Safety evaluation of medroxyprogesterone acetate: a pharmacovigilance analysis using FDA adverse event reporting system data DOI Creative Commons

Luyang Su,

Ren Xu,

Yanan Ren

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Дек. 11, 2024

Medroxyprogesterone acetate (MPA), a synthetic progestogen, is extensively used for the treatment of various conditions, including contraception, irregular menstruation, functional uterine bleeding, and endometriosis. However, like all pharmaceutical agents, MPA associated with adverse drug reactions. This study aimed to evaluate events (AEs) in by analyzing real-world data from U.S. Food Drug Administration's Adverse Event Reporting System (FAERS). By providing comprehensive assessment safety profile MPA, this seeks support informed clinical decision-making. Data covering period first quarter 2004 2024 were collected FAERS database. Disproportionality analyses conducted using several statistical methods, reporting odds ratio (ROR), proportional (PRR), empirical Bayesian geometric mean (EBGM). Additionally, time-to-onset (TTO) analysis was employed quantify signals MPA-associated AEs. A dataset comprising 21,035,995 AE reports compiled. Among these, 3,939 women reported as contraceptive method. The covered 27 system organ classes (SOCs) 25 high-frequency signals. Notably, significant AEs identified, some which not previously detailed medication's prescribing information. Unforeseen such unintended pregnancy (n = 623; ROR, 6.65; ROR025, 6.1; χ2, 2,482.38; PRR, 6.41; EBGM, 5.69; EBGM05, 5.29), bone pain 35; 13.78; 9.4; 311.2; 13.75; 10.59; 7.69), gait disturbance 34; 2.82; 1.99; 37.31; 2.88; 2.7; 2.02), dental caries 15; 23.16; 12.32; 204.26; 23.14; 15.23; 8.98), decrease blood pressure 3.88; 2.29; 29.35; 3.63; 2.33), osteonecrosis 9; 23.44; 10.36; 123.67; 23.43; 15.35; 7.75) identified that outlined information medication. Our findings align observations, highlighting emergence unreported their demographic TTO characteristics. Further pharmaco-epidemiological studies are required substantiate these observations.

Язык: Английский

Spatial transcriptomics unveils estrogen-modulated immune responses and structural alterations in the ectocervical mucosa of depot medroxyprogesterone acetate users DOI Creative Commons
Vilde Kaldhusdal, Mathias Franzén Boger, Annelie Tjernlund

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 6, 2025

Abstract The injectable contraceptive, depot medroxyprogesterone acetate (DMPA), is associated with compromised cervical mucosal barriers. High-resolution spatial transcriptomics applied here to reveal the localization of these altered molecular markers. Ectocervical tissue samples from Kenyan sex workers using DMPA, or non-hormonal contraceptives, underwent and gene set enrichment analyses. Integrated systemic estradiol levels bulk expression data a larger cohort enhanced study’s scope. Unsupervised clustering unveiled four epithelial seven submucosal layers, showcasing spatially restricted diverse functional responses, less structured ordering. DMPA mucosal-wide immunoglobulin upregulation, verified by CD20 + B-cell immunostaining, upregulated immune markers adjacent basal membrane. Downregulated genes represented disrupted barrier integrity extracellular matrix dysfunction. transcriptional profile was estrogen regulation. Collectively, our findings estrogen-modulated distinct ectocervical profiles usage. While upregulation occurs throughout mucosa, activation innate responses dysregulation are restricted. These results extend previous analyses provide insights into landscape influenced shedding light on contraceptive effects health implications.

Язык: Английский

Процитировано

0
Injectable Contraceptives Differentially Affect Select CD4+ HIV‐1 Target Cells in the Genital Tract but Not Systemically: Implications for HIV‐1 Acquisition DOI Creative Commons
Chanel Avenant, Alexis J. Bick, Johnson M. Moliki

и другие.

American Journal of Reproductive Immunology, Год журнала: 2025, Номер 93(5)

Опубликована: Май 1, 2025

ABSTRACT Problem Observational data suggest lower HIV susceptibility in women using the injectable contraceptive norethisterone enanthate (NET‐EN) versus intramuscular depo medroxyprogesterone acetate (DMPA‐IM). Clinical investigating effects of injectables on target cells are inconsistent or limited. No available from head‐to‐head randomized trials comparing DMPA‐IM and NET‐EN, nor at peak progestin concentrations. Method Study The women's health, contraception, (WHICH) trial to NET‐EN two South African sites (2018–2019). Cells blood cytobrushes one site, taken baseline 1 week post 24‐week injection (at levels), were analyzed by flow cytometry for select HIV‐1 (CD4 + expressing co‐receptors, an integrin and/or activation markers). Results Systemically, similarly reduced frequency number some CD4 expression cell surface markers. In contrast, female genital tract (FGT) results showed significantly different numbers between contraceptives most populations; tended increase, but decrease numbers. Excluding non‐study use revealed significant increases several FGT populations 25 weeks, within arm. Conclusions Both exert minimal systemic have differential FGT. changes investigated, particularly after exclusion use, that may increase acquisition compared use.

