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Observational and laboratory studies suggest that some hormonal contraceptive methods, particularly intramuscular depot medroxyprogesterone acetate (DMPA-IM), might increase women's susceptibility to HIV acquisition. We aimed to compare DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant among African women seeking effective contraception and living in areas of high HIV incidence. We did a randomised, multicentre, open-label trial across 12 research sites in eSwatini, Kenya, South Africa, and Zambia. We included HIV-seronegative women aged 16–35 years who were seeking effective contraception, had no medical contraindications to the trial contraceptive methods, agreed to use the assigned method for 18 months, and reported not using injectable, intrauterine, or implantable contraception for the previous 6 months. Participants were randomly assigned (1:1:1) to receive an injection of 150 mg/mL DMPA-IM every 3 months, a copper IUD, or a LNG implant with random block sizes between 15 and 30, stratified by site. Participants were assigned using an online randomisation system, which was accessed for each randomisation by study staff at each site. The primary endpoint was incident HIV infection in the modified intention-to-treat population, including all randomised participants who were HIV negative at enrolment and who contributed at least one HIV test. The primary safety endpoint was any serious adverse event or any adverse event resulting in method discontinuation, until the trial exit visit at 18 months and was assessed in all enrolled and randomly assigned women. This study is registered with ClinicalTrials.gov, number NCT02550067. Between Dec 14, 2015, and Sept 12, 2017, 7830 women were enrolled and 7829 were randomly assigned to the DMPA-IM group (n=2609), the copper IUD group (n=2607), or the LNG implant group (n=2613). 7715 (99%) participants were included in the modified intention-to-treat population (2556 in the DMPA-IM group, 2571 in the copper IUD group, and 2588 in the LNG implant group), and women used their assigned method for 9567 (92%) of 10 409 woman-years of follow-up time. 397 HIV infections occurred (incidence 3·81 per 100 woman-years [95% CI 3·45–4·21]): 143 (36%; 4·19 per 100 woman-years [3·54–4·94]) in the DMPA-IM group, 138 (35%: 3·94 per 100 woman-years [3·31–4·66]) in the copper IUD group, and 116 (29%; 3·31 per 100 woman-years [2·74–3·98]) in the LNG implant group. In the modified intention-to-treat analysis, the hazard ratios for HIV acquisition were 1·04 (96% CI 0·82–1·33, p=0·72) for DMPA-IM compared with copper IUD, 1·23 (0·95–1·59, p=0·097) for DMPA-IM compared with LNG implant, and 1·18 (0·91–1·53, p=0·19) for copper IUD compared with LNG implant. 12 women died during the study: six in the DMPA-IM group, five in the copper IUD group, and one in the LNG implant group. Serious adverse events occurred in 49 (2%) of 2609 participants in the DMPA-IM group, 92 (4%) of 2607 participants in the copper IUD group, and 78 (3%) of 2613 participants in the LNG implant group. Adverse events resulting in discontinuation of the randomly assigned method occurred in 109 (4%) women in the DMPA-IM group, 218 (8%) women in the copper IUD group, and 226 (9%) women in the LNG implant group (p<0·0001 for DMPA-IM vs copper IUD and for DMPA-IM vs LNG implant). 255 pregnancies occurred: 61 (24%) in the DMPA-IM group, 116 (45%) in the copper IUD group, and 78 (31%) in the LNG implant group. 181 (71%) pregnancies occurred after discontinuation of randomly assigned method. We did not find a substantial difference in HIV risk among the methods evaluated, and all methods were safe and highly effective. HIV incidence was high in this population of women seeking pregnancy prevention, emphasising the need for integration of HIV prevention within contraceptive services for African women. These results support continued and increased access to these three contraceptive methods. Bill & Melinda Gates Foundation, US Agency for International Development and the President's Emergency Plan for AIDS Relief, Swedish International Development Cooperation Agency, South African Medical Research Council, and UN Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development.

AbstractObjectiveTo assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy.DesignTwo nested case-control studies.SettingUK general practices contributing to the QResearch or Clinical Practice Research Datalink (CPRD) databases, and linked to hospital, mortality, and social deprivation data.Participants80 396 women aged 40-79 with a primary diagnosis of venous thromboembolism between 1998 and 2017, matched by age, general practice, and index date to 391 494 female controls.Main outcome measuresVenous thromboembolism recorded on general practice, mortality, or hospital records. Odds ratios were adjusted for demographics, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs.ResultsOverall, 5795 (7.2%) women who had venous thromboembolism and 21 670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Of these two groups, 4915 (85%)and 16 938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64), for both oestrogen only preparations (1.40, 1.32 to 1.48) and combined preparations (1.73, 1.65 to 1.81). Estradiolhad a lower risk than conjugated equine oestrogen for oestrogen only preparations (0.85, 0.76 to 0.95) and combined preparations (0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate had the highest risk (2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted odds ratio 0.93, 95% confidence interval 0.87 to 1.01).ConclusionsIn the present study, transdermal treatment was the safest type of hormone replacement therapy when risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.

