Depot Medroxyprogesterone Acetate Use Research Articles

Effects of long-term high-dose medroxyprogesterone acetate use on bone mineral density in postmenopausal women

Aims: The aim of this study was to investigate the relationship between long-term depot medroxyprogesterone acetate (DMPA) use and bone mineral density (BMD) in postmenopausal women. Methods: This study was conducted on 40 postmenopausal women who presented at the SSK Okmeydanı Training and Research Hospital Gynecology and Obstetrics Polyclinic. The sample for the study was randomly selected from postmenopausal women and divided into the control group (N=20) and the medroxyprogesterone acetate group (N=19). Results: A total of 39 participants were included in this study, 19 cases and 20 controls. Long-term DMPA users had higher BMD compared with the control group. These differences from the control group were statistically and potentially clinically significant. The BMD in the control group has decreased significantly during one year of study. Based on the results, the longterm use of DMPA significantly affects the bone mineral density in postmenopausal women, increasing BMD. Conclusion: Long-term use of DMPA was associated with improved BMD after treatment. The findings demonstrate the need for long-term, controlled, prospective studies with adequate sample size to evaluate the potential clinical impact of DMPA use on bone health outcomes in postmenopausal women.

Potential effect of immediate postpartum use of injectable contraception on lactogenesis

ObjectivesWe evaluated the effect of immediate postpartum use of depot medroxyprogesterone acetate (DMPA) on the timing of lactogenesis stage II (LS-II). Study DesignThe initial design randomly assigned adults who delivered a full-term infant in 2019-2021 to receive within 48 hours of delivery: 1) DMPA, 2) placebo injection, or 3) no injection. Due to low enrollment, we changed in 2021-2023 to a non-randomized design using matching at recruitment for obesity and delivery method and propensity score weighting for analysis. We combined data from both designs to compare immediate postpartum DMPA use (N=55) versus control (placebo or no injection) group (N=95). We defined noninferiority a priori as being met if the upper bound of a two-sided 95% confidence interval (CI) for mean difference in time to LS-II between groups was <6 hours. ResultsThe unweighted mean time to LS-II was 57.8 hours in the DMPA group (SD, 29.4) and 64.1 hours in the control group (SD, 36.1). Using propensity score weighting to make the groups comparable with respect to age, race, delivery method, and previous live births, the mean time to LS-II was 5.5 hours shorter (95% CI, -16.4, 5.5) for women in the DMPA relative to control group. ConclusionsWe found no evidence that DMPA use inhibits the onset of LS-II. Findings support immediate postpartum DMPA initiation among those intending to engage in human milk feeding. ImplicationsA controlled trial (N=150) did not detect any difference in time to lactogenesis stage II (“milk let-down”) between injectable contraception use within the first 48 hours postpartum and those without this exposure.

Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

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.

Acceptance, Adherence, and Side Effects of Depot Medroxyprogesterone Acetate: A Prospective Observational Study.

Introduction In India, one of the world's most populous and swiftly growing countries, it is crucial to prioritize the utilization of safe and effective contraception, as contraceptive strategies play a pivotal role in bolstering community health. It is widely acknowledged that ensuring appropriate timing and spacing of pregnancies is crucial for the well-being of reproductive, maternal, neonatal, child, and adolescent health. Adoption of reversible or spacing contraceptive methods can significantly enhance women's health outcomes by reducing the occurrence of undesired, closely timed, and mistimed pregnancies. Consequently, in response to the pressing need for dependable contraception in India, this study seeks to assess the acceptance, adherence, and side effects of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) among its users. Methods This prospective observational study was done at the State Government Taluk Hospital in the Cuddalore District of Tamil Nadu from July 2022 to October 2022. A total of 40 women of reproductive age who opted for DMPA as their contraceptive method and met the inclusion criteria were recruited through a purposive sampling method. A structured questionnaire was used to collect the data. Results The majority of the participants were women aged 21-25 years (n=14; 35%). The participants were predominantly Hindu(n=39; 97.5%), and 35 (87.5%) had completed higher secondary education. All participants (n=40; 100%) resided in rural areas and the majority were homemakers. A significant proportion of the participants had two children (n=21; 52.5%), and all of them received information on DMPA primarilyfrom health personnel. At the initial point of data collection, three-fourths of them took the first dose(n=13; 32.5%)and only a few took more than three doses (n=3; 7.5%).In the third month, the results showed a drop in DMPA use, which indicates a lower adherenceparticularly linked to side effects like irregular bleeding (n=15; 37.5%) and amenorrhea (n=9; 22.5%). Furthermore, 35 (87.5%) of the women chose DMPA for birth spacing due to its efficacy and convenience, with few initiating it during postpartum (n=4; 10%) and post-abortal (n=1; 2.5%) periods.The reasons for continuing DMPA use included efficacy (n=20; 50%), discreet usage (n=15; 37.5%), and curiosity (n=13; 32.5%). Half of the participants reported no side effects.The study identified associations between DMPA users and the number of living children and occupational statusinferring that DMPA contraception is used forspacing births. Conclusion The results of this study imply that the use and adherence to injectable contraceptive DMPA need to be strengthened among rural women. Thus, the study suggests incorporating information, education, and communication strategies, to enhance awareness among rural women about injectable contraceptives.

