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J Infect Dis. 2016 May 15;213(10):1532-40. doi: 10.1093/infdis/jiw004. Epub 2016 Jan 5.

Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor-Based Combination Antiretroviral Therapy.

Author information

1
Toronto General Research Institute, University Health Network.
2
Women's College Research Institute, Women's College Hospital Department of Medicine.
3
Department of Medicine St. Michael's Hospital.
4
St. Michael's Hospital.
5
Department of Medicine Mount Sinai Hospital, Toronto.
6
Toronto General Research Institute, University Health Network Department of Medicine.
7
University of Western Ontario, London, Canada.
8
Toronto General Research Institute, University Health Network Women's College Research Institute, Women's College Hospital Department of Immunology, University of Toronto.

Abstract

BACKGROUND:

It has been reported that pregnant women receiving protease inhibitor (PI)-based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level.

METHODS:

We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)-infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism.

RESULTS:

HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P= .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00-4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66-1.26 AU;P= .002). Prolactin, a key regulator of 20α-HSD, was lower (P= .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART-induced decreases in progesterone levels.

CONCLUSIONS:

Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women.

KEYWORDS:

20-α-hydroxysteroid dehydrogenase; HIV; adverse birth outcomes; antiretrovirals; birth weight; pregnancy; progesterone; prolactin; protease inhibitors

PMID:
26740274
PMCID:
PMC4837912
DOI:
10.1093/infdis/jiw004
[Indexed for MEDLINE]
Free PMC Article

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