Background In acute exacerbation periods of chronic obstructive pulmonary disease (COPD), patients may experience hypoxemia or hypercapnia. Noninvasive ventilation (NIV) and respiratory stimulant drugs are used to treat this condition. Medroxyprogesterone acetate (MPA) can cross the blood-brain barrier and cause breathing stimulation and hyperventilation. This study was conducted to investigate the effectiveness of MPA in hypercapnic exacerbated COPD patients and the possibility of faster weaning of patients from NIV. Materials and methods This double-blind clinical trial was conducted on consecutive exacerbated COD patients referred to Shahid Rahnemoun Hospital, Yazd, Iran, from February 2022 to August 2022. Through a block randomized sampling method with a 1:1 allocation ratio, 58 eligible patients with hypercapnic exacerbated COPD on NIV were divided into two study groups: the intervention (treated with MPA 10 mg every 8 h) and the control (treated with placebo). The clinical and arterial blood gas (ABG) parameters were investigated in both groups. Results Out of 50 patients, 27 and 23 intervention and control arms cases were analyzed. Although there was a significant difference in the amount of ABG parameters during the study in each group, there was no statistically significant difference between the two groups. Also, There was no significant difference in the total weaning rate of the patients in the two groups. Despite the higher number of early weaning in the MPA group, no significant difference was reported between the two groups in this regard. In addition, there was no difference between the two groups in the rate of ICU hospitalization, the length of stay of hospitalization and ICU, and the mortality rate. Conclusion The administration of MPA has not improved clinical and laboratory results, and MPA is not superior to placebo in the weaning process of patients undergoing NIV. Trial registration IRCT20190810044500N21 (01/02/2022), (https//irct.behdasht.gov.ir/user/trial/59402/view)

AbstractObjectivesTo evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain.DesignThe PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial.Setting34 UK hospitals.Participants405 women of reproductive age undergoing conservative surgery for endometriosis.InterventionsParticipants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill.Main outcome measuresThe primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment).Results405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference −0.8, 95% confidence interval −5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00).ConclusionsPostoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some.Trial registrationISRCTN registry ISRCTN97865475.

ObjectivesTo evaluate the cost-effectiveness of long-acting progestogens (LAP), including levonorgestrel-releasing intrauterine system (LNG-IUS) and depot-medroxyprogesterone acetate (DMPA), compared with the combined oral contraceptives pill (COCP) in preventing recurrence of endometriosis-related pain postsurgery.DesignWithin-trial economic evaluation alongside a multicentre, pragmatic, parallel-group, open-label, randomised controlled trial (Preventing Recurrence of Endometriosis by means of Long-Acting Progestogen Therapy trial).SettingThirty-four UK hospitals recruiting participants from November 2015 to March 2019.PatientsFour hundred and five women aged 16–45 years undergoing conservative endometriosis surgery.InterventionsThe ratio of 1:1 randomisation to receive LAPs (LNG-IUS or DMPA) or COCP.Main outcome measuresThe primary evaluation was a cost-utility analysis based on cost per quality-adjusted life-year (QALY) gained at 3 years. We adopted a UK National Health Service perspective. Secondary analyses in the form of cost-effectiveness analysis based on a range of outcomes were also undertaken.ResultsFor the primary analysis, the COCP group incurred an additional cost of £533 (95% CI £52 to £983) per woman compared with LAPs. Treatment with COCP generated additional QALYs of 0.031 (95% CI −0.079 to 0.139) compared with the LAP group over 36-month follow-up. The incremental cost-effectiveness ratio for COCP compared with LAPs is therefore approximately £17 193 per QALY. The probabilistic sensitivity analysis suggested that there was a 54.7% probability that COCP would be cost-effective at the £20 000/QALY threshold. The secondary analyses revealed results more in favour of LAPs.ConclusionAlthough the COCP has a slightly higher probability of being cost-effective at £20 000/QALY threshold, there remains considerable uncertainty, with only marginal differences in outcomes between the two treatments. The lower rates of further surgery and second-line medical treatment for women allocated to LAPs may make this option preferable for some women.Trial registration numberISRCTN 97865475.

