Depot Medroxyprogesterone Acetate Users Research Articles

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.

Effect of depot medroxyprogesterone acetate on cardiometabolic risk factors among women of reproductive age in Rwanda: A prospective cohort study

Objectives: Depot medroxyprogesterone acetate (DMPA) injectable contraceptive is a widely used hormonal method that offers reversible and effective birth control for women worldwide. However, various studies have raised concerns regarding its potential association with increased cardiovascular disease risk, attributed to its influence on cardiometabolic risk factors. While previous studies have primarily focused on lipid profile, weight gain, blood pressure, and blood glucose, important aspects such as central obesity, glycated hemoglobin (HbA1C), and systemic inflammation have remained under-investigated. Thus, this study aimed to explore the influence of DMPA injectable contraceptives on lipid panel, HbA1C, visceral fat deposition, blood pressure, and inflammatory markers among women of childbearing age in Rwanda. Materials and Methods: The study was a prospective cohort and recruited an equal number of DMPA users (45) as the study group and users of nonhormonal (NH) contraceptives (45) as the control group. We recruited participants from two selected family planning centers in Kigali and collected data at baseline, 6 months, and 12 months. We measured the waist circumference, blood pressure, lipids profile (high-density lipoprotein cholesterol [HDL], low-density lipoprotein cholesterol [LDL], total cholesterol [TC], and triglycerides [TG]), HbA1C, and high-sensitivity C-reactive protein (hs-CRP). We run the Mann–Whitney to compare the median (MD) change between DMPA and NH users. Data were presented as MD (interquartile range), with a significance level of 5%. Results: After a follow-up of 12 months, DMPA users experienced a significant increase in waist circumference, TG, LDL, TC, hs-CRP, and HbA1C (P < 0.05), whereas they experienced a significant decrease in HDL than controls (P < 0.05). However, our data did not indicate a significant difference in blood pressure changes between DMPA and NH users (P > 0.05). Conclusion: The effect of DMPA injectable on cardiometabolic parameters was minimal in the first 6 months of use; however, it manifested statistically significant at 12 months of follow-up. It is recommended to initiate a follow-up with users at least 12 months of use and repeat every 6 months to check the status of cardiometabolic markers and intervene where necessary.

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.

Hematological parameters of reproductive-age women using hormonal contraceptives at University of Gondar Comprehensive Specialized Referral Hospital, Northwest Ethiopia: A comparative cross-sectional study.

More than one-third of reproductive aged women in Ethiopia use hormonal contraceptives to prevent conception. The present study aimed to compare the hematological parameters of reproductive-age women taking hormonal contraceptives at the University of Gondar Comprehensive Specialized Referral Hospital, Northwest Ethiopia in 2021. A comparative cross-sectional study was conducted from April to June 2021. A total of 240 study participants were recruited by using a consecutive sampling technique. Data on socio-demographic variables and clinical data were collected through face-to-face interviews using a structured questionnaire and medical record reviews, respectively. Three milliliter venous blood was collected for complete blood count analysis using Unicel DxH 800 coulter hematology analyzer. Data was entered into Epi-data 4.4.3.1 version then exported to IBM SPSS v25 for analysis. Kruskal-Wallis H, Dunn-Bonferroni pairwise comparison test, and Spearman's correlation analysis were used for inferential statistics. P<0.05 were considered statistically significant. The median and interquartile range of platelet count among combined oral contraceptive users was 285(238-332) which is significantly higher than that of depot medroxyprogesterone acetate users 246(220-226) (p = 0.010), implant user 247(221-297) (p = 0.034), and controls 256(224-278) (p = 0.015). The result also showed long-term use of implant negatively correlated with red blood cell count (p = 0.033). This finding concludes that combined oral contraceptive users had a higher platelet counts than controls while long-term use of implants can result in low red blood cells count. Therefore, a baseline evaluation of complete blood count in women desiring contraceptive methods would also be recommended.

Statement of Retraction: “Correlation between uterine artery Doppler indices and menstrual irregularities among levonorgestrel releasing intrauterine system and depot medroxyprogesterone acetate users: a prospective observational study”

Statement of Retraction: “Correlation between uterine artery Doppler indices and menstrual irregularities among levonorgestrel releasing intrauterine system and depot medroxyprogesterone acetate users: a prospective observational study”

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.

What Distinguishes Women Who Choose to Self-Inject? A Prospective Cohort Study of Subcutaneous Depot Medroxyprogesterone Acetate Users in Ghana.

