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Purpose: To evaluate the association between postpartum hormonal contraceptive use and postpartum depression., Materials and Methods: We searched the literature through March 2018 on the association between postpartum hormonal contraception use and incident postpartum depression. We used the United States Preventive Services Task Force framework to assess study quality., Results: Of 167 articles identified, four met inclusion criteria. Two studies found no differences in rates of postpartum depression between women using postpartum depot medroxyprogesterone and those not using hormonal contraception; however, a study of women receiving injectable norethisterone enanthate immediately postpartum found a 2-3-fold increased risk of depression at 6 weeks, though not at 3 months. One study compared combined hormonal contraception, progestin-only pills (POPs), etonogestrel implants and levonorgestrel intrauterine devices (LNG-IUDs) with no hormonal contraception, and found a 35-44% decreased risk of postpartum depression with POPs and LNG-IUDs, a small increased risk of postpartum antidepressant use among women using the etonogestrel implant and vaginal ring, and a decreased risk of antidepressant use with POPs., Conclusions: Limited evidence found no consistent associations between hormonal contraceptive use and incidence of postpartum depression. Future research would be strengthened by using validated diagnostic measures, careful consideration of confounders, and ensuring adequate follow-up time.

Objective: The purpose of this study was to determine whether interactions between non-rifamycin antibiotics and hormonal contraceptives result in decreased effectiveness or increased toxicity of either therapy., Study Design: We searched MEDLINE, Embase, clinicaltrials.gov, and Cochrane libraries from database inception through June 2016. We included trials, cohort, case-control, and pharmacokinetic studies in any language that addressed pregnancy rates, pharmacodynamics, or pharmacokinetic outcomes when any hormonal contraceptive and non-rifamycin antibiotic were administered together vs apart. Of 7291 original records that were identified, 29 met criteria for inclusion., Study Appraisal and Synthesis Methods: Two authors independently assessed study quality and risk of bias using the United States Preventive Services Task Force evidence grading system. Findings were tabulated by drug class., Results: Study quality ranged from good to poor and addressed only oral contraceptive pills, emergency contraception pills, and the combined vaginal ring. Two studies demonstrated no difference in pregnancy rates in women who used oral contraceptives with and without non-rifamycin antibiotics. No differences in ovulation suppression or breakthrough bleeding were observed in any study that combined hormonal contraceptives with any antibiotic. No significant decreases in any progestin pharmacokinetic parameter occurred during co-administration with any antibiotic. Ethinyl estradiol area under the curve decreased when administered with dirithromycin, but no other drug., Conclusion: Evidence from clinical and pharmacokinetic outcomes studies does not support the existence of drug interactions between hormonal contraception and non-rifamycin antibiotics. Data are limited by low quantity and quality for some drug classes. Most women can expect no reduction in hormonal contraceptive effect with the concurrent use of non-rifamycin antibiotics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

CDC's U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) (first published in 2010 and updated in 2016) provides evidence-based guidance for the safe use of contraceptive methods among U.S. women with certain characteristics or medical conditions (1), and is adapted from global guidance from the World Health Organization (WHO) and kept up to date based on continual review of published literature (2).* CDC recently evaluated the evidence and the updated WHO guidance on the risk for human immunodeficiency virus (HIV) acquisition among women using hormonal contraception. † After careful review, CDC adopted the updated WHO guidance for inclusion in the U.S. MEC guidance; this guidance states that the advantages of progestin-only injectable contraceptive use (including depot medroxyprogesterone acetate [DMPA]) by women at high risk for HIV infection outweigh the theoretical or proven risks (U.S. MEC category 2). The guidance also includes an accompanying updated clarification, which states that "there continues to be evidence of a possible increased risk of acquiring HIV among progestin-only injectable users. Uncertainty exists about whether this is due to methodological issues with the evidence or a real biological effect. In many settings, unintended pregnancies and/or pregnancy-related morbidity and mortality are common, and progestin-only injectables are among the few types of methods widely available. Women should not be denied the use of progestin-only injectables because of concerns about the possible increased risk. Women considering progestin-only injectables should be advised about these concerns, about the uncertainty over whether there is a causal relationship, and about how to minimize their risk of acquiring HIV." Recommendations for other hormonal contraceptive methods (including combined hormonal methods, implants, and progestin-only pills) remain the same; there is no restriction for their use among women at high risk for HIV infection (U.S. MEC category 1).

Background: Migraine with aura and combined hormonal contraceptives are independently associated with an increased risk of ischemic stroke. However, little is known about whether there are any joint effects of migraine and hormonal contraceptives on risk of stroke., Objective: We sought to estimate the incidence of stroke in women of reproductive age and examine the association among combined hormonal contraceptive use, migraine type (with or without aura), and ischemic stroke., Study Design: This study used a nationwide health care claims database and employed a nested case-control study design. Females ages 15-49 years with first-ever stroke during 2006 through 2012 were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification inpatient services diagnosis codes. Four controls were matched to each case based on age. Migraine headache with and without aura was identified using inpatient or outpatient diagnosis codes. Current combined hormonal contraceptive use was identified using the National Drug Code from the pharmacy database. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals of ischemic stroke by migraine type and combined hormonal contraceptive use., Results: From 2006 through 2012, there were 25,887 ischemic strokes among females ages 15-49 years, for a cumulative incidence of 11 strokes/100,000 females. Compared to those with neither migraine nor combined hormonal contraceptive use, the odds ratio of ischemic stroke was highest among those with migraine with aura using combined hormonal contraceptives (odds ratio, 6.1; 95% confidence interval, 3.1-12.1); odds ratios were also elevated for migraine with aura without combined hormonal contraceptive use (odds ratio, 2.7; 95% confidence interval, 1.9-3.7), migraine without aura and combined hormonal contraceptive use (odds ratio, 1.8; 95% confidence interval, 1.1-2.9), and migraine without aura without combined hormonal contraceptive use (odds ratio, 2.2; 95% confidence interval, 1.9-2.7)., Conclusion: The joint effect of combined hormonal contraceptives and migraine with aura was associated with a 6-fold increased risk of ischemic stroke compared with neither risk factor. Use of combined hormonal contraceptives did not substantially further increase risk of ischemic stroke among women with migraine without aura. Determining migraine type is critical in assessing safety of combined hormonal contraceptives among women with migraine., (Published by Elsevier Inc.)

