Assessing the effect of concerns about contraceptive-induced fertility impairment on hormonal contraceptive use by parity and residence: evidence from PMA Ethiopia 2020 cross-sectional survey.

OBJECTIVES: This study aims to describe patterns of beliefs about contraceptive-induced infertility and assess their relationship with current contraceptive use, including whether these relationships vary by parity and residence. DESIGN: We use data from Performance Monitoring for Action Ethiopia, a nationally representative, cross-sectional survey of 7491 women, aged 15-49, to assess agreement with the statement 'If I use family planning, I may have trouble getting pregnant next time I want to.' We used multilevel hierarchical models to identify the association between agreement and use of a hormonal method of contraception among 3882 sexually active, fecund women who wish to prevent pregnancy. We include interaction terms for parity and residence. RESULTS: 4 in 10 women disagreed (42.3%) and 2 in 10 strongly disagreed (20.7%) with the statement. Relative to women who strongly disagreed, women who disagreed and women who agreed had significantly lower odds of using a hormonal method of contraception (adjusted OR (aOR) 0.65, 95% CI 0.44 to 0.97 and 0.46, 95% CI 0.46, 95% CI 0.30 to 0.70). The effect of agreeing with the statement was strongest among high parity women (aOR 0.54, 95% CI 0.30 to 0.95). Greater agreement with the statement at the community-level use was associated with a reduction in the odds of using hormonal contraception but only among rural women. CONCLUSIONS: Efforts to address concerns around contraceptive-induced fertility impairment through the provision of comprehensive counselling and through community education or mass media campaigns are necessary, particularly among high-parity women and in rural communities. Interventions should acknowledge the possibility of delayed return to fertility for specific methods and attempt to address the root causes of concerns.

A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

PURPOSE: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. METHODS: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. RESULTS: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. CONCLUSIONS: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

Usage of the levonorgestrel releasing intrauterine system in perimenopause.

Levonorgestrel releasing intrauterine system have excellent contraceptive efficacy with simultaneous lowering of menstruation's blood loss. It could be used for therapy of endometrial hyperplasia in perimenopause. In position of gestagen part of the hormone replacement therapy it has high control of endometrial proliferation. It is conjoined with the zero increasing of risk of thromboembolic disease in combination with transdermal oestrogen's application.

Hormonal contraceptive use among women living with hypertension in sub-Saharan Africa: insights from 12 countries.

OBJECTIVES: Given the well-established link between hormonal contraceptives and hypertension risk, and the paucity of research on hormonal contraceptive use dynamics in this particular demographic, we hypothesize that there is a likelihood of low utilization of high-risk hormonal contraceptives among women living with hypertension in SSA. This study investigates the prevalence and factors associated with hormonal contraceptive use among women living with hypertension in the SSA. RESULTS: Only 18.5% of women living with hypertension used hormonal contraceptives. Hormonal contraceptive use was high among women with a higher level of education (aOR = 2.33; 95%CI: 1.73-3.14), those currently working (aOR = 1.38; 95%CI: 1.20-1.59), those who have heard about family planning on the radio (aOR = 1.27, 95%CI: 1.09-1.47), listened to the radio at least once a week (aOR = 1.29, 95%CI: 1.10-1.51), and those residing in rural areas (aOR = 1.32; 95%CI: 1.14-1.54). Conversely, women aged 45-49 exhibited a substantial decrease in the odds of hormonal contraceptive use (aOR = 0.23, 95%CI: 0.14-0.38) compared to younger women (15-19 years). Likewise, the odds of HCU were low among cohabiting (aOR = 0.66; 95%CI: 0.48-0.89) and previously married women (aOR = 0.67; 95%CI: 0.50-0.91) than never married women.

Auditing the representation of hormonal contraceptives in studies assessing exercise performance in women.

