a method of contraception, dual protection from the simultaneous risk for HIV and other STDs also should be considered. Although hormonal contraceptives and IUDs are highly effective at preventing pregnancy, they do not protect against STDs, including HIV. Consistent and correct use of the male latex condom reduces the risk for HIV infection and other STDs, including chlamydial infection, gonococcal infection, and trichomoniasis (12). Although evidence is limited, use of female condoms can provide protection from acquisition and transmission of STDs (12). All patients, regardless of contraceptive choice, should be counseled about the use of condoms and the risk for STDs, including HIV infection (12). Additional information about prevention and treatment of STDs is available from the CDC Sexually Transmitted Diseases Treatment Guidelines () (12).

# Unintended Pregnancy and Increased Health Risk
For women with conditions that might make pregnancy an unacceptable health risk, long-acting, highly effective contraceptive methods might be the best choice to avoid unintended pregnancy (Figure). Women with these conditions should be advised that sole use of barrier methods for contraception and behavior-based methods of contraception might not be the most appropriate choice because of their relatively higher typical-use rates of failure (Figure). Conditions included in U.S. MEC that are associated with increased risk for adverse health events as a result of pregnancy are identified throughout the document (Box 2). Some of the medical conditions included in U.S. MEC recommendations are treated with teratogenic drugs. While the woman's medical condition may not affect her eligibility to use certain contraceptive methods, women using teratogenic drugs are at increased risk for poor pregnancy outcomes; long-acting, highly effective contraceptive methods might be the best option to avoid unintended pregnancy or delay pregnancy until teratogenic drugs are no longer needed.

# Keeping Guidance Up to Date
Updating the evidence-based recommendations as new scientific evidence becomes available is a challenge. CDC will continue to work with WHO to identify and assess new relevant evidence as it becomes available and to determine whether changes in the recommendations are warranted (7). In most cases, U.S. MEC follows the WHO guidance updates, which typically occur every 5 years (or sooner if warranted by new data). However, CDC will review all WHO updates for their application in the United States. CDC also will identify and assess any new literature for the recommendations and medical conditions that are not included in the WHO guidance. CDC will completely review U.S. MEC every 5 years as well. Updates to the guidance will appear on the CDC U.S. MEC website (/ UnintendedPregnancy/USMEC.htm).

# Breast cancer
Complicated valvular heart disease Cystic fibrosis Diabetes: insulin dependent; with nephropathy, retinopathy, or neuropathy or other vascular disease; or of >20 years' duration Endometrial or ovarian cancer Epilepsy Hypertension (systolic 160 mm Hg or diastolic 100 mm Hg) History of bariatric surgery within the past 2 years HIV: not clinically well or not receiving antiretroviral therapy Ischemic heart disease Gestational trophoblastic disease Hepatocellular adenoma and malignant liver tumors (hepatoma) Peripartum cardiomyopathy Schistosomiasis with fibrosis of the liver Severe (decompensated) cirrhosis Sickle cell disease Solid organ transplantation within the past 2 years Stroke Systemic lupus erythematosus Thrombogenic mutations Tuberculosis - Long-acting, highly effective contraceptive methods might be the best choice for women with conditions that are associated with increased risk for adverse health events as a result of pregnancy. These women should be advised that sole use of barrier methods for contraception and behaviorbased methods of contraception might not be the most appropriate choice because of their relatively higher typical-use rates of failure.

# Handling Conflicts of Interest
To promote transparency, all participants were asked to disclose any potential conflicts of interest to CDC prior to the expert meeting and to report any potential conflicts of interest during the introductory portion of the expert meeting. All potential conflicts of interest are listed above. No participants were excluded from discussion based on potential conflicts of interest. CDC staff who ultimately decided and developed these recommendations have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters relevant to these recommendations. 1 = A condition for which there is no restriction for the use of the contraceptive method. 2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks. 3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method. 4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
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.