Язык: Английский

Процитировано

0
Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls DOI Creative Commons
Mélodie A. Nasr, Annette Aldous,

Jason Daniels

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(7), С. e0306237 - e0306237

Опубликована: Июль 15, 2024

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

Язык: Английский

Процитировано

2
Safety and effectiveness of seahorse extract (Hippocampus comes L.) on the hematological profile and body weight of male rats induced by depo medroxyprogesterone acetate DOI Creative Commons
Trisnawati Mundijo, Franciscus D. Suyatna, Agung Eru Wibowo

и другие.

Journal of Advanced Veterinary and Animal Research, Год журнала: 2024, Номер 11(3), С. 717 - 717

Опубликована: Янв. 1, 2024

The objective of this study was to investigate the effectiveness and safety seahorse

Язык: Английский

Процитировано

0
NET-EN treatment leads to delayed HSV-2 infection, enhanced mucin and T cell functions in the female genital tract when compared to DMPA in a preclinical mouse model DOI Creative Commons
M. Firoz Mian,

Sidney Pa,

Nuzhat Rahman

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 6, 2024

Depot-medroxyprogesterone acetate (DMPA) and Norethisterone Enanthate (NET-EN) are progestin-only injectable contraceptives widely used by women in sub-Sharan Africa, where incidence of HIV-1 HSV-2 infection remains high. Studies indicate that DMPA usage can increase the risk infection, but limited data no increased with use NET-EN. We therefore investigated effects NET-EN on susceptibility to vaginal ovariectomized (OVX) mice immune responses, particularly tract (VT). OVX mice, when treated infected intravaginally, had delayed genital pathology, decreased viral shedding, extended survival compared DMPA- or untreated mice. CD4+ T cells isolated from VT showed significant change frequency either contraceptive. However, significantly total number CD8+ IFN-γ producing CD4 CD8 percentage TNF-α In contrast, enhanced percentages frequencies IFN-γ+ Comparative analysis splenic lymphocytes indicated treatment resulted reduction cell frequency, TNF-α+ cells, as well CD4, spleen Importantly, we found reduced mucin production, whereas expression cell-associated VT. High levels were associated lower virus detected tract. This study provides first evidence delay DMPA.

Язык: Английский

Процитировано

0
Safety evaluation of medroxyprogesterone acetate: a pharmacovigilance analysis using FDA adverse event reporting system data DOI Creative Commons

Luyang Su,

Ren Xu,

Yanan Ren

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Дек. 11, 2024

Medroxyprogesterone acetate (MPA), a synthetic progestogen, is extensively used for the treatment of various conditions, including contraception, irregular menstruation, functional uterine bleeding, and endometriosis. However, like all pharmaceutical agents, MPA associated with adverse drug reactions. This study aimed to evaluate events (AEs) in by analyzing real-world data from U.S. Food Drug Administration's Adverse Event Reporting System (FAERS). By providing comprehensive assessment safety profile MPA, this seeks support informed clinical decision-making. Data covering period first quarter 2004 2024 were collected FAERS database. Disproportionality analyses conducted using several statistical methods, reporting odds ratio (ROR), proportional (PRR), empirical Bayesian geometric mean (EBGM). Additionally, time-to-onset (TTO) analysis was employed quantify signals MPA-associated AEs. A dataset comprising 21,035,995 AE reports compiled. Among these, 3,939 women reported as contraceptive method. The covered 27 system organ classes (SOCs) 25 high-frequency signals. Notably, significant AEs identified, some which not previously detailed medication's prescribing information. Unforeseen such unintended pregnancy (n = 623; ROR, 6.65; ROR025, 6.1; χ2, 2,482.38; PRR, 6.41; EBGM, 5.69; EBGM05, 5.29), bone pain 35; 13.78; 9.4; 311.2; 13.75; 10.59; 7.69), gait disturbance 34; 2.82; 1.99; 37.31; 2.88; 2.7; 2.02), dental caries 15; 23.16; 12.32; 204.26; 23.14; 15.23; 8.98), decrease blood pressure 3.88; 2.29; 29.35; 3.63; 2.33), osteonecrosis 9; 23.44; 10.36; 123.67; 23.43; 15.35; 7.75) identified that outlined information medication. Our findings align observations, highlighting emergence unreported their demographic TTO characteristics. Further pharmaco-epidemiological studies are required substantiate these observations.

Язык: Английский

Процитировано

0