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Hormonal contraceptive use and risk of HIV-1 disease progression.

ABSTRACT: For HIV-1-infected women, hormonal contraception prevents unintended pregnancy, excess maternal morbidity, and vertical HIV-1 transmission. Hormonal contraceptives are widely used but their effects on HIV-1 disease progression are unclear.In a prospective study among 2269 chronically HIV-1-infected women from seven countries in eastern and southern Africa and with enrollment CD4 cell counts at least 250?cells/?l, we compared rates of HIV-1 disease progression among those using and not using hormonal contraception (i.e. oral or injectable methods). The primary outcome was a composite endpoint of CD4 decline to less than 200?cells/?l, initiation of antiretroviral therapy, or death.Three hundred and seventy-two women experienced HIV-1 disease progression during 3242 years of follow-up (incidence rate?=?11.5 events per 100 person-years). Rates of HIV-1 disease progression among women who were currently using and not using hormonal contraception were 8.54 and 12.31 per 100 person-years, respectively (adjusted hazard ratio 0.74, 95% confidence interval 0.56-0.98, P?=?0.04). Rates were 8.58 and 8.39 per 100 person-years for the subsets using injectable and oral contraception (adjusted hazard ratio?=?0.72, P?=?0.04 for injectable users and adjusted hazard ratio?=?0.83, P?=?0.5 for oral users compared to women not using hormonal contraception). Sensitivity analyses assessing enrollment or cumulative contraceptive use during the study demonstrated risk estimates closer to 1.0 with no evidence for accelerated disease progression.Among African women with chronic HIV-1 infection, use of hormonal contraception was not associated with deleterious consequences for HIV-1 disease progression.

SUBMITTER: Heffron R

PROVIDER: S-EPMC3740957 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Hormonal contraceptive use and risk of HIV-1 disease progression.

Heffron Renee R Mugo Nelly N Ngure Kenneth K Celum Connie C Donnell Deborah D Were Edwin E Rees Helen H Kiarie James J Baeten Jared M JM

AIDS (London, England) 20130101 2

<h4>Background</h4>For HIV-1-infected women, hormonal contraception prevents unintended pregnancy, excess maternal morbidity, and vertical HIV-1 transmission. Hormonal contraceptives are widely used but their effects on HIV-1 disease progression are unclear.<h4>Methods</h4>In a prospective study among 2269 chronically HIV-1-infected women from seven countries in eastern and southern Africa and with enrollment CD4 cell counts at least 250 cells/μl, we compared rates of HIV-1 disease progression a ...[more]

PMID: 23079806

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Project description:BackgroundThe evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies.MethodsWe updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features.FindingsWe identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1·40, 95% CI 1·16-1·69). This risk was lower in the eight studies done in women in the general population (pooled HR 1·31, 95% CI 1·10-1·57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I(2) 51·1%, 95% CI 0-79·3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection (I(2) 54%, 0-88·7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1·00, 0·86-1·16) or five studies of norethisterone enanthate (pooled HR 1·10, 0·88-1·37).InterpretationOur findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive.FundingNone.

Project description:Important questions remain on how hormonal contraceptives alter the local immune environment and the microbiota in the female genital tract and how such effects may impact susceptibility to HIV infection. We leveraged samples from a previously conducted clinical trial of Malawian women with (n = 73) and without (n = 24) HIV infection randomized to depot medroxyprogesterone acetate (DMPA) or the levonogestrel implant in equal numbers within each group and determined the effects of these hormonal contraceptives (HCs) on the vaginal immune milieu and the composition of the vaginal microbiota. Longitudinal data for soluble immune mediators, measured by multiplex bead arrays and enzyme-linked immunosorbent assays (ELISAs), and vaginal microbiota, assessed by 16S rRNA gene amplicon, were collected prior to and over a period of 180 days post-HC initiation. DMPA and levonogestrel had only minimal effects on the vaginal immune milieu and microbiota. In women with HIV, with the caveat of a small sample size, there was an association between the median log10 change in the interleukin-12 (IL-12)/IL-10 ratio in vaginal fluid at day 180 post-HC compared to baseline when these women were classified as having a community state type (CST) IV vaginal microbiota and were randomized to DMPA. Long-lasting alterations in soluble immune markers or shifts in microbiota composition were not observed. Furthermore, women with HIV did not exhibit increased viral shedding in the genital tract after HC initiation. Consistent with the results of the ECHO (Evidence for Contraceptive Options and HIV Outcomes) trial, our data imply that the progestin-based HC DMPA and levonorgestrel are associated with minimal risk for women with HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT02103660). IMPORTANCE The results of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, the first large randomized controlled clinical trial comparing the HIV acquisition risk of women receiving DMPA, the levonorgestrel (LNG) implant, or the copper intrauterine device (IUD), did not reveal an increased risk of HIV acquisition for women on any of these three contraceptives. Our study results confirm that the two different progestin-based hormonal contraceptives DMPA and levonogestrel will not increase the risk for HIV infection. Furthermore, DMPA and levonogestrel have only minimal effects on the immune milieu and the microbiota in the vaginal tract, attesting to the safety of these hormonal contraceptives.

