Depot Medroxyprogesterone Acetate Use Research Articles

Cardiovascular Disease Risk Associated With the Long-term Use of Depot Medroxyprogesterone Acetate

BackgroundDepot medroxyprogesterone acetate (DMPA) contraception is widely used all over the world; however, it may lead to a decrease in high-density lipoproteins and an increase in low-density lipoproteins (LDL) and triglycerides. These changes in lipid profile have a direct effect on cardiovascular disease risk. This study has been conducted to investigate the relationship between DMPA use and lipid profile, and the effect of worsening of lipid profile on fasting blood glucose. The objective of the present study is to ascertain the effects of DMPA on lipid profiles and Castelli indices, and to estimate the risk of cardiovascular disease in the women using progesterone-only methods for contraception. MethodsThis was a multicenter case-control study including females of reproductive age. A total of 893 women were selected according to inclusion and exclusion criteria described below with the age range of 19-49 years. Among these, 477 were females who were beginning DMPA for contraception whereas 416 were the matched controls of same age and socioeconomic status. The lipid profiles, Castelli indices and fasting blood sugar were evaluated before initiation of DMPA and thereafter at 3, 6, 9 and 12 months. Controls were also analyzed for the same parameters in the same manner as that of treated group. The results were analyzed by repeated measure analysis of variance followed by Tukey׳s post hoc test for the multiple comparisons. ResultsThe results showed statistically significant differences in all parameters of lipid profile, namely cholesterol (180.7 ± 38.8 versus 133.03 ± 14.8mg/dL, and P = 0.000), LDL (120.04 ± 36.2 versus 94.27 ± 19.6mg/dL, and P = 0.000), very low-density lipoprotein cholesterol (24.6 ± 10.0 versus 20.99 ± 8.66mg/dL, and P = 0.000), high-density lipoprotein (39.67 ± 3.6 versus 44.13 ± 4.22mg/dL, and P = 0.000), total cholesterol (713.05 ± 110.2 versus 569.19 ± 80.4mg/dL, and P = 0.000), triglycerides (126.33 ± 48.8 versus 99.03 ± 30.6mg/dL, and P = 0.000), Castelli index I (4.61 ± 1.2 versus 3.02 ± 0.31, and P = 0.000) and Castelli index II (3.08 ± 1.07 versus 2.13 ± 0.41, and P = 0.000) between treated and control groups, respectively. Serum glucose levels were significantly higher (P ≤ 0.001) among the cases of DMPA (84.6394 ± 7.425mg/dL) compared with that in the control (77.822 ± 7.733mg/dL). ConclusionsThis study clearly revealed that there is an increase in all deleterious lipid parameters and a decrease in favorable lipid measures. Hence, it can be concluded that continued use of DMPA may predispose females to the risk of cardiovascular disease in the long run.

A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk.

Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition.

Interest in self-administration of subcutaneous depot medroxyprogesterone acetate in the United States

ObjectiveSubcutaneous depot medroxyprogesterone acetate (DMPA-SC) is a low-dose formulation of depot medroxyprogesterone acetate (DMPA) that nonmedical personnel can administer safely and effectively. We sought to determine United States women's interest in self-administration of DMPA-SC to understand whether such use can overcome barriers to contraceptive access. Study designWe analyzed survey data on contraceptive attitudes collected in March–July 2011 from 1592 women at 13 family planning and six abortion clinics throughout the US. A mixed-effects logistic regression model with random site effects examined the determinants of interest in self-administering DMPA-SC. ResultsOverall, 21% [95% confidence interval (CI): 19%–23%] of women reported interest in self-administration. A multivariable model found that women currently using DMPA (Adjusted Odds Ratio [AOR]=3.93, 95% CI: 2.37–6.53, p<.001) and women who previously used DMPA (AOR=1.71, 95% CI: 1.26–2.32, p<.001) were more likely to have an interest in DMPA-SC than those who never used it. Women reporting difficulty obtaining or refilling a prescription were almost twice as likely to have interest in DMPA-SC as women who reported no difficulty (AOR=1.99, 95% CI: 1.43–2.77, p<.001). Women surveyed at abortion sites were more likely to report interest in self-administration than women surveyed at family planning sites (AOR=1.55, 95% CI: 1.05–2.30, p<.05). Interest in DMPA-SC was primarily driven by a desire to eliminate unnecessary return visits to a facility for repeat injections. ConclusionsOffering women the option to self-administer DMPA-SC at home can expand access and tailor contraceptive provision to the needs of clients, thus supporting client-centered care. To the extent that self-administration may improve contraceptive continuation, DMPA-SC can prevent unintended pregnancies among women who discontinue DMPA use because of difficulty returning for repeat injections. ImplicationsThere is substantial interest in self-administration of DMPA-SC among current DMPA users, women who have recently had an abortion and women reporting difficulty returning to a family planning provider. Offering self-administration of DMPA-SC could potentially increase contraceptive continuation, reduce unintended pregnancies and enhance reproductive autonomy among DMPA users.

