Dataset Information

Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women.

ABSTRACT: OBJECTIVE:The effects of sex hormones on the immune defenses of the female genital mucosa and its susceptibility to infections are poorly understood. The injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may increase the risk for HIV-1 acquisition. We assessed the local concentration in the female genital mucosa of cationic polypeptides with reported antiviral activity in relation to DMPA use. METHODS:HIV-1-uninfected women were recruited from among couples testing for HIV in Nairobi, Kenya. Cervicovaginal secretion samples were collected, and the concentrations of HNP1-3, LL-37, lactoferrin, HBD-2, and SLPI were measured by enzyme-linked immunosorbent assays. Levels of cationic polypeptides in cervicovaginal secretions were compared between women who were not using hormonal contraception and those using DMPA, oral, or implantable contraception. RESULTS:Among 228 women, 165 (72%) reported not using hormonal contraception at enrollment, 41 (18%) used DMPA, 16 (7%) used an oral contraceptive, and 6 (3%) used a contraceptive implant. Compared with nonusers of hormonal contraception, DMPA users had significantly higher mean levels of HNP1-3 (2.38 vs. 2.04 log?? ng/mL; P = 0.024), LL-37 (0.81 vs. 0.40 log10 ng/mL; P = 0.027), and lactoferrin (3.03 vs. 2.60 log?? ng/mL; P = 0.002), whereas SLPI and HBD-2 were similar. CONCLUSIONS:Although all analyzed cationic polypeptides have intrinsic antiviral capacity, their interaction and cumulative effect on female genital mucosa susceptibility to infections in vivo has yet to be unraveled. This study suggests a potential mechanism underlying the effect of DMPA on the innate immune defenses, providing a rationale to investigate its effect on HIV-1 acquisition risk.

SUBMITTER: Guthrie BL

PROVIDER: S-EPMC4424097 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women.

Guthrie Brandon L BL Introini Andrea A Roxby Alison C AC Choi Robert Y RY Bosire Rose R Lohman-Payne Barbara B Hirbod Taha T Farquhar Carey C Broliden Kristina K

Journal of acquired immune deficiency syndromes (1999) 20150501 1

<h4>Objective</h4>The effects of sex hormones on the immune defenses of the female genital mucosa and its susceptibility to infections are poorly understood. The injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may increase the risk for HIV-1 acquisition. We assessed the local concentration in the female genital mucosa of cationic polypeptides with reported antiviral activity in relation to DMPA use.<h4>Methods</h4>HIV-1-uninfected women were recruited from among couple ...[more]

PMID: 25622059

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Project description:ObjectiveInvestigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.MethodsWe conducted a cohort study in the Detroit, Michigan, area that involved four clinic visits at 20-month intervals over 5 years (2010-2018) and used a standardized ultrasonography protocol to prospectively measure leiomyomas 0.5 cm or more in diameter. Participants were 1,693 self-identified Black women aged 23-35 years with no prior leiomyoma diagnosis and no hysterectomy. For this substudy, years since last use of DMPA was ascertained from questionnaire data at every visit. Leiomyoma incidence was defined as the first visit with an observed leiomyoma among women who were leiomyoma-free at enrollment. Depot medroxyprogesterone acetate associations were examined with Cox models. Leiomyoma growth was calculated as the change in log-volume for leiomyomas matched at successive visits and was modeled using linear mixed models accounting for clustered data. Leiomyoma loss, defined as a reduction in leiomyoma number in successive visits, was modeled using Poisson regression. All models used time-varying exposure and covariates.ResultsOf participants with at least one follow-up visit (N=1,610), 42.9% had ever used DMPA. Participants exposed to DMPA within the previous 2 years experienced reduced leiomyoma development during the subsequent observation interval compared with never users, including lower leiomyoma incidence (5.2% vs 10.7%), adjusted hazard ratio 0.6 (95% CI 0.4-1.0), 42.0% lower leiomyoma growth (95% CI -51.4 to -30.7) and 60% greater leiomyoma loss (adjusted risk ratio 1.6, 95% CI 1.1-2.2). Excess leiomyoma loss was also seen for those who used DMPA 2-4 years before the visit compared with never users, 2.1-fold increase (95% CI 1.4-3.1).ConclusionRecent use of DMPA was associated with reduced leiomyoma development and increased leiomyoma loss. Such changes in early leiomyoma development in young women could delay symptom onset and reduce the need for invasive treatment.