Objective: To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI)., Study Design: We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force., Results: From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable., Conclusion: Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness., (Copyright © 2017. Published by Elsevier Inc.)

Objectives: St. John's wort (SJW) is a known strong inducer of the cytochrome P450 (CYP) 3 A4 enzyme, and both the ethinyl estradiol and progestin components of hormonal contraceptives are substrates of CYP3A4. This systematic review examined whether the co-administration of SJW and hormonal contraceptives leads to significant safety or efficacy concerns., Study Design: Systematic review., Methods: PubMed and Cochrane Library databases were searched for articles of any comparative study design (clinical or pharmacokinetic) that examined potential interactions between SJW and hormonal contraceptives in women of reproductive age., Results: Of the 48 identified articles, four studies met inclusion criteria and compared use of combined oral contraceptives (COCs) alone to the use of COCs co-administered with SJW. Two studies demonstrated no change in markers of ovulation, but one study demonstrated increased follicular growth and probable ovulation when COCs were co-administered with SJW. Three studies demonstrated an increased risk of breakthrough bleeding with COCs and SJW. Three studies showed changes in at least one pharmacokinetic parameter that suggested a significantly decreased exposure to hormone concentrations when COCs were co-administered with SJW. The only study that did not demonstrate any significant pharmacokinetic differences examined a SJW product containing a low amount of hypericin., Conclusion: Limited evidence showing increased risk of ovulation and breakthrough bleeding raises concern for decreased contraceptive efficacy when COCs are co-administered with SJW. The pharmacokinetic evidence is mixed but suggests that SJW administration may be associated with weak to moderate induction of the metabolism of COCs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated with an increased risk of ischemic stroke. Use of hormonal contraception among women with migraine might further elevate the risk of stroke among women of reproductive age., Objective: To identify evidence regarding the risk of arterial thromboembolism (stroke or myocardial infarction) among women with migraine who use hormonal contraceptives., Methods: We searched the PubMed database for all articles published from database inception through January 2016. We included studies that examined women with migraine overall or separated by subtype (with or without aura). Hormonal contraceptives of interest included combined hormonal methods (COCs, patch and ring) and progestin-only methods (progestin-only pills, injectables, implants and progestin intrauterine devices)., Results: Seven articles met inclusion criteria. All were case-control studies of fair to poor quality reporting on use of COCs or oral contraceptives (OCs) not further described and all reported stroke outcomes. Four studies demonstrated that, among women with migraine (not separated by subtype), COC use was associated with approximately two to four times the risk of stroke compared with nonuse. The only study to examine specific migraine subtypes found an elevated risk of stroke among women with migraine with aura, and this risk was similar regardless of OC use, although these odds ratios were not reported. Two studies did not report risks among women with migraine and COC use combined, but both found increased risks of stroke with migraine and COC use independently. No evidence was found on other hormonal contraceptives or on risk of myocardial infarction., Conclusion: Limited evidence suggests a two- to fourfold increased risk of stroke among women with migraine who use COCs compared with nonuse. Additional study is needed on the risks of hormonal contraceptives, including combined and progestin-only methods, among women with different migraine subtypes., (Published by Elsevier Inc.)

Background: With dramatic improvements in life expectancy for cystic fibrosis (CF) patients, contraception for women with CF has become an important issue. There are theoretical concerns that hormonal contraceptive use among women with CF may impact disease severity or risk for other adverse health outcomes, including thrombosis and poor bone health, as well as concerns that malabsorption or altered drug metabolism might impact contraceptive effectiveness., Objective: To evaluate evidence on the safety and effectiveness of contraceptive methods among women with CF., Search Strategy: We searched the PubMed database for all articles published from database inception through October 2015., Selection Criteria: We included studies that examined measures of disease severity, other health outcomes or indicators of contraceptive effectiveness among women with CF initiating or continuing a contraceptive method., Results: Seven studies met our inclusion criteria. Three observational studies of fair to poor quality suggest that use of oral contraceptives (OCs) does not negatively impact CF disease severity, defined as changes in pulmonary function, number of exacerbations or need for intravenous antibiotics. Three small studies of poor quality reported on contraceptive failure among women with CF using combined hormonal contraceptives (combined OCs, patch or ring). One pregnancy was reported in a patch user out of 43 hormonal contraceptive users across all studies. One pharmacokinetic study reported that women with CF achieve steroid hormone plasma concentrations similar to healthy women after ingestion of combined OCs., Conclusions: Limited evidence suggests that hormonal contraceptive use does not negatively impact disease severity among women with CF and that hormonal contraceptive effectiveness is not impaired by CF. Studies were limited by small sample sizes and short duration of follow-up. No studies examined the effect of hormonal contraception on thrombosis or bone health among women with CF., (Published by Elsevier Inc.)