Hormonal contraceptive (HC) users have a different ovarian hormonal profile compared to eumenorrheic women. Due to the prevalence of HC use amongst sportswomen, there has been increased research efforts to understand their impact on exercise performance. The aim was to audit this research. Studies identified were assessed for HC type, athlete calibre, performance outcome, study design, and quality of methodological control regarding ovarian hormonal profiles. Sixty-eight different HCs were reported across 61 studies. Monophasic combined oral contraceptive (OCP) pills represented 60% of HCs, followed by other pills [34%, phasic-combined, progestogen-only, and un-specified], phasic and long acting reversible contraceptives [5%, vaginal ring, patch, implant, injection, intrauterine system] and unspecified HCs (1%). Eleven percent of participants using HCs were classified as highly trained or elite/international with no participants being classed as world class. Whilst the number of studies involving HCs has increased two-fold over the past decade, the number of studies ranked as gold standard has not increased (HC; 2003-57%, 2011-55%, 2022-43%. OCP; 2003-14%, 2011-17%, 2022-12%). Future research assessing HCs and exercise performance should adopt high-quality research designs and include a broader range of HCs in highly trained to world-class populations to increase the reach and impact of research in this area.

Long-term efficacy and safety of levonorgestrel releasing intrauterine system in the treatment of adenomyosis: evidence mapping.

PURPOSE: To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps. METHODS: Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy. RESULTS: Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a + LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a + LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision + LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision + LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5 years are needed. CONCLUSIONS: Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation.

Sexual function, quality of life, anxiety, and depression in women of reproductive age using hormonal, nonhormonal, and no contraceptive methods.

BACKGROUND: Hormonal contraceptive use has been related to adverse effects, including impacts on sexual function and sexual satisfaction, although the difference in the effects on sexual function with the use of hormonal vs nonhormonal contraceptive methods remains controversial. AIM: In this study we sought to compare the prevalence of dyspareunia, sexual function, sexual satisfaction, quality of life, anxiety, and depression between women using hormonal, nonhormonal, or no contraceptive methods and to compare these outcomes between the most frequently used contraceptive methods. METHODS: This cross-sectional study included sexually active women of reproductive age who were stratified into 3 groups: women using hormonal, nonhormonal, or no contraceptive methods. Based on the use of questionnaires administered to the study participants, we compared sexual function in the 3 groups and more specifically among users of oral contraceptives, copper and hormonal intrauterine devices, and barrier methods. OUTCOMES: Participants completed 4 questionnaires to assess sexual function (Female Sexual Function Index), sexual satisfaction (Sexual Quotient-Feminine Version), quality of life (12-item Medical Outcomes Short Form Health Survey), and anxiety and depression (Hospital Anxiety and Depression Scale). RESULTS: This study included 315 women classified into 3 groups on the basis of contraceptive use: 161 in the hormonal contraceptives group (median [interquartile range] age, 24 [23-28] years), 97 in the nonhormonal contraceptives group (age 26 [23-30] years), and 57 in the no contraceptive methods group (age 28 [24-35] years). Dyspareunia prevalence showed no difference between the groups. In the quality of life domain, compared with women in the nonhormonal contraceptive group, women in the hormonal contraceptive group were younger and had lower sexual function satisfaction, reduced arousal, and heightened pain (P < .05), as well as higher anxiety and depression levels (P = .03, for both), increased pain (P = .01), and poorer overall health (P = .01). No difference was found between these groups in other quality of life domains. Regarding contraceptive methods, women using copper intrauterine devices had better sexual function, including higher rates of arousal and lower anxiety, than women using oral contraceptives (P < .05). CLINICAL IMPLICATIONS: The results of this study highlight worse sexual function and sexual satisfaction and higher levels of anxiety and depression in women using hormonal contraceptive methods than in women using nonhormonal methods. STRENGTHS AND LIMITATIONS: The findings of this study strengthen the evidence of differences in sexual function between women using oral contraceptives and those using copper intrauterine devices. Sexual function was also compared among users of oral contraceptives, copper and hormonal intrauterine devices, and barrier methods. However, less frequently used contraceptive methods, such as hormonal injections and vaginal rings, could not be compared in this sample. CONCLUSION: Women using hormonal contraceptive methods were younger, had lower sexual function and satisfaction, and experienced higher anxiety and depression levels than women using nonhormonal contraceptive methods.

Use of hormones and risk of venous thromboembolism.