Depot medroxyprogesterone acetate administered subcutaneously (DMPA-SC) is an all-in-one injectable contraceptive administered every 3 months, either by a trained health care provider or community health worker or by training a client to self-inject. Using a prospective cohort of family planning (FP) clients in Ghana, this study explores patterns of DMPA-SC use and mode of injection administration over a 6-month period. This study also examines the predictors of self-injection adoption 6 months after initiating DMPA-SC. Our analysis focuses on 378 women who were using DMPA-SC at the 6-month interview. Adjusted odds ratios accounting for clustering show that clients who were new FP users, never married, or attended high school/attained higher education were significantly more likely to self-inject by the third injection. Results of this study suggest that in Ghana, adding DMPA-SC to the method mix may improve access to FP, especially among new users. Results of this study may inform FP projects and programs aiming to improve access to contraceptive methods and increase contraceptive prevalence by introducing or scaling up DMPA-SC self-injection. The findings also provide a sociodemographic profile of FP clients most likely to adopt DMPA-SC self-injection over time, which could serve as an evidence base for social marketing strategies.

The Role of Subcutaneous Depot Medroxyprogesterone Acetate in Equitable Contraceptive Care: A Lesson From the Coronavirus Disease 2019 (COVID-19) Pandemic.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, health care professionals have made swift accommodations to provide consistent and safe care, including emphasizing remote access to allow physical distancing. Depot medroxyprogesterone acetate intramuscular injection (DMPA-IM) prescription is typically administered by a health care professional, whereas DMPA-subcutaneous has the potential to be safely self-injected by patients, avoiding contact with a health care professional. However, DMPA-subcutaneous is rarely prescribed despite its U.S. Food and Drug Administration approval in 2004 and widespread coverage by both state Medicaid providers and many private insurers. Depot medroxyprogesterone acetate users are disproportionately non-White, and thus the restriction in DMPA-subcutaneous prescribing may both stem from and contribute to systemic racial health disparities. We review evidence on acceptability, safety, and continuation rates of DMPA-subcutaneous, consider sources of implicit bias that may impede prescription of this contraceptive method, and provide recommendations for implementing DMPA-subcutaneous prescribing.

Duration, recency, and type of hormonal contraceptive use and antimüllerian hormone levels

To assess whether the duration, recency, or type of hormonal contraceptive used is associated with antimüllerian hormone (AMH) levels, given that the existing literature regarding the association between hormonal contraceptive use and AMH levels is inconsistent. Cross-sectional study. Baseline data from the Study of the Environment, Lifestyle and Fibroids Study, a 5-year longitudinal study of African American women. The patients were 1,643 African American women aged 23-35 years at the time of blood drawing (2010-2012). None. Serum AMH level was measured by an ultrasensitive enzyme-linked immunosorbent assay. Linear regression models were used to estimate percent differences in mean AMH levels and 95% confidence intervals (CIs) according to use of hormonal contraceptives, with adjustment for potential confounders. In multivariable-adjusted analyses, current users of hormonal contraceptives had 25.2% lower mean AMH levels than non-users of hormonal contraceptives (95% CI: -35.3%, -13.6%). There was little difference in AMH levels between former users and non-users of hormonal contraceptives (-4.4%; 95% CI: -16.3%, 9.0%). AMH levels were not appreciably associated with cumulative duration of use among former users or time since last use among non-current users. Current users of combined oral contraceptives (-24.0%; 95% CI: -36.6%, -8.9%), vaginal ring (-64.8%; 95% CI: -75.4%, -49.6%), and depot medroxyprogesterone acetate (-26.7%; 95% CI: -41.0%, -8.9%) had lower mean AMH levels than non-users. The present data suggest that AMH levels are significantly lower among current users of most forms of hormonal contraceptives, but that the suppressive effect of hormonal contraceptives on AMH levels is reversible.

Hormonal contraceptive use, bone density and biochemical markers of bone metabolism in British Army recruits

IntroductionHormonal contraceptive use might impair bone health and increase the risk of stress fracture by decreasing endogenous oestrogen production, a central regulator of bone metabolism. This cross-sectional study investigated bone...

Task Sharing of Injectable Contraception Services in Pakistan: A Randomized Controlled Trial.

Provision of injectable contraceptive services by lay health workers is endorsed by normative bodies, but support for this practice is not universal. We assessed whether lay providers (lady health workers, LHWs) could perform as well as clinically trained providers (family welfare workers, FWWs) on appropriate screening, counseling, and injection of intramuscular and subcutaneous depot medroxyprogesterone acetate (DMPA) using a randomized controlled trial. In the urban sample (n = 355), 88 percent of FWW DMPA clients were appropriately screened versus 77 percent of LHW clients (noninferiority test p = 0.88). In rural facilities (n = 105), over 90 percent of both providers' clients were screened appropriately. Appropriate counseling was low overall, but LHWs were significantly noninferior to FWWs (p = 0.003). Notably, LHWs demonstrated better injection technique than FWWs. We could not conclude that LHWs screened new DMPA users as well as FWWs from an urban sample of providers but results from the rural sample suggests that service delivery context played an important role.