This report provides the final results of the Women's Health Initiative trial comparing estrogen plus progestin and placebo in postmenopausal women. For the primary end point of coronary heart disease, there was no protective effect of hormone therapy over a five-year period, and there was the possibility of an adverse effect, especially during the first year of the trial. Combined hormone therapy cannot be recommended for the purpose of preventing coronary heart disease. The final results of the Women's Health Initiative trial show no protective effect. Our understanding of the effect of postmenopausal hormone therapy on the risk of coronary heart disease (CHD) has recently undergone a major change. Although previous observational studies had suggested that postmenopausal hormone therapy was associated with a reduction of 40 to 50 percent in the risk of CHD, 1 , 2 recent randomized clinical trials have provided no evidence of cardiac protection and even some evidence of harm with postmenopausal hormone therapy. 3 – 8 The primary findings of the Estrogen plus Progestin trial of the Women's Health Initiative (WHI) suggested an overall increase in the risk of CHD (hazard ratio, 1.29) among women . . .

Contraceptive use has complex effects on sexual behaviour and mood, including those related to reduced concerns about unintended pregnancy, direct hormonal effects and effects on endogenous sex hormones. We set out to obtain robust evidence on the relative effects of three contraceptive methods on sex behaviours, which is important for guiding contraceptive choice and future contraceptive developments. This is a secondary analysis of data from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial in which 7,829 HIV-uninfected women from 12 sites in Eswatini, Kenya, South Africa and Zambia seeking contraception were randomly assigned to intramuscular depot-medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. Data collected for 12 to 18 months using 3-monthly behavioural questionnaires that relied on recall from the preceding 3 months, were used to estimate relative risk of post-baseline sex behaviours, as well as sexual desire and menstrual bleeding between randomized groups using modified Poisson regression. We observed small but generally consistent effects wherein DMPA-IM users reported lower prevalence of specified high risk sexual behaviours than implant users than Cu-IUD users (the '>' and '<' symbols indicate statistically significant differences): multiple sex partners 3.6% < 4.8% < 6.2% respectively; new sex partner 3.0% < 4.0% <5.3%; coital acts 16.45, 16.65, 17.12 (DMPA-IM < Cu-IUD); unprotected sex 65% < 68%, 70%; unprotected sex past 7 days 33% <36%, 37%; sex during vaginal bleeding 7.1%, 7.1% < 8.9%; no sex acts 4.1%, 3.8%, 3.4% (DMPA-IM > Cu-IUD); partner has sex with others 10% < 11%, 11%. The one exception was having any sex partner 96.5%, 96.9% < 97.4% (DMPA-IM < Cu-IUD). Decrease in sexual desire was reported by 1.6% > 1.1% >0.5%; amenorrhoea by 49% > 41% >12% and regular menstrual pattern by 26% <35% < 87% respectively. These findings suggest that women assigned to DMPA-IM may have a modest decrease in libido and sexual activity relative to the implant, and the implant relative to the Cu-IUD. We found more menstrual disturbance with DMPA-IM than with the implant (and as expected, both more than the Cu-IUD). These findings are important for informing the contraceptive choices of women and policymakers and highlight the need for robust comparison of the effects of other contraceptive methods as well.