•The risk of venous thromboembolism (VTE) is not increased in women using long-acting reversible contraceptive methods (LARCs) with progestogens. •Oral contraceptives with levonorgestrel or norgestimate confer half the risk of VTE compared to oral contraceptives containing desogestrel, gestodene or drospirenone. •Progestogen-only pills do not confer an increased risk of VTE. •Women using transdermal contraceptive patches and combined oral contraceptives (COCs) are at an approximately eight times greater risk of VTE than non-users of hormonal contraceptives (HCs), corresponding to 9.7 events per 10,000 women/years. •Vaginal rings increase the risk of VTE by 6.5 times compared to not using HC, corresponding to 7.8 events per 10,000 women/years. •Several studies have demonstrated an increased risk of VTE in transgender individuals receiving hormone therapy (HT). •Hormone therapy during menopause increases the risk of VTE by approximately two times, and this risk is increased by obesity, thrombophilia, age over 60 years, surgery and immobilization. •The route of estrogen administration, the dosage and type of progestogen associated with estrogen may affect the risk of VTE in the climacteric. •Combined estrogen-progesterone therapy increases the risk of VTE compared to estrogen monotherapy. •Postmenopausal HT increases the risk of thrombosis at atypical sites.

Migration of etonogestrel subcutaneous contraceptive implants: systematic review and recommendations for practice.

INTRODUCTION: Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent. PURPOSE: To document and characterise cases of etonogestrel contraceptive implant migration in the scientific literature. METHODS: A systematic review of Medline, Embase and Global Health databases was carried out between January 2000 and January 2023 to identify articles presenting implant migrations. Narrative reviews, conference abstracts and articles not written in English or French were excluded. RESULTS: Forty-five articles, mostly published since 2016, were identified (eight case series and 37 case reports), for a total of 148 independent cases of migration: in pulmonary blood vessels (n = 74), in non-pulmonary blood vessels (n = 16) and extravascular (n = 58). Many patients are asymptomatic and migration is often an incidental finding. A non-palpable implant and symptoms related to implant location (intra- or extra-vascular) may be indicative of migration. Inadequate insertion and normal or underweight appear to increase the risk of migration. Scientific societies and authors offer practical strategies to deal with implant migration. CONCLUSION: Professionals who insert and remove contraceptive implants must be adequately trained. They need to be on the lookout for implant migration, and promptly refer patients to appropriate care if migration is suspected.

This systematic review documents and characterises 148 cases of vascular and extravascular etonogestrel contraceptive implant migration. Healthcare professionals must be aware of this rare but serious complication and be adequately trained to insert and remove contraceptive implants.

Hormonal Contraception and Sexual Function: A Review, Clinical Insights, and Management Considerations.

Most sexually active women of reproductive age have used contraception, with hormonal methods constituting approximately 40% of contraceptive choices. Among these hormonal options, combined oral contraceptives stand out as the most selected. Within this same demographic, sexual issues are prevalent. Although specific hormonal contraceptives have been implicated in sexual dysfunction among these women, the correlation lacks consistency across studies and varies between different types of hormonal contraception. This article assesses the available literature on the associations between various hormonal contraceptive methods and sexual function and provides practical management insights.

Effect of Menstrual Cycle Phase and Hormonal Contraceptives on Resting Metabolic Rate and Body Composition.

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.

Longitudinal changes in sexual desire and attraction among women who started using the Natural Cycles app.

Many women experience sexual side effects, such as decreased libido, when taking hormonal contraceptives (HCs). However, little is known about the extent to which libido recovers after discontinuing HCs, nor about the timeframe in which recovery is expected to occur. Given that HCs suppress the activities of multiple endogenous hormones that regulate both the ovulatory cycle and women's sexual function, resumption of cycles should predict libido recovery. Here, using a combination of repeated and retrospective measures, we examined changes in sexual desire and partner attraction (among partnered women) across a three-month period in a sample of Natural Cycles users (Survey 1: n = 1596; Survey 2: n = 550) who recently discontinued HCs. We also tested whether changes in these outcomes coincided with resumption of the ovulatory cycle and whether they were associated with additional factors related to HC use (e.g., duration of HC use) or relationship characteristics (e.g., relationship length). Results revealed that both sexual desire and partner attraction, on average, increased across three months after beginning to use Natural Cycles. While the prediction that changes in sexual desire would co-occur with cycle resumption was supported, there was also evidence that libido continued to increase even after cycles resumed. Together, these results offer new insights into relationships between HC discontinuation and women's sexual psychology and lay the groundwork for future research exploring the mechanisms underlying these effects.

