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This preliminary study evaluated the biocompatibility of a novel degradable intravaginal plug contraceptive composed of PEG 4000 and chitosan in cats using haematological profiling and vaginal cytology. Five healthy, non-pregnant female cats were fully anaesthetised and fitted with an intravaginal plug (10 × 0.3 mm) using an applicator, following oestrogen administration 3 h prior. Blood samples were collected from the cephalic vein on days 0 (pre-insertion) and 3 and 7 (post-insertion). Vaginal cytology examinations were conducted on day 0 (pre- and post-oestrogen injection) and days 1, 3 and 7 post-insertion. Haematological parameters, including red blood cell count, haemoglobin levels, haematocrit values, total white blood cell count and differentiation, showed no significant changes after contraceptive insertion (p > 0.05). Vaginal cytology indicated an acute inflammatory response in one out of five subjects on day three post-insertion. The distribution of vaginal epithelial cells (parabasal, intermediate and superficial) remained unaffected by contraception. Oestrogen injection resulted in the dominance of superficial cells up to day 7 of observation (p < 0.05). Overall, PEG 4000 and chitosan-based intravaginal plug contraceptives demonstrated sufficient biocompatibility, indicating their potential as viable contraceptive options for feline use., (© 2024 Wiley‐VCH GmbH.)

Research Question: Do the various forms of hormonal and non-hormonal contraceptives have any association with ovarian stimulation outcomes, such as oocyte yield and maturation, in patients undergoing planned oocyte cryopreservation (POC)?, Design: This retrospective cohort study included all patients who underwent POC cycles between 2011 and 2023. The use of types of contraception before a POC cycle was recorded. The study evaluated the median number of cumulus-oocyte complexes obtained after vaginal oocyte retrieval and the proportion of metaphase II oocytes that underwent vitrification among all the cohorts., Results: A total of 4059 oocyte freezing cycles were included in the analysis. Eight types of contraceptive method were recognized in patients undergoing ovarian stimulation: intrauterine device (IUD), copper (n = 84); IUD, levonorgestrel low dose (<52 mg) (n = 37); IUD, levonorgestrel (n = 192); subdermal etonogestrel implant (n = 14); injectable medroxyprogesterone acetate (n = 11); etonogestrel vaginal ring (n = 142); combined oral contraceptive pills (n = 2349); and norelgestromin transdermal patch (n = 10). The control group included patients not using contraceptives or using barrier or calendar methods (n = 1220). Among all the cohorts the median number of cumulus-oocyte complexes retrieved during oocyte retrieval was comparable (P = 0.054), and a significant difference in oocyte maturity rate with median number of vitrified oocytes was found (P = 0.03, P < 0.001, respectively). After adjusting for confounders a multivariate analysis found no association between the type of contraceptive and proportion of metaphase II oocytes available for cryopreservation., Conclusions: Among the various forms of contraception, none was shown to have an adverse association with oocyte yield or maturation rate in patients undergoing POC., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Melengestrol acetate (MGA) implants are a progestin-based reversible contraceptive used to manage fertility in animals. MGA implants are recommended for replacement every 2 years; however, reproduction may be suppressed longer if implants are not removed. In this study, we investigated whether the probability of reproducing (pR) differed among nonimplanted females, females with MGA implants removed, and females whose implants were not removed. In addition, since implant loss in hamadryas baboons is a concern, we explored whether female age, institution, implant placement year, implant location, or implant placement type (intramuscular vs. subcutaneous) differed for females whose implants were lost compared to those that were not. The pR differed significantly across all three treatment conditions with the nonimplanted group having the highest pR. The pR plateaued at 63% after 40 months for the implant-removed group compared to 96% after 84 months in the nonimplanted group. There was no reproduction after contraception if implants were not removed (7.83-45.53 months). In the nonimplanted group, pR was significantly higher for older and parous females. In terms of implant loss, we found that implant placement type was significantly associated with implant loss, such that there were fewer losses when implants were placed intramuscularly (IM) as compared to subcutaneously. Our results suggest that placing MGA implants IM is likely to reduce loss. When loss is prevented, MGA implants are an effective form of contraception and are reliably reversibly in most individuals when removed. However, if not removed, they can prevent reproduction longer than 2 years., (© 2024 Wiley Periodicals LLC.)

HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical trial, conducted at two sites in South Africa from 2018-2019, randomized HIV-negative women aged 18-40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214-218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p < 0.0001); NET-EN D0 0.551, 25W 0.253 nmol/L, -54.1%, (p < 0.0001)], SHBG [DMPA-IM D0 45.0, 25W 32.7 nmol/L, -29.8% (p < 0.0001); NET-EN D0 50.2, 25W 17.6 nmol/L, -65.1% (p < 0.0001)], and calculated free testosterone levels [DMPA-IM D0 6.87, 25W 5.38 pmol/L, -17.2% (p = 0.0371); NET-EN D0 6.00, 25W 3.70, -40.0% (p < 0.0001)]. After adjusting for change from D0, the total testosterone, SHBG and calculated free testosterone levels were significantly higher for DMPA-IM than NET-EN (64.9%, p < 0.0001; 101.2%, p < 0.0001; and 38.0%, p = 0.0120, respectively). The substantial and differential decrease in testosterone and SHBG levels does not explain our previous finding of no detected decrease in risky sexual behavior or sexual function for DMPA-IM or NET-EN users from D0 to 25W. Medroxyprogesterone (MPA) and NET are androgenic and are both present in molar excess over testosterone and SHBG concentrations at 25W. Any within or between contraceptive group androgenic effects on behavior in the brain are likely dominated by the androgenic activities of MPA and NET and not by the decreased endogenous testosterone levels. The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Avenant et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1β, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1β) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p<0.01), MIP-3α (0.02), Elafin (p = 0.03) and RANTES (p<0.01) differed significantly by race whereas IL-6 was significantly different by age (p = 0.03). We conclude that 3-month use of LNG-IUD, ETNG and DMPA have minimal effects on adolescent vaginal immune microenvironment, and therefore unlikely to impact HIV risk. Future studies with larger sample size and longer follow-up are recommended to continue to evaluate effects of contraceptives on the lower genital tract immunity and susceptibility to sexually transmitted infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nasr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To estimate the incidence of ovulation suppression within five days of etonogestrel 68 mg implant insertion in the presence of a dominant follicle with and without same-day ulipristal acetate., Study Design: This single site non-masked, exploratory randomized trial recruited people age 18-35 years with regular menstrual cycles, no pregnancy risk, and confirmed ovulatory function. We initiated transvaginal ultrasound examinations on menstrual day 7-9 and randomized participants 1:1 to etonogestrel implant alone or with concomitant ulipristal acetate 30 mg oral when a dominant follicle reached ≥14 mm in diameter. We completed daily sonography and serum hormone levels for up to seven days or transitioned to labs alone if sonographic follicular rupture occurred. We defined ovulation as follicular rupture followed by progesterone >3 ng/mL. We calculated point estimates, risk ratios and 95% confidence intervals for ovulation for each group. Ovulation suppression of ≥44% in either group (the follicular rupture suppression rate with oral levonorgestrel emergency contraception), would prompt future method testing., Results: From October 2020 to October 2022, we enrolled 40 people and 39 completed primary outcome assessments: 20 with etonogestrel implant alone (mean follicular size at randomization: 15.2 mm ± 0.9 mm) and 19 with etonogestrel implant + ulipristal acetate (mean follicular size at randomization: 15.4 mm ± 1.2 mm, p = 0.6). Ovulation suppression occurred in 13 (65%) of etonogestrel implant-alone participants (Risk ratio 0.6 (95% CI: 0.3, 1.1), p = 0.08) and seven (37%) of implant + ulipristal acetate participants., Conclusions: Ovulation suppression of the etonogestrel implant alone exceeds threshold testing for future research while the implant + ulipristal acetate does not., Implications: Data are lacking on midcycle ovulation suppression for the etonogestrel implant with and without oral ulipristal acetate. In this exploratory study, ovulation suppression occurred in 65% of implant participants and 37% of implant + ulipristal acetate participants. Ovulation suppression of the implant alone exceeds threshold testing for future emergency contraception research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Contraception is a practice with extensive and complicated social and scientific histories. From cycle tracking, to the very first prescription contraceptive pill, to now having over-the-counter contraceptives on demand, family planning is an aspect of healthcare that has undergone and will continue to undergo several transformations through time. This review provides a comprehensive overview of current reversible hormonal and non-hormonal birth control methods as well as their mechanism of action, safety, and effectiveness specifically for individuals who can become pregnant. Additionally, we discuss the latest Food and Drug Administration (FDA)-approved hormonal method containing estetrol and drospirenone that has not yet been used worldwide as well as the first FDA-approved hormonal over-the-counter progestin-only pills. We also review available data on novel hormonal delivery through microchip, microneedle, and the latest FDA-approved non-hormonal methods such as vaginal pH regulators. Finally, this review will assist in advancing female contraceptive method development by underlining constructive directions for future pursuits. Information was gathered from the NCBI and Google Scholars databases using English and included publications from 1900 to present. Search terms included contraceptive names as well as efficacy, safety, and mechanism of action. In summary, we suggest that investigators consider the side effects and acceptability together with the efficacy of contraceptive candidate towards their development., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess the bleeding profiles of the levonorgestrel 13.5 mg intrauterine device (LNG13.5-IUD) and Nova T copper 380 mm 2 IUD (Cu380-IUD)., Study Design: Single-center, evaluator-masked, randomized study conducted in women aged 18-45 years starting these methods. Primary outcomes were number of bleeding days, self-reported bleeding intensity, Pictorial Blood Assessment Chart (PBAC) score, and blood biochemical values at baseline, months 3, 6, 12, 24, and 36 per 90-day reference periods except for PBAC (months). Secondary objectives were presence/duration/intensity of dysmenorrhea and tolerability., Results: We included 106 women aged 32.5 ± 6.7 years: 55 with LNG13.5-IUD and 51 with Cu380-IUD. Data for LNG13.5-IUD versus Cu380-IUD at baseline and month 36 (both respectively) were as follows: (1) median (25th; 75th percentile) number of bleeding days: 12 (9.0; 15.0) versus 12 (9.0; 15.0), p = 0.82, and 4 (0; 13.7) versus 15 (14.2; 20.0), p < 0.001; (2) mean bleeding intensity: 1.7 for both, p = 0.66, and 0.7 and 2.2, p < 0.001. Forty percent versus 0% presented with amenorrhea at month 36; (3) mean PBAC score (95% Confidence interval (CI): 50.7 (16.6; 84.7) versus 130.4 (95.7; 165.0) at month 1, and 7.9 (-26.7; 42.6) versus 126 (90.7; 161.2), p < 0.001; (4) median (25th; 75th percentile) ferritin levels (Ug/L) 33 (19; 53) versus 30 (19; 45), p = 0.70, and 59 (42; 84) versus 21 (8; 39). We did not observe changes or differences between groups in hemoglobin and hematocrit. The duration and intensity of dysmenorrhea were significantly lower with LNG13.5-IUD versus Cu380-IUD. Adverse events were those expected., Conclusions: LNG13.5-IUD is associated with a significant reduction in blood loss and dysmenorrhea compared with Cu380-IUD., Implications: Women eligible for a levonorgestrel 13.5 mg intrauterine device (IUD) or a copper 380 mm 2 IUD should be informed of the differences in bleeding profiles-one of the main causes for IUD discontinuation-so they can compare this information against their bleeding expectations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: It is 100 years since the discovery of oestrogen and nearly that since the discovery of progesterone. It is over 50 years since the concept of using intrauterine progesterone. Ten years after its synthesis, the research using levonorgestrel as an intrauterine agent was introduced., Areas Covered: The pharmacodynamics and pharmacokinetics of LNG-IUSs and the LNG-IUS 52 mg in particular explain why intrauterine LNG is so highly effective for contraception. When intrauterine LNG is used therapeutically it should ideally be based on clinical monitoring of the pathology being treated rather than a fixed time period While the LNG-IUS 52 mg is probably required for most medical conditions, consideration should be given for using the LNG-IUS 13.5 mg for hyperplasia and endometrial protection during oestrogen therapy and for older women who appear more prone to a low rate of LNG induced breast cancer, although there is not yet an official indication for this., Conclusion: The desire for fertility control, therapy for various genital pathological conditions and reduction of repeated endometrial decidualization and inflammatory breakdown and its consequences, and menopausal problems can be aided by intrauterine LNG. This review explains how a contraceptive also became a WHO listed essential medicine.