# 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.

# 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.

# BOX B1. Categories for classifying intrauterine devices
1 = A condition for which there is no restriction for the use of the contraceptive method. 2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks. 3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method. 4 = A condition that represents an unacceptable health risk if the contraceptive method is used. 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 .

# 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 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.   (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 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 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.    Evidence: Limited evidence indicates that insertion of the LNG-IUD does not pose major bleeding risks in women receiving chronic anticoagulant therapy (70)(71)(72)(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)

# 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.   (73,(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(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). 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 ( ).
ii. With aura 1 1

# Epilepsy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2). 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).
See table footnotes on page 30. 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 -hCG levels for appropriate disease surveillance.

# TABLE B1. (Continued) Classifications for intrauterine devices, including the copper-containing intrauterine device and levonorgestrelreleasing intrauterine device
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. 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 -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 -hCG levels have decreased to nonpregnant levels, the risk for disease progression is likely to be very low.
ii. Decreasing -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 -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).
See table footnotes on page 30.

# TABLE B1. (Continued) Classifications for intrauterine devices, including the copper-containing intrauterine device and levonorgestrelreleasing intrauterine device Condition

# Category

# Clarifications/Evidence/Comments Cu-IUD LNG-IUD
iii. Persistently elevated -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 -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 -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 -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. 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.

# 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.
See table footnotes on page 30. 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   Anemias Thalassemia 2 1 Comment: Concern exists about an increased risk for blood loss with Cu-IUDs.

# TABLE B1. (Continued) Classifications for intrauterine devices, including the copper-containing intrauterine device and levonorgestrelreleasing intrauterine device

# Sickle cell disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
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).
) 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 - See

# TABLE B1. (Continued) Classifications for intrauterine devices, including the copper-containing intrauterine device and levonorgestrelreleasing intrauterine device Condition

# Category

# Clarifications/Evidence/Comments Cu-IUD LNG-IUD
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

# 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.

# BOX C1. Categories for classifying progestin-only contraceptives
1 = A condition for which there is no restriction for the use of the contraceptive method. 2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks. 3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method. 4 = A condition that represents an unacceptable health risk if the contraceptive method is used.  (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.
See   (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.  (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.
See

# 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).

# 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.  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

# 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)(135)(136)(137)(138)(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)(142)(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)(145)(146)(147)(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)(142)(143)(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)(148)(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)  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.
1 1 1 - See
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).  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. 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.
See  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.

# Appendix D Classifications for Combined Hormonal Contraceptives
Combined hormonal contraceptives (CHCs) include lowdose (containing 35 g 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 . 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.

# BOX D1. Categories for classifying combined hormonal contraceptives
1 = A condition for which there is no restriction for the use of the contraceptive method. 2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks. 3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method. 4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
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

# Age
Evidence: Evidence is inconsistent about whether CHC use affects fracture risk (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(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 g ethinyl estradiol) (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59). CHC use has little to no effect on BMD in premenopausal women (60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74) and might preserve bone mass in those who are perimenopausal (75)(76)(77)(78)(79)(80)(81)(82)(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)(85)(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. 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)(91)(92)(93)(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/m 2 , postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking)
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)(91)(92)(93)(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.
See table footnotes on page 69.

# TABLE D1. (Continued) Classifications for combined hormonal contraceptives, including pill, patch, and ring

# Condition Category CHCs Clarifications/Evidence/Comments
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)(91)(92)(93)(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.  (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)(91)(92)(93)(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.
See   (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)(91)(92)(93)(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)(91)(92)(93)(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) 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)(91)(92)(93)(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   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)(97)(98)(99)(100)(101)(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).  (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)(119)(120)(121)(122)(123)(124)(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/m 2 2 b. Menarche to <18 years and BMI 30 kg/m 2 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)
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: 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)(114)(115)(116)(129)(130)(131)(132)(133)(134)(135)(136)(137)(138)(139)(140)(141)(142)(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)(114)(115)(116)(129)(130)(131)(132)(133)(134)(135)(136)(137)(138)(139)(140)(141)(142)(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)(146)(147)(148)(149)(150)(151). 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.  Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.

