Abstract

BackgroundA high endogenous progesterone luteal state in the menstrual cycle has been independently associated with Human Immunodeficiency Virus (HIV) incidence in epidemiological studies. Hormonal contraception particularly high dose Depot Medroxyprogesterone Acetate (DMPA) is also thought to increase the risk of HIV acquisition. Inconsistent reports of this association have led us to hypothesize that unsuppressed endogenous progesterone level in women who reported hormonal contraception (HC) use may be an explanation for increased vulnerability to HIV.MethodsThis pilot study was a secondary cross-sectional analysis of data and laboratory testing of stored specimens collected from women who participated in the SAMRC HIV prevention MDP 301 trial during 2005–2009 in South Africa. Serum progesterone levels were measured in 39 women at the point of first positive HIV diagnosis during study follow-up and 36 women who remained HIV uninfected at the 52-week study exit visit.ResultsOverall, the median (IQR) progesterone level in 49 women using hormonal contraception was 0.39 ng/ml (IQR 0.13–0.45) and 48 (97.9%) women had a progesterone level < 3.0 ng/ml suggestive of adequate progesterone suppression for contraceptive efficacy. After excluding the one woman with a progesterone level of > 3.0 ng/ml, the median progesterone level in women using DMPA remained marginally higher at 0.42 ng/ml (IQR 0.27–0.45) than women using Norethisterone Enanthate (NET-EN) (0.31 ng/ml; IQR 0.13–0.41, p = 0.061). For women using hormonal contraception, the median progesterone level did not differ between women with recent HIV infection or women who remained HIV negative (0.39 vs 0.38 ng/ml, p = 0.959). Similarly, the median progesterone level in women using DMPA or NET-EN did not differ by HIV status (0.43 vs 0.41 ng/ml, p = 0.905; 0.24 vs 0.31 ng/ml, p = 0.889).ConclusionAmong women using hormonal contraception, DMPA or NET-EN we did not observe a significant difference in progesterone levels between women with recently acquired HIV infection and women who remained HIV negative. Our findings suggest that endogenous progesterone levels remain suppressed in the presence of hormonal contraception and are not likely to be associated with HIV acquisition.

Highlights

  • A high endogenous progesterone luteal state in the menstrual cycle has been independently associated with Human Immunodeficiency Virus (HIV) incidence in epidemiological studies

  • Implications In one of a handful of studies in women, our findings are suggestive that the endogenous progesterone level remains adequately suppressed in the presence of high dose hormonal contraception (HC) and may not be associated with recently acquired HIV acquisition

  • In the presence of hormonal contraception (DMPA or Norethisterone Enanthate (NET-EN)), the lack of an association between endogenous progesterone levels and recently acquired HIV infection in our sub-study is suggestive of other potential mechanisms of risk for HIV acquisition associated with Depot Medroxyprogesterone Acetate (DMPA)

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Summary

Introduction

A high endogenous progesterone luteal state in the menstrual cycle has been independently associated with Human Immunodeficiency Virus (HIV) incidence in epidemiological studies. Hormonal contraception high dose Depot Medroxyprogesterone Acetate (DMPA) is thought to increase the risk of HIV acquisition. Inconsistent reports of this association have led us to hypothesize that unsuppressed endogenous progesterone level in women who reported hormonal contraception (HC) use may be an explanation for increased vulnerability to HIV. An estimated 7 million South Africans are living with Human Immunodeficiency Virus (HIV) and women aged 15 and older constitute more than 57% of those affected [1] In comparison to their male counterparts, young women are disproportionately affected by incident HIV infections [2]. Evidence of increased vulnerability to HIV during the luteal phase of the menstrual cycle, during pregnancy, lactation and menopause are suggestive of an association between high endogenous progesterone levels and altered mucosal immunity during these progesterone dominant periods [12,13,14]

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