The Effect of Exogenous Sex Steroids on the Vaginal Microbiota: A Systematic Review.

Larissa K Ratten, Erica L Plummer, Catriona S Bradshaw, Christopher K Fairley, Gerald L Murray, Suzanne M Garland, Deborah Bateson, Gilda Tachedjian, Lindi Masson, Lenka A Vodstrcil

Journal: Frontiers in cellular and infection microbiology 2022;11():732423

PMID: 34869054

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Plain Language Summary

A vaginal microbiota associated with optimal reproductive and sexual health outcomes is characterised by Lactobacillus spp., although microbiome composition varies across geographical locations and specific populations. The aim of this study was to summarise the effect of specific oestrogen-containing or progestin-only contraceptives as well as menopausal hormonal therapy (MHT) on the vaginal microbiota, and evaluate the strength of these findings. This study is a systematic review of twenty-nine studies out of which 25 studies reported on the effect of hormonal contraception among reproductive-aged women and four on the effect of MHT among post-menopausal women. This review shows that: - oestrogen-containing contraceptives, particularly the combined oestrogen and progestin-containing oral contraceptive pill, had a positive effect on the composition of the vaginal microbiota. - among post-menopausal women using MHT, exogenous oestrogen also appeared to positively influence the vaginal microbiota. - exogenous-oestrogen as an adjunctive therapy does not impact the composition of the vaginal microbiota in a detrimental way. - the impact of progestin-only hormonal contraceptives was less consistent as there was equal evidence that they have either a negative or neutral impact on the vaginal microbiota. Authors conclude that their findings confirm the potential benefits of exogenous oestrogen in conferring a vaginal microbiota associated with optimal health outcomes for women.

Abstract

BACKGROUND

Exogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms, without consideration of their effects on the vaginal microbiota. This is largely because their use predates our understanding of the importance of the vaginal microbiome on human health. We conducted a systematic review (PROSPERO: CRD42018107730) to determine the influence of exogenous sex steroids, stratified by oestrogen-containing or progestin-only types of contraception, and MHT on the vaginal microbiome, as measured by molecular methods.

METHODS

Embase, PubMed and Medline were searched for relevant literature published through to December 1st 2020. Eligible studies reported on the effect of specific exogenous sex steroids on the vaginal microbiome using a molecular method. Data regarding the 'positive', 'negative' or 'neutral' effect of each type of contraceptive or MHT on the vaginal microbiome was extracted and summarised. A positive effect reflected sex steroid exposure that was associated with increased abundance of lactobacilli, a change to, or maintenance of, an optimal vaginal microbiota composition, or a decrease in bacterial diversity (specifically reflecting a low-diversity optimal microbiota state), relative to the control group. An exogenous sex steroid was designated as having a negative effect on the vaginal microbiome if it resulted in opposing effects (i.e. loss of lactobacilli, a non-optimal microbiota state). When no significant change was found, this was considered neutral/inconclusive.

RESULTS

We identified 29 manuscripts reporting on the effect of exogenous sex steroids on the vaginal microbiome; 25 investigating hormonal contraceptