EVO100 prevents chlamydia and gonorrhea in women at high risk of infection.

BACKGROUND: According to the Centers for Disease Control and Prevention, rates of infection for Chlamydia trachomatis and Neisseria gonorrhoeae are increasing in the United States. EVO100 is an investigational antimicrobial, pH-modulating, vaginal gel with active ingredients L-lactic acid, citric acid, and potassium bitartrate that is being evaluated for the prevention of sexually transmitted infections. OBJECTIVE: The objective of this phase 2B/3 study was to assess the efficacy and safety of EVO100 for the prevention of chlamydia and gonorrhea. STUDY DESIGN: AMPREVENCE was a double-blinded, placebo-controlled, multicenter study based in the United States conducted over approximately 16 weeks in women at the age of 18 to 45 years who were at risk of urogenital chlamydia and gonorrhea infection. Enrolled women had been diagnosed as having and treated for chlamydia or gonorrhea ≤16 weeks before enrollment. Women received either EVO100 or placebo vaginal gel and were instructed to apply the study drug immediately before or up to 1 hour before each act of vaginal sexual intercourse. The primary and secondary endpoints were the prevention of urogenital chlamydia and gonorrhea, respectively. Exploratory outcomes include women's overall satisfaction with EVO100. RESULTS: In total, 860 women were randomized 1:1 to receive EVO100 (n=426) or placebo (n=434), and 764 women (EVO100, n=376; placebo, n=388) were documented as using the study drug at least once. Baseline characteristics were similar between treatment arms. Overall, women had a mean age of 27.7 years (standard deviation, 6.9) and body mass index of 28.9 kg/m2 (standard deviation, 8.0). Most women were of White (54.3% [467 of 860]) or African American (41.6% [358 of 860]) race and of non-Hispanic/Latina ethnicity (67.1% [577 of 860]). The chlamydia infection rate in EVO100 users was 4.8% (14 of 289) compared with 9.7% (28 of 290) among placebo users (P=.0256), representing a relative risk reduction of 50%. For gonorrhea, the infection rate was 0.7% (2 of 280) in the EVO100 arm compared with 3.2% (9 of 277) in the placebo arm (P=.0316), representing a relative risk reduction of 78%. Increased efficacy was observed with increased adherence, and chlamydia infection rates were significantly reduced with increased adherence in the EVO100 group compared with placebo. Across both arms, there were similar rates of all-cause adverse events (EVO100, 21.3% [80 of 376]; placebo, 20.4% [79 of 388]) and treatment-related adverse events (EVO100, 7.2% [27 of 376]; placebo, 7.5% [29 of 388]). The most common adverse events in the EVO100 arm were vulvovaginal candidiasis (5.1% [19 of 376]), vaginal discharge (3.2% [12 of 376]), and urinary tract infection (3.2% [12 of 376]) and, in the placebo arm, bacterial vaginosis (4.6% [18 of 388]), urinary tract infection (2.6% [10 of 388]), and vaginal discharge (2.6% [10 of 388]). Few women discontinued owing to adverse events in either arm (EVO100, 1.1% [4 of 376]; placebo, 1.5% [6 of 388]). No treatment-related serious adverse events were reported. Most EVO100 users (88%) were satisfied or very satisfied with EVO100 after 16 weeks of use. CONCLUSION: EVO100 significantly reduced the risk of chlamydia and gonorrhea infections in women at high risk of Chlamydia trachomatis and Neisseria gonorrhoeae infection and was well tolerated, with observed adverse events consistent with its known safety profile.

A novel vaginal pH regulator: results from the phase 3 AMPOWER contraception clinical trial.

OBJECTIVE: The objective was to evaluate the contraceptive effectiveness, safety, and acceptability of a novel vaginal pH regulator over seven cycles of use. STUDY DESIGN: A single-arm, open-label, phase 3 study was conducted across 112 sites in the United States in sexually active 18-35-year-old women at risk of pregnancy. Women administered the study treatment ≤ 1 h before each episode of intercourse. Women recorded use of study drug, coital information, and any symptoms experienced in electronic diaries. The primary outcome was the seven-cycle cumulative pregnancy rate as calculated using the Kaplan-Meier methodology; secondary outcomes included safety. Overall satisfaction was assessed via written questionnaires. RESULTS: A total of 1384 women were enrolled in the study from July 2017 to November 2018. Mean age was 27.7 ±â€¯4.4 years; most women were white (69.0%). The seven-cycle cumulative pregnancy percentage was 13.7% [95% confidence interval (CI): 10.0%-17.5%], meeting the prespecified primary endpoint of having the upper bound 95% CI ≤ 21%. Most common adverse events (AEs) occurring in ≥ 2% of women were vulvovaginal burning sensation, vulvovaginal pruritus, urinary tract infection, vulvovaginal pain, mycotic infection, bacterial vaginosis, and nasopharyngitis. Of 1330 women who used the study drug at least once, fewer than 2% of women discontinued due to any AEs, and < 1% of women discontinued due to genitourinary symptoms. Overall, > 80% of women reported being "very satisfied" or "satisfied" with study treatment. CONCLUSIONS: In this phase 3 study, the novel vaginal pH regulator demonstrated 86.3% contraceptive effectiveness, was safe and well tolerated, and was highly acceptable. IMPLICATIONS: This novel vaginal pH regulator is a safe, nonhormonal, woman-controlled method of contraception that expands women's options.

Safety of contraceptive method use among women with systemic lupus erythematosus: a systematic review.

OBJECTIVE: To evaluate the evidence on the safety of contraceptive method use among women with systemic lupus erythematosus (SLE). DATA SOURCES: We searched the PubMed, MEDLINE, and LILACS databases for peer-reviewed articles published from database inception through January 2009, concerning the safety of contraceptive use among women with SLE. METHODS OF STUDY SELECTION: We included studies that examined health outcomes among women using a contraceptive method after the diagnosis of SLE. The quality of each individual piece of evidence was assessed using the U.S. Preventive Services Task Force grading system. TABULATION, INTEGRATION, AND RESULTS: Our search yielded 275 articles. A total of 14 articles that reported on 13 studies met our inclusion criteria. Available evidence, including two good-quality randomized controlled trials, indicates that use of combined oral contraceptives does not lead to increased flares of disease or worsening disease activity in women with inactive or stable active SLE. No increase in disease activity with use of progestogen-only contraceptives was noted in four studies. Limited evidence indicates a possible increased risk of thrombosis in women with positive antiphospholipid antibodies and history of oral contraceptive use. Limited evidence indicates that the use of the copper intrauterine device is not associated with worsening disease activity or infection in women with SLE. CONCLUSION: Available evidence indicates that many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives. The benefits of contraception for many women with SLE likely outweigh the risks of unintended pregnancy in this population. Women with positive antiphospholipid antibodies are not good candidates for combined hormonal contraception given their elevated baseline risk of thrombosis.

Changes in prescription contraceptive use, 1995-2002: the effect of insurance status.

OBJECTIVE: To examine changes in prescription contraception use between 1995 and 2002 by insurance status among women at risk for unintended pregnancy. METHODS: Data from the National Survey of Family Growth, including 4,767 women at risk of unintended pregnancy in 1995 and 3,569 in 2002, were used to evaluate changes in primary contraception methods by health insurance status and year of survey. Logistic regression models tested differences in the likelihood of prescription contraceptive use among privately insured, publicly insured, and uninsured women in each year, after controlling for age, race and ethnicity, education, income, employment, marital status, number of children, religion, and self reported overall health. RESULTS: Overall prescription contraceptive use increased between 1995 and 2002 by 3% (48.9% to 51.9%, P=.049). Nonuse of contraception also increased (11.6% to 16.1%, P<.001). The change in the likelihood of prescription contraceptive use was greatest and only significant among privately insured women (+5.5%, P=.002). In multiple regression analysis, women in 1995 were 10% less likely to report use of prescription contraceptives compared with women in 2002 (relative risk 0.90, 95% confidence interval 0.82-0.98), and uninsured women were more than 20% less likely to report prescription contraceptive use compared with privately insured women (relative risk 0.78, 95% confidence interval 0.67-0.90). CONCLUSION: Prescription contraceptive use increased most significantly among privately insured women between 1995 and 2002, potentially reflecting state mandates enacted during that period requiring contraceptive coverage by private insurers. It is important for clinicians to understand these differences and address issues of insurance coverage with patients when discussing contraceptive options. LEVEL OF EVIDENCE: III.

The association of health insurance with use of prescription contraceptives.

CONTEXT: Given that substantial proportions of women of reproductive age lack health insurance coverage, it is important to assess whether lack of insurance is associated with the use of prescription contraceptives, which are the most expensive but also the most effective methods for preventing pregnancy. METHODS: Data from 26,674 females aged 18-44 who participated in the 2002 Behavioral Risk Factor Surveillance System survey (representing more than 25 million women in the U.S. population) were used to assess risk of unintended pregnancy, prescription contraceptive use and health insurance status. Logistic regression models tested the likelihood of prescription contraceptive use among insured versus uninsured respondents after controlling for socioeconomic characteristics and self-reported overall health. RESULTS: A significantly higher proportion of insured women than of uninsured women reported use of prescription contraceptives (54% vs. 45%). In multiple regression analysis, women lacking health insurance were 30% less likely to report using prescription contraceptive methods than were women with private or public health insurance. Results were similar across racial, age and income subgroups. CONCLUSIONS: Lack of health insurance is associated with reduced use of prescription contraceptives. Universal insurance coverage is needed to ensure access to the most effective contraceptive methods for all women in need.

Effect of Immediate Compared With Delayed Insertion of Etonogestrel Implants on Medical Abortion Efficacy and Repeat Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of insertion of etonogestrel implants with mifepristone compared with after the abortion on the risks of medical abortion failure and repeat pregnancy over the subsequent 6 months. METHODS: In a randomized trial, we assigned patients undergoing medical abortion to receive etonogestrel implants either with the mifepristone (Quickstart group) or after the abortion (Afterstart group). We followed them for 7 months to ascertain abortion outcome, pregnancies, and contraception use. RESULTS: Between September 2013 and August 2014, we enrolled 236 participants in the Quickstart group and 240 in the Afterstart group. To examine abortion failure, we conducted a noninferiority analysis from which we excluded nine participants who had missing outcome data and four with specified protocol violations. Of the rest, 9 of 229 (3.9%) and 9 of 234 (3.8%) in the Quickstart and Afterstart groups, respectively, had surgery to complete the abortion; the difference of 0.08% (90% confidence interval -3.1% to 3.3%) excluded our prestipulated noninferiority margin of 5 percentage points. Among participants with pregnancy follow-up through 6 months, 1 of 213 (0.5%) and 3 of 208 (1.4%) in the Quickstart and Afterstart groups, respectively, became pregnant within that time; 6-month pregnancy rates did not differ significantly by group (exact log-rank test, P=.28). At enrollment, significantly more participants in the Quickstart group than in the Afterstart group were satisfied with their group assignments (187/236 [79%] compared with 129/240 [54%], respectively; P<.001). CONCLUSION: Insertion of etonogestrel implants with mifepristone did not appreciably increase medical abortion failure risk and it enhanced patient satisfaction, but we found no evidence that it decreased repeat pregnancy rates. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01902485.

Effects of Depot Medroxyprogesterone Acetate Injection Timing on Medical Abortion Efficacy and Repeat Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of timing of depot medroxyprogesterone acetate injection on medical abortion outcome and risk of repeat pregnancy within the subsequent 6 months. METHODS: In a multinational randomized trial, we assigned women undergoing medical abortion who wanted depot medroxyprogesterone acetate to administration either with mifepristone (Quickstart group) or after the abortion (Afterstart group). We ascertained abortion outcome, pregnancies, and contraception use over 7 months. RESULTS: From August 2013 to March 2015, we enrolled 461 participants with pregnancy durations of 75 days or less. Of participants included in the abortion outcome analyses, 14 of 220 (6.4%) and 12 of 226 (5.3%) in the Quickstart and Afterstart groups, respectively, had surgery to complete the abortion; the upper 90% confidence limit on this difference was 4.9%, within our prestipulated 5% noninferiority margin. Ongoing pregnancy after initial abortion treatment was significantly more common in the Quickstart group (8/220 [3.6%]) than in the Afterstart group (2/226 [0.9%]); the difference was 2.7% (90% confidence interval 0.4-5.6%). By 6 months, 5 of 213 (2.3%) and 7 of 217 (3.2%) in the Quickstart and Afterstart groups, respectively, became pregnant (exact log-rank test, P=.64). Use of highly effective contraceptives was significantly more common in the Quickstart group at 31 days (P<.001), but no difference was apparent at 6 months. The Quickstart group was significantly more satisfied with group assignment. CONCLUSION: Depot medroxyprogesterone acetate administration with mifepristone did not appreciably increase the risk of surgery after medical abortion but did increase the risk of ongoing pregnancy. It enhanced patient satisfaction, but we found no evidence that it decreased 6-month risk of repeat pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01902485.