Project description:ImportanceThe association between the use of hormonal contraceptive and pancreatic cancer among premenopausal women has until now been unclear. This is the first study to investigate the risk of pancreatic cancer in pre-menopausal women.ObjectiveTo determine whether hormonal contraception increases the risk of developing pancreatic cancer in pre-menopausal women.DesignA nationwide prospective cohort study followed all women in Denmark in the age range of 15-49 years without previous cancer or venous thrombosis from 1995 to 2014. The Danish National Prescription Registry provided individually updated exposure information on use of hormonal contraception. The Danish Cancer Registry provided cancer diagnoses, and the Danish National Patient Register containing clinical diagnoses and surgical codes at discharge from public and private hospitals.SettingPopulation-based cohort study.ParticipantsAll women living in Denmark aged 15-49 years at January 1st, 1995, and those subsequently reaching age 15 years up to December 31st, 2014 were eligible for the study.ResultsAmong 1.9 million women who were followed on average for 11.4 years, 235 pancreatic cancers occurred. Compared to never users, ever users of any type of hormonal contraception had a relative risk (RR) of pancreatic cancer of 0.90 (95% confidence interval (CI) 0.68-1.19). No overall association between duration of hormonal contraceptive use and pancreatic cancer risk was found. Neither was long-term use of hormonal contraception associated with pancreas cancer, RR 0.83 (95% CI 0.47-1.50). The risk did not vary between users of combined and progestogen-only products. All models were adjusted for age, completed or ongoing education, polycystic ovary syndrome, endometriosis and among parous women; parity, age at first birth, smoking and body mass index.Conclusions and relevanceCompared to never users the risk of pancreatic cancer is not significantly higher among current and recent users of contemporary hormonal contraception and does not vary between users of combined and progestogen-only products. In conclusion, our study suggests no risk of pancreatic cancer with use of any type of hormonal contraception.

Project description:BACKGROUND/OBJECTIVES:Experiments in animal models have shown a positive association between in utero exposure to pharmacologic sex hormones and offspring obesity. The developmental effects of such hormones on human obesity are unknown. SUBJECTS/METHODS:Using data from a large, prospective pregnancy cohort study (n=19?652), with linkage to a national prescription registry, we evaluated the association between use of hormonal contraceptives before and after conception (defined from dispensed prescription data and characterized by last date of use relative to conception, 12 to >4 months before (n=3392), 4 to >1 months before (n=2541), 1 to >0 months before (n=2997) and 0-12 weeks after (n=567)) in relation to offspring overweight or obesity at age 3 years. RESULTS:We observed a weak, inverse association between early pregnancy use of a combination oral contraceptive and offspring overweight or obesity at age 3 (adjusted odds ratio (OR): 0.75, 95% confidence interval (CI): 0.53, 1.08) and a positive, but imprecise, association with use of a progestin-only oral contraceptive in early pregnancy (adjusted OR: 1.26, 95% CI: 0.79, 2.02). In general, no association was observed between the use of a hormonal contraceptive before conception and offspring overweight or obesity. A sensitivity analysis comparing combination oral contraceptive users in early pregnancy to other unplanned pregnancies without hormonal contraceptive use further strengthened the inverse association (adjusted OR: 0.70, 95% CI: 0.48, 1.02). Other sensitivity analyses were conducted to evaluate the robustness of the associations observed given varying assumptions. CONCLUSIONS:Pharmacologic sex hormones in early pregnancy may be inversely or positively associated with offspring overweight or obesity at age 3, depending on the specific formulation used. The present study provides support for the potential for environmental sources of hormonally active agents to exert developmental effects.

Project description:BackgroundThe incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurrence of depression in females that begins in early adolescence. In this study, we examine whether and how introducing synthetic estrogen and progestin derivatives through the use of combined hormonal contraceptives (CHC), affects adolescent females' risk for developing depression. We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning.MethodsUsing a longitudinal cohort design, we will follow a sample of adolescent females over the span of three years. Participants will be assessed at three time points: once when they are between 13 and 15 years of age, and at approximately 18 and 36 months after their initial assessment. Each time point will consist of two online sessions during which participants will complete a clinical interview that screens for key symptoms of mental health disorders, along with a series of questionnaires assessing their level of depressive symptoms and history of contraceptive use. They will also complete a standardized social-evaluative stress test and an emotion recognition task, as well as provide saliva samples to allow for assessment of their circulating free cortisol levels.DiscussionIn this study we will assess the effect of CHC use during adolescence on development of Major Depressive Disorder (MDD). We will control for variables previously found to or proposed to partially account for the observed relationship between CHC use and MDD, including socioeconomic status, age of sexual debut, and CHC-related variables including age of first use, reasons for use, and its duration. In particular, we will discover whether CHC use increases depressive symptoms and/or MDD, whether elevated depressive symptoms and/or MDD predict a higher likelihood of starting CHC, or both. Furthermore, this study will allow us to clarify whether alterations in stress reactivity and social-emotional functioning serve as pathways through which CHC use may result in increased risk of depressive symptoms and/or MDD.

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Hormonal contraceptive use and risk of HIV-1 disease progression.

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Hormonal contraceptive use and risk of HIV-1 disease progression.

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