Objective: To examine whether the co-administration of hormonal contraceptives (HC) and psychotropic drugs commonly used to treat anxiety and/or depression results in safety or efficacy concerns for either drug., Methods: We searched PubMed and Cochrane libraries for clinical or pharmacokinetic (PK) studies that examined co-administration of any HC with psychotropic drugs [selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), oral benzodiazepines, bupropion, mirtazapine, trazadone, buspirone, hydroxyzine, monoamine oxidase inhibitors (MAOIs), or atypical antipsychotics] in reproductive aged women., Results: Of 555 articles identified, 22 articles (18 studies) met inclusion criteria. We identified 5 studies on SSRIs, four on TCAs, one on bupropion, three on atypical antipsychotics and five on oral benzodiazepines. No articles met inclusion criteria for SNRIs, mirtazapine, trazadone, buspirone, hydroxyzine or MAOIs. Overall, clinical studies did not demonstrate differences in unintended pregnancy rates when HCs were administered with and without psychotropic drugs or in psychotropic drug treatment outcomes when psychotropic drugs were administered with and without HCs. PK studies did not demonstrate changes in drug exposure related to contraceptive safety, contraceptive effectiveness or psychotropic drug effectiveness for most classes of psychotropic drugs. However, limited PK data raise concern for HCs increasing systemic exposure of amitriptyline and imipramine (both TCAs), theoretically posing safety concerns., Conclusion: Limited quality and quantity evidence on use of psychotropic drugs and HCs suggests low concern for clinically significant interactions, though no data exist specifically for non-oral formulations of HC. Given the high frequency of use for both HCs and psychotropic drugs among reproductive-age women in the US, this review highlights a need for further research in this area., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and infant health outcomes., Objectives: We investigated the clinical outcomes of breastfeeding duration, initiation of supplemental feeding and weaning, as well as infant outcomes including infant growth, health and development among breastfeeding women using POCs compared with breastfeeding women not using POCs., Search Strategy: We searched the PubMed database for all articles published from database inception through December 2014., Selection Criteria: We included primary research studies of breastfeeding women of any age or parity who received POCs, including progestogen-only pills, injectables, implants or hormonal intrauterine devices (IUDs). The main outcomes were breastfeeding performance (as measured by initiation, continuation, frequency and exclusivity of breastfeeding) and infant health (as measured by growth, development or adverse health effects)., Results: Forty-nine articles reporting on 47 different studies were identified that investigated the use of POCs in breastfeeding women and reported clinically relevant outcomes of infant growth, health or breastfeeding performance. Studies ranged from poor to fair methodological quality and generally failed to show negative effects of the use of POCs on breastfeeding outcomes or on infant growth or development. One randomized controlled trial (RCT) raises concerns that immediate insertion of the levonorgestrel IUD postpartum may be associated with poorer breastfeeding performance when compared with delayed insertion, although two other RCTs evaluating early etonogestrel implants compared with delayed initiation of implants or depot medroxyprogesterone acetate failed to find such an association., Conclusion: The preponderance of evidence fails to demonstrate adverse breastfeeding outcomes or negative health outcomes in infants such as restricted growth, health problems or impaired development. Evidence newly added to this review was largely consistent with previous evidence., (Copyright © 2016. Published by Elsevier Inc.)

Background: Contraception is important for women who are postpartum, including those who are breastfeeding. Use of combined hormonal contraceptives (CHCs) may affect breastfeeding performance and infant health outcomes., Objective: The objective was to identify evidence examining clinical outcomes for breastfeeding and infant health among breastfeeding women using CHCs compared to nonusers., Search Strategy: We searched the PubMed database for all articles published from database inception through September 30, 2014., Selection Criteria: We included primary research studies that compared breastfeeding women using CHCs with breastfeeding women using nonhormonal or no contraception, or compared breastfeeding women initiating combined hormonal contraception at early versus later times postpartum. Breastfeeding outcomes of interest included duration, rate of exclusive breastfeeding and timing of supplementation. Infant outcomes of interest included growth, health and development., Results: Fifteen articles describing 13 studies met inclusion criteria for this review. Studies ranged from poor to fair methodological quality and demonstrated inconsistent effects of combined oral contraceptives (COCs) on breastfeeding performance with COC initiation before or after 6 weeks postpartum; some studies demonstrated greater supplementation and decreased breastfeeding continuation among COC users compared with nonusers, and others demonstrated no effect. For infant outcomes, some studies found decreases in infant weight gain for COC users compared with nonusers when COCs were initiated at <6 weeks postpartum, while other studies found no effect. None of the studies found an effect on infant weight gain when COCs were started after 6 weeks postpartum, and no studies found an effect on other infant health outcomes regardless of time of COC initiation., Conclusion: Limited evidence of poor to fair quality demonstrates an inconsistent impact of COCs on breastfeeding duration and success. The evidence also demonstrated conflicting results on whether early initiation of COCs affects infant outcomes but generally found no negative impact on infant outcomes with later initiation of COCs. The body of evidence is limited by older studies using different formulations and doses of estrogen and poor methodologic quality. Given the significant limitations of this body of evidence, the importance of contraception for postpartum women and the theoretical concerns that have been raised about the use of combined hormonal contraception by women who are breastfeeding, rigorous studies examining these issues are needed. In addition, postpartum women should be counseled about the full range of safe alternative contraceptive methods, particularly during the first 6 weeks postpartum when the risk of venous thromboembolism is highest and use of estrogen may exacerbate this risk., (Copyright © 2016. Published by Elsevier Inc.)

Context: Dyslipidemias represent a spectrum of lipid disorders that are important risk factors for cardiovascular disease. In addition, elevated triglycerides are known to be associated with pancreatitis. Though less clear, it is possible that dyslipidemias may also contribute to risk for venous thromboembolism (VTE). Ethinyl estradiol and progestogen, contained within combined hormonal contraception, are known to impact lipid metabolism., Objectives: To evaluate from the literature whether use of combined hormonal contraception (CHC), including combined oral contraception (COC) pills, transdermal patch, vaginal ring or injectables, modifies the relative risk of acute myocardial infarction (MI), stroke, VTE or pancreatitis among women with known dyslipidemias and to determine if existing lipid abnormalities worsen with CHC use., Methods: PubMed and the Cochrane Library databases were searched for all articles in all languages published between inception and September 2014 relevant to dyslipidemia, CHC use and serious adverse events (MI, stroke, VTE or pancreatitis). The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force., Results: From 306 articles identified by our search strategy, 3 articles met inclusion criteria. In a poor-quality case-control study, women with hypercholesterolemia but no COC use had an increased risk of MI (adjusted odds ratio [adj OR] 3.3, 95% confidence interval [CI] 1.6-6.8), as did women who used COCs but did not have hypercholesterolemia (adj OR 2.0, 95% CI 1.4-2.8), compared with non-COC users without hypercholesterolemia; women with both COC use and hypercholesterolemia had an adjusted OR of 24.7 (95% CI 5.6-108.5) compared with women with neither risk factor. A poor-quality cohort study examined COC users and reported that women with dyslipidemia had increased risk for VTE [crude risk ratio (RR) 1.39, 95% CI 1.04-1.85] and transient ischemic attacks or cerebrovascular accidents (CVAs) (RR 1.76, 95% CI 1.51-2.06) compared to those without dyslipidemia. Another poor-quality cohort study provided direct evidence on changes in lipid levels among COC users with dyslipidemia. A minority of women with elevated total cholesterol or triglyceride levels at baseline showed normal results (25% and 28%, respectively) after 6 cycles of COC use. No evidence regarding risks associated with use of other CHC methods was identified. No evidence was identified for the outcome of pancreatitis., Conclusion: Limited data from poor-quality observational studies suggest that women with known dyslipidemias using CHC may be at increased risk for MI and may experience a minimal increase in risk for CVA or VTE. No evidence was identified on risk for pancreatitis in this context. The impact of CHC exposure on the status of lipid abnormalities over time, an intermediate marker for disease, is also unclear. Given the significant limitations of this body of evidence, the importance of access to effective contraception and theoretical concerns raised about the use of CHCs by women with known dyslipidemias, additional rigorous studies are needed to best estimate true associations. Contraceptive decision making should include consideration of both the known and theoretical risks of a given CHC method, safety and acceptability of alternative contraceptive methods, and risks associated with unintended pregnancy., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hormonal contraceptives are important for the health and well-being of some women living with HIV, so evaluation of evidence regarding their safety vis-à-vis HIV-related risks is important., Methods: We updated two prior systematic reviews on the impact of hormonal contraception (HC) on HIV disease progression and female-to-male HIV transmission., Results: One new study finds no increased risk for HIV disease progression or death associated with oral contraceptive use [adjusted (adj) hazard ratio (HR) 0.83, confidence interval [CI] 0.48-1.44] or injectables (adj HR 0.72, CI 0.53-0.98). Three new studies did not find significantly increased risks for measures of female-to-male HIV transmission with HC use., Conclusions: Hormonal contraceptive methods do not appear to accelerate HIV disease progression. More research is needed to clarify whether HC impacts HIV transmissibility., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness., Study Design: A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350 cells/mm(3), ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method., Results: During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods., Conclusion: Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection., Implications: Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection., (Published by Elsevier Inc.)

Background: Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated with changes in bone mineral density in women. Whether such changes affect the risk of fractures later in life is unclear. Hormonal contraceptives are among the most effective and most widely-used contraceptives. Concern about fractures may limit the use of these effective contraceptives. Observational studies can collect data on premenopausal contraceptive use as well as fracture incidence later in life., Objectives: We systematically reviewed the evidence from observational studies of hormonal contraceptive use for contraception and the risk of fracture in women., Search Methods: Through June 2015, we searched for observational studies. The databases included PubMed, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for recent clinical trials through ClinicalTrials.gov and the ICTRP. For other studies, we examined reference lists of relevant articles and wrote to investigators for additional reports., Selection Criteria: We included cohort and case-control studies of hormonal contraceptive use. Interventions included comparisons of a hormonal contraceptive with a non-hormonal contraceptive, no contraceptive, or another hormonal contraceptive. The primary outcome was the risk of fracture., Data Collection and Analysis: Two authors independently extracted the data. One author entered the data into RevMan, and a second author verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale (NOS), developed for case-control and cohort studies. Sensitivity analysis included studies of moderate or high quality based on our assessment with the NOS.Given the need to control for confounding factors in observational studies, we used adjusted estimates from the models as reported by the authors. Where we did not have adjusted analyses, we calculated the odds ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did not conduct meta-analysis., Main Results: We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs), depot medroxyprogesterone acetate (DMPA), and the hormonal intrauterine device (IUD). This section focuses on the sensitivity analysis with six studies that provided moderate or high quality evidence.All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study reported OC ever-users had increased risk for all fractures (RR 1.20, 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (OR 1.55, 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (OR 1.09, 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use.Two case-control studies also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (OR 1.44, 95% CI 1.01 to 2.06), more than four years of use (OR 2.16, 95% CI 1.32 to 3.53), and women over 50 years old. The other reported increased risk for any past use, including one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and for current use of 3 to 9 prescriptions (OR 1.36, 95% CI 1.15 to 1.60) or 10 or more (OR 1.54, 95% CI 1.33 to 1.78). For the levonorgestrel-releasing IUD, one study reported reduced fracture risk for ever-use (OR 0.75, 95% CI 0.64 to 0.87) and for longer use., Authors' Conclusions: Observational studies do not indicate an overall association between oral contraceptive use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Investigators should be clear about the variables examined in multivariate analysis.

Background: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. Osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally., Objectives: Our aim was to evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women., Search Methods: Through April 2014, we searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as ClinicalTrials.gov and ICTRP. We examined reference lists of relevant articles for other trials. For the initial review, we wrote to investigators to find additional trials., Selection Criteria: Randomized controlled trials (RCTs) were considered if they examined fractures, bone mineral density (BMD), or bone turnover markers in women with hormonal contraceptive use prior to menopause. Eligible interventions included comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive that differed in terms of drug, dosage, or regimen. They also included providing a supplement to one group., Data Collection and Analysis: We assessed all titles and abstracts identified through the literature searches. Mean differences were computed using the inverse variance approach. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) was calculated. Both included the 95% confidence interval (CI) and used a fixed-effect model. Due to differing interventions, no trials could be combined for meta-analysis. We applied principles from GRADE to assess the evidence quality and address confidence in the effect estimates. In addition, a sensitivity analysis included trials that provided sufficient data for this review and evidence of at least moderate quality., Main Results: We found 19 RCTs that met our eligibility criteria. Eleven trials compared different combined oral contraceptives (COCs) or regimens of COCs; five examined an injectable versus another injectable, implant, or IUD; two studied implants, and one compared the transdermal patch versus the vaginal ring. No trial had fracture as an outcome. BMD was measured in 17 studies and 12 trials assessed biochemical markers of bone turnover. Depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density (BMD). The placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo supplement. COCs did not appear to negatively affect BMD, and some formulations had more positive effects than others. However, no COC trial was placebo-controlled. Where studies showed differences between groups in bone turnover markers, the results were generally consistent with those for BMD. For implants, the single-rod etonogestrel group showed a greater BMD decrease versus the two-rod levonorgestrel group but results were not consistent across all implant comparisons.The sensitivity analysis included 11 trials providing evidence of moderate or high quality. Four trials involving DMPA showed some positive effects of an estrogen supplement on BMD, a negative effect of DMPA-subcutaneous on lumbar spine BMD, and a negative effect of DMPA on a bone formation marker. Of the three COC trials, one had a BMD decrease for the group with gestodene plus EE 15 μg. Another indicated less bone resorption in the group with gestodene plus EE 30 μg versus EE 20 μg., Authors' Conclusions: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. The evidence quality was considered moderate overall, largely due to the trials of DMPA, implants, and the patch versus ring. The COC evidence varied in quality but was low overall. Many trials had small numbers of participants and some had large losses. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Whether or not the use of hormonal contraception affects risk of HIV acquisition is an important question for public health. We did a systematic review, searching PubMed and Embase, aiming to explore the possibility of an association between various forms of hormonal contraception and risk of HIV acquisition. We identified 20 relevant prospective studies, eight of which met our minimum quality criteria. Of these eight, all reported findings for progestin-only injectables, and seven also reported findings for oral contraceptive pills. Most of the studies that assessed the use of oral contraceptive pills showed no significant association with HIV acquisition. None of the three studies that assessed the use of injectable norethisterone enanthate showed a significant association with HIV acquisition. Studies that assessed the use of depot-medroxyprogesterone acetate (DMPA) or non-specified injectable contraceptives had heterogeneous methods and mixed results, with some investigators noting a 1·5-2·2 times increased risk of HIV acquisition, and others reporting no association. Thus, some, but not all, observational data raise concern about a potential association between use of DMPA and risk of HIV acquisition. More definitive evidence for the existence and size of any potential effect could inform appropriate counselling and policy responses in countries with varied profiles of HIV risk, maternal mortality, and access to contraceptive services., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Provision of contraception is often linked with physical examination, including clinical breast examination (CBE) and pelvic examination. This review was conducted to evaluate the evidence regarding outcomes among women with and without physical examination prior to initiating hormonal contraceptives., Study Design: The PubMed database was searched from database inception through March 2012 for all peer-reviewed articles in any language concerning CBE and pelvic examination prior to initiating hormonal contraceptives. The quality of each study was assessed using the United States Preventive Services Task Force grading system., Results: The search did not identify any evidence regarding outcomes among women screened versus not screened with CBE prior to initiation of hormonal contraceptives. The search identified two case-control studies of fair quality which compared women who did or did not undergo pelvic examination prior to initiating oral contraceptives (OCs) or depot medroxyprogesterone acetate (DMPA). No differences in risk factors for cervical neoplasia, incidence of sexually transmitted infections, incidence of abnormal Pap smears or incidence of abnormal wet mount findings were observed., Conclusions: Although women with breast cancer should not use hormonal contraceptives, there is little utility in screening prior to initiation, due to the low incidence of breast cancer and uncertain value of CBE among women of reproductive age. Two fair quality studies demonstrated no differences between women who did or did not undergo pelvic examination prior to initiating OCs or DMPA with respect to risk factors or clinical outcomes. In addition, pelvic examination is not likely to detect any conditions for which hormonal contraceptives would be unsafe., (Published by Elsevier Inc.)

Background: The review was conducted to examine studies that assess whether the number of pill packs dispensed, or prescribed, affects method continuation and other measures of use., Study Design: PubMed database was searched from inception through March 2012 for all peer-reviewed articles, in any language, that examined the effect of the number of oral contraceptive pill packs dispensed on method continuation, and other measures of use. The quality of each study was assessed using the United States Preventive Services Task Force grading system., Results: Four studies met the inclusion criteria for this review. Studies that compared 1 vs. 12, 1 vs. 12-13, or 3 vs. 7 packs found increased method continuation. However, one study that examined the difference between providing one and then three packs versus providing four packs all at once did not find a difference in continuation. In addition to continuation, evidence from the individual studies included found that a greater number of pill packs was associated with fewer pregnancy tests, fewer pregnancies and less cost per client. A greater number of pill packs was, however, also associated with increased pill wastage., Conclusions: A small body of evidence suggests that dispensing a greater number of oral contraceptive pill packs may increase continuation of use., (Published by Elsevier Inc.)

Background: Combined hormonal contraceptives (CHCs) are popular methods of reversible contraception in the United States, but adherence remains an issue as reflected in their lower rates of typical use effectiveness. The objective of this systematic review was to evaluate evidence on the effect of missed CHCs on pregnancy rates as well as surrogate measures of contraceptive effectiveness (e.g., ovulation, follicular development, changes in hormone levels, cervical mucus quality)., Study Design: We searched the PubMed database for peer-reviewed articles published in any language from database inception through April 2012. We included studies that examined measures of contraceptive effectiveness during cycles with extended hormone-free intervals or nonadherence (e.g., omission of pills, delayed patch replacement) on days not adjacent to the hormone-free interval. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence., Results: The search strategy identified 1387 articles, of which 26 met our study selection criteria. There is wide variability in the amount of follicular development and risk of ovulation among women who extended the pill-free interval to 8-14 days; in general, the risk of ovulation was low, and among women who did ovulate, cycles were usually abnormal (i.e., low progesterone levels, small follicles and/or poor cervical mucus) (Level I, good, indirect to Level II-3, fair, indirect). Studies of women who missed one to four consecutive pills or 1-3 consecutive days of delay before patch replacement at times other than adjacent to the hormone-free interval reported little follicular activity and low risk of ovulation (Level I, fair, indirect to Level II-3, poor, indirect). Studies comparing 30 mcg versus 20 mcg mc ethinyl estradiol pills showed more follicular activity when 20 mcg ethinyl estradiol pills were missed (Level I, good, indirect)., Conclusion: Most of the studies in this evidence base relied on surrogate measures of pregnancy risk and ranged in quality. For studies providing indirect evidence on the effects of missed CHCs, it is unclear how differences in surrogate measures correspond to pregnancy risk. Fewer studies examined the transdermal patch and vaginal ring than combined oral contraceptives., (Published by Elsevier Inc.)

Background: Women with hypertension who use hormonal methods of contraception may have an increased risk for cardiovascular events. This review was conducted to evaluate the evidence regarding whether blood pressure should be measured prior to initiating hormonal contraceptives., Study Design: The PubMed database was searched from database inception through March 2012 for all peer-reviewed articles in any language concerning blood pressure measurement prior to initiation of hormonal contraceptives. Articles were included if they reported on women with and without blood pressure measurement prior to current hormonal contraceptive usage and assessed cardiovascular outcomes. The quality of each study was assessed using the United States Preventive Services Task Force grading system., Results: Six fair-quality articles from three studies met inclusion criteria for this review. Three case-control studies showed that women who did not have blood pressure measurement prior to initiating combined oral contraceptives (COCs) had a higher risk for acute myocardial infarction (AMI) than women who did have blood pressure measurement. Two case-control studies showed that women who did not have blood pressure measurement prior to initiating COCs had a higher risk for ischemic stroke than women who did have blood pressure measurement. One case-control study showed no difference in the risk for hemorrhagic stroke among women who initiated COCs based on whether or not blood pressure was measured., Conclusions: Fair-quality evidence from five reports showed that women who did not have blood pressure measurement prior to COC initiation had a higher risk for AMI and ischemic stroke than women who did have blood pressure measurement. One fair-quality study showed no increased risk for hemorrhagic stroke based on whether or not blood pressure was measured. Studies that examined hormonal contraceptive methods other than COCs were not identified., (Published by Elsevier Inc.)

Objective: Systematically assess from the literature whether women living with HIV who use hormonal contraception are at increased risk of HIV-disease progression compared with those who do not use hormonal contraception., Methods: We searched PUBMED and EMBASE for articles published in peer-reviewed journals through December 15, 2011 for evidence relevant to all hormonal contraceptive methods and HIV-disease progression., Results: Twelve reports of 11 studies met inclusion criteria. One randomized controlled trial (RCT) found increased risk for the composite outcome of a reduced CD4 cell count or death among hormonal contraceptive users when compared with copper intrauterine device (IUD) users. Ten cohort studies reported no increased risk for HIV disease progression (as measured by mortality, time to a CD4 cell count below 200, time to initiation of antiretroviral therapy, an increase in HIV-RNA viral load, or a decrease in CD4 count) among women who used hormonal contraception compared with those who did not., Conclusion: The preponderance of evidence indicates that HIV-positive women can use hormonal contraceptive methods without concerns related to HIV-disease progression. Cohort studies consistently found no association between hormonal contraceptive use and HIV-disease progression compared with nonuse of hormonal contraceptives. One RCT found that hormonal contraceptive use was associated with increased risk of HIV-disease progression when compared with IUD use, but this study had important methodological shortcomings. Prevention of unintended pregnancy among women living with HIV remains a public health priority to safeguard women's and infants' health and to prevent vertical transmission of HIV.

Background: Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated with changes in bone mineral density in women. Whether such changes affect the risk of fractures later in life is unclear. Hormonal contraceptives are among the most effective and most widely-used contraceptives. Concern about fractures may limit the use of these effective contraceptives. Observational studies can collect data on premenopausal contraceptive use as well as fracture incidence later in life., Objectives: We systematically reviewed the evidence from observational studies of hormonal contraceptive use for contraception and the risk of fracture in women., Search Methods: In May 2012, we searched for observational studies. The databases included MEDLINE, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for recent clinical trials through ClinicalTrials.gov and the ICTRP. For other studies, we examined reference lists of relevant articles and wrote to investigators for additional reports., Selection Criteria: We included cohort and case-control studies of hormonal contraceptive use. Interventions included comparisons of a hormonal contraceptive with a nonhormonal contraceptive, no contraceptive, or another hormonal contraceptive. The primary outcome was the risk of fracture., Data Collection and Analysis: Two authors independently extracted the data. One author entered the data into RevMan, and a second author verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale (NOS), developed for case-control and cohort studies. Sensitivity analysis included studies of moderate or high quality based on our assessment with the NOS.Given the need to control for confounding factors in observational studies, we used adjusted estimates from the models as reported by the authors. Where we did not have adjusted analyses, we calculated the odds ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did not conduct meta-analysis., Main Results: We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs) (N=12), depot medroxyprogesterone acetate (DMPA) (N=4), and the hormonal intrauterine device (IUD) (N=1). This section focuses on evidence from the six studies with moderate or high quality evidence that we included in the sensitivity analysis.All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study found OC ever-users had increased risk for all fractures (reported RR 1.20; 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (reported OR 1.55; 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (reported OR 1.09; 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use.Two case-control studies in the sensitivity analysis also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (reported OR 1.44 (95% CI 1.01 to 2.06), more than four years of use (reported OR 2.16; 95% CI 1.32 to 3.53), and women over 50 years old. The other noted increased risk for any past use, including one or two prescriptions (reported OR 1.17; 95% CI 1.07 to 1.29), and for current use of 3 to 9 or 10 or more prescriptions. In addition, one study reported reduced fracture risk for ever-use of the hormonal IUD (reported OR 0.75; 95% CI 0.64 to 0.87) and longer use of that IUD., Authors' Conclusions: Observational studies do not indicate an overall association between OC use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Researchers should be clear about the variables examined in multivariate analysis.

Background: While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required., Study Design: We used data from a multicenter, population-based, case-control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC., Results: Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk., Conclusions: These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk., (Published by Elsevier Inc.)

Background: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. Osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally., Objectives: To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women, Search Strategy: We searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as ClinicalTrials.gov and ICTRP. We wrote to investigators to find additional trials., Selection Criteria: Randomized controlled trials (RCTs) were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Interventions could include comparing a hormonal contraceptive with a placebo or another hormonal contraceptive or could compare providing a supplement versus a placebo., Data Collection and Analysis: We assessed all titles and abstracts identified through the literature searches. Mean differences were computed using the inverse variance approach. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) was calculated. Both included the 95% confidence interval (CI) and used a fixed-effect model. Due to different interventions, no trials could be combined for meta-analysis., Main Results: Of the 16 RCTs we found, 2 used a placebo and 1 used a non-hormonal method as the comparison, while 13 compared two hormonal contraceptives. No trial had fracture as an outcome. Most measured BMD and several assessed bone turnover. Depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density. The placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo. Combination contraceptives did not appear to negatively affect bone health, but none were placebo-controlled. For implants, the single-rod etonogestrel group showed a greater BMD decrease versus the two-rod levonorgestrel group. However, results were not consistent across all implant comparisons., Authors' Conclusions: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Background: The review was conducted to evaluate from the literature the safety of hormonal methods of contraception in women with liver tumors, specifically in benign and malignant disease., Study Design: We searched PubMed and Cochrane databases to find all articles published from database inception through July 2008 that were relevant to hormonal contraception use and liver tumors., Results: Of 148 articles, three publications of two studies met the criteria for inclusion in this review; both investigated the use of hormonal contraception in women with the benign liver tumor focal nodular hyperplasia (FNH). In one small, retrospective case series, use of combined oral contraceptives (COCs) over a 4-year average follow-up was not associated with a change in either the number or size of hepatic lesions. In another case series, use of either COCs or progestogen-only contraceptives (POCs) after FNH diagnosis had no influence on disease progression or resolution., Conclusions: The studies identified examined oral contraceptive use among women with FNH. We did not identify any studies of hormonal contraceptive use among women with hepatocellular adenoma or with malignant liver tumors. Limited, poor-quality evidence suggests that for women with FNH, use of low-dose COCs or POCs does not appear to influence either liver lesion resolution or progression.

Background: The objective of this systematic review is to determine whether obese women who use progestogen-only contraceptives are more likely to experience weight gain or serious adverse events as compared to nonobese users., Study Design: We searched PubMed for all articles (in all languages) published in peer-reviewed journals from database inception through October 2008, for evidence relevant to obesity and progestogen-only contraceptives. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence., Results: From 579 articles, we identified nine studies fitting our selection criteria. Evidence from five studies suggests that among adult women, baseline weight or body mass index is not associated with weight gain among depot medroxyprogesterone acetate (DMPA) users (Level II-2, Fair). Evidence from three studies suggests that among adolescent women, overweight or obese DMPA users may gain more weight than normal weight DMPA users or overweight/obese nonusers (Level II-2, Fair). Evidence from one small study of Norplant users showed no differences in weight gain by baseline weight (Level II-3, Poor). We did not identify studies of other progestogen-only contraceptive methods that examined weight change by baseline weight, nor did we identify studies that reported on any serious adverse events by baseline weight., Conclusions: Adolescent DMPA users who are obese may gain more weight than normal weight users. This observation was not seen in adult DMPA users or adolescent Norplant users.

Background: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. However, osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally., Objectives: To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women, Search Strategy: We searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as in clinical trials databases (ClinicalTrials.gov and ICTRP). We wrote to investigators to find additional trials., Selection Criteria: Randomized controlled trials were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Studies were excluded if hormones were provided for treatment of a specific condition rather than for contraception. Interventions could include comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive. Interventions could also include the provision of a supplement versus a placebo., Data Collection and Analysis: We assessed for inclusion all titles and abstracts identified through the literature searches with no language limitation. The mean difference was computed with 95% confidence interval (CI) using a fixed-effect model., Main Results: We found 13 RCTs, 2 of which used a placebo. No trial had fracture as an outcome but most measured BMD. Combination contraceptives did not appear to affect bone health. Of progestin-only methods, depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density, while results were inconsistent for implants. The two placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo., Authors' Conclusions: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Due to different interventions, no trials could be combined for meta-analysis. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

A discussion of the issues that affect the study design of hormonal contraception is presented, including ethical issues, measurement of contraceptive efficacy. Observational studies, experimental studies, and meta-analysis in hormonal contraception are also reviewed.

Questions have been raised about the effects of progestogen-only contraceptive use on bone health, particularly among young women who have not yet reached peak bone mass and perimenopausal women who may be starting to lose bone mass. We conducted a systematic review that evaluated the association between progestogen-only contraceptive use and fracture risk or bone mineral density (BMD). We identified 39 articles from MEDLINE and EMBASE, published through July 2005. One study reported that depot medroxyprogesterone acetate (DMPA) users were more likely to experience stress fractures than nonusers; this association was not statistically significant after controlling for baseline bone density. In cross-sectional studies, the mean BMD in DMPA users was usually below that of nonusers, but within 1 SD. In longitudinal studies, BMD generally decreased more over time among DMPA users than among nonusers, but women gained BMD upon discontinuation of DMPA. Limited evidence suggested that use of progestogen-only contraceptives other than DMPA did not affect BMD.

Previous research has suggested that hormonal contraceptive users, compared with nonusers, may be at increased risk for acquiring sexually transmitted infections (STIs). We searched the MEDLINE and EMBASE databases for all articles from January 1966 through February 2005 for evidence relevant to all hormonal contraceptives and STIs (including cervical chlamydial and gonococcal infection, human papillomavirus, trichomoniasis, herpes and syphilis). We used standard abstract forms and grading systems to summarize and assess the quality of 83 identified studies. Studies of combined oral contraceptive and depot medroxyprogesterone use generally reported positive associations with cervical chlamydial infection, although not all associations were statistically significant. For other STIs, the findings suggested no association between hormonal contraceptive use and STI acquisition, or the results were too limited to draw any conclusions. Evidence was generally limited in both amount and quality, including inadequate adjustment for confounding, lack of appropriate control groups and small sample sizes. The observed positive associations may be due to a true association or to bias, such as differential exposure to STIs by contraceptive use or increased likelihood of STI detection among hormonal contraceptive users.

Because use of combined oral contraceptives (COCs) confers some risk of venous thromboembolism (VTE), there is concern that this effect may be greater among women with thrombogenic mutations. We searched the MEDLINE and EMBASE databases for all articles published from January 1966 through September 2004 for evidence relevant to hormonal contraception and thrombogenic mutations. Of 301 articles identified by the search strategy, 16 evaluated COCs, and no studies were found for other hormonal methods. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence. A total of 10 studies together provided "good" evidence of a greater risk of VTE (risk ratios of 1.3-25.1) and cerebral vein or cerebral sinus thrombosis among COC users with factor V Leiden mutation when compared with nonusers who have the mutation. The evidence for prothrombin and other thrombogenic mutations was not as strong as for factor V Leiden mutation. It is unclear whether the type of COC or duration of use modifies the risk of VTE among women with thrombogenic mutations.