Introduction: Hormonal contraceptive use might impair bone health and increase the risk of stress fracture by decreasing endogenous oestrogen production, a central regulator of bone metabolism. This cross-sectional study investigated bone density and biochemical markers of bone metabolism in women taking hormonal contraceptives on entry to basic military training., Methods: Forty-five female British Army recruits had biochemical markers of bone metabolism, areal bone mineral density (aBMD) and tibial speed of sound (tSOS) measured at the start of basic military training. Participants were compared by their method of hormonal contraception: no hormonal contraception (NONE), combined contraceptive pill (CP) or depot-medroxyprogesterone acetate (DMPA) (20±2.8 years, 1.64±0.63 m, 61.7±6.2 kg)., Results: aBMD was not different between groups (p≥0.204), but tSOS was higher in NONE (3%, p=0.014) when compared with DMPA users. Beta C-terminal telopeptide was higher in NONE (45%, p=0.037) and DMPA users (90%, p=0.003) compared with CP users. Procollagen type 1 N-terminal propeptide was higher in DMPA users compared with NONE (43%, p=0.045) and CP users (127%, p=0.001), and higher in NONE compared with CP users (59%, p=0.014). Bone alkaline phosphatase was higher in DMPA users compared with CP users (56%, p=0.044)., Conclusions: DMPA use was associated with increased bone turnover and decreased cortical bone integrity of the tibia. Lower cortical bone integrity in DMPA users was possibly mediated by increased intracortical remodelling, but trabecular bone was not affected by contraceptive use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Problem: Both luteal phase progesterone (P4) levels and use of the intramuscular (IM) injectable progestin-only contraceptive depo-medroxyprogesterone acetate (DMPA-IM) have been linked to increased S/HIV acquisition in animal, clinical and in vitro models. Several plausible mechanisms could explain MPA-induced HIV-1 acquisition while those for the luteal phase are underexplored., Method of Study: Peripheral blood mononuclear cells (PBMCs) were treated with P4 and estrogen at concentrations mimicking the luteal phase, follicular phase or with levels of MPA mimicking peak serum levels in DMPA-IM users. Cells were infected with an R5-tropic infectious molecular clone and HIV-1 infection was measured. A role for the glucocorticoid receptor (GR) was investigated using the GR/PR antagonist RU486. CCR5 protein levels and activation status, assessed by levels of the activation marker CD69, were measured by flow cytometry after treatment in vitro and in PBMCs from naturally-cycling women or DMPA-IM users., Results: Both MPA and luteal phase hormones significantly increased HIV-1 infection in vitro. However, MPA but not luteal phase hormones increased the CD4+/CD8+ T cell ratio, CCR5 protein expression on CD4+ T cells and increased expression of the activation marker CD69. The GR is involved in MPA-induced, but not luteal phase hormone-induced increased HIV-1 infection. In DMPA-IM users, the frequency of CCR5-expressing CD3+ and CD8+ cells was higher than for women in the luteal phase., Conclusions: MPA increases HIV-1 infection in a manner different from that of luteal phase hormones, most likely involving the GR and at least in part changes in the frequency and/or expression of CCR5 and CD69., (© 2022 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Background: Cervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells., Methods: Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry., Results: Unlike the LNG implant or copper-IUD, DMPA-IM was associated with higher frequencies of cervical Th17-like cells within 1 month of initiation (P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and α4β7 (P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD (P = .0002) or LNG implant (P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non-Lactobacillus-dominant microbiome at baseline was associated with more Th17-like cells post-DMPA-IM (P = .03), although this did not influence barrier function., Conclusions: Our data suggest that DMPA-IM-driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity., Clinical Trials Registration: NCT02550067., Competing Interests: Potential conflicts of interest. J.-A. S. P. reports the following grants or contracts all paid to the author’s institution and unrelated to this work: Bill and Melinda Gates Foundation (BMGF) Vaginal Microbiome Research Consortium (VMRC) Planning Grant (Principal Investigator [PI]: Dr Jo-Ann Passmore. Co-PI: Dr Leila Mansoor; Co-Investigators: Nigel Garrett, Cheryl Baxter, Sinaye Ngcapu, Lenine Liebenberg, Aida Sivro, Brian Kullin, Anna Happel. US $512 088 for 12 months); European and Developing Countries Clinical Trials Partnership (EDCTP) RIA2020I (3297) for project entitled “GIFT for HIV Prevention” (Passmore, Co-PI: Masson (Burnett Institute, Australia); Co-Investigators: Suzanna Francis and Katharina Kranzer (The London School of Hygiene & Tropical Medicine, UK), Janneke van der Wijgert (University Medical Center, Netherlands), Tania Crucitti (Institute Pasteur Madegascar, Madagascar), David Anderson (Burnet Institute, Australia), Ayako Honda (Sophia University, Japan), Chido Dziva-Chikwari (The Organization for Public Health Interventions and Development, Zimbabwe), Katherine Gill (Desmond Tutu Health Foundation, South Africa) (Euro 3 508 462 for 36 months); BMGF Calestous Juma Scientific Leadership Award for project entitled “VMRC4Africa” (PI: Passmore. US $1 million over 5 years); and Medical Research Council Strategic Health Innovation Partnerships (South Africa), Genital inflammation test for females (GIFT) (PIs: Dr Jo-Ann Passmore and Dr Lindi Masson, ZAR 5 million per year for 4 years). J.-A. S. P. also reports a patent granted in 2022 with no payment made (Method for diagnosing an inflammatory condition in the female genital tract; PCT/IB2014/065740; EP3063542B1); and unpaid participation on a Data Safety Monitoring Board (DSMB) or Advisory Board for a phase 2 placebo-controlled randomized trial of LACTIN-V (Lactobacillus crispatus CTV-05) among women at high risk of HIV acquisition in Durban, South Africa (Chair DSMB; Cohen et al National Institute of Child Health and Human Development [NICHD] grant 1R01HD098978). R. H. reports grants or contracts unrelated to this work and paid to the author’s institution from the NICHD. H. J. reports support for attending meetings and/or travel from World Vaccine Congress. S. E. B. reports grants or contracts unrelated to this work from the National Institutes of Health (NIH R01 HD089831): Effects of Hormonal Contraceptives on Genital Immunity and HIV Susceptibility. B. P. B. reports support for attending meetings and/or travel (NIH R01HD089831). J. M. H. reports grants to institution unrelated to this work from the NIH, USAID, and BMGF; and employment (with stocks and stock options) with Gilead Sciences. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Problem: Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation., Methods: This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors., Results: Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines., Conclusion: We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response., (© 2022 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Background: Ulipristal acetate 30 mg became available as prescription-only emergency contraception in British Columbia, Canada, in September 2015, as an addition to over-the-counter levonorgestrel emergency contraception. In this study, we determined dispensing and practice use patterns for ulipristal acetate, as well as facilitators of and barriers to emergency contraception for physicians, pharmacists and patients in BC., Methods: In the quantitative component of this mixed-methods study, we examined ulipristal acetate use from September 2015 to December 2018 using a database that captures all outpatient prescription dispensations in BC (PharmaNet) and another capturing market sales numbers for all oral emergency contraception in BC (IQVIA). We analyzed the quantitative data descriptively. We conducted semistructured interviews from August to November 2019, exploring barriers and facilitators affecting the use of ulipristal acetate. We performed iterative qualitative data collection and thematic analysis guided by Michie's Theoretical Domains Framework., Results: Over the 3-year study period, 318 patients filled 368 prescriptions for ulipristal acetate. Use of this agent increased between 2015 and 2018. However, levonorgestrel use by sales (range 118 897-129 478 units/yr) was substantially higher than use of ulipristal acetate (range 128-389 units/yr). In the 39 interviews we conducted, from the perspectives of 12 patients, 12 community pharmacists, and 15 prescribers, we identified the following themes and respective theoretical domains as barriers to access: low awareness of ulipristal acetate (knowledge), beliefs and experiences related to shame and stigma (beliefs about consequences), and multiple health system barriers (reinforcement)., Interpretation: Use of ulipristal acetate in BC was low compared with use of levonorgestrel emergency contraception; lack of knowledge, beliefs about consequences and health system barriers may be important impediments to expanding use of ulipristal acetate. These findings illuminate potential factors to explain low use of this agent and point to the need for additional strategies to support implementation., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

The aim of this study was to investigate the effect of a one-rod levonorgestrel implant on the blood chemistry profile, including random blood glucose (RBG), haemoglobin (Hb), alanine transferase (ALT), aspartate transferase (AST), and the lipid profile, including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. This prospective cohort study was conducted at Raden Saleh Clinic, Jakarta, from 2010 to 2012. The implants were inserted subdermally in 30 patients. The subjects were evaluated every 6 month up to 2 years. Bivariate analysis using t-test or Wilcoxon signed rank test was performed for all variables. p < 0.05 was considered a significant value. The Hb, RBG, AST, and lipid profile levels were significantly different before and 6 months after one-rod implant insertion (p < 0.05). However, for 24 months, all of the parameters were still within normal limits and did not differ clinically. One-rod levonorgestrel implant insertion has a minimal effect on all blood chemistry profiles., (© 2021. The Author(s).)