P018 Evolving contraceptive options in indigenous communities in Panama

Background Use of contraception in Panamanian indigenous groups is significantly lower than in the general population. Birth-rates in the Ng-be-Bugle group are the highest in the country. A large proportion of the Ng-be-Bugle live in isolated, rural communities with limited sanitation and education facilities and poor access to local health services. A non-governmental organisation (NGO) has been providing primary healthcare to these communities since 2011 and introduced the contraceptive injection in 2013. Aims To assess the level and trends of contraceptive injection use and to identify associated challenges. Methods An observational study of depot medroxyprogesterone acetate (DMPA) use in women attending the NGO clinics was carried out. Results 143 women from 16 communities have used DMPA from the NGO; 46.9% started in the last 6 months. The most common reason for commencing is family completion. Average age at commencing is 27.6 years (range 12–46) and number of children is 4 (range 0–14). Since starting, 13.3% have discontinued use and 25.9% have missed their most recent dose. Missed doses are commonly due to clinic non-attendance. Influence from spouses and misconceptions regarding side-effects are key factors in discontinuation. Discussion Ng-be-Bugle communities are experiencing unsustainable population growth. Contraceptive options available to these communities remain limited. Despite a recent surge in the uptake of DMPA from the NGO, major challenges regarding long-term use and compliance remain. Our ongoing work aims to broaden contraceptive options for these people and includes implementation of a pilot study introducing the contraceptive implant.

The role of training in effective simulated self-injection of subcutaneous depot medroxyprogesterone acetate: observations from a usability study

ObjectivesThe need for quarterly clinic visits is a barrier to use of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) contraception. The ability to self-inject at home may enhance method acceptance. Since efficacy depends on proper administration, we evaluated whether women could correctly perform simulated injections of DMPA-SC in a Uniject™ injection system using printed Instructions for Use (IFU), with and without hands-on training. Study designAdult female volunteers (N=120) injected DMPA-SC into a rubber trainer at two visits, 3 months apart. Women were randomly assigned to receive hands-on training before the first injection or no training. The primary outcome was the proportion of women who successfully operated the injection system. An attempt was defined as successful if the participant correctly performed all critical steps in the injection procedure (getting ready, selecting an injection area, preparing the injector, mixing the medicine, activating the injector, injecting the dose) and expelled the dose without unexpected interruption. The success rate at month 3 was considered the primary endpoint. A one-sided 95% confidence limit >80% was used to declare the delivery system and IFU “fit for purpose.” ResultsWith training, the success rate (one-sided 95% confidence limit) was 90.0% (81.8%) at day 1 and 96.7% (90.4%) at month 3; without training, rates were 76.7% (66.7%) and 88.3% (79.8%), respectively. The trained (96.4%) and untrained (92.2%) groups successfully completed injecting into the trainer at first injection, the final critical step of the injection procedure, despite the fact that about one third of participants considered expelling depot medroxyprogesterone acetate (one component of this step) to be difficult. ConclusionMost participants understood the IFU and successfully operated the injection system. Initial hands-on training improved success rates at both visits. For women interested in self-injection, providers should review all steps of the IFU, provide a demonstration, supervise initial injection(s) and ensure that the patient is aware of future injection dates. The potential for self-injection to improve adherence should be studied. ImplicationsAfter initial training, women performed simulated self-injections of DMPA-SC in the Uniject system proficiently using printed instructions. Women who are motivated and demonstrate competent injection technique during training can be relied upon to self-inject correctly at home. DMPA-SC users not suitable for self-injection should continue receiving injections at the clinic.

Association Between Depot-Medroxyprogesterone Acetate Injection and Periodontal Health in Reproductive Age Women: A Case Control Study in Iran

Background: It seems that depot-medroxyprogesterone acetate (DMPA) use can have an effect on a woman’s oral health, and cause periodontal changes in adult women. However, there is little research in this regard and consensus has not been reached in the literature. Objectives: This study aimed to investigate the association between DMPA injection and periodontal health in reproductive age women. Materials and Methods: This descriptive analytical study was conducted on 194 women aged 20 - 40 years in Ahvaz health care centers, southwest of Iran, during 2015. Ninety-seven women taking DMPA were assigned to the case group and 97 women who did not use DMPA were assigned to the control group. Periodontal parameters such as bleeding on probing, probing pocket depth and clinical attachment loss were measured. Data were analyzed by SPSS software version 19 using descriptive and analytic (Chi-square, Mann-Whitney and student’s t-test) statistical methods. Results: There was a statistically significant difference regarding bleeding on probing, probing pocket depth and clinical attachment loss between the case and control groups. Totally, 56.7% of the women in the case group had periodontitis compared to 16.5% in the control group (P < 0.0001). Conclusions: Based on our findings, the use of DMPA can affect the periodontal health status of women. Therefore, women who use this method must have a strict oral hygiene care program.

Changes in Vaginal Microbiota and Immune Mediators in HIV-1-Seronegative Kenyan Women Initiating Depot Medroxyprogesterone Acetate.

Depot medroxyprogesterone acetate (DMPA) is associated with HIV acquisition. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation. In a cohort of HIV-negative Kenyan women, we collected monthly vaginal swabs over 1 year before and after DMPA. Using quantitative polymerase chain reaction, we compared quantities of Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis, and total bacterial load (16S ribosomal RNA gene levels). Six vaginal immune mediators were measured with enzyme-linked immunosorbent assay. Trends in the detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression. From 2010 to 2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median, 6 visits/woman; range, 3-8 visits/woman). The median time of DMPA-exposed follow-up was 8.4 months (range, 1.5-11.6 months). Seven women (46%) had bacterial vaginosis within 70 days before DMPA start. L. iners was detected in 13 women (87%) before DMPA start, but other lactobacilli were rarely detected. Gardnerella vaginalis decreased by 0.21 log10 copies per swab per month after DMPA exposure (P = 0.01). Total bacterial load decreased by 0.08 log10 copies per swab per month of DMPA (P = 0.02). Sustained decreases in interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.04), and IL-1 receptor antagonist (P < 0.001) were also noted. Nine women (60%) had L. crispatus detected post-DMPA, which significantly correlated with reduced IL-6 (P < 0.01) and IL-8 (P = 0.02). Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. Further studies are warranted to outline components of the vaginal microbiota influenced by DMPA use and impact on HIV susceptibility.

Eating disorders, menstrual dysfunction, weight change and DMPA use predict bone density change in college-aged women

IntroductionThere are limited longitudinal studies that have evaluated bone mineral density (BMD) changes in college-aged women. Our objective was to simultaneously evaluate factors influencing 4-year BMD change. MethodsThis was a longitudinal cohort study of healthy, physically active women in the US Military Academy (n=91; average age=18.4years). Assessments over four years included: height, weight, calcium intake, physical fitness, menstrual function (annual number cycles), oral contraceptives (OCs) or depot-medroxyprogesterone acetate (DMPA) use, and eating disorder behavior (Eating Disorder Inventory; (EDI)). BMD was measured annually at the lumbar spine and total hip by dual X-ray absorptiometry and calcaneal BMD by PIXI. Slope of 4year BMD change at each skeletal site (spine total hip and calcaneus) was calculated for each woman. ResultsBMD gains occurred at the spine in 50% and the hip in 36% of women. In unadjusted analyses, spine bone gain was positively related to menstrual cycle frequency (p=0.04). Spine and hip BMD loss occurred in those using DMPA (p<0.01) and those with the highest EDI quartile scores (p<0.05). BMD change was unrelated to OC use. Hip and calcaneus BMD decreased with weight loss (average 4.8+2.2lb/year) as compared to those with stable weight/weight gain (p<0.05). In multivariable analysis, spine BMD increase was significantly related to African American (AA) race, normal EDI score and normal menses. Hip BMD increase was related to AA race, weight increase and normal menses. DMPA use was associated with spine, hip, and calcaneus bone loss. ConclusionOn average, BMD may modestly increase in college-aged women, in the absence of risk factors. However, risk factors including subclinical eating disorders, weight loss, menstrual dysfunction and DMPA use can have significant detrimental effects on BMD in young healthy physically active women.

Women's experiences after Planned Parenthood's exclusion from a family planning program in Texas

ObjectiveWe assessed the impact on depot medroxyprogesterone continuation when a large care provider was banned from a state-funded family planning program. Study DesignWe used three methods to assess the effect of the ban: (a) In a records review, we compared how many state program participants returned to two Planned Parenthood affiliates for a scheduled dose of depot medroxyprogesterone acetate (DMPA) immediately after the ban; (b) We conducted phone interviews with 224 former Planned Parenthood patients about DMPA use and access to contraception immediately after the ban; (c) We compared current contraceptive method of our interviewees to that of comparable DMPA users in the National Survey of Family Growth 2006–2010 (NSFG). Results(a) Fewer program clients returned for DMPA at a large urban Planned Parenthood, compared to a remotely located affiliate (14.4%, vs. 64.8%), reflecting different levels of access to alternative providers in the two cities. (b) Among program participants who went elsewhere for the injection, only 56.8% obtained it at no cost and on time. More than one in five women missed a dose because of barriers, most commonly due to difficulty finding a provider. (c) Compared to NSFG participants, our interviewees used less effective methods of contraception, even more than a year after the ban went into effect. ConclusionsInjectable contraception use was disrupted during the rollout of the state-funded family planning program. Women living in a remote area of Texas encountered more barriers. ImplicationsRequiring low-income family planning patients to switch healthcare providers has adverse consequences.

Effect of depot medroxyprogesterone acetate (DMPA) on bone mineral density (BMD) and evaluating changes in BMD after discontinuation of DMPA in adolescent women

Objective To compare bone mineral density (BMD) between users of intramuscular depot medroxyprogesterone acetate (DMPA) and nonhormonal subjects and evaluated the changes in BMD after discontinuation of DMPA. Methods The study included 102 women aged 16–18 years using DMPA for 24 months and 97 same-age nonusers. BMD of the lumbar spine and femoral neck were measured using dual-energy X-ray absorptiometry. The mean BMD values were compared between DMPA users (DMPA group) and nonusers (control group) and the changes of BMD during 36 months after discontinuation of DMPA were observed. Results Mean BMD at the spine and femoral neck did not differ significantly between DMPA group and control group over 12 months, but the BMD values at both anatomical sites were significantly lower in DMPA group than in control group after 24 months treatment. After DMPA discontinuation, the mean BMD values in DMPA users increased substantially. At 24 months after DMPA discontinuation, there were no significant differences between DMPA group and control group. But the values of the lumbar spine and femoral neck BMD in DMPA group were still 1.70% and 1.87%, respectively, below nonusers at 36 months after DMPA discontinuation. Conclusion The use of DMPA for short-term (=12 months) had no significant effects on BMD at spine and femoral neck, but long-term exposure to DMPA had significant loss in BMD in adolescents. Bone loss occurring with DMPA use is reversible after DMPA discontinuation.