Heavy menstrual bleeding in women with inherited bleeding disorders in use of LNG-IUS: A systematic review and single-arm meta-analysis.

OBJECTIVES: Inherited bleeding disorders may cause heavy menstrual bleeding in women, impacting quality of life and impairing daily and social activities. The levonorgestrel-releasing intrauterine system is a potential treatment for these women, which might reduce menstrual blood loss. STUDY DESIGN: We performed a systematic review and single-arm meta-analysis to examine the levonorgestrel-releasing intrauterine system in women with inherited bleeding disorders and heavy menstrual bleeding. RESULTS: A systematic search on PubMed, Embase and Cochrane yielded 583 results, of which six observational studies (n = 156) met inclusion criteria. Levonorgestrel-releasing intrauterine system use in patients with inherited bleeding disorders and heavy menstrual bleeding was associated with amenorrhea in 60% of patients and a significant increase of 1.40 g/dL in hemoglobin and of 19.75 ng/mL in ferritin levels when comparing post- and pre-treatment levels. The post-treatment mean hemoglobin was 13.32 g/dL and the mean ferritin was 43.22 ng/dL. The rate of intrauterine device expulsion or removal due to mal position was low (13%), as was the need for intrauterine device removal due to lack of efficacy (14%). CONCLUSION: The levonorgestrel-releasing intrauterine system may improve bleeding patterns and quality of life in patients with inherited bleeding disorders and heavy menstrual bleeding. IMPLICATIONS: Women with inherited bleeding disorders could benefit from levonorgestrel-releasing intrauterine system, so its use should be an option for this women.

Depot medroxyprogesterone acetate concentrations in patients with and without the use of antiseizure medications.

OBJECTIVES: To measure plasma concentrations of medroxyprogesterone acetate (MPA) in users with epilepsy treated with antiseizure medications and compare these to MPA concentrations in those without epilepsy. STUDY DESIGN: For this multisite cross-sectional study, we obtained a single blood sample from those with epilepsy treated with various antiseizure medications (n = 18) within the week before their next depot medroxyprogesterone injection. Among the participants without epilepsy (n = 20), 10 similarly were scheduled within the week prior to the next injection, and 10 were scheduled at earlier intervals to attempt to balance the time intervals between groups. MPA concentrations were determined by a validated assay. RESULTS: MPA concentrations were similar among those with epilepsy and controls and between groups with and without the use of enzyme-inducing medications. The lowest MPA concentrations, under 0.07 ng/mL, were observed among two of eight using enzyme-inducing antiseizure medications, one of 10 using noninducing medications, and one of 19 controls had concentrations below 0.2 ng/mL. CONCLUSIONS: In this exploratory study, lower MPA concentrations in some participants using enzyme-inducing antiseizure medications suggest a potential interaction that could reduce depot medroxyprogesterone efficacy.

Pilot study of a novel, alternative subdermal scapular insertion site for the etonogestrel contraceptive implant.

OBJECTIVES: To assess the pharmacokinetics and pharmacodynamics of the etonogestrel (ENG) contraceptive implant when inserted at an alternative scapular site. STUDY DESIGN: We conducted a pilot study of healthy, reproductive-age females who underwent subdermal insertion of an ENG implant over the inferior edge of the nondominant scapula (scapular insertion). We measured serum ENG levels over 1 year at nine time points. Participants completed questionnaires on insertion site and bleeding side effects. We collected photographs and video recordings of insertion and removal techniques. RESULTS: We enrolled five participants (as prespecified), their median age was 26.0 years (range: 19.6-30.3), and median body mass index was 25.0 kg/m2 (range: 22.0-28.0). All serum ENG concentrations remained >90 pg/mL and were within the range of published data for arm insertion of ENG implant at all time points. The mean serum ENG level was 511.7 pg/mL (±168.2) at 1 week and 136.6 pg/mL (±21.8) at 12 months. During the first week after insertion, four of five participants noted insertion site pain with a median pain score of 2 (range 1-3), but all noted resolution by week two. Participants reported variable bleeding patterns consistent with standard ENG implant placement. At the end of the study, all participants reported satisfaction with the implant and would recommend scapular insertion to a friend. CONCLUSIONS: Scapular insertion of the ENG contraceptive implant has similar pharmacokinetics to arm insertion over 1 year of use. This novel, alternative site was well tolerated and demonstrated similar bleeding side effects to standard arm insertion. IMPLICATIONS: Subdermal scapular insertion of the etonogestrel contraceptive implant demonstrated similar pharmacokinetics to arm insertion over 1 year of use. Our pilot data support scapular insertion as an alternative site for ENG contraceptive implants, which could be beneficial for certain patient populations.

Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women.

BACKGROUND: Extensive evidence is available on hormonal contraceptive (HC) use and the risk of a first venous thromboembolism (VTE) event. Despite recommendations to discontinue combined HC (CHC) use, some women continue or start its use after a first VTE. OBJECTIVES: We aimed to evaluate the VTE recurrence risk associated with HC use in premenopausal women. METHODS: Premenopausal women with a first VTE included in the Multiple Environmental and Genetic Assessment of Venous Thrombosis study between 1999 and 2004 were followed for a recurrence until 2010. Data on HC use were available through linkage to the Dutch Foundation for Pharmaceutical Statistics. The risk of recurrence was assessed 1) during anticoagulant therapy and 2) after cessation of anticoagulant therapy. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs adjusted for age and body mass index at baseline and thromboprophylaxis use during follow-up. RESULTS: Six hundred fifty women were uniquely linked and followed for a total of 3538 person-years (median, 6.1 years), during which 57 VTE recurrences occurred. Five occurred (8.8%) during anticoagulation treatment, with no clear risk difference for CHC use vs nonuse (HR, 0.8; 95% CI, 0.1-8.2). After anticoagulation cessation, CHC use was associated with a 2.4-fold higher risk of recurrence (HR, 2.4; 95% CI, 1.2-5.0) compared with nonuse. Recurrence risk for levonorgestrel-releasing intrauterine device use was similar to that for nonuse (HR, 0.9; 95% CI, 0.3-3.1). CONCLUSION: CHC use after a first VTE is safe during anticoagulant use but substantially increases the risk of a recurrent VTE event in absence of anticoagulant use. This study adds to the evidence regarding the use of a levonorgestrel-releasing intrauterine device as a safe alternative.

The use of hormonal contraceptives in fertility treatments: a committee opinion.

The use of hormonal contraception can be considered to aid in the timing of assisted reproductive technology cycles, reduce the risk of ovarian cysts at in vitro fertilization cycle initiation, and optimize visualization before hysteroscopy.

A randomized trial of double vs single-dose etonogestrel implant to overcome the interaction with efavirenz-based antiretroviral therapy.