Endometriosis is a common gynaecological pathology characterized by the presence of endometrial tissue outside the uterine cavity, and the most frequent locations of endometriosis are ovaries and posterior compartment of the pelvis. In this paper we report the case of a rare bilateral endometriosis location of posas muscle diagnosed and treated in a 25-year-old patient. This is the third case of psoas endometriosis location reported, but the first one successfully treated by hormone estrogen-progestogen treatment alone. Psoas endometriosis is a rare location and the medical management in first line can be an alternative to surgery and provide optimal patient relief., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Access to safe, effective, and affordable contraception is important for women's health and essential to mitigate maternal and fetal mortality rates. The progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) is a popular contraceptive choice with a low failure rate and convenient administration schedule., Aim: In this review, we compiled observational data from human cohorts that examine how DMPA influences the mucosal biology of the female genital tract (FGT) that are essential in maintaining vaginal health, including resident immune cells, pro-inflammatory cytokines, epithelial barrier function, and the vaginal microbiome MATERIALS AND METHODS: This review focused on the recent published literature published in 2019 and 2020., Results: Recent longitudinal studies show that DMPA use associates with an immunosuppressive phenotype, increase in CD4+CCR5+ T cells, and alterations to growth factors. In agreement with previous meta-analyses, DMPA use is associated with minimal effects of the composition of the vaginal microbiome. Cross-sectional studies associate a more pro-inflammatory relationship with DMPA, but these studies are confounded by inherent weaknesses of cross-sectional studies, including differences in study group sizes, behaviors, and other variables that may affect genital inflammation., Discussion & Conclusion: These recent results indicate that the interactions between DMPA and the vaginal mucosa are complex emphasizing the need for comprehensive longitudinal studies that take into consideration the measurement of multiple biological parameters., (© 2021 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Objective: To compare the effects of depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant, and copper intrauterine device (IUD) on mood and sexual function., Methods: At the Effective Care Research Unit in South Africa, women already randomized in the ECHO Trial to the three methods were asked to participate in this study. Participants were interviewed at 3 and 12 months after enrollment using the Beck Depression Inventory and Arizona Sexual Experiences Scale, and at 12 months using the WHO-5 Wellbeing Index and the Patient Global Impression scale., Results: A total of 605 women participated. There was little difference in depression at 3 months across the three study groups. Contrary to our hypothesis, at 12 months, depression was lowest among DMPA-IM users (16/167, 9.6%) and highest among IUD users (28/158, 17.7%) (p = 0.032). There was little difference in sexual function at any time-point. More women in the DMPA-IM group felt "very much better" on the PGI scale than in the IUD and LNG implant groups (p = 0.003)., Conclusion: Depression may be less likely with DMPA-IM than with the other methods 1 year after initiation. Major differences in sexual functioning are unlikely. Unhappiness related to not using DMPA-IM, the most popular method in our setting, may have skewed results., Trial Registration Number: PACTR201706001651380., (© 2021 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Azadirachta indica A. Juss. is an Indian medicinal plant with innumerable pharmacological properties. Studies have proven that the phytochemicals from neem possess remarkable contraceptive abilities with limited knowledge on its mechanism of action., Purpose: The present review aims to summarize the efficiency of A. indica treatment as a contraceptive., Methods: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used. Published scientific articles on antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient activities of A. indica were collected from reputed Journals from 1980 to 2020 using electronic databases. Specific keywords search was completed to collect numerous articles with unique experiment design and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles., Results: A total of 27 studies were considered for reviewing, which included key pharmacological investigations. In the beginning, authors evaluated a number of publications on the contraceptive properties of A. indica, in which it was revealed that most of the publications were made between 2005 and 2009. All the collected articles were categorised and reviewed as antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient. Authors also assessed studies based on the plant parts used for pharmacological evaluations including leaves, seeds, stem-bark, and flowers. The article was primarily divided into different sections based on the previous works of authors on phytochemistry and pharmacological review articles., Conclusion: Although A. indica is not reported with the complete alleviation of reproductive system in both male and female animal models, studies have proven its efficacy as a contraceptive. Extracts and phytochemicals from neem neither reduced the libido nor retarded the growth of secondary sexual characters, thus indicating only a temporary and reversible contraceptive activity. However, there is a dearth for clinical studies to prove the efficacy of A. indica as a herbal contraceptive., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Tigers (Panthera tigris spp.) are endangered in the wild; ensuring sustainable insurance populations requires careful planning within zoological collections. In captive situations, contraceptives are often used to control breeding and ensure genetically viable populations that contain manageable numbers of animals; reversible contraceptives are ideal because they offer flexibility for breeding management. Historically, synthetic progestins, such as melengestrol acetate implants, were used in female tigers, but these are associated with an increased risk of reproductive pathology and subsequent infertility. Recent management advice to ex-situ collections has been to transition to the use of gonadotropin-releasing hormone agonists, such as deslorelin acetate implants, which do not appear to have a similar risk of reproductive pathology but are associated with highly variable reversal times in exotic felids. Using data from 917 contraceptive records in female tigers captured by the Association of Zoos and Aquariums Reproductive Management Center and the European Association of Zoos and Aquaria Reproductive Management Group's joint Contraception Database and from supplementary surveys, this study reviews the changing use of contraceptives in captive female tigers. The aim was to describe the historical and current use of contraceptives and provide a comprehensive assessment on the use of deslorelin implants, including data on product protocols, efficacy, pathology, and reversibility. This study determined that current dose, frequency, reversibility, and anatomical placement sites of deslorelin implants are highly variable, indicating that specific, readily available, unified, evidence-based recommendations on the use of deslorelin would be useful for future contraceptive use in managed tiger populations., (© 2021 Wiley Periodicals LLC.)

Despite the existence of a variety of contraceptive products for women, as well as decades of research into the prevention and treatment of human immunodeficiency virus (HIV), there is still a globally unmet need for easily accessible, acceptable, and affordable products to protect women's sexual and reproductive health. Microarray patches (MAPs) are a novel platform being developed for the delivery of hormonal contraception and antiretroviral drugs. MAPs provide enhanced drug delivery to the systemic circulation via the transdermal route when compared to transdermal patches, oral and injectable formulations. These minimally invasive patches can be self-administered by the user, reducing the burden on health care personnel. Since MAPs represent needle-free drug delivery, no sharps waste is generated after application, thereby eliminating possible MAP reuse and risk of needle-stick injuries. This review discusses the administration of contraceptive and antiretroviral drugs using MAPs, their acceptability by end-users, and the future perspective of the field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To develop a bleeding-pattern prediction model to inform counselling on amount and regularity of bleeding after levonorgestrel-releasing intrauterine system (LNG-IUS) placement., Materials and Methods: Fixed-cluster and regression-tree models were developed using bleeding data pooled from two clinical trials of LNG-IUSs. Models were trained and cross-validated on LNG-IUS 12 data, then applied to LNG-IUS 20 and LNG-IUS 8 data. Three clusters were generated for the fixed-cluster model: predominantly amenorrhoea; predominantly spotting; and predominantly bleeding. A random-forest model predicted the future-bleeding cluster, then the probability of cycle regularity was calculated. In the regression-tree model, women were assigned by the model to less- or more-bleeding groups., Results: With LNG-IUS 12 ( n  = 1351) in the fixed-cluster model, 70.4% of women were correctly classified. The correct classification rates for LNG-IUS 20 ( n  = 216) and LNG-IUS 8 ( n  = 1300) were 72.2% and 69.0%. The probability distribution for cycle regularity showed regular and irregular bleeding were best separated with LNG-IUS 12 data, and less well with LNG-IUS 20 and LNG-IUS 8 data. In the regression-tree model there was high variability in the more- and less-bleeding group distributions with LNG-IUS 12 data., Conclusions: A fixed-cluster model predicted bleeding patterns better than a regression-tree model in women using LNG-IUS, yielding understandable, informative output.

This study aimed to evaluate the effect of a levonorgestrel-releasing intrauterine system (LNG-IUS) on the sexual function of women. Participants who had abnormal uterine bleeding (AUB) complaints with LNG-IUSs were included (study registration: Kanuni Sultan Suleyman Training and Research Hospital, 2018/10/34). The demographic data of all participants were recorded. The female sexual function index (FSFI) questionnaire was used to participants before the insertion of LNG-IUSs and 6 months after its insertion. FSFI scores were calculated at both timepoints and were compared. The total FSFI score after LNG-IUS insertion was significantly higher than the total FSFI score application ( p  < .001). The scores of the desire, arousal, lubrication, orgasm, satisfaction and pain categories significantly increased after LNG-IUS compared to those before LNG-IUS. As a result, the present study demonstrated that after LNG-IUS insertion, these women had higher FSFI scores.Impact Statement What is already known on this subject? There are many publications in the literature comparing the effects of LNG-IUSs, IUSs, OCs and other contraceptive methods on female sexuality. However, there are markedly few studies that compare sexual function before and after LNG-IUS insertion. What do the results of this study add? The total FSFI score after LNG-IUS insertion was significantly higher than the total FSFI score before the insertion ( p < .001). The scores of the desire, arousal, lubrication, orgasm, satisfaction and pain categories significantly increased after LNG-IUS insertion compared to those before the application. The number of participants with FSFI scores ≥26.5 before LNG-IUS insertion was 17 (12.5%), and this number increased to 71 (52.5%) after the application What are the implications of these findings for clinical practice and/or further research? This study contributes to the literature because there are few researches that compare sexual function before and after LNG-IUS insertion. As a result of our study, sexual dysfunction decreased after LNG-IUS, and the scores increased in all sub-groups together with the total FSFI scores.