Comparison of Depot Medroxyprogesterone Acetate and Postpartum Intrauterine Contraceptive Device in a Teaching Institute of Rural Bengal: A Longitudinal Cohort Study

Introduction: Contraception is one of the proximate determinants of fertility and the most important predictor of fertility transition. Depot Medroxy Progesterone Acetate (DMPA) and Intrauterine contraceptive device share some common features- both are Long Acting and Reversible Contraceptives (LARC), but the mechanisms are different. DMPA is a noninvasive, hormonal manoeuvre IUCD is an invasive, nonhormonal one. Aim: To compare the acceptance and reasons for refusal or non-compliance between DMPA and Postpartum Intrauterine Contraceptive (PPIUCD). Materials and Methods: A longitudinal cohort study was done in which total of 110 post partum women (55 in each group) using either DMPA or IUCD were selected randomly and were interviewed and followed up for minimum of six months. Data (variables- number of candidates accepting or refusing PPIUCD or DMPA) from the questionnaires were entered in Microsoft Office Excel 2007 and was transferred to IBM SPSS software, version 20.0 (SPSS Inc. Chicago, IL, USA). Pearson’s Chi-square test was used for variables and p-values were calculated using to find out the statistical significance of the variables and p-value <0.05 was considered statistically significant. Results: The overall acceptance of DMPA (87.3%) was found to be much more than that of PPIUCD (63.6%). In respect to different age groups, the acceptances of both PPIUCD and DMPA were significantly higher in women of age group 21-25. In respect to parity, acceptance of PPIUCD was more in women with one child, whereas the acceptances of DMPA were almost similar in women with either one or two children. Women using PPIUCD, 36.4% refused to continue with the method, whereas only 12.7% of DMPA users refused further injections, the main reason for both the groups being the same irregular bleeding. Conclusion: The acceptance as well as compliance of DMPA as a method of postpartum contraception is much better than PPIUCD in women of this part of part of rural Bengal.

Bone Mineral Density in Antiretroviral Therapy-Naïve HIV-1-Infected Young Adult -Women Using Depot Medroxyprogesterone Acetate or Nonhormonal Contraceptives in Uganda.

ABSTRACTMost studies evaluating BMD in human immunodeficiency virus (HIV)‐infected populations have focused on antiretroviral therapy (ART)‐experienced patients. In this study, the association between HIV‐1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV‐1–infected women in a resource‐limited setting was assessed before long‐term exposure to ART. The data were then compared with that of the 2005–2008 United States National Health and Nutrition Examination Survey data for non‐Hispanic White and Black women. Women aged 18–35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV‐1 status and DMPA use: (i) HIV‐1–infected current DMPA users, (ii) HIV‐1–infected previous DMPA users, (iii) HIV‐1–infected nonhormonal‐contraceptive users, and (iv) HIV‐uninfected nonhormonal‐contraceptive users. All HIV‐1–infected women reported being ART‐naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV‐1 and/or DMPA and BMD Z‐scores. Baseline data were analyzed for 452 HIV‐1–infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV‐1–uninfected nonhormonal‐contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12‐48]. A higher proportion of HIV‐1–infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z‐score ≤−2 at any of the three sites) compared with age‐matched HIV‐1–uninfected women (2.9%). HIV‐1 infection and DMPA use were independently associated with significantly lower mean BMD Z‐scores at all sites, with the greatest difference being among HIV‐1–infected current DMPA users (5.6%–8.0%) versus uninfected nonhormonal users. Compared with non‐Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV‐1–infected women in resource‐limited settings. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Responding to the ECHO trial results: modelling the potential impact of changing contraceptive method mix on HIV and reproductive health in South Africa.