Changes in bone mineral density among women aged 19–24 years using injectable contraceptive depot medroxyprogesterone acetate

Objective To compare bone mineral density (BMD) between users of intramuscular depot medroxyprogesterone acetate (DMPA) and nonhormonal control subjects. Methods The study included 87 women aged between 19 and 24 years using DMPA (DMPA group) for 24 months and 83 same-age women using nonhormonal contraception as control group. BMD of the lumbar spine and femoral neck were measured using dual-energy X-ray absorptiometry, comparing mean BMD changes in DMPA group with the control. Results After 24 months of DMPA treatment, as compared with baseline, the mean BMD in lumbar spine and femoral neck were decreased by 2.67% and 2.71%, respectively. The mean lumbar spine and femoral neck BMD in DMPA group at 24 months were not significantly different compared with baseline (P=0.080 and P=0.076, respectively). In comparison, in control group, there was a trend toward increasing BMD. After 24 months of observation, the mean percentage changes from baseline in lumbar spine and femoral neck BMD were increased by 1.24% and 1.30%, respectively. There was no significantly difference compared with baseline (P=0.436 and P=0.373, respectively). Mean BMD at the spine and femoral neck did not differ significantly between DMPA users and nonusers over 12 months (P=0.153 and P=0.140, respectively), but the BMD at both anatomical sites was significantly lower in DMPA group than in the control after 24 months of treatment (P=0.012 and P=0.008, respectively). Conclusion The use of DMPA for short-term (≤ 12-month) had no significant effects on BMD at spine and femoral neck, but long-term exposure to DMPA had significant loss in BMD in women aged between 19 and 24 years.

Gasto energético e medidas antropométricas de novas usuárias do contraceptivo injetável trimestral de acetato de medroxiprogesterona de depósito

Objetivo:Avaliar o gasto energético e as medidas antropométricas de mulheres durante o primeiro ano de uso do método contraceptivo de acetato de medroxiprogesterona de depósito.Métodos:Estudo prospectivo com grupo de comparação. Foram incluídas mulheres saudáveis, não obesas, nunca usuárias de acetato de medroxiprogesterona de depósito e sem antecedentes que pudessem contribuir para a variação do peso corporal; foram distribuídas em dois grupos, 28 usuárias de acetato de medroxiprogesterona e 24 usuárias de dispositivo intrauterino de cobre, pareadas por idade (±1 ano) e índice de massa corporal (kg/m2). As variáveis estudadas foram sociodemográficas (idade, etnia, tabagismo, etilismo, atividade física, classe econômica e escolaridade), peso (kg), índice de massa corporal, gasto energético basal e total, medidas de circunferência de cintura e quadril (cm) e relação cintura-quadril.Resultados:A idade das mulheres variou de 20-39 anos. As médias de idade/índice de massa corporal foram 29,6 (DP=±5,2) anos/23,9 (±3,6 kg/m2), no grupo de acetato de medroxiprogesterona de depósito, e de 28,6 (DP=±5,2) anos/ 24,5 (±2,7 kg/m2), no grupo de dispositivo intrauterino de cobre. Após análise de variância para medidas repetidas, as usuárias de acetato de medroxiprogesterona de depósito apresentaram ganho de 2,2 kg no peso corporal e de -0,2 kg no grupo do dispositivo intrauterino de cobre, sem diferença estatisticamente significativa entre eles. Não houve discrepância nas demais variáveis estudadas.Conclusão:Mulheres saudáveis e jovens não apresentaram mudança no peso, nas medidas e nos gastos energéticos durante o primeiro ano de uso do contraceptivo acetato de medroxiprogesterona. A orientação em relação aos hábitos saudáveis de vida e o monitoramento de medidas são importantes para o controle do peso corporal em usuárias de métodos contraceptivos.