This study explores the therapeutic effects of combining clindamycin phosphate tablets (CPT) with medroxyprogesterone acetate tablets (MAT) in treating endometritis. A total of 80 patients with endometritis, admitted between March 2021 and March 2024, were randomly divided into two groups: the control group (n=40) received CPT alone at a dosage of 0.3g per administration, 3 times daily; the observation group (n=40) received CPT (same dosage as control group) plus MAT at 6mg per administration, 3 times daily. Both groups continued treatment for 14 days. The observation group demonstrated a significantly higher treatment efficacy (92.50% vs. 75.00%) and better menstrual recovery. Clinical symptoms, such as pelvic pain and abnormal vaginal secretions, resolved more quickly in the observation group. Additionally, inflammatory markers IL-4, TNF-α, MMP-2, and MMP-9 decreased significantly post-treatment, while TGF-β1 increased and VCAM-1 decreased, indicating improved endometrial repair. No severe adverse reactions were observed. These findings suggest that the combination of CPT and MAT is more effective than CPT alone in alleviating symptoms, reducing inflammation, and promoting menstrual normalization in patients with endometritis Cette étude explore les effets thérapeutiques de l’association de comprimés de phosphate de clindamycine (CPT) et de comprimés d’acétate de médroxyprogestérone (MAT) dans le traitement de l’endométrite. Au total, 80 patientes atteintes d’endométrite, admises entre mars 2021 et mars 2024, ont été réparties aléatoirement en deux groupes : le groupe témoin (n = 40) a reçu du CPT seul à la dose de 0,3 g par administration, 3 fois par jour ; le groupe d’observation (n = 40) a reçu du CPT (même dosage que le groupe témoin) plus MAT à la dose de 6 mg par administration, 3 fois par jour. Les deux groupes ont poursuivi le traitement pendant 14 jours. Le groupe d’observation a démontré une efficacité thérapeutique significativement supérieure (92,50 % contre 75,00 %) et une meilleure récupération menstruelle. Les symptômes cliniques, tels que les douleurs pelviennes et les sécrétions vaginales anormales, ont disparu plus rapidement dans le groupe d’observation. De plus, les marqueurs inflammatoires IL-4, TNF-α, MMP-2 et MMP-9 ont diminué significativement après le traitement, tandis que TGF-β1 a augmenté et VCAM-1 a diminué, indiquant une amélioration de la réparation endométriale. Aucun effet indésirable grave n’a été observé. Ces résultats suggèrent que l’association CPT et MAT est plus efficace que la CPT seule pour soulager les symptômes, réduire l’inflammation et favoriser la normalisation menstruelle chez les patientes atteintes d’endométrite.

Injectable depot medroxyprogesterone acetate (DMPA) is one of the most popular contraception methods in areas of high HIV seroprevalence. Evidence is accumulating that use of DMPA might be associated with an increased risk of HIV-1 acquisition by women; however, mechanisms of this association are not completely understood. The goal of this study was to gain insight into mechanisms underlying the possible link between use of DMPA and risk of HIV-1 acquisition, exploring transcription profiling of ectocervical tissues. Healthy women received either DMPA (n = 31) or combined oral contraceptive (COC), which has not been linked to an increased risk of HIV acquisition (n = 32). We conducted a comparative microarray-based whole-genome transcriptome profiling of human ectocervical tissues before and after 6 weeks of hormonal contraception use. The analysis identified that expression of 235 and 76 genes was significantly altered after DMPA and COC use, respectively. The most striking effect of DMPA, but not COC, was significantly altered expression (mostly downregulation) of many genes strategically involved in the maintenance of mucosal barrier function; the alterations, as indicated by Ingenuity Pathway Analysis (IPA), were most likely due to the DMPA-induced estrogen deficiency. Furthermore, IPA predicted that transcriptome alterations related to ectocervical immune responses were in general compatible with an immunosuppressive effect of DMPA, but, in some women, also with an inflammatory-like response. Our results suggest that impairment of cervicovaginal mucosal integrity in response to DMPA administration is an important mechanism contributing to the potential increased risk of HIV-1 acquisition in DMPA users. ClinicalTrials.gov NCT01421368. This study was supported by the United States Agency for International Development (USAID) under Cooperative Agreement GPO-A-00-08-00005-00.

Hormonal treatment is the preferred initial systemic therapy for patients with advanced or recurrent G1 or G2 endometrial cancer (EC) in terms of efficacy, toxicity, and economy. Few reports are available on the topic and we, therefore, conducted a retrospective study. Patients with EC who received high-dose medroxyprogesterone (MPA) at our Hospital between January 2010 and December 2022 were reviewed. Patients who were treated for fertility preservation or had a history of systemic chemotherapy other than adjuvant therapy were excluded. Sixteen patients who were eligible for study inclusion had recurrent G1 or G2 EC. Their median age was 65 years (range=51-82 years), median body mass index was 22.6 kg/m (range=15.3-43.2 kg/m ), and all patients had an ECOG Performance Status of 0. All patients received 200 mg/day of MPA, and eight patients concomitantly received 100 mg/day of aspirin. None of the patients experienced severe adverse events. One patient had grade 2 deep vein thrombosis. Two patients discontinued MPA treatment because of adverse events. The response rate was 44% [95% confidence interval (CI)=20-68%] and median progression-free survival (PFS) was 6.9 months (95% CI=7.5-26 months). Four of 16 patients had PFS longer than 12 months, all of whom had positive tissue estrogen receptor (ER) and progesterone receptor (PR), and PFS at 2 years was 35% (95% CI=10.2-59.8%). Hormone therapy is effective long-term in ER- and PR-positive EC and can be recommended as initial systemic therapy. Toxicity is mild and manageable.