Hormonal Contraception and Risk of Cardiometabolic Disease in Women with HIV.

Objective: We sought to determine the association of hormonal contraception (HC) and cardiometabolic outcomes among women with human immunodeficiency virus (HIV). Methods: We included women with HIV aged 18-45 years in clinical care in the Southeastern United States between 1998 and 2018. Oral and injectable HC use was captured from medication records. Our outcomes included incident cardiovascular/thrombotic disease (CVD) (atherosclerosis, hypertension, cerebrovascular disease, thrombosis, and heart failure) and incident metabolic disorders (diabetes, dyslipidemia, obesity, and non-alcoholic steatohepatitis). We excluded women with prevalent conditions. We used multivariable marginal structural models to examine time-varying current and cumulative HC use and cardiometabolic outcomes in separate analyses, adjusting for age, race, smoking, time-varying comorbidities, CD4 cell count, HIV RNA, and antiretroviral use. Women with HC exposure were compared with women without HC exposure. Results: Among the 710 women included, 201 women (28%) used HC. CVD analyses included 603 women without prevalent CVD and 93 incident events; metabolic analyses included 365 women without prevalent metabolic disease and 150 incident events. Current and cumulative oral HC use was associated with increased odds of CVD, though this was not statistically significant (adjusted odds ratio [aOR] = 2.08, [95% confidence interval (CI): 0.80-5.43] and aOR = 1.24 [95% CI: 0.96-1.60] per year of use, respectively). Oral HC was not associated with risk of incident metabolic disorders. Depot medroxyprogesterone acetate (DMPA) was not associated with risk of incident CVD. Current and cumulative DMPA use was significantly associated with decreased odds of incident metabolic disorders (aOR = 0.48 [95% CI: 0.23, 1.00] and aOR = 0.65 [95% CI: 0.42-1.00] per year of use, respectively). Conclusion: Our results suggest that cardiovascular risk should be considered when selecting contraception for women with HIV.

Depot-medroxyprogesterone acetate: Lipid profile changes and associated cardiovascular risks among acceptors in Sagamu, South West Nigeria.

Depot-medroxyprogesterone acetate (DMPA) is a highly effective long acting reversible contraceptive. Alterations in lipid profile have been associated with use of DMPA, however there is considerable debate about how profound these effects are. Hence the aim of this study is to determine the effect of DMPA on lipid profile and the associated cardiovascular risks. This was a prospective longitudinal study conducted at the family planning clinic of Olabisi Onabanjo University Teaching Hospital Sagamu, Ogun State. Sixty eight new acceptors of DMPA who had their blood samples collected for lipid profile assays at initiation of DMPA, and then at 3 months and 6 months. Data were analyzed using SPSS version 24. After 3 months of DMPA use, there was statistically significant increase in serum Total Cholesterol (TC) concentration (P=0.022), serum Low Density Lipoprotein (LDL) concentration (P=0.033), non significant increase in serum Triglyceride (TG) concentration (P=0.150) and non-significant decrease in serum Higher Density Lipoprotein (HDL) concentration (P=0.076). However, after 6 months of DMPA use, there was statistically significant increase in serum TC concentration (P=0.002), serum LDL concentration (P=0.003), serum TG concentration (P=0.001) and significant decrease in serum HDL concentration (P=0.001). DMPA use is associated with increased serum TC, TG, LDL, and reduction in HDL after 6 months of use. These changes in lipid profile may increase the risk of cardiovascular diseases.

A framework for assessing interactions for risk stratification models: the example of ovarian cancer.

Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models.

Patient’s experience and satisfaction with self-administered subcutaneous depot medroxyprogesterone acetate use during the first year of COVID-19