Adesão à dupla contracepção entre mulheres infectadas pelo HIV

To determine adherence to dual contraception using depot-medroxyprogesterone acetate (DMPA) and condom among HIV-infected women. A cross-sectional study carried out from December 2013 to September 2014 at a local reference center, with application of questionnaire elaborated after Delphi panel and content validation to 114 HIV(+) women aged 15 to 49 years, using DMPA plus condom for contraception. Mean age was 33.2 ± 7.2 years, mean time since HIV detection was 8.1 ± 5.2 years, mean time of antiretroviral use was 6.8 ± 5 years and mean CD4 cells/mm3 count was 737.6 ± 341.1. Sexual HIV acquisition was reported by 98.2% (112/114), antiretroviral use by 85.9% (98/114), and 77.7% (84/114) had a CD4>500/mm3 count. Having a single sex partner was reported by 78.9% (90/114), with HIV serodiscordance in 41.2% (47/114) of couples, 21.9% did not know the serological status of their partner and in 37.7% of cases (43/114) the partner was unaware of the HIV(+) status of the woman. The last pregnancy was unplanned in 71.9% of cases (82/114) and 14.9% of the women had become pregnant the year before, with pregnancy being unplanned in 70.5% (12/17) of cases. Current use of DMPA was reported by 64.9% (74/114), with genital bleeding in 48.2% (55/114) and weight gain in 67.5% (77/114). Use of a male condom was reported by 62.2% of the subjects (71/114). Three reported that they always used a female condom and ten that they eventually used it. Unprotected vaginal sex was reported by 37.7% (43/114) and unprotected anal intercourse was reported by 32.4% (37/114). Partner resistance to use a condom occurred in 30.7% of cases (35/114). Dual contraception using DMPA with condom was reported by 42.9% (49/114). A partner who resisted wearing a condom was associated with poor adhesion (PR=0.3; 95%CI 0.2-0.7; p<0.001). A partner who was unaware that a woman was infected with HIV favored adherence (PR=1.8; 95%CI 1.2-2.7; p=0.013). The percentage of dual contraception using DMPA plus condom was 42.9%, maintaining unplanned pregnancies and unprotected sex. Resistance of partners to use a condom increased three times the chance of a woman not adhering to dual contraception, and the partner not knowing women's HIV infection almost doubled the chance to adhere to safe contraception. to offer new hormonal contraceptives and to involve the partners in contraception and serologic detection tests.

P06.07 The effects of contraception on the vaginal microbiota

Introduction The human microbiota plays important roles in immune system development and resistance to infection. However, factors that influence vaginal bacterial community composition and dynamics are not well understood. There have been conflicting reports of altered vaginal microbiota and infection susceptibility with contraception use. The objective of this study was to determine if contraception use altered the vaginal microbiota. Methods Vaginal swab samples were obtained from over 400 women during their first year of using hormonal contraception (levonorgestrel intrauterine system (LNG-IUS), depot medroxyprogesterone acetate (DMPA), combined oral contraceptive, contraceptive patch and etonogestrel implant) or a non-hormonal copper intrauterine device. Samples were obtained at baseline, 6 months and 12 months as part of the Contraceptive CHOICE study. The V4 region of the bacterial 16S rRNA-encoding gene was amplified from the vaginal swab DNA and sequenced with an Illumina MiSeq. The 16S rRNA gene sequences were processed and analysed using the software package mothur. After clustering the sequences into operational taxonomic units (OTUs) based on sequence similarity we calculated several ecological metrics including θYC distances (a metric that takes relative abundances of both shared and non-shared OTUs into account) between communities. Results The vaginal microbiota in this study clustered into 3 major vaginal bacterial community types: one dominated by Lactobacillus iners, one dominated by Lactobacillus crispatus and one more diverse community type. Initial analysis indicates differences between the microbiota at baseline and after LNG-IUS use. Additionally, specific OTUs were enriched with the use of certain contraceptive methods. For example, higher levels of 2 Prevotella OTUs were associated with DMPA use. Conclusion Alterations of the vaginal microbiota are associated with the use of certain contraceptives. Further studies and analysis will be needed to verify these findings and determine the implications for infection susceptibility. Disclosure of interest statement We did not receive any commercial contributions for this study.

