Format

Send to

Choose Destination
Dis Model Mech. 2019 Oct 23;12(10). pii: dmm039669. doi: 10.1242/dmm.039669.

Medroxyprogesterone acetate alters the vaginal microbiota and microenvironment in women and increases susceptibility to HIV-1 in humanized mice.

Author information

1
McMaster Immunology Research Centre, Michael G. DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
2
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
3
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
4
Department of Medical Microbiology, University of Nairobi, P.O. BOX 30197-00100, Nairobi, Kenya.
5
Kenyan AIDS Control Program, P.O. Box 19361 - 00202, Nairobi, Kenya.
6
Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Pavillon CHUL, Québec City, Québec G1V 4G2, Canada.
7
Department of Microbiology and Immunology Medical Biology, Université Laval, Québec City, Québec G1V 0A6, Canada.
8
Public Health Laboratories, Public Health Ontario, Toronto, Ontario M5G 1V2, Canada.
9
Mount Sinai Hospital/University Health Network, Department of Microbiology, Toronto, Ontario M5G 1X5, Canada.
10
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
11
Department of Medicine, Farncombe Family Digestive Health Institute, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
12
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
13
McMaster Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
14
McMaster Immunology Research Centre, Michael G. DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, Ontario L8S 4K1, Canada kaushic@mcmaster.ca.

Abstract

The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA-mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

Amylase; DMPA; Glycogen; Humanized mouse; Polymicrobial vaginal microbiota

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center