Background: Although medroxyprogesterone acetate (MPA) is used commonly as a contraceptive in women and female non-human primates, its effects on social behavior remain unclear. This study examined whether MPA treatment and introduction of new adult males during the breeding season influence the social behaviors of group-housed adult female rhesus macaques., Methods: Subjects were 12 MPA-treated and 12 matched case-control females. Aggressive, affiliative, and sexual behaviors were measured., Results: MPA-treated females showed less affiliative and sexual behavior compared to matched controls during the breeding season. MPA treatment was associated with decreased aggression emitted toward and received from females during the breeding season., Conclusion: MPA treatment is associated with differences in social behavior of female rhesus macaques during the breeding season, when normal hormonal cycles are attenuated by the treatment, but there is no indication that MPA-treated females bring an additional risk for more aggression during the male introduction and breeding season., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Ex vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence., Methods: We measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA)., Results and Conclusions: There was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower., Implications: In ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Half of all pregnancies worldwide are unintended, and the rate is even higher in women aged ≤25 years. We sought to identify which method of contraception was the most effective option to prevent unintended pregnancy in young women and adolescents., Methods: Systematic searches, without language restrictions, were carried out of the PubMed, Embase, Lilacs and Cochrane databases from inception to July 2020. Abstracts and full-text articles of observational studies and randomised controlled trials comparing the use of multiple methods of long-acting reversible contraception (LARC) and short-acting reversible contraception (SARC) in young women and adolescents were screened and reviewed. Risk ratios (RRs) and mean differences with their 95% confidence interval (CI) were derived using a random-effects meta-analytical model. Meta-analyses provided pooled estimates for adverse events, continuation rates and efficacy of LARC methods in young women and adolescents. Nine of the 25 included studies compared LARC with SARC, and 16 compared LARC methods only., Results: At 12 months, young women had better adherence with LARC compared with SARC ( n  = 1606; RR 1.60; 95% CI 1.21, 2.12; I 2 = 88%), which suggests a better unintended pregnancy prevention outcome for young women. However, more young women chose SARC ( n  = 2835; RR 0.37; 95% CI 0.17, 0.80; I 2 = 99%). Pregnancy during LARC use was rare., Conclusion: LARC methods are the most efficacious in preventing pregnancy, and women should be informed of this if pregnancy prevention is their priority. The evidence, however, is of low quality., Prospero Registration Number: CRD42017055452.

Objective: To assess the safety of the levonorgestrel 52-mg intrauterine system (LNG-IUS) in women with a history of thrombosis or coagulopathy and to evaluate bleeding patterns., Methods: A retrospective chart review was conducted of 117 women attending a clinic between 2007 and 2019. Their sociodemographic characteristics, hematologic status, reasons for using LNG-IUS, duration of use, use of oral anticoagulants, complications, and bleeding patterns were analyzed., Results: Ninety-nine women had a history of thrombosis (71.7% in use of oral anticoagulants) and 18 had coagulopathies. No bleeding or any other complications occurred during placement of the LNG-IUS. Around two-thirds of the women reported amenorrhea or oligomenorrhea at 12, 24, and 54 months of follow-up, with no difference between the groups using the IUS for contraception or to treat heavy menstrual bleeding (HMB) (P=0.07), those with a history of thrombosis or coagulopathy (P=0.53), and users or non-users of oral anticoagulants (P=0.59)., Conclusion: The LNG-IUS is safe for women with hematologic disorders. It was associated with amenorrhea or oligomenorrhea in a large proportion of users up to 54 months of follow-up regardless of use of oral anticoagulants, reason for use of LNG-IUS (contraception or HMB), or history of coagulopathy or thrombosis., (© 2020 International Federation of Gynecology and Obstetrics.)

Background: Though long-acting reversible contraceptives (LARCs) are highly effective, have minimal side effects, require minimal follow-up, and are low cost, only 10% of contraceptives used in Ethiopia are LARCs. The reason for this low uptake is not understood at the country or regional level. Therefore, this study identified determinants of LARC utilization in Northwest Ethiopia., Methods: A facility-based unmatched case control study, using LARC users as cases and short- acting reversible contraception (SARC) users as controls, had been conducted at fourteen public health institutions in Northwest Ethiopia. A systematic random sampling technique was used to select participants with a 1:2 case to control ratio (n = 1167). Binary logistic regression analysis was used to identify determinants of LARC utilization among family planning service users., Results: Wealth status [AOR:1.87, 95%CI (1.08, 3.24)], history of abortion [AOR:2.69, 95%CI (1.41, 5.12)], limiting family size [AOR: 2.38, 95%CI (1.01, 5.62)], good knowledge about LARCs [AOR: 2.52, 95%CI (1.17, 5.41)], method convenience [AOR: 0.23, 95%CI (0.16, 0.34)], good availability of method [AOR:0.10 (0.05, 0.19)], less frequent visits to health facility [AOR:2.95, 95% CI(1.89, 4.62)], health care providers advice [AOR:10.69, 95%CI (3.27, 34.87)], partner approval [AOR:0.66, 95%CI (0.45, 0.97)], and favorable attitude towards LARCs [AOR:13.0, 95%CI (8.60, 19.72)] were significantly associated with LARC utilization., Conclusion: Professional support, favorable attitude towards LARC use, high economic status, history of abortion, advantage of less frequent visits, having good knowledge towards LARC and interest of limiting births were significantly associated with LARC Utilization. On the other hand, perceived method convenience, and contraception availability were inversely associated with it. Family planning education about the benefits of LARC should be done by health providers and media. Male involvement in the counselling and decision making about the advantage of using LARC may improve the negative influence of partners on LARC utilization. It is also recommended that, future qualitative research further explore perceptions of LARC use., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The contraceptive activity of synthetic progestins is mediated through three basic mechanisms: (a) An anti-gonadotrophic action leading to the inhibition of ovulation; (b) Changes in cervical mucus characteristics that inhibit sperm penetration and (c) desynchronization of the endometrial picture necessary for implantation., Areas Covered: Mechanisms involved in the progestin-induced endometrium desynchronization are individually reviewed for each of the routes of administration and, whenever possible, by individual members of the various families of synthetic progestin derivatives., Expert Opinion: For contraceptive purposes, progestins are today administered through several routes: orally, as injections, subdermally and via the vagina or the uterine cavity. Given this variety of modalities, their effects may differ, depending on the route of administration, concentration reached at the level of the endometrium and the duration of use. These are characterized by inactivation of the endometrium. Progestin-only contraception provides a safe and effective control of fertility regulation, although, they are associated with the problem of endometrial break through bleeding that may lead to discontinuation. Unfortunately, in spite of a major research effort over two decades, there is not, as yet, an established long-term intervention available to manage bleeding irregularities, making mandatory a deeper understanding of the mechanisms involved is required.

Objectives: To evaluate whether hormonal contraceptive use among cisgender women is associated with differences in pharmacokinetic (PK) parameters of a long-acting injectable formulation of the integrase strand transfer inhibitor, cabotegravir (CAB-LA)., Setting: This is a secondary analysis of 85 cisgender women enrolled in HPTN 077, a phase 2a multicenter study that enrolled HIV-uninfected, low-risk individuals in Malawi, Brazil, South Africa, and the United States., Methods: Participants received 4-week daily oral cabotegravir lead-in, followed by CAB-LA 800 mg injection every 12 weeks (cohort 1) or 600 mg every 8 weeks (after 4-week initial interval between injections, cohort 2), over 41 weeks. Participants were followed 52-76 weeks subsequent to final injection. Generalized estimating equations and linear regression were used to evaluate differences in CAB-LA PK parameters (peak concentration, trough concentration, area under the curve, apparent terminal half-life, and time to lower limit of quantification) and self-reported hormonal contraceptive stratified by type (oral, injectable, implants, and other), controlling for body mass index and cohort., Results: Compared to women reporting no hormonal contraception (n = 6), oral contraceptive use (n = 18) was associated with lower CAB-LA peak concentration but was not associated with differences in other PK parameters. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters., Conclusion: Although oral contraceptive use was associated with differences in CAB-LA peak concentration, no differences were observed in other PK parameters, suggesting that this association is not likely to be clinically significant. However, these data highlight the need for further research exploring potential drug-drug interactions between CAB-LA and hormonal contraceptives.

