Study on Effects of Medroxyprogesterone Acetate on Serological Parameters, Ultrasonographic and Histopathological Profile of Uterine Endometrial Morphology in Female Rabbits

Background: Rabbits are small mammals from the family Leporidae. Rapid multiplication profile of the rabbits often necessitates contraceptive controls in which ovario-hysterectomy is the only recommended method worldwide but still rabbit owners avoid surgical manipulation and opt for the contraceptive injections but contraceptive injections are also known to cause undesired effects in different animal species. The present study was conducted to evaluate effects of Medroxyprogesterone acetate on liver enzymes, lipid profile, blood glucose and uterine endometrial morphology. Methods: The study was conducted on 20 breeding female rabbits at Pet Centre, University of Veterinary and Animal Sciences, Lahore, Pakistan. The study animals were divided into two groups, A and B having 10 rabbits each. Group A was treated with single dose of Medroxyprogesterone acetate (10 mg/kg IM). While group B was kept as control and was given a single dose of 0.9% normal saline placebo injection. Pre and post treatment serum sampling was performed on days 0, 7, 14, 21, 28, 35, 42 and histopathological evaluation of reproductive tract (mainly uterus) was conducted at the end of study. Result: Serological parameters i.e. liver profile, lipid profile and blood glucose level (random) were significantly increased after treatment along with congestion, engorgement of blood vessels, degeneration, hyperplasia of uterine epithelium and uterine glands in Treatment group in contrast to control group. On the basis of this study it was concluded that Medroxyprogesterone acetate poses undesirable effect on the uterine endometrium and different serological parameters of body like liver enzymes (total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase), blood glucose, lipid profile (cholesterol, high density lipoprotein, low density lipoprotein, triglyceride).

Medroxyprogesterone acetate inhibits wound closure of human endometrial epithelial cells and stromal fibroblasts in vitro

Mucosal integrity in the endometrium is essential for immune protection. Since breaches or injury to the epithelial barrier exposes underlying tissue and is hypothesized to increase infection risk, we determined whether endogenous progesterone or three exogenous progestins (medroxyprogesterone acetate (MPA), norethindrone (NET), and levonorgestrel (LNG)) used by women as contraceptives interfere with wound closure of endometrial epithelial cells and fibroblasts in vitro. Progesterone and LNG had no inhibitory effect on wound closure by either epithelial cells or fibroblasts. MPA significantly impaired wound closure in both cell types and delayed the reestablishment of transepithelial resistance by epithelial cells. In contrast to MPA, NET selectively decreased wound closure by stromal fibroblasts but not epithelial cells. Following epithelial injury, MPA but not LNG or NET, blocked the injury-induced upregulation of HBD2, a broad-spectrum antimicrobial implicated in wound healing, but had no effect on the secretion of RANTES, CCL20 and SDF-1α. This study demonstrates that, unlike progesterone and LNG, MPA and NET may interfere with wound closure following injury in the endometrium, potentially conferring a higher risk of pathogen transmission. Our findings highlight the importance of evaluating progestins for their impact on wound repair at mucosal surfaces.

A protocol for a scoping review of implementation strategies to scale up self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception v1

Self-administration of depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is effective, safe and registered in many countries. It shows great potential to improve contraceptive access, continuation, and autonomy, including in low-income and middle-income countries. However, there are challenges to roll out this new efficacious intervention, and major implementation issues have been encountered for scale-up. This study aims to describe the implementation strategies to scale up self-administered DMPA-SC programs, the barriers, and facilitators to these programs, and the outcome of the implementation strategy used.