O18.2 Injectable progestin contraception and acquisition of hsv-2 infection among south african women participating in the voice trial

Introduction Observational data suggest HIV-1 acquisition differs between users of two common injectable progestin-only contraceptives (IPC), depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN). Data are limited on the potential impact of both IPC types on herpes simplex virus type 2 (HSV-2) acquisition. Methods We conducted a secondary analysis among IPC users enrolled at South African sites in VOICE, a multi-centre randomised trial of topical and oral HIV-1 chemoprophylaxis. Contraceptive use assessment was conducted monthly. HSV-2 was diagnosed by Focus HerpeSelect EIA at enrollment and repeat EIA at study exit in all participants (seroconversion cutoff value ≥3.5); quarterly EIA was available for a subset to assess seroconversion timing. Using Cox proportional hazards regression, we assessed the association between IPC type and HSV-2 acquisition with adjustment for potential confounders (age, marriage/cohabitation, education, condom use, number of partners, VOICE study arm). Results Among 1776 IPC users who were HSV-2-seronegative at enrollment, 922 (51.9%) used DMPA, 716 (40.3%) used NET-EN, and 138 (7.8%) used both IPC types at different times during follow-up. Among the 1638 IPC users who did not switch IPC type during follow-up, 1506 (91.9%) had baseline and exit HSV-2 serology available. Over 1534.1 person-years (py) of follow-up, 178 incident HSV-2 cases occurred: 107 in DMPA users (crude incidence rate [IR] 11.3/100 py) and 71 in NET-EN users (crude IR 12.1/100 py). Among 640 participants with quarterly HSV-2 serology, 45 cases occurred among DMPA users over 350.4 py and 31 among NET-EN users over 231.1 py (HR = 0.97; 95% CI 0.61–1.53; aHR = 1.02; 95% CI 0.64–1.62). Conclusion HSV-2 risk did not differ by DMPA versus NET-EN use. These results are consistent with our findings that DMPA users in VOICE did not have higher risk of genital tract infection (gonorrhoea, chlamydia or trichomoniasis) compared to NET-EN users, despite having higher risk for HIV-1 infection. Disclosure of interest statement The authors report no conflicts of interest.

Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness

ObjectiveTo examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. Study designA prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350cells/mm3, ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method. ResultsDuring a total of 5233months follow-up among participants not using ART with enrollment CD4 ≥350cells/mm3 (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56–1.48] nor DMPA (aHR 1.28, 95% CI 0.71–2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. ConclusionHormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. ImplicationsHormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.

Impact of Reminder Systems in Clinical Settings to Improve Family Planning Outcomes: A Systematic Review.

This systematic review evaluated the evidence on the impact of family planning reminder systems-interventions intended to remind patients of behaviors to achieve reproductive health goals (e.g., daily text messages reminding oral contraceptive [OC] users to take a pill)-to provide information to guide national recommendations on quality family planning services. Multiple databases including PubMed were searched during 2010-2011 for peer-reviewed articles published in English from January 1985 through February 2011 describing studies evaluating reminder systems to improve family planning outcomes. Studies were excluded if they focused primarily on HIV or sexually transmitted infection prevention, focused solely on men, or were conducted outside the U.S., Europe, Australia, or New Zealand. The initial search identified 16,129 articles, five of which met the inclusion criteria. Three studies examined the impact of OC reminder systems; two found a statistically significant positive impact on correct use. Two studies examined the impact of reminder systems among depot medroxyprogesterone acetate (DMPA) users; one found a statistically significant positive impact on correct use. Although mixed support was found for the effectiveness of reminder system interventions on correct use of OCs and DMPA, the highest-quality evidence yielded null findings. The evidence base would be strengthened by the development of additional studies, especially RCTs, which objectively measure outcomes, examine additional contraceptive methods, and have sufficient sample sizes to detect behavioral outcomes at least 12 months post-intervention.