# Deep venous thrombosis/
Evidence: Among women with thrombogenic mutations, COC users had a twofold to twentyfold higher risk for thrombosis than did nonusers . 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).
See  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).

# Stroke (history of cerebrovascular accident)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).

# 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)
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.  (179)(180)(181)(182)(183)(184)(185)(186)(187)(188)(189)(190)(191)(192)(193)(194)(195)(196)(197).
Evidence: Antiphospholipid antibodies are associated with a higher risk for both arterial and venous thrombosis (198,199  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)(204)(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)(204)(205).

# 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)
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).
See  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 gonadotropinreleasing 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 -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 -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).

# 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).  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).

# 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).

# 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).
See

# Respiratory Conditions

# Cystic fibrosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2). 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).
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).
See  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 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)(276)(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)(276)(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).
See  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).   (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 g 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)(304)(305)(306)(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 , patch (345), or ring (346). 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 g ethinyl estradiol should be used.

# Evidence:
The balance of the evidence suggests that rifampin reduces the effectiveness of COCs (363)(364)(365)(366)(367)(368)(369)(370)(371)(372)(373)(374)(375)(376)(377)(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.
See   (380).
Abbreviations: ARV = antiretroviral; BMD = bone mineral density; BMI = body mass index; CHC = combined hormonal contraceptive; COC = combined oral contraceptive; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; IBD = inflammatory bowel disease; LDL = low-density lipoprotein; PE = pulmonary embolism; PID = pelvic inflammatory disease; SLE = systemic lupus erythematosus; SSRI = selective serotonin reuptake inhibitor; STD = sexually transmitted infection; VTE = venous thromboembolism.
Classifications for barrier contraceptive methods include those for condoms, which include male latex condoms, male polyurethane condoms, and female condoms; spermicides; and diaphragm with spermicide or cervical cap (Box E1) (Table E1).
Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention might not be appropriate for those who cannot use them consistently and correctly because of the relatively higher typical-use failure rates of these methods. Women should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs). Use of female condoms can provide protection from transmission of STDs, although data are limited.

# Postabortion

# Caution Delay
Clarification: After abortion, women are likely to have sufficient ovarian function to produce detectable fertility signs, hormonal changes, or both; likelihood increases with time postabortion. Women can start using calendar-based methods after they have had at least one postabortion menses (e.g., women who before this pregnancy primarily had cycles of 26-32 days can then use the standard days method). Methods appropriate for the postabortion period should be offered before that time.

# Reproductive Tract Infections and Disorders
Irregular vaginal bleeding Delay Delay Clarification: Presence of this condition makes FAB methods unreliable. Therefore, barrier methods should be recommended until the bleeding pattern is compatible with proper method use. The condition should be evaluated and treated as necessary.
Vaginal discharge Delay Accept Clarification: Because vaginal discharge makes recognition of cervical secretions difficult, the condition should be evaluated and treated if needed before providing methods based on cervical secretions.

# Other
Use of drugs that affect cycle regularity, hormones, or fertility signs Caution /Delay Caution/Delay Clarification: Use of certain mood-altering drugs such as lithium, tricyclic antidepressants, and antianxiety therapies, as well as certain antibiotics and anti-inflammatory drugs, might alter cycle regularity or affect fertility signs. The condition should be carefully evaluated and a barrier method offered until the degree of effect has been determined or the drug is no longer being used. Diseases that elevate body temperature a. Chronic diseases Caution Accept Clarification: Elevated temperatures might make basal body temperature difficult to interpret but have no effect on cervical secretions. Thus, use of a method that relies on temperature should be delayed until the acute febrile disease abates. Temperature-based methods are not appropriate for women with chronically elevated temperatures. In addition, some chronic diseases interfere with cycle regularity, making calendar-based methods difficult to interpret.

# b. Acute diseases Delay Accept
Abbreviations: FAB = fertility awareness-based; NA = not applicable.