BACKGROUND: Concomitant use of efavirenz-based antiretroviral therapy and a standard-dose etonogestrel contraceptive implant led to 82% lower etonogestrel exposure when compared with women who do not receive antiretroviral therapy. The clinical impact of this reduced exposure is supported by retrospective cohort evaluations that demonstrated higher rates of unintended pregnancies when contraceptive implants were combined with efavirenz. We hypothesized that placement of 2 etonogestrel implants in those taking efavirenz-based antiretroviral therapy could increase etonogestrel exposure and improve measures of contraceptive efficacy. OBJECTIVE: This study compared the rate of ovulation and etonogestrel pharmacokinetics among women on efavirenz-based antiretroviral therapy who received 2 etonogestrel implants (136 mg; double implant group) in comparison with those who received 1 etonogestrel implant (68 mg; control group). STUDY DESIGN: This randomized, open-label study enrolled Ugandan women with regular menstrual periods who were receiving efavirenz-based antiretroviral therapy for the treatment of HIV. Participants were randomized 1:1 to the double implant or control group, and the etonogestrel implant(s) were placed in the same arm at enrollment. All participants used a copper intrauterine device to prevent pregnancy. Ovulation was evaluated by weekly serum progesterone concentrations measured over 4 consecutive weeks at months 3 (weeks 9-12), 6 (weeks 21-24), and 12 (weeks 45-48). Progesterone concentrations >3 ng/mL were interpreted as ovulation. The ovulation rate in each group was compared using Fisher's exact tests for each month and generalized estimating equations over 48 weeks. Plasma was collected at day 3 and weeks 1, 4, 12, 24, 36, and 48 after implant placement and analyzed using a validated liquid chromatography-triple quadrupole mass spectrometry method for etonogestrel. Etonogestrel concentrations were summarized as median (interquartile range) and compared between groups by geometric mean ratio with 90% confidence intervals. RESULTS: All participants (n=72) were cisgender Ugandan women with a median age of 31 years (interquartile range, 29-36), and 36 participants were enrolled in each study group. Two participants in the control group discontinued the trial; 1 at week 1 because of undetected pregnancy at entry and another at week 45 because of clinically significant depression. There were 47 ovulations over 104 person-months (45%) in 25 of 34 participants in the control group, and 2 ovulations over 108 person-months (2%) in 2 of 36 participants in the double implant group (month 3: 11 [31%] vs 0 [0%]; month 6: 17 [49%] vs 0 [0%]; month 12: 19 [56%] vs 2 [6%], respectively; all P<.001). The odds of ovulation were reduced by 97.7% (95% confidence interval, 90.1-99.5) in the double implant group over 48 weeks. At each time point, etonogestrel concentration was more than 2-fold higher in the double implant group than in the controls (geometric mean ratio, 2.30-2.83) with a geometric mean ratio of 2.83 (90% confidence interval, 1.89-3.35) at week 48. There were no differences in the adverse events between groups and no participant discontinued because of adverse events. CONCLUSION: Over 48 weeks of combined use, placing 2 etonogestrel implants suppressed ovulation and increased plasma etonogestrel exposure when compared with 1 etonogestrel implant among women on efavirenz-based antiretroviral therapy. Doubling the dose of etonogestrel during efavirenz-based antiretroviral therapy could improve contraceptive effectiveness.

Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review / Uso de anticoncepcional oral combinado e o risco de câncer cervical: Revisão da literatura

Abstract Cervical cancer (CC) is caused by persistent infection of human papillomavirus of high oncogenic risk (hr-HPV); however, several cofactors are important in its carcinogenesis, such as smoking, multiparity, and prolonged use of oral hormonal contraceptives (COCs). Worldwide, 16% of women use COCs, whereas in Brazil this rate is of ~ 30%. The safety and adverse effects of COCs are widely discussed in the literature, including the increase in carcinogenic risk. Due to the existence of several drugs, combinations, and dosages of COCs, it is hard to have uniform information in epidemiological studies. Our objective was to perform a narrative review on the role of COCs use in the carcinogenesis of cervical cancer. Several populational studies have suggested an increase in the incidence of cervical cancer for those who have used COCs for > 5 years, but other available studies reach controversial and contradictory results regarding the action of COCs in the development of CC.

Resumo O câncer cervical (CC) é causado pela infecção persistente pelo papilomavírus humano de alto risco oncogênico (hr-HPV); entretanto, vários cofatores são importantes na sua carcinogênese, como tabagismo, multiparidade e uso prolongado de contraceptivos hormonais orais (COCs). No mundo, 16% das mulheres usam AOCs, enquanto no Brasil essa taxa é de ~ 30%. A segurança e os efeitos adversos dos COCs são amplamente discutidos na literatura, incluindo o aumento do risco carcinogênico. Devido à existência de várias drogas, combinações e dosagens de COCs, é difícil ter informações uniformes em estudos epidemiológicos. Nosso objetivo foi realizar uma revisão narrativa sobre o papel do uso de COCs na carcinogênese do câncer cervical. Vários estudos populacionais têm sugerido aumento da incidência de câncer de colo uterino para aquelas que usam COCs há mais de 5 anos, mas outros estudos disponíveis chegam a resultados controversos e contraditórios quanto à ação dos COCs no desenvolvimento do CCU.