Project description:ObjectiveTo examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle development.Study designWe assigned enrolled participants to one of three preassigned dominant follicle size groups: 12-14?mm, 15-17?mm and?? 18?mm. We followed dominant follicles via serial transvaginal ultrasound (TVUS) until the follicles reached their assigned size, at which time we administered DMPA. For 5 consecutive days thereafter, we followed the follicles via TVUS to observe follicle rupture and obtained serum luteinizing hormone (LH), estradiol, and progesterone concentrations. In the following 2 weeks, we collected serum progesterone concentrations twice weekly to detect possible ovulatory delay or dysfunction. We also collected serum medroxyprogesterone acetate (MPA) concentrations at 1 and 24?h after DMPA administration to examine against ovulatory outcomes.ResultsTwenty-six of 29 enrolled women completed the study. DMPA suppressed ovulation in 17/26 (65%) and caused ovulatory dysfunction in 1/26 (4%) participants. Larger follicles were more likely to rupture despite DMPA (12-14?mm: 0/10 (0%); 15-17?mm: 3/10 (30%); ? 18?mm: 6/6 (100%); p?<?.01). Pre-DMPA LH concentrations ranged from 13.8 to 93.7?IU/L (mean 49.0?IU/L) in cases of follicle rupture. We observed no cases of follicle rupture when DMPA was administered through cycle day 12. All 24-h MPA concentrations exceeded those needed for ovulation suppression.ConclusionDMPA suppressed and additionally disrupted ovulation in 65% and 4% of observed cycles, respectively. DMPA may provide effective emergency contraception as well as ongoing contraception if administered prior to an expected ovulation and specifically before the LH surge.ImplicationsDMPA may be an alternative form of emergency contraception that can also self-bridge to ongoing contraception. As ovulation was not observed among any follicles when DMPA was given through cycle day 12, women who initiate DMPA up through cycle day 12 may not require backup contraception.

Project description:ObjectivesTo evaluate feasibility, acceptability, continuation, and trough serum levels following self-administration of subcutaneous (sc) depot medroxyprogesterone acetate (DMPA).Study designWomen presenting to a family planning clinic to initiate, restart or continue DMPA were offered study entry. Participants were randomized in a 2:1 ratio to self- or clinician administered sc DMPA 104 mg. Those randomized to self-administration were taught to self-inject and were supervised in performing the initial injection; they received printed instructions and a supply of contraceptive injections for home use. Participants randomized to clinician administration received usual care. Continued DMPA use was assessed by self-report and trough medroxyprogesterone acetate levels at 6 and 12 months.ResultsTwo hundred fifty women were invited to participate, and 137 (55%) enrolled. Of these, 91 were allocated to self-administration, and 90/91 were able to correctly self-administer sc DMPA. Eighty-seven percent completed follow-up. DMPA use at 1 year was 71% for the self-administration group and 63% for the clinic group (p=0.47). Uninterrupted DMPA use was 47% and 48% for the self and clinic administration groups at 1 year (p=0.70), respectively. Serum analyses confirmed similar mean DMPA levels in both groups and therapeutic trough levels in all participants.ConclusionsSixty-three percent of women approached were interested in trying self-administration of DMPA, even in the context of a randomized trial, and nearly all eligible for enrollment were successful at doing so. Self-administration and clinic administration resulted in similar continuation rates and similar DMPA serum levels. Self-administration of sc DMPA is feasible and may be an attractive alternative for many women.ImplicationsSelf-administration of sc DMPA is a feasible and attractive option for many women. Benefits include increased control over contraceptive measures and less time spent on contracepting behaviors. Globally, self-administration has the potential to revolutionize contraceptive uptake by increasing the number of women with access to DMPA.

Project description:BackgroundThe vaginal microbiome plays a key role in women's reproductive health. Use of exogenous hormones, such as intramuscular depot medroxyprogesterone acetate (DMPA-IM), may alter the composition of vaginal bacterial community.MethodsVaginal swab samples were collected from postpartum Kenyan women initiating DMPA-IM or nonhormonal contraception (non-HC). Bacterial vaginosis was assessed by Nugent score (Nugent-BV) and bacterial community composition was evaluated using broad-range 16S ribosomal RNA gene polymerase chain reaction with high-throughput sequencing. Changes in Nugent score, alpha diversity (Shannon diversity index), and total bacterial load between contraceptive groups from enrollment to 3 months after initiation were estimated using multivariable linear mixed effects regression.ResultsAmong 54 human immunodeficiency virus-negative women, 33 choosing DMPA-IM and 21 choosing non-HC, Nugent-BV was more common among DMPA-IM users at enrollment. At follow-up, Nugent score had decreased significantly among DMPA-IM users (change, -1.89; 95% confidence interval [CI], -3.53 to -.25; P = .02) while alpha diversity remained stable (0.03; -.24 to .30; P = .83). Conversely, Nugent score remained relatively stable among non-HC users (change, -0.73; 95% CI, -2.18 to .73; P = .33) while alpha diversity decreased (-0.34; -.67 to -.001; P = .05). The total bacterial load decreased slightly in DMPA-IM users and increased slightly among non-HC users, resulting in a significant difference in change between the contraceptive groups (difference, -0.64 log10 gene copies per swab sample; 95% CI, -1.19 to -.08; P = .02). While significant changes in Nugent score and alpha diversity were observed within contraceptive groups, changes between groups were not significantly different.ConclusionsPostpartum vaginal bacterial diversity did not change in DMPA-IM users despite a reduction in Nugent-BV, but it decreased significantly among women using non-HC. Choice of contraception may influence Lactobacillus recovery in postpartum women.

Dataset Information

Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women.

Publications

Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women.

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