The classical steroid receptors (nuclear receptors), including those for progesterone (nPRs), are thoroughly characterized. The knowledge about so-called non-genomic effects, which are mediated by extra-nuclear initiated signals, has increased immensely the last decades. In a previous clinical study of endometrial hyperplasia, we observed that the antiproliferative progestin effect persisted after 3 months treatment with levonorgestrel (LNG) intrauterine system (IUS) even with a complete downregulation of nPRs. This raised the question of what other mechanisms than signaling through nPRs could explain such an observation. In the present study, RT-qPCR was employed to characterize mRNA expression for nPRs, membrane progesterone receptors (mPRs) and progesterone receptor membrane components (PGRMCs) in women (n = 42) with endometrial hyperplasia that received intrauterine low dose LNG for 6 months. At the end of this period endometrial tissue showed that nPRs were virtually completely downregulated (≈ 10 % of baseline) whereas the levels of remaining mPRs, subtype-α, -β and -γ were 76 %, 59 % and 73 % of baseline, respectively. PGRMC1 was downregulated to 15 % of baseline, in contrast to PGRMC2, which was upregulated to about 30 % above baseline. We used human cancer cells from uterine cervix (C-4I cells) as control. Progesterone caused a concentration-dependent antiproliferative effect but in several and separate studies, we were unable to detect nPRs (immunocytochemistry) in the C-4I cells. The use of RT-qPCR showed that nPRs were undetectable in C-4I cells, in contrast to mPRs and PGRMCs with a distinct mRNA expression. The present study suggests that mPRs and/or PGRMCs preserve the antiproliferative effect of LNG in the human endometrium and are responsible for the concentration-dependent antiproliferative effect of progesterone in C-4I cells., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The contraceptive effectiveness of intrauterine devices (IUDs) has been attributed in part to a foreign body reaction in the endometrium. We performed this study to better understand mechanisms of action of contraceptives of by studying their effects on endometrial and cervical transcriptomes. We collected endometrial and cervical biopsies from women using the levonorgestrel-releasing intrauterine system (LNG-IUS, n = 11), copper intrauterine device (cu-IUD, n = 13) or levonorgestrel-containing combined oral contraceptives (COC, n = 12), and from women not using contraceptives (control group, n = 11). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. In endometrial samples from cu-IUD users, there were no genes with statistically significant differential expression compared to controls. In LNG-IUS users, 2509 genes were differentially expressed and mapped predominantly onto immune and inflammatory pathways. The cervical samples showed no statistically significant differential gene expression compared to controls. Hormonal and copper IUDs have significantly different effects on the endometrial transcriptome, with the LNG-IUS transcriptome showing pronounced inflammation and immune activation compared to controls whereas the cu-IUD transcriptome was indistinguishable from luteal phase endometrium. These findings argue against a foreign body reaction as a common mechanism of action of IUDs.

Problem: Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T-cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net-En)., Method of Study: Peripheral blood mononuclear cells collected from women aged 18-34 years prior to, at steady state, and nadir concentrations after initiating DMPA (n = 30) or Net-En (n = 36) and from women initiating copper intrauterine device (CU-IUD; n = 32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T-cells expressing programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4)., Results: Compared to baseline, there were decreased numbers of CD4+CTLA4+ (P < .001) and CD8+CTLA4+ (P < .01) T-cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P = .781 and P = .463, respectively). In Net-En users, no differences in CD4+CTLA4+ T-cells at steady state (P = .087) and nadir concentrations (P = .217) were observed. DMPA users had fewer CD4+PD-1+ (P < .001) and CD8+PD-1+ (P < .001) T-cells at nadir concentrations. Number of CD4+PD-1+ and CD8+PD-1+ T-cells decreased at steady state concentration (P = .002 and P = .001, respectively) and at nadir concentrations after Net-En initiation (P < .001 and P < .001). In CU-IUD users, there were no changes in number of CD4+CTLA4+ (P = .426) and CD8+CTLA4+ (P = .169) and no changes in CD4+PD-1+ (P = .083) and CD8+PD-1+ (P = .936) compared to baseline., Conclusion: Activation of T-cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To characterize the role of steroid hormone and antihormone exposure on neurotrimin (NTM) expression in human leiomyoma and myometrial tissue and cells., Design: Laboratory study of placebo and ulipristal acetate (UPA)-treated patient tissue. In vitro assessment of immortalized myometrial and leiomyoma cell lines after hormone and antihormone exposure., Setting: Academic research center., Patient(s): Not applicable., Interventions(s): Exposure of leiomyoma cell lines to 17β-E 2 , medroxyprogesterone acetate (MPA), UPA, and fulvestrant., Main Outcome Measure(s): Messenger RNA expression quantified with the use of RNASeq analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels quantified by means of Western blot analysis. Immunohistochemistry (IHC) on placebo- and UPA-treated patient uterine tissue specimens., Result(s): Expression of NTM in human uterine leiomyoma specimens according to RNASeq was increased compared with myometrium (5.22 ± 0.57-fold), which was confirmed with the use of qRT-PCR (1.95 ± 0.05). Furthermore, NTM protein was elevated in leiomyoma tissue compared with matched myometrium (2.799 ± 0.575). IHC revealed increased staining intensity in leiomyoma surgical specimens compared with matched myometrium of placebo patients. Western blot analysis in immortalized leiomyoma cell lines demonstrated an up-regulation of NTM protein expression (2.4 ± 0.04). Treatment of leiomyoma cell lines with 17β-E 2 yielded a 1.98 ± 0.11-fold increase in NTM protein expression; however, treatment with fulvestrant showed no significant change compared with control. Leiomyoma cell lines demonstrated a 1.91 ± 0.97-fold increase in NTM protein expression after progesterone treatment. RNASeq analysis demonstrated a reduced expression in patient leiomyoma after UPA treatment (0.75 ± 0.14). Treatment of leiomyoma cells with UPA demonstrated a reduced total NTM protein amount (0.54 ± 0.31) in patients, which was confirmed with the use of IHC (UPA10 147.2 ± 9.40, UPA20 182.8 ± 8.98). In vitro studies with UPA treatment revealed a concentration-dependent effect that supported these findings., Conclusion(s): NTM, a neural cell adhesion molecule, is increased in leiomyoma compared with myometrium in patient tissue and in vitro models after estrogen and progesterone treatment. Down-regulation of expression occurs after UPA treatment, but not after fulvestrant exposure., Clinical Trial Registration Number: NCT00290251., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To determine whether users of the non-fundal levonorgestrel-releasing intrauterine system (LNG-IUS) present with unfavorable bleeding patterns more frequently than fundal LNG-IUS users., Methods: A prospective cohort was conducted from June, 2016 to January, 2018 involving women aged 18-45 years who wished to use the LNG-IUS as contraception and had no contraindications, endometrial polyps, submucosal myomas, irregular menstrual cycle, or anticoagulant use. Two study groups comprised women using fundal insertion and non-fundal insertion LNG-IUS. Bleeding was evaluated using a diary and pictogram chart., Results: Of the 92 women who participated in the study, those with non-fundal LNG-IUS insertion sustained bleeding at rates greater than 83% (31) in the first 3 months of use, and 58% (14) at 6 months, versus 51% (22) at 3 months and 33% (19) at 6 months in those with fundal insertion (P=0.002 at 3 months; P=0.037 at 6 months). Blood loss in the non-fundal LNG-IUS group was higher than in the fundal LNG-IUS group according to pictograms drawn by participants., Conclusion: Women with non-fundal LNG-IUS placement had a higher frequency of sustained bleeding and blood loss volume according to self-reported charts than those with fundal LNG-IUS placement., (© 2019 International Federation of Gynecology and Obstetrics.)

Objective: To evaluate calcium metabolism and bone mineral density (BMD) in new users of depot medroxyprogesterone acetate (DMPA) in the first year of use., Methods: This prospective, non-randomized study, conducted at the University of Campinas, São Paulo, Brazil, was carried out between February 2011 and February 2013. Women aged from 18 to 40 with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) <30 and with no known history of disease or medication use who chose to use DMPA were paired by age (±1 year) and BMI (±1) with women commencing the use of a copper intrauterine device (IUD). The primary outcomes were BMD measured by dual-energy X-ray absorptiometry and calcium metabolism markers; other variables were body composition and lifestyle habits. Repeated measures analysis of variance (ANOVA) and multiple regression analyses were used to evaluate associations., Results: Twenty-seven women using DMPA and 24 using IUD were evaluated, with a mean age of 29.7 years and 28.6 years, respectively. The DMPA group presented with a 3.6% (P<0.001) loss of lumbar spine BMD, a 2.1% (P=0.100) loss of femoral neck BMD and higher phosphorus (P=0.014) concentrations at 12 months compared to the IUD group. The decreases in BMD were associated with the use of DMPA, while total mass and coffee intake were found to be protective factors., Conclusion: Changes in calcium metabolism and a decrease in BMD were found in the DMPA group at 12 months., (© 2019 International Federation of Gynecology and Obstetrics.)