IntroductionSome observational data suggest that the progestogen injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase a woman’s risk of HIV acquisition but a randomized clinical trial did not find a statistically significant increase in HIV risk for women using DMPA compared to two other methods. However, it could not rule out up to 30% increased HIV risk for DMPA users. We evaluate changes to contraceptive method mix in South Africa under different assumptions about the existence and strength of a possible undetected relationship between DMPA use and HIV risk.MethodsA mathematical model was developed to simulate the ongoing HIV epidemic and contraceptive method mix in South Africa to estimate how changes in method mix could impact HIV‐ and reproductive health‐related outcomes. We made different assumptions about the relationship between DMPA use and HIV risk, from no relationship to a 30% increase in HIV risk for women using DMPA. Scenario analyses were used to investigate the impact of switching away from DMPA predominance to new patterns of contraceptive use.ResultsIn South Africa, the HIV‐related benefits of reduced DMPA use could be as great as the harms of increased adverse reproductive health outcomes over 20 years, if DMPA did increase the risk of HIV acquisition by a relative hazard of infection of 1.1 or greater. A reduction in DMPA use among HIV‐positive women would have no benefit in terms of HIV infections, but would incur additional negative reproductive health outcomes. The most important driver of adverse reproductive health outcomes is the proportion of women who switch away from DMPA to no contraceptive method.ConclusionsIf there is any real increased HIV risk for DMPA users that has not been detected by the recent randomized trial, a reduction in DMPA use could reduce the ongoing number of new HIV infections. However, such a change would place more women at risk of adverse reproductive health effects. It is imperative that these effects are minimized by focusing on expanding access to safe, effective and acceptable alternative contraceptive methods for all women.

Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: Results of an ex vivo fusion assay

IntroductionEx vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence. MethodsWe measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA). Results and conclusionsThere was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower. ImplicationsIn ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells.

Regular Use of Depot Medroxyprogesterone Acetate Causes Thinning of the Superficial Lining and Apical Distribution of Human Immunodeficiency Virus Target Cells in the Human Ectocervix.

BackgroundThe hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with an increased risk of acquiring human immunodeficiency virus (HIV). We hypothesize that DMPA use influences the ectocervical tissue architecture and HIV target cell localization.MethodsQuantitative image analysis workflows were developed to assess ectocervical tissue samples collected from DMPA users and control subjects not using hormonal contraception.ResultsCompared to controls, the DMPA group exhibited a significantly thinner apical ectocervical epithelial layer and a higher proportion of CD4+CCR5+ cells with a more superficial location. This localization corresponded to an area with a nonintact E-cadherin net structure. CD4+Langerin+ cells were also more superficially located in the DMPA group, although fewer in number compared to the controls. Natural plasma progesterone levels did not correlate with any of these parameters, whereas estradiol levels were positively correlated with E-cadherin expression and a more basal location for HIV target cells of the control group.ConclusionsDMPA users have a less robust epithelial layer and a more apical distribution of HIV target cells in the human ectocervix, which could confer a higher risk of HIV infection. Our results highlight the importance of assessing intact genital tissue samples to gain insights into HIV susceptibility factors.

Depot medroxyprogesterone acetate and norethisterone enanthate differentially impact T-cell responses and expression of immunosuppressive markers.

Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T-cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net-En). Peripheral blood mononuclear cells collected from women aged 18-34years prior to, at steady state, and nadir concentrations after initiating DMPA (n=30) or Net-En (n=36) and from women initiating copper intrauterine device (CU-IUD; n=32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T-cells expressing programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4). Compared to baseline, there were decreased numbers of CD4+CTLA4+ (P<.001) and CD8+CTLA4+ (P<.01) T-cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P=.781 and P=.463, respectively). In Net-En users, no differences in CD4+CTLA4+ T-cells at steady state (P=.087) and nadir concentrations (P=.217) were observed. DMPA users had fewer CD4+PD-1+ (P<.001) and CD8+PD-1+ (P<.001) T-cells at nadir concentrations. Number of CD4+PD-1+ and CD8+PD-1+ T-cells decreased at steady state concentration (P=.002 and P=.001, respectively) and at nadir concentrations after Net-En initiation (P<.001 and P<.001). In CU-IUD users, there were no changes in number of CD4+CTLA4+ (P=.426) and CD8+CTLA4+ (P=.169) and no changes in CD4+PD-1+ (P=.083) and CD8+PD-1+ (P=.936) compared to baseline. Activation of T-cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient.

What impact could DMPA use have had in South Africa and how might its continued use affect the future of the HIV epidemic?