Understanding women's desires for contraceptive counseling at the time of first-trimester surgical abortion.

OBJECTIVE: The objective was to investigate whether or not women presenting for a first-trimester surgical abortion want to discuss contraception on the day of their procedure. STUDY DESIGN: Between October 2012 and January 2013, an anonymous self-administered survey was distributed to women receiving first-trimester surgical abortions at four northern California family planning clinics. The survey obtained demographic information about each woman and inquired about her desire for contraceptive counseling during her appointment. Results were analyzed using both univariate and multivariable regression analyses to assess trends in responses related to desire for contraceptive counseling based on demographic and other variables. RESULTS: Of the 199 respondents, 64% reported that they did not want to talk to a counselor or doctor about contraception on the day of their abortion. About half of the women (52%) who did not want to discuss contraception indicated they already knew what they wanted for pregnancy prevention. Of the 25% who reported that they did want to discuss contraception, the most important topic desired from the counseling was identification of methods that were easier to use than what they used previously. CONCLUSION: The majority of women seeking first-trimester surgical abortion may not desire additional information about contraception on the day of the procedure. IMPLICATIONS STATEMENT: This study demonstrates that a significant proportion of women may not want contraceptive counseling on the day of a planned surgical abortion.

Addressing barriers to safe abortion.

The latest World Health Organization data estimate that the total number of unsafe abortions globally has increased to 21.6 million in 2008. There is increasing recognition by the international community of the importance of the contribution of unsafe abortion to maternal mortality. However, the barriers to delivery of safe abortion services are many. In 68 countries, home to 26% of the world's population, abortion is prohibited altogether or only permitted to save a woman's life. Even in countries with more liberal abortion legal frameworks, additional social, economic, and health systems barriers and the stigma surrounding abortion prevent adequate access to safe abortion services and postabortion care. While much has been achieved to reduce the barriers to comprehensive abortion care, much remains to be done. Only through the concerted action of public, private, and civil society partners can we ensure that women have access to services that are safe, affordable, confidential, and stigma free.

A multicenter randomized clinical trial of one-rod etonogestrel and two-rod levonorgestrel contraceptive implants with nonrandomized copper-IUD controls: methodology and insertion data.

BACKGROUND: Comparative data on etonogestrel and two-rod levonorgestrel contraceptive implants are lacking. STUDY DESIGN: A multicenter, open, parallel-group trial with random allocation of implants was performed. For every second implant user, an age-matched woman choosing an intrauterine device (IUD) (TCu380A) was admitted. Methods and data on implant/IUD insertion and 6-week follow-up are reported. RESULTS: A total of 2008 women were randomized to an implant, and 974 women were enrolled in the IUD group. Results from 997 etonogestrel implant users, 997 levonorgestrel implant users and 971 IUD users were analyzed. In the etonogestrel and levonorgestrel groups, respectively, mean insertion durations were 51 (SD 50.2) s and 88 (SD 60.8) s; complication rates at insertion were 0.8% and 0.2%; and at follow-up, 27.2% and 26.7% of women, respectively, had signs or symptoms at the insertion site. At follow-up within 6 weeks after insertion, all implants were in situ, while 2.1% of IUDs were expelled. CONCLUSION: Performance of etonogestrel and levonorgestrel implants at insertion and within the first 6 weeks is similar. Short-term (6 weeks) continuation rates appear higher for implants than TCu380A.

The use of hormonal contraception among women taking anticonvulsant therapy.