ObjectivesSelf-administered subcutaneous (SC) depot medroxyprogesterone acetate (DMPA) can improve contraception access by eliminating a health center visit for administration. For patients at our New York City health centers who were offered a switch to self-administered DMPA-SC at the onset of the coronavirus 2019 (COVID-19) pandemic, we sought to understand their experience of choosing to switch, of accessing and using the method, and their method satisfaction. Study designIndividual interview study of 22 patients using intramuscular DMPA prior to the start of the pandemic. All had a telehealth visit to discuss switching to self-administered DMPA-SC and received a DMPA-SC prescription during the first months of COVID-19. We used a grounded theory analysis approach. ResultsRespondents viewed switching to self-administered DMPA-SC as a decision they had to make if they wanted to continue DMPA. Most respondents experienced logistical challenges acquiring DMPA-SC from their pharmacy. Issues around convenience were important to respondents; however what respondents found convenient varied. Despite all this, respondents appreciated having the option of DMPA-SC and felt it to be overall empowering. ConclusionsThis study exploring patients' experience with self-administered DMPA-SC during the initial year of the COVID-19 pandemic found that, notwithstanding initial hesitation about self-administered injections and logistical challenges getting the SC formulation, many found the experience of trying self-administered DMPA-SC to be empowering and appreciated having this option. Thus, self-administered DMPA-SC should be included in clinicians’ routine contraception counseling and provision, insurance companies should cover DMPA-SC without requiring prior authorization, and pharmacies should consistently stock DMPA-SC. ImplicationsSelf-administered DMPA-SC is an acceptable contraception option that provides an opportunity to maintain contraception access while eliminating need for an in-person visit. Thus, self-administered DMPA-SC should be included in clinicians’ routine contraception counseling and provision, insurance companies need to cover this contraceptive without need for prior authorization, and pharmacies should consistently stock DMPA-SC.

New approaches for developing biomarkers of hormonal contraceptive use

To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC–MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users’ saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.

Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery

ObjectiveThe presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery. MethodsThis analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS. ResultsMenopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46–0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43–0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65–1.25, p = 0.53). ConclusionsThe association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Multi-omics analysis of the cervical epithelial integrity of women using depot medroxyprogesterone acetate.

Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive used by millions of women worldwide. However, experimental studies have associated DMPA use with genital epithelial barrier disruption and mucosal influx of human immunodeficiency virus (HIV) target cells. We explored the underlying molecular mechanisms of these findings. Ectocervical biopsies and cervicovaginal lavage (CVL) specimens were collected from HIV-seronegative Kenyan sex workers using DMPA (n = 32) or regularly cycling controls (n = 64). Tissue samples were assessed by RNA-sequencing and quantitative imaging analysis, whereas protein levels were measured in CVL samples. The results suggested a DMPA-associated upregulation of genes involved in immune regulation, including genes associated with cytokine-mediated signaling and neutrophil-mediated immunity. A transcription factor analysis further revealed DMPA-associated upregulation of RELA and NFKB1 which are involved in several immune activation pathways. Several genes significantly downregulated in the DMPA versus the control group were involved in epithelial structure and function, including genes encoding keratins, small proline-rich proteins, and cell-cell adhesion proteins. Pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development, including keratinization and cornification processes. The cervicovaginal microbiome composition (Lactobacillus dominant and non-Lactobacillus dominant) had no overall interactional impact on the DMPA associated tissue gene expression. Imaging analysis verified that DMPA use was associated with an impaired epithelial layer as illustrated by staining for the selected epithelial junction proteins E-cadherin, desmoglein-1 and claudin-1. Additional staining for CD4+ cells revealed a more superficial location of these cells in the ectocervical epithelium of DMPA users versus controls. Altered protein levels of SERPINB1 and ITIH2 were further observed in the DMPA group. Identification of specific impaired epithelial barrier structures at the gene expression level, which were verified at the functional level by tissue imaging analysis, illustrates mechanisms by which DMPA adversely may affect the integrity of the genital mucosa.

Depot Medroxyprogesterone acetate reduces spermatogonia cells and spermatid cells in the seminiferous tubules of male mice

Background: Until now the existing male contraceptive methods are periodic abstinence, interrupted intercourse (coitus interruptus), the use of condoms, and vasectomy. Another alternative method of contraception for men is the use of the hormone depot medroxyprogesterone acetate (DMPA) as has been done in female contraceptives. Research with DMPA at a dose of 1.25 mg was effective in reducing the concentration and viability of spermatozoa and testosterone secretion in male rats.&#x0D; Aim: to discover if DMPA as a gonadotropin hormon could effectively inhibit the process of spermatogenesis in male mice.&#x0D; Methods: This research is an experimental research with post-test control group design. A total of 36 samples were grouped by simple random sampling into two groups. Control group (P0): consisted of 18 male mice given 0.3 ml of intramuscular aquabides. Treatment group (P1): 18 male mice were given DMPA intramuscularly (IM) with a dose of 3 mg as much as 0.3 ml. Data obtained from examination of the mean of 60 tubules (30 tubules from the right testis and 30 tubules from the left testis) for each treatment with HE staining at 400x magnification.&#x0D; Results: The results showed a significant difference in the decrease in the number of spermatogonia cells in the treatment group compared to the control group (9.83±2.33 vs 12.78±1.67 cells/tubule), with p value = 0.000 (p&lt;0.01) and Spermatid cells (76.50±7.66 vs 86.44±6.06 cells/tubule), with p value = 0.000 (p&lt;0.01). The administration of DMPA could significantly reduce the number of spermatogonia and spermatid cells in the seminal tubules of male mice.&#x0D; Conclusion: The results of the study have implications for further research on the use of DMPA as a male contraceptive in higher experimental animals such as rabbits, then clinical trials in humans.