The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion

The association between the use of the injectable contraceptive depot medroxyprogesterone acetate and HIV-1 susceptibility has been addressed mainly in respect to the changes occurring in the female genital mucosa and blood. However, one of the main sites of HIV-1 pathogenesis is lymphoid organs. To investigate the immunoregulatory effect of medroxyprogesterone acetate (MPA) at this site, human tonsillar tissue explants were infected ex vivo with either a CCR5 (BaL) or CXCR4 (LAI) HIV-1 variant and the release of p24gag and cytokines was measured in culture supernatant. The response to MPA was compared with that elicited by treatment with progesterone (P4) and dexamethasone (DEX), which selectively binds the glucocorticoid receptor, in donor-matched explant cultures. MPA treatment reduced the replication of both tested HIV-1 strains as well as the production of the mediators of inflammation IL-1β, IL-17A and CCL5, but not CCL20, in a similar way to DEX, whereas P4 had no effect on HIV-1 replication. The magnitude of both MPA and DEX-mediated responses was proportional to the length of exposure and/or administered dose. Blockage of the progesterone and glucocorticoid receptors with mifepristone abolished all observed changes in HIV-1 and cytokine production, and was associated with increased IL-22 levels in HIV-infected explants. Our data indicate that elevated doses of MPA may affect the immune responses in lymphoid tissue in a glucocorticoid-like fashion with an immediate impact on local HIV-1 replication.

The Association Between Immediate Postpartum Depot Medroxyprogesterone Acetate Use and Postpartum Depressive Symptoms

Objective While postpartum depot medroxyprogesterone acetate (DMPA) is a highly effective form of contraception, some data suggest an association with depressive symptoms. Our objective was to evaluate the relationship between receipt of DMPA in the immediate postpartum period and postpartum depressive symptoms. Methods This retrospective cohort study included all women who received prenatal and postpartum care at academic obstetric clinics affiliated with a tertiary care institution between January 1, 2008 and December 31, 2014. All women were counseled on contraception prior to hospital discharge. DMPA was available in the hospital pharmacy, and its utilization was documented in the electronic health record. The Patient Health Questionnaire 9 (PHQ-9) was used to screen for postpartum depression for all women at all postpartum visits. A score of 10 or greater was categorized as positive. Bivariable and multivariable analyses were used to identify the association between immediate postpartum DMPA use and a positive postpartum depression screen. Results Of the 5,073 women who met inclusion criteria, 410 (8.1%) received DMPA prior to hospital discharge. Compared with women who did not receive DMPA, women who received DMPA prior to hospital discharge were younger, more likely to identify as Black race or Latinx ethnicity, and more likely to be publicly insured. Clinical characteristics also differed. Women who received DMPA were more likely to be obese and to have experienced prenatal depressive symptoms, been diagnosed with a hypertensive disorder of pregnancy, delivered preterm, and delivered vaginally. Receipt of immediate postpartum DMPA was not associated with having a positive screen for postpartum depression in bivariable (5.4 vs. 6.0%, p = 0.29) or multivariable (adjusted odds ratio 0.94, confidence interval 0.53–1.68) analyses. Conclusion Receipt of postpartum DMPA is not associated with a positive postpartum PHQ-9 screen. Concerns about precipitating postpartum depression should not preclude the utilization of DMPA as a contraceptive agent. Key Points

Self-administered subcutaneous medroxyprogesterone acetate for improving contraceptive outcomes: a systematic review and meta-analysis

Background Subcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of self-injection versus provider-administered subcutaneous depot medroxyprogesterone acetate for improving continuation of contraceptive use. Methods We searched for randomized controlled trials on November 1, 2020 in Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, Embase, Web of Science, Scopus, Open Grey, clinical trials registries, and reference lists of relevant studies. We did not impose any search restrictions. We included randomized trials comparing self- versus provider-administered subcutaneous depot medroxyprogesterone acetate. Two authors independently screened trials, extracted data, and assessed the risk of bias in the included studies. We used risk ratio and 95% confidence intervals for dichotomous outcomes. Results We identified 3 randomized trials (9 reports; 1264 participants). The risk of bias in the included studies was low except for performance bias and detection bias of participant-reported outcomes in unmasked trials. Self-administration, compared to provider-administration, increased continuation of contraceptive use (risk ratio 1.35; 95% confidence intervals 1.10–1.66); moderate-certainty evidence). Self-injection appears to be making more of an impact on continuation for younger women compared to women 25 years and older and on women living in low and middle income compared to high income countries. There was no subgroup difference by the type of care provider (community health worker vs. clinic-based provider). Conclusions Self-injection of subcutaneous depot medroxyprogesterone acetate probably improves continuation of contraceptive use. The effects on other outcomes remain uncertain because of the very low certainty of evidence.