BACKGROUND: Drug interactions between hormonal contraceptives and anticonvulsants, resulting in reduced contraceptive effectiveness and/or increased seizure activity, have been published. STUDY DESIGN: We conducted a systematic review, searching PUBMED and The Cochrane Library for articles in any language on use of hormonal contraceptive methods among women taking anticonvulsant therapy from 1966 through 3 May 2010. Forty-three articles were identified and evaluated. RESULTS: Evidence suggests drug interactions occur when combined oral contraceptives (COCs), the levonorgestrel implant (Norplant), or the etonogestrel implant (Implanon) are used concomitantly with carbamazepine, phenobarbital, phenytoin, topiramate or lamotrigine. Significant drug interactions were not observed during sodium valproate intake and COC use nor among women using progestogen-only contraceptives and taking lamotrigine. CONCLUSIONS: To avoid contraceptive failure or increased seizure activity, women with epilepsy should be offered contraceptive methods that do not interact with anticonvulsant medication.

Critical gaps in universal access to reproductive health: contraception and prevention of unsafe abortion.

Unsafe abortion accounts for a significant proportion of maternal deaths, yet it is often forgotten in discussions around reducing maternal mortality. Prevention of unsafe abortion starts with prevention of unwanted pregnancies, most effectively through contraception. When unwanted pregnancies occur, provision of safe, legal abortion services can further prevent unsafe abortions. If complications arise from unsafe abortion, emergency treatment must be available. Recommendations made on this issue during the Precongress Workshop held prior to the 2009 FIGO World Congress in Cape Town, South Africa, were part of a report that was adopted by the FIGO General Assembly. These recommendations address prevention of unsafe abortion and its consequences and support access to safe abortion care to the full extent allowed by national laws, along with 6 strategies for implementation, including integration of family planning into other reproductive health services, adequate training for providers, task-sharing with mid-level providers, and using evidence to discuss this issue with key stakeholders.

Use of contraceptive methods by women with current venous thrombosis on anticoagulant therapy: a systematic review.

BACKGROUND: As nearly all women with venous thromboembolism (VTE) will be treated with anticoagulant therapy, it is important to consider how anticoagulation affects the safety of contraceptive use. STUDY DESIGN: We conducted a systematic review of the literature regarding use of contraceptive methods in women with current VTE on anticoagulant therapy. Due to the limited direct evidence that was identified, we expanded our search to include women on anticoagulant therapy for indications other than VTE and women with bleeding disorders. RESULTS: Six articles met our inclusion criteria. Three observational studies found the levonorgestrel-releasing IUD (LNG-IUD) was an effective treatment for menorrhagia for women on anticoagulation therapy or with bleeding disorders. Prevention of recurrent hemorrhagic ovarian cysts was seen in women on chronic anticoagulation treated with depot-medroxyprogesterone acetate (DMPA) in one small observational study. Among women with bleeding disorders, no complications were seen in 16 women with placement of the LNG-IUD. One pharmacokinetic study found no statistically significant interaction between combined oral contraceptives and warfarin. Other than one case report, no evidence was found regarding the risk of recurrent thrombosis in women on anticoagulation therapy using a contraceptive method. CONCLUSION: The majority of studies in this review examined treatment effects of the LNG-IUD or DMPA on complications of anticoagulation and found overall beneficial effects of their use in these circumstances. Minimal evidence in women with inherited bleeding disorders suggests that insertion of the LNG-IUD does not pose major bleeding risks in these women with appropriate management.

Oral contraceptives and family history of breast cancer.

BACKGROUND: Questions remain regarding whether oral contraceptive (OC) use among women with a family history of breast cancer increases disease risk. STUDY DESIGN: We conducted a systematic review by searching MEDLINE and CENTRAL databases for evidence (in all languages) published in peer-reviewed journals from 1966 to July 2008 that provided estimates of breast cancer risk according to family history. Twelve articles were identified and the quality of each study was assessed using the United States Preventive Services Task Force grading system. RESULTS: Results from 10 studies and one pooled analysis of 54 studies suggest that the use of OCs does not significantly modify the risk of breast cancer among women with a familial history of breast cancer; however, evidence from four studies shows that some women may be at a greater risk, particularly women who took OCs prior to 1975. CONCLUSIONS: Current evidence shows that women with a family history of breast cancer do not increase their disease risk by using OCs.