Depot Medroxyprogesterone Acetate Use and the Development and Progression of Uterine Leiomyoma.

Investigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development. We 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. Of 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). Recent 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.

Awareness of the non-contraceptive benefits of reversible contraceptive methods in a cohort of Brazilian women: an exploratory study

Purpose We assess the awareness of Brazilian women about non-contraceptive benefits of contraceptives and compare non-health with health care providers. Material and methods We conducted a survey in Brazil using a questionnaire administered via Google Forms asking women to respond about the awareness of non-contraceptive benefits of combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS), etonogestrel (ENG)-implant, copper intrauterine device (Cu-IUD), and male condom. Results We received 2,068 completed questionnaires, 720 women (34.8%) aged ≤ 29 years and 236 (11.4%) were physicians or nurses. Only one third of the respondents were aware that COC use is associated with decreased risks of ovarian and endometrial cancers; 296 (16.1%) about that the use of DMPA is associated with a decreased risk of endometrial cancer, and 253 (13.8%) were aware about that the users of the Cu-IUD present lower risk of cervical cancer. We identified significant differences between non-health care providers when compared to physicians or nurses. Conclusions We found low awareness regarding the associated lower risk of ovarian, endometrial and cervical cancer associated with the use of some contraceptives, evidencing the need to provide more information about the non-contraceptive benefits during training for health care providers.

Society of Family Planning committee consensus on self-administration of subcutaneous depot medroxyprogesterone acetate (DMPA-SC)

Depot medroxyprogesterone acetate (DMPA) is a highly-effective, injectable contraceptive method that requires injections every 12 to 15 weeks. The need for return visits to a healthcare provider may present barriers to access, use, and continuation of DMPA. Studies demonstrate that self-administration of subcutaneous DMPA (DMPA-SC) outside clinical settings is safe, effective, feasible, acceptable, and can improve continuation. Based on existing evidence and potential to improve contraceptive access and autonomy, the Society of Family Planning recommends that DMPA-SC self-administration be made widely available as an additional option for patients. Provider-administered DMPA must also remain available to meet patients’ individual needs and preferences.

Incidence of Herpes Simplex Virus Type 2 Infection Among African Women Using Depot Medroxyprogesterone Acetate, a Copper Intrauterine Device, or a Levonorgestrel Implant for Contraception: A Nested Randomized Trial.

BackgroundGlobally, women have higher herpes simplex virus type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM).MethodsWithin a randomized trial of the effect of 3 contraceptive methods—DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant—on human immunodeficiency virus (HIV) acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16–35 years, and seeking effective contraception were followed for 12–18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015 to 2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method.ResultsAt baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI], .65–.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI, .71–1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI, .89–1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55; 95% CI, 2.78–4.48).ConclusionsIn a randomized trial, we found no association between HSV-2 acquisition and use of 3 contraceptive methods.Trial registrationClinicalTrials.gov number NCT02550067.

Changing US trends in contraceptive choices.

Long-acting reversible contraceptives (ie, intrauterine devices and the etonogestrel subdermal implant) have become increasingly popular methods of contraception because of their convenience and safety profile. At the same time, the use of depot medroxyprogesterone acetate, one of the most prescribed contraceptives in the United States since its approval in 1992, is on the wane. The history and pros and cons of these contraceptive methods are reviewed.

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.

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. 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. 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. 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. · Contraception is an important issue for obstetricians to address with postpartum patients.. · Concerns have been raised over the relationship between DMPA and depression.. · Our study shows that DMPA is not associated with a positive postpartum depression screen..

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life.

Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone metabolism (e.g., contraceptives, glucocorticoids, antidiabetic medications, antiepileptic drugs). Although oral contraceptives are often believed to be neutral with regard to bone health, depot medroxyprogesterone acetate (DMPA) and gonadotropin-releasing hormone (GnRH) agonists have been associated with decreases in BMD. Development of newer medical therapies, principally GnRH antagonists (e.g., ASP1707, elagolix, linzagolix, relugolix), for treatment of endometriosis-associated pelvic pain and heavy menstrual bleeding due to uterine fibroids has renewed interest in the short- and long-term impacts of changes in BMD experienced by premenopausal women. It is important to understand how these drugs influence BMD and put the findings into context with regard to measurement variability and naturally occurring factors that influence bone health. This review summarizes what is known about the effects on bone health pregnancy, lactation, and use of DMPA, GnRH agonists, and GnRH antagonists in premenopausal women and potential consequences later in life. ClinicalTrials.gov identifier: NCT03213457.