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

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. 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. 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 log₁₀ 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 log₁₀ ng/mL; P = 0.002), whereas SLPI and HBD-2 were similar. 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.

Effect of hormonal contraception on the function of plasmacytoid dendritic cells and distribution of immune cell populations in the female reproductive tract.

Epidemiological evidence suggests an association between the use of hormonal contraception and an increased risk of acquiring sexually transmitted diseases including HIV-1. We sought to elucidate the biological mechanisms underlying the effect of hormonal contraception on the immune system. Cross-sectional study. To delineate the biological mechanisms underlying the effect of hormonal contraceptives on the immune system, we analyzed the functional capacity of circulating plasmacytoid dendritic cells (pDCs), the distribution of vaginal immune cell populations, and the systemic and genital levels of immune mediators in women using depot medroxyprogesterone acetate (DMPA), NuvaRing, or combined oral contraceptives (COC). The use of DMPA or NuvaRing was associated with reduced capacity of circulating pDCs to produce interferon (IFN)-α and tumor necrosis (TNF-α) in response to TLR-9 stimulation. Systemic levels of IFN-α and cervicovaginal fluid levels of IFN-α, CXCL10, monocyte chemotactic protein-1, and granulocyte-colony stimulating factor were significantly lower in DMPA users compared to control volunteers not using hormonal contraception. The density of CD207 Langerhans cells in the vaginal epithelium was reduced in NuvaRing and combined oral contraceptive users but not in DMPA users. The presented evidence suggests that the use of some types of hormonal contraception is associated with reduced functional capacity of circulating pDCs and altered immune environment in the female reproductive tract.

Use of depot medroxyprogesterone acetate and prevalent leiomyoma in young African American women.

Is use of depot medroxyprogesterone acetate (DMPA) a risk factor for or a protective factor against prevalent uterine leiomyoma? Ever use of DMPA was associated with a decreased risk (adjusted risk ratio (RR): 0.8, 95% confidence interval (CI): 0.6, 0.9) of prevalent leiomyoma in young African American women. Although progesterone is associated with growth of leiomyoma, previous epidemiological studies have shown a protective association for DMPA use. These previous studies may have been biased by studying clinically diagnosed leiomyoma (DMPA may mask symptoms thus delaying diagnoses). Cross sectional analysis of baseline data from a cohort study of 1696 African American women. Community-based recruitment (e.g. letters, flyers, radioand TV announcements) were used to enroll African American women between 23 and 34 years old without a previous diagnosis of leiomyoma in the Metropolitan Detroit area. Extensive questionnaire data were used to determine DMPA use and screening ultrasound detected the presence of leiomyoma ≥0.5 cm in diameter. Relative risks with adjustment for covariates were calculated for the presence of leiomyoma based on ever use of DMPA as well as duration and recency of use. Among the 1696 volunteers who enrolled, 43% had used DMPA. Leiomyoma were detected in 17% of those who had ever used DMPA compared with 26% of those who had never used DMPA. The reduction in prevalence remained after adjustment for potential confounders and was highest among women who had used DMPA for more than 4 years (adjusted RR: 0.5, 95% CI: 0.3, 0.8). The reduction in risk was seen for women whose most recent use was up to 8 years prior to study enrollment. The use of cross-sectional data means that the timing of initial fibroid development is not known, so the temporality of the association is uncertain. However in this sample of young women, most fibroids were small, suggesting that DMPA exposure may have occurred before leiomyoma development. Our findings are in agreement with previous epidemiological studies, but protected from the bias inherent in the use of clinically diagnosed leiomyoma. Although further studies will be needed to elucidate the mechanism, use of DMPA as a contraceptive appears to provide long lasting protection against uterine leiomyoma. No competing interests. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, and in part by funds allocated for health research by the American Recovery and Reinvestment Act. N/A.