Objective: The aim of this proof of concept study was to determine the effect of depot medroxyprogesterone acetate on host and viral factors in HIV infected and uninfected women., Results: In this study, the gene expression levels for CCL5, CCR5 and CXCR4 was significantly higher in HIV positive women when compared to HIV negative women (p < 0.05). An upregulation of CCR5 and CXCR4 was evident in less than 20% of the HIV infected women and none of the HIV uninfected women. The mean fold change for CCL3 was much higher in HIV uninfected when compared to infected women with a borderline significance (p = 0.062). In HIV uninfected women, the mean fold change in CCL3, CCL4, and CCL5 gene expression was not statistically different between women on DMPA versus women not on hormonal contraception. The proportion of women with an upregulation of CCL4 and CCR5 was higher in HIV infected women on DMPA. There was no association between endogenous progesterone level and chemokines and the HIV-1 receptors. The gene expression levels in the chemokine receptors CCR5 and CXCR4 were significantly higher in the HIV infected women when compared to the women who remained HIV uninfected.

Background: Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease. These issues have been raised primarily with contraceptives containing estrogen., Objectives: To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight., Search Methods: In April 2014, we searched the computerized databases MEDLINE, POPLINE, CENTRAL, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. The initial search also included EMBASE., Selection Criteria: All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Comparisons could be a placebo, a non-hormonal contraceptive, or another hormonal contraceptive that differed in drug, dosage, or regimen. Interventions included at least three cycles. Outcomes included glucose and insulin measures., Data Collection and Analysis: We assessed all titles and abstracts identified during the literature searches. The data were extracted and entered into RevMan. We wrote to researchers for missing data. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated., Main Results: We found 31 trials that met the inclusion criteria. No new trials were eligible in 2014. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome. Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36). Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38). Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73). Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17β-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly., Authors' Conclusions: Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods. We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal)., (Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Analyzing ectocervical biopsy tissue from women before and after they initiated use of depot-medroxyprogesterone acetate (DMPA), we previously reported this progestin reduces levels of the cell-cell adhesion molecule (CCAM) desmoglein-1 and increases genital mucosal permeability. We likewise saw treating mice with 1.0 mg of DMPA reduced vaginal CCAM expression and increased genital pathogen susceptibility. Herein, we used dose-response studies to delimit DMPA doses and serum MPA levels in mice associated with impaired genital mucosal barrier function and enhanced susceptibility to low-dose herpes simplex virus type 2 (HSV-2) infection., Study Design: We compared genital CCAM expression, genital mucosal permeability, and susceptibility to genital inoculation with 10 3 plaque-forming units of HSV-2 among mice in estrus vs. after treatment with 0.01 mg, 0.1 mg, 0.3 mg, or 1.0 mg of DMPA., Results: Compared to mice in estrus, DMPA treatment in a dose-dependent fashion significantly reduced desmoglein 1α (Dsg1a) and desmocollin-1 (Dsc1) gene expression, reduced DSG1 protein levels, and increased genital mucosal permeability to a low molecular weight molecule. While no mice infected with HSV-2 in estrus died, we respectively saw 50% and 100% mortality in mice administered 0.1 mg or 0.3 mg of DMPA. At time of infection, mean serum MPA levels in mice administered the 0.1 mg or 0.3 mg doses were 3.8 nM and 13.0 nM respectively (values comparable to trough and peak MPA serum levels in women using DMPA)., Conclusions: Mice with pharmacologically relevant serum MPA concentrations display significant changes in genital CCAM expression, genital mucosal barrier function, and HSV-2 susceptibility., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Some studies suggest that use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase susceptibility to HIV infection. We aim to determine the influence that such an association could have had on the HIV epidemic in South Africa., Methods: We simulate the heterosexual adult HIV epidemic in South Africa using a compartmental model stratified by age, behavioural risk group, sex, male circumcision status and contraceptive use. We model two possible scenarios: (1) The "With Effect" scenario assumes that DMPA increases susceptibility to HIV infection by 1.20-fold (95% confidence interval 1.06 to 1.36) based on a combination of the results of a recent randomised controlled trial (ECHO trial) and a number of observational studies. (2) The "No Effect" scenario assumes that DMPA has no effect on HIV acquisition risk. We calculate the difference in HIV-related outcomes between the With Effect and No Effect scenarios to determine the potential impact that DMPA use could have had on the HIV epidemic., Results: A causal association between DMPA and HIV acquisition could have caused 430,000 (90% of model runs 160,000 to 960,000) excess HIV infections and 230,000 (90,000 to 470,000) AIDS deaths in South Africa from 1980 to 2017. These figures represent 4.3% (1.6% to 9.6%) and 6.9% (2.6% to 15.2%) of the total modelled estimates of HIV infections and AIDS deaths respectively in South Africa in that period. Of the additional infections, 36% (25% to 48%) would have occurred among men. If DMPA use continues at current levels, a potential causal association could cause an additional 130,000 (50,000 to 270,000) infections between 2018 and 2037. The excess infections would have required an additional 640,000 (190,000 to 1,660,000) years of ART from 1980 to 2017, and a further 2,870,000 (890,000 to 7,270,000) years of ART from 2018 to 2037., Conclusions: If there is a causal association between DMPA use and HIV risk, it could have substantially increased the scale of the HIV epidemic in South Africa, affecting not only the users of DMPA, but also their partners and the wider population. The magnitude of this potential effect demands careful data collection and a careful consideration of policy choices for contraception in settings with large HIV epidemics., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Voluntary control of fertility is of paramount importance to the modern society. But since the contraceptive methods available for women have their limitations such as urinary tract infections, allergies, cervical erosion and discomfort, a desperate need exists to develop safe methods. Vaginal contraceptives may be the answer to this problem, as these are the oldest ways of fertility regulation, practiced over the centuries. With minimal systemic involvement, these are also the safest. Natural substances blocking or impairing the sperm motility offer as valuable non-cytotoxic vaginal contraceptives. Antimicrobial peptides (AMPs) isolated from plants, animals and microorganisms are known to possess sperm immobilizing and spermicidal properties. Following this, in the quest for alternative means, we have cloned, over expressed and purified the recombinant sperm agglutinating factor (SAF) from Staphylococcus warneri, isolated from the cervix of a woman with unexplained infertility., Methods: Genomic library of Staphylococcus warneri was generated in Escherichia coli using pSMART vector and screened for sperm agglutinating factor (SAF). The insert in sperm agglutinating transformant was sequenced and was found to express ribonucleotide-diphosphate reductase-α sub unit. The ORF was sub-cloned in pET28a vector, expressed and purified. The effect of rSAF on motility, viability, morphology, Mg ++ -dependent ATPase activity and acrosome status of human sperms was analyzed in vitro and contraceptive efficacy was evaluated in vivo in female BALB/c mice., Results: The 80 kDa rSAF showed complete sperm agglutination, inhibited its Mg 2+ -ATPase activity, caused premature sperm acrosomal loss in vitro and mimicked the pattern in vivo showing 100% contraception in BALB/c mice resulting in prevention of pregnancy. The FITC labeled SAF was found to bind the entire surface of spermatozoa. Vaginal application and oral administration of rSAF to mice for 14 successive days did not demonstrate any significant change in vaginal cell morphology, organ weight and tissue histology of reproductive and non-reproductive organs and had no negative impact in the dermal and penile irritation tests., Conclusion: The Sperm Agglutinating Factor from Staphylococcus warneri, natural microflora of human cervix, showed extensive potential to be employed as a safe vaginal contraceptive.