IntroductionSome studies suggest that use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase susceptibility to HIV infection. We aim to determine the influence that such an association could have had on the HIV epidemic in South Africa.MethodsWe simulate the heterosexual adult HIV epidemic in South Africa using a compartmental model stratified by age, behavioural risk group, sex, male circumcision status and contraceptive use. We model two possible scenarios: (1) The “With Effect” scenario assumes that DMPA increases susceptibility to HIV infection by 1.20‐fold (95% confidence interval 1.06 to 1.36) based on a combination of the results of a recent randomised controlled trial (ECHO trial) and a number of observational studies. (2) The “No Effect” scenario assumes that DMPA has no effect on HIV acquisition risk. We calculate the difference in HIV‐related outcomes between the With Effect and No Effect scenarios to determine the potential impact that DMPA use could have had on the HIV epidemic.ResultsA causal association between DMPA and HIV acquisition could have caused 430,000 (90% of model runs 160,000 to 960,000) excess HIV infections and 230,000 (90,000 to 470,000) AIDS deaths in South Africa from 1980 to 2017. These figures represent 4.3% (1.6% to 9.6%) and 6.9% (2.6% to 15.2%) of the total modelled estimates of HIV infections and AIDS deaths respectively in South Africa in that period. Of the additional infections, 36% (25% to 48%) would have occurred among men. If DMPA use continues at current levels, a potential causal association could cause an additional 130,000 (50,000 to 270,000) infections between 2018 and 2037. The excess infections would have required an additional 640,000 (190,000 to 1,660,000) years of ART from 1980 to 2017, and a further 2,870,000 (890,000 to 7,270,000) years of ART from 2018 to 2037.ConclusionsIf there is a causal association between DMPA use and HIV risk, it could have substantially increased the scale of the HIV epidemic in South Africa, affecting not only the users of DMPA, but also their partners and the wider population. The magnitude of this potential effect demands careful data collection and a careful consideration of policy choices for contraception in settings with large HIV epidemics.

Changes in calcium metabolism and bone mineral density in new users of medroxyprogesterone acetate during the first year of use

To evaluate calcium metabolism and bone mineral density (BMD) in new users of depot medroxyprogesterone acetate (DMPA) in the first year of use. This prospective, non-randomized study, conducted at the University of Campinas, São Paulo, Brazil, was carried out between February 2011 and February 2013. Women aged from 18 to 40 with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) <30 and with no known history of disease or medication use who chose to use DMPA were paired by age (±1year) and BMI (±1) with women commencing the use of a copper intrauterine device (IUD). The primary outcomes were BMD measured by dual-energy X-ray absorptiometry and calcium metabolism markers; other variables were body composition and lifestyle habits. Repeated measures analysis of variance (ANOVA) and multiple regression analyses were used to evaluate associations. Twenty-seven women using DMPA and 24 using IUD were evaluated, with a mean age of 29.7years and 28.6years, respectively. The DMPA group presented with a 3.6% (P<0.001) loss of lumbar spine BMD, a 2.1% (P=0.100) loss of femoral neck BMD and higher phosphorus (P=0.014) concentrations at 12months compared to the IUD group. The decreases in BMD were associated with the use of DMPA, while total mass and coffee intake were found to be protective factors. Changes in calcium metabolism and a decrease in BMD were found in the DMPA group at 12months.

Hormonal Contraception and Vaginal Infections Among Couples Who Are Human Immunodeficiency Virus Serodiscordant in Lusaka, Zambia.

To examine the relationship between hormonal contraception and vaginal infections with bacterial vaginosis, vaginal candidiasis, or trichomoniasis. Couples who were human immunodeficiency virus (HIV) serodiscordant in Zambia were enrolled in a longitudinal cohort study. From 1994 to 2002, both partners were seen quarterly and received physical exams including genital examinations. Separate rates for three outcome infections of interest (bacterial vaginosis, vaginal candidiasis, and trichomoniasis) were calculated. Bivariate associations between baseline and time-varying covariates and outcome infections of interest were evaluated using unadjusted Anderson-Gill survival models. Adjusted hazard ratios (aHRs) were generated using multivariable Anderson-Gill survival models that included demographic and clinical factors associated with both hormonal contraceptive use and each infection of interest. There were 1,558 cases of bacterial vaginosis, 1,529 cases of vaginal candidiasis, and 574 cases of trichomoniasis over 2,143 person-years of observation. Depot medroxyprogesterone acetate (DMPA) users had significantly lower rates of trichomoniasis and bacterial vaginosis. In adjusted models, DMPA was protective for bacterial vaginosis (aHR=0.72; 95% CI 0.54-0.95), candidiasis (aHR 0.75, 95% CI 0.57-1.00) and trichomoniasis (aHR=0.43, 95% CI 0.25-0.74). Oral contraceptive pills were protective for candidiasis (aHR=0.79, 95% CI 0.65-0.97). We confirm that DMPA use was associated with reduced rates of the three most common causes of vaginitis, and oral contraceptive pill use was associated with reduced rates of candidiasis among women in couples who were HIV discordant.