Male Hormonal Contraception.

The economic and public health burdens of unplanned pregnancies are evident globally. Since the introduction of the condom >300 years ago, assumptions about male willingness to participate in contraception, as well as concerns about failure rates and side effects, have stagnated the development of additional reversible male contraceptives. However, changing attitudes and recent research advances have generated renewed interest in developing reversible male contraceptives. To achieve effective and reversible suppression of spermatogenesis, male hormonal contraception relies on suppression of testicular testosterone and sperm production using an androgen-progestin combination. While these may be associated with side effects-changes in libido, weight, hematocrit, and cholesterol-recently, novel androgens and progestins have shown promise for a "male pill" with reduced side effects. Here we summarize landmark studies in male contraceptive development, showcase the most recent advances, and look into the future of this field, which has the potential to greatly impact global public health.

Genital Abnormalities, Hormonal Contraception, and Human Immunodeficiency Virus Transmission Risk in Rwandan Serodifferent Couples.

BACKGROUND: We explored the role of genital abnormalities and hormonal contraception in human immunodeficiency virus (HIV) transmission among heterosexual serodifferent couples in Rwanda. METHODS: From 2002 to 2011, HIV-serodifferent couples who were not using antiretroviral treatment were followed up, and sociodemographic and clinical data were collected, family planning provided, and HIV-negative partners retested. Couples were assessed for genital ulcers; nonulcerative genital sexually transmitted infection (STIs), including gonorrhea, chlamydia, and trichomoniasis; and non-STI vaginal infections, including bacterial vaginosis and candida. Multivariable models evaluated associations between covariates and HIV transmission genetically linked to the index partner. RESULTS: Among 877 couples in which the man was HIV positive, 37 linked transmissions occurred. Factors associated with women's HIV acquisition included genital ulceration in the female partner (adjusted hazard ratio, 14.1) and nonulcerative STI in the male partner (8.6). Among 955 couples in which the woman was HIV positive, 46 linked transmissions occurred. Factors associated with HIV acquisition in men included nonulcerative STI in the female partner (adjusted hazard ratio, 4.4), non-STI vaginal dysbiosis (7.1), and genital ulceration in the male partner (2.6). Hormonal contraception use was not associated with HIV transmission or acquisition. CONCLUSIONS: Our findings underscore the need for integrating HIV services with care for genital abnormalities. Barriers (eg, cost of training, demand creation, advocacy, and client education; provider time; and clinic space) to joint HIV/STI testing need to be considered and addressed.

Hormonal contraception and risk of STIs and bacterial vaginosis in South African adolescents: secondary analysis of a randomised trial.

OBJECTIVES: Young women in sub-Saharan Africa are at high risk of STIs and unintended pregnancies, yet hormonal contraceptive (HC) use may affect STI risk. We compared the influence of three HCs on the incidence and prevalence of STIs and bacterial vaginosis (BV) in South African adolescents. METHODS: One hundred and thirty adolescents between 15 and 19 years were randomised to the injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) (Triphasil or Nordette) or a combined contraceptive vaginal ring (CCVR; NuvaRing) for 16 weeks (clinicaltrials.gov/NCT02404038). Vaginal samples were collected at baseline and 16 weeks post contraceptive initiation for STI and BV testing. RESULTS: In an intention-to-treat analysis, no significant differences in BV prevalence were found between study arms. The overall incidence of any STI at follow-up was high: 16.2% in the COC arm; 25.7% in the Net-En arm; and 37.1% in the CCVR arm. The incidence rate (IR) of any STI was similar between Net-En (IR 0.74 (95% CI 0.34 to 1.41)) and the oestrogen-containing contraceptives (IR 0.78 (95% CI 0.47 to 1.22)). A lower IR of Chlamydia trachomatis (incidence rate ratio (IRR) 0.68 (95% CI 0.19 to 1.99)) and Neisseria gonorrhoeae (IRR 0.25 (95% CI 0.01 to 1.35)) but a higher IR of Mycoplasma genitalium (IRR 16.0 (95% CI 2.96 to 400)), was observed in the Net-En arm compared with the oestrogen-containing contraceptives, although the overall incidence of M. genitalium was low (4.7%). In an exploratory analysis, the risk of any STI and N. gonorrhoeae was lower in the COC arm compared with CCVR. A per-protocol analysis yielded similar results. CONCLUSION: Our results suggest that use of Net-En may be associated with increased risk of M. genitalium compared with oestrogen-containing contraceptives but not with overall STI risk. COC use may decrease STI risk relative to CCVR.

Initiating Hormonal Contraception.

Most patients can safely begin using hormonal contraception at any point in their menstrual cycle. An evidence-based, flexible, patient-centered approach to initiating contraception promotes health and enhances patients' reproductive autonomy. A recent Papanicolaou test is not necessary before prescribing hormonal contraception. Most patients can begin using progestin-only contraceptives immediately after childbirth. Patients can begin any appropriate contraceptive method immediately after an abortion or early pregnancy loss, except for an intrauterine device following septic abortion. Delaying contraception to wait for the next menses or for an appointment creates unnecessary barriers for patients. Clinicians can facilitate the use of hormonal contraception by providing anticipatory guidance about common side effects (e.g., spotting, other menstrual cycle changes), giving comprehensive information about available contraceptive choices, honoring patients' preferences, and eliminating office-related barriers. Prescribing or dispensing a one-year supply of contraceptives lowers costs and improves adherence. Counseling via telemedicine or a patient portal eliminates unnecessary office visits.

The difficult journey to treatment for women suffering from heavy menstrual bleeding: a multi-national survey.

PURPOSE: Up to 30% of women of reproductive age experience HMB, which has a substantial impact on their quality of life. A clinical care pathway for women with HMB is an unmet need, but its development requires better understanding of the factors that characterise current diagnosis and management of the condition. MATERIALS AND METHODS: This observational, survey-based study assessed the burden, personal experiences, and path through clinical management of women with HMB in Canada, the USA, Brazil, France and Russia using a detailed, semi-structured online questionnaire. After excluding those reporting relevant organic pathology, responses to the questionnaire from 200 women per country were analysed. RESULTS: Around 75% of women with HMB had actively sought information about heavy periods, mostly through internet research. The mean time from first symptoms until seeking help was 2.9 (Standard deviation, 3.1) years. However, 40% of women had not seen a health care professional about the condition. Furthermore, 54% had never been diagnosed or treated. Only 20% had been diagnosed and received appropriate treatment. Treatment was successful in 69% of those patients currently receiving treatment. Oral contraceptives were the treatment most commonly prescribed for HMB, although the highly effective levonorgestrel-intrauterine system was used by only a small proportion of women. CONCLUSIONS: This study provides insight into the typical journey of a woman with HMB which may help patients and health care professionals improve the path to diagnosis and treatment, although further research with long-term outcomes is needed.

Combined hormonal contraception and COVID-19.

Aim: This article reviews the possibility of using combined hormonal contraception during the COVID-19 pandemic. Methods: narrative reviewResults: The factors that protect women from the severity of the disease are analysed, as well as the risk factors for the use of this type of contraception, especially related to the increased risk of a thrombotic event in patients affected by the disease. Finally, the information available on the guidelines for action in patients with COVID-19 using combined hormonal contraception is collected.Conclusions: We can continue to prescribe and use hormonal methods with EE.

Qualitative findings about stigma as a barrier to contraception use: the case of Emergency Hormonal Contraception in Britain and implications for future contraceptive interventions.

BACKGROUND: Emergency Hormonal Contraception (EHC) has been underused in Britain and internationally since its introduction. 'Stigmatisation' has been identified as one of the barriers to EHC. However, few, if any publications have focussed on the significance of this factor in the British context, the social meanings for women of seeking EHC and the implications for future contraceptive provision and innovation. METHOD: In-depth qualitative material from 27 women across two British studies was analysed. The first, in which 11 young women were interviewed in-depth regarding EHC specifically, was supplemented by material from a multi-stage narrative study of 15 women concerning their life history experiences of using contraception more broadly. RESULTS: Stigmatisation of EHC use is a key barrier and derives from associations with irresponsible behaviour. This irresponsibility exists on a continuum with some behaviours and some women more ir/responsible than others. In addition, despite not being an abortifacient, EHC may be closely aligned with abortion meaning users can be perceived as 'bad women' in a similar way to abortion seekers. This stigma can deter participants seeking EHC when they may need it. CONCLUSION: Stigma is a powerful barrier to EHC use due to the social significance of responsibility and expectations pertaining to the behaviour of 'good women.' Understandings about stigmatisation in the case of EHC should be translated to other aspects of contraceptive service delivery and future innovations, to ensure effective provision of methods and safeguard their uptake.

Characteristics of women who use hormonal contraceptives and their population-level impacts on HIV infection in a cohort of South African women (2002-2016).

PURPOSE: Women's choice of contraceptive can have broader implications and may play a significant role in shaping their sexual practices. We aim to identify the characteristics of women who use hormonal injectables and those at high-risk of HIV infection. We also quantify the population-level impact of their shared characteristics on HIV incidence rates. MATERIALS AND METHODS: Data from 9948 women who enrolled in six-HIV prevention trials conducted in South Africa (2002-2016) were included. We used logistic and Cox regression models and estimated the population-level impact of the use of injectables on HIV incidence in the multifactorial-model setting. RESULTS: Using hormonal injectables were associated with increased risk of HIV infection (adjusted Hazard ratio (aHR):1.51, 95% CI:1.22, 1.86). At the population level less than 20% of the infections were associated with injectable contraceptives among younger women (i.e., less than 35 years of age). Factors including being single/not-cohabiting, using condoms at last sex, partner-related factors, and STI diagnosis were all identified as shared characteristics of women who preferred using hormonal injectables and those at high-risk of HIV infection. At the population level, these factors were associated with more than 50% of the infections among women younger than 35 years of age. CONCLUSIONS: Our analysis presented evidence for the overlapping characteristics of the women who used hormonal injectables and those at high-risk of HIV infection. These findings reinforce the importance of comprehensive contraceptive counselling to women about the importance of dual protection, such as male condoms and hormonal contraceptives use.

Hormonal Contraception and Female Sexuality: Position Statements from the European Society of Sexual Medicine (ESSM).

INTRODUCTION: Hormonal contraception is available worldwide in many different forms. Fear of side effects and health concerns are among the main reasons for not using contraceptives or discontinuing their use. Although the safety and efficacy of contraceptives have been extensively examined, little is known about their impact on female sexual function, and the evidence on the topic is controversial. AIM: To review the available evidence about the effects of hormonal contraceptives on female sexuality in order to provide a position statement and clinical practice recommendations on behalf of the European Society of Sexual Medicine. METHODS: A comprehensive review of the literature was performed. MAIN OUTCOME MEASURE: Several aspects of female sexuality have been investigated, including desire, orgasmic function, lubrication and vulvovaginal symptoms, pelvic floor and urological symptoms, partner preference, and relationship and sexual satisfaction. For each topic, data were analyzed according to the different types of hormonal contraceptives (combined estrogen-progestin methods, progestin-only methods, and oral or non-oral options). RESULTS: Recommendations according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence criteria and specific statements on this topic, summarizing the European Society of Sexual Medicine position, were developed. CLINICAL IMPLICATIONS: There is not enough evidence to draw a clear algorithm for the management of hormonal contraception-induced sexual dysfunction, and further studies are warranted before conclusions can be drawn. A careful baseline psychological, sexual, and relational assessment is necessary for the health care provider to evaluate eventual effects of hormonal contraceptives at follow-up. STRENGTHS & LIMITATIONS: All studies have been evaluated by a panel of experts who have provided recommendations for clinical practice. CONCLUSION: The effects of hormonal contraceptives on sexual function have not been well studied and remain controversial. Available evidence indicates that a minority of women experience a change in sexual functioning with regard to general sexual response, desire, lubrication, orgasm, and relationship satisfaction. The pathophysiological mechanisms leading to reported sexual difficulties such as reduced desire and vulvovaginal atrophy remain unclear. Insufficient evidence is available on the correlation between hormonal contraceptives and pelvic floor function and urological symptoms. Both S, Lew-Starowicz M, Luria M, et al. Hormonal Contraception and Female Sexuality: Position Statements from the European Society of Sexual Medicine (ESSM). J Sex Med 2019;16:1681-1695.

Clinical factors affecting the efficacy of melasma treatment using the Q-switched 1064 Nd: YAG laser mode in a group of Venezuelan female patients.

The influence of melasma risk factors on the effectiveness of laser toning treatment in Venezuelan females was investigated. Clinical evaluation was performed (n = 64) including ultrasound and thyroid hormone profile. All patients underwent face exposure with laser toning, eight sessions weekly. VISIA percentiles corresponding to dark brown spots determined before and after treatment were compared by ANOVA. Differences between percentile values before and after treatment for each patient were calculated and expressed as percentages. An improvement of ≥30% was considered as significant. Spearman rank correlations between improvement and clinical parameters were determined. A significant increase (p > .005) of the median of the percentiles in the overall group was observed. However, only 62.5% of the patients exhibited an improvement of ≥30% at the right malar, 73.4% at the frontal and 71.8% at the left malar areas. Hormonal contraception during treatment (right malar: p < .0001 left malar: p = .0035), thyroid disorders (right malar: p < .0001; frontal: p = .011; left malar: p < .0001) and photoaging (right malar: p = .0235; frontal: p = .0237; left malar: p = .0137) were inversely associated to melasma improvement after treatment. Prolonged use of sunscreen improved significantly (right malar: p < .001; frontal: p = .016 and left malar: p = .025) treatment effectiveness.

Update on Novel Hormonal and Nonhormonal Male Contraceptive Development.

BACKGROUND: The advent of new methods of male contraception would increase contraceptive options for men and women and advance male contraceptive agency. Pharmaceutical R&D for male contraception has been dormant since the 1990s. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969 and supports most ongoing hormonal male contraceptive development. Nonhormonal methods are in earlier stages of development. CONTENT: Several hormonal male contraceptive agents have entered clinical trials. Novel single agent products being evaluated include dimethandrolone undecanoate, 11ß-methyl-nortestosterone dodecylcarbonate, and 7α-methyl-19-nortestosterone. A contraceptive efficacy trial of Nestorone®/testosterone gel is underway. Potential nonhormonal methods are at preclinical stages of development. Many nonhormonal male contraceptive targets that affect sperm production, sperm function, or sperm transport have been identified. SUMMARY: NICHD supports development of reversible male contraceptive agents. Other organizations such as the World Health Organization, the Population Council, and the Male Contraception Initiative are pursuing male contraceptive development, but industry involvement remains limited.

Hormonal contraception and HIV acquisition among women: an updated systematic review.

OBJECTIVE: To update a 2016 systematic review on hormonal contraception use and HIV acquisition. METHODS: We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses. RESULTS: In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk. CONCLUSIONS: High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.

Hormonal Contraception and Bone Health in Adolescents.

Hormonal contraception is prescribed commonly to adolescents for myriad indications from pregnancy prevention to treatment for acne, hirsutism or dysmenorrhea. Although use of these hormones generally has no effect or benefits bone health in mature premenopausal women, the same may not be true for adolescents. The teen years are a critical period for acquiring peak bone strength. Sex hormones, growth hormone, and insulin-like growth factors (IGFs) interact to modulate the changes in bone size, geometry, mineral content, and microarchitecture that determine skeletal strength. Combined oral contraceptives (COCs) and intramuscular depo medroxyprogesterone (DMPA) can compromise the expected gains in adolescence by altering estrogen and IGF concentrations. Use of these medications has been associated with slower accrual of bone mineral density (BMD) and increased fracture risk in some studies. Far less is known about the skeletal effects of the newer long acting reversible contraceptives (LARCs). This review takes a critical look at the gaps in current knowledge of the skeletal effects of COCs, DMPA, and LARCs and underscores the need for additional research.

Pharmacist self-perception of readiness to prescribe hormonal contraception and additional training needs.

INTRODUCTION: Our objectives were to describe pharmacist perceptions of training and preparation to prescribe hormonal contraception (HC), identify training gaps, and elicit preferred training methods. METHODS: In this cross-sectional survey, pharmacists in the United States (US) completed an online 29-item survey. Descriptive statistics were used to analyze responses. RESULTS: Of 823 participating pharmacists, 58% felt they received adequate training to prescribe HC. Prescribing any medications within the last five years or completion of residency training were significantly associated with more participants feeling adequately trained. Of those who indicated HC was not covered in their pharmacy school curriculum, most (78%) felt they were either not adequately trained or unsure. Only 36% were aware of the Centers for Disease Control and Prevention US Medical Eligibility Criteria for Contraceptive Use (CDC MEC). Residency-trained pharmacists were statistically more likely to have used the CDC MEC and feel comfortable prescribing for adolescents. Most participants desired more training about switching between products (80%) and patient specific product selection (72%). Preferred methods for additional training were basic (

An implementation project to expand access to self-administered depot medroxyprogesterone acetate (DMPA).