Ebola virus disease (EVD) is caused by Ebola virus (EBOV) and characterized in humans by hemorrhagic fever with high fatality rates. Human-to-human EBOV transmission occurs by physical contact with infected body fluids, or indirectly by contaminated surfaces. Sexual transmission is a route of infection only recently documented despite isolating EBOV virus or genome in the semen since 1976. Data on dissemination of EBOV from survivors remain limited and EBOV pathogenesis in humans following sexual transmission is unknown. The in vitro antiviral efficacy of polyphenylene carboxymethylene (PPCM) against EBOV was investigated considering the limited countermeasures available to block infection through sexual intercourse. PPCM is a vaginal topical contraceptive microbicide shown to prevent sexual transmission of HIV, herpes virus, and bacterial infections in several different models. Here we demonstrate its antiviral activity against EBOV. No viral replication was detected in the presence of PPCM in cell culture, including vaginal epithelial (VK2/E6E7) cells. Specifically, PPCM reduced viral attachment to cells by interfering with EBOV glycoprotein, and possibly through binding the cell surface glycosaminoglycan heparan sulfate important in the infection process. EBOV-infected VK2/E6E7 cells were found to secrete type III interferon (IFN), suggesting activation of distinct PRRs or downstream signaling factors from those required for type I and II IFN. The addition of PPCM following cell infection prevented notably the increase of these inflammation markers. Therefore, PPCM could potentially be used as a topical microbicide to reduce transmission by EBOV-positive survivors during sexual intercourse., (Published by Elsevier B.V.)

Objective: To compare weight gain between women using etonogestrel implants and those using levonorgestrel implants 12 months after insertion., Methods: A multicenter prospective cohort study was performed on women recruited from family planning clinics between July 2016 and August 2017. The main study outcome was mean weight gain after 12 months of insertion of the implants., Results: The present study included 150 women (age range 18-45 years) using levonorgestrel implants and 167 women using etonogestrel implants. The women recruited had been using implants for less than 6 months; implants had been inserted 6-12 months after their last pregnancy. Participants were followed up until 12 months after insertion through telephone conversations. Baseline parameters were obtained from the clinic records and weight was measured within 6 weeks of the 12-month anniversary of insertion of the implants. Data were analyzed with SPSS version 23. Weight gain in the levonorgestrel group was significantly higher than in the etonogestrel group (3.16 ± 4.08 vs 0.77 ± 3.76, P = 0.013; relative risk 1.69, 95% confidence interval 1.46-1.96). There were no differences in the occurrence of menstrual irregularities and client satisfaction., Conclusion: Women using levonorgestrel implants were more likely to gain weight compared to those using etonogestrel implants after 12 months of insertion., (© 2019 International Federation of Gynecology and Obstetrics.)

We aimed to evaluate the reproductive performance of Nelore lactating cows submitted to a resynchronization 12 days after timed artificial insemination (TAI) with or without a long-acting progesterone (P4-LA) treatment. Nelore cows were submitted to a P4/oestradiol-based TAI protocol (D0 = insemination). On D12, cows in the control group (n = 184) received a new P4 intravaginal device (0.96 g), whereas cows in the P4-LA group (n = 192) received the P4 device and 75 mg P4-LA. Cows identified as non-pregnant (n = 120) by regression of corpus luteum using colour Doppler ultrasonography on D20 had the P4 device removed and received 500ug of sodium cloprostenol, 1 mg of oestradiol cypionate and 300 IU of eCG and were re-inseminated on D22. There was no difference (p > 0.10) in the pregnancy rate at D20, D30 and D60 after first TAI between the control (69%, 59.7% and 57%, respectively) and P4-LA (67%, 55.7%, and 55.2%, respectively) groups. Pregnancy losses were similar between both groups (p > 0.1). For cows submitted to the second TAI, the pre-ovulatory follicle size did not differ (p > 0.1), but the oestrous detection and pregnancy rates were greater (p < 0.05) in the P4-LA group (92.2% [59/64] and 60.9% [39/64], respectively) than in controls (75% [42/56] and 44.6% [25/56]). The cumulative pregnancy rate after two TAIs did not differ (p > 0.1) between control (73.3% [135/184]) and P4-LA (76% [146/192]) groups. The use of P4-LA at 12 days after TAI potentially increases the pregnancy rates for a new early resynchronization strategy associated with the Doppler imaging for pregnancy diagnosis and results in an alternative to perform two TAIs in 22 days in beef cows., (© 2019 Blackwell Verlag GmbH.)

Objective: To describe contraceptive knowledge and counseling practices of postpartum nurses., Methods: We surveyed postpartum nurses at the largest women's hospital in Rhode Island., Results: We distributed 117 anonymous questionnaires and received 58 responses (response rate=50%). Twenty-three of 51 nurses (45%) reported routinely offering contraceptive advice to new mothers. Only 5/55 (9%) responded correctly that combined hormonal contraceptives were an "unacceptable health risk" in the immediate postpartum period. A minority of respondents correctly classified the progestin-only pill, depot medroxyprogesterone acetate, the etonogestrel implant, the levonorgestrel intrauterine system and the copper intrauterine device as safe to use during lactation [14/56 (25%), 24/56 (43%), 27/56 (48%), 19/55 (35%) and 9/55 (16%), respectively]. Thirty-three of 51 nurses (65%) incorrectly responded that depot medroxyprogesterone acetate decreases milk supply if started immediately postpartum., Conclusion: There are opportunities to improve knowledge regarding contraceptive safety and impact on lactation among postpartum nurses at our institution., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To estimate the proportion of women for whom use of hormonal contraception was associated with reporting a decreased breast milk supply., Study Design: The Lactational Effects of Contraceptive Hormones: an Evaluation ("LECHE") Study was an anonymous, internet-based, exploratory, cross-sectional survey of postpartum women using approximately 70 questions. Women were eligible to participate in the survey if they were 18 years or older, had a singleton infant between 3 and 9 months of age, had breastfed this infant for any amount of time and could read English. The survey included questions about breastfeeding, reproductive health, demographic characteristics and the timing of postpartum events., Results: A total of 3971 participants clicked on the survey. Our final study population included 2922 participants. Overall, 1201 (41%) reported having had milk supply concerns at some point in the first 12 weeks postpartum. The median time from birth until milk supply concerns was 3 weeks (IQR 1-7). Eight hundred fifty-two women (29%) started hormonal contraception in the first 12 weeks postpartum. Fifteen percent (127/852) of women reported new or additional milk supply concerns after starting hormonal contraception. Reported milk supply concerns were higher for women who used hormonal contraception than those who did not (44% vs. 40%; p=.05) Adjusted hazard ratios (HRs) assessing the association between contraceptive use and time to milk supply concerns were not statistically significant (HR 1.18, 95% confidence interval 0.94-1.47 for any type of hormonal contraception)., Conclusions: This study found a slightly increased proportion of reported milk supply concerns among women who started hormonal contraception., Implications: It is important for caregivers in the postpartum period to recognize the potential for multiple factors, including initiation of hormonal contraception, to affect breastfeeding. Patient-centered counseling can help elicit women's values and preferences regarding breastfeeding and pregnancy prevention., (Copyright © 2019. Published by Elsevier Inc.)

Background: Progestin contraception has been linked to higher risk of female to male sexual HIV transmission., Setting: A clinical trial among HIV-infected women in Lilongwe, Malawi, randomized to initiation of depomedroxyprogesterone acetate injectable or levonorgestrel implant, and followed for up to 33 months, with the outcome of HIV shedding in the genital tract., Methods: We compared the frequency and magnitude of HIV genital shedding before and after initiation of contraception and between study arms among women receiving antiretroviral therapy (ART). Genital HIV RNA was measured in TearFlo Strips using the Abbott RealTime HIV-1 assay., Results: Among 68 HIV-infected Malawian women on ART, randomization to depot medroxyprogesterone acetate compared with the levonorgestrel implant was not associated with genital shedding and neither progestin contraceptive was associated with increased HIV genital shedding, for up to 33 months after contraceptive initiation. Having detectable plasma HIV [adjusted risk ratio (RR) 10.5; 95% confidence interval (CI): 3.18 to 34.7] and detectable genital shedding before contraceptive initiation (adjusted RR 3.53; 95% CI: 1.31 to 9.47) were associated with a higher risk of detectable genital shedding after contraceptive initiation. Higher plasma efavirenz concentrations were associated with a lower risk of detectable genital shedding (adjusted RR 0.85; 95% CI: 0.73 to 0.99, per increase of 1000 ng/mL)., Conclusion: Among HIV-infected women receiving ART, our results provide evidence that progestin contraception does not impact women's risk of transmission of HIV to partners. Our finding that detectable genital shedding before contraceptive initiation independently predicts shedding suggests that there may be other individual-level biological or behavioral factors that increase the risk for shedding.