OBJECTIVE: To describe the implementation and results of a proactive patient outreach project to offer self-administered, depot medroxyprogesterone (DMPA) subcutaneous (SC) to interested patients at a California safety-net clinic following expanded state Medicaid coverage. STUDY DESIGN: We contacted non-pregnant patients at an urban, safety-net hospital-based primary care clinic who had been prescribed DMPA intramuscular (IM) in the past year to gauge interest in self-administered DMPA-SC. Interested patients received a prescription for DMPA-SC and a telehealth appointment with a clinic provider to learn self-injection. We recorded patient interest in DMPA-SC, completed appointments, and completed first injections. We conducted initial outreach in May, 2020 and recorded appointment attendance and completed injections through August, 2020. RESULTS: Of 90 eligible patients (age 17-54), we successfully contacted and discussed DMPA-SC with 70 (78%). Twenty-six (37%) patients expressed interest in DMPA-SC and scheduled telehealth appointments to learn to self-administer the medication. Fifteen (58%) of those interested (21% of the total) successfully self-injected DMPA-SC. Of the 44 (63%) patients not interested in DMPA-SC, the three most common reasons were fear of self-injection (n = 23 [52%]), wanting to stop DMPA (n = 11 [25%]), and satisfaction with DMPA-IM (n = 6 [14%]). CONCLUSION: There is interest in and successful initiation of self-administered DMPA-SC among patients at an urban safety net hospital-based primary care clinic who have used DMPA-IM in the last year. IMPLICATIONS: Our data provide evidence for the interest and successful first injection rate after offering self-administered DMPA-SC to patients on DMPA-IM. Expanding coverage of self-administered DMPA-SC could increase patient-centeredness and accessibility of contraception as well as reduce patient anxiety around COVID-19 transmission without losing contraceptive access.

Assessing safety in hormonal male contraception: a critical appraisal of adverse events reported in a male contraceptive trial.

INTRODUCTION: There is unmet need for male contraceptive options, but a recent injectable combination male contraceptive trial was terminated early due to adverse events (AEs). METHODS: We examined the frequency of reported AEs by male research participants compared with AEs reported in prescribing information of approved female hormonal contraceptive methods. Published data from trials of the top five most-used female hormonal contraceptives, supplemented by contemporary contraceptive research, were compared with the frequency of AEs reported in a male injectable hormonal contraceptive trial. RESULTS: We observed similar frequencies of AEs reported by users of male contraceptives compared with those reported by female users. Among quantitatively comparable AEs, compared with men, women reported experiencing higher frequencies of headaches, pelvic pain, and weight gain and similar frequencies of decreased libido. Compared with women, men reported experiencing higher frequencies of acne and mood changes. Men discontinued participation due to AEs at a lower frequency than women. CONCLUSIONS: Female hormonal methods generally have similar frequencies of AEs to those reported in a recent male hormonal contraceptive trial, and male users had lower rates of discontinuation due to AEs. There were fewer serious AEs of the male contraceptive than reported in contemporary female trials which resulted in FDA licensure. This suggests there may be implicit bias in the scientific community regarding the level of acceptable risk for users of male contraceptive methods.

Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumours: guidelines from the French national network dedicated to rare gynaecological cancers.

INTRODUCTION: Rare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours. MATERIAL AND METHODS: A panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds. RESULTS: Thirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type. DISCUSSION: Overall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours. CONCLUSION: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Potential user interest in new long-acting contraceptives: Results from a mixed methods study in Burkina Faso and Uganda.

Method-related concerns represent an important cause of contraceptive non-use and discontinuation. User preferences must be incorporated into the design of new contraceptive technologies to ensure product success and improve family planning outcomes. We assessed preferences among potential users in Burkina Faso and Uganda for six contraceptive methods currently under development or ready for introduction: a new copper intra-uterine device (IUD), a levonorgestrel intra-uterine system, a new single-rod implant, a biodegradable implant, a longer-acting injectable, and a method of non-surgical permanent contraception. Questions were added to nationally-representative PMA2020 household surveys that asked 2,743 and 2,403 women in Burkina Faso and Uganda, respectively, their interest in using each new method. We assessed factors associated with interest through multivariable logistic regression models. We conducted qualitative interviews and focus groups with 398 women, 78 men, and 52 family planning providers and key informants to explore perceived advantages and disadvantages of the methods. Respondents expressed interest in using all new methods, with greatest interest in the longer-acting injectable (77% in Burkina Faso, 61% in Uganda), followed by a new single-rod implant. Least interest was expressed in a new copper IUD (26% Burkina Faso, 15% in Uganda). In both countries, women with less education had higher odds of interest in a longer-acting injectable. Interest in most new methods was associated with desiring a method lasting longer than one year and acceptance of lack of menstrual bleeding as a contraceptive side effect. Perceived advantages and disadvantages were similar between countries, including concerns about menstrual side effects and fear of the biodegradable nature of the biodegradable implant. Potential users, their partners, and providers are interested in new longer-acting methods, however, familiar forms including the injectable and implant may be the most immediately acceptable. A biodegradable implant will require clear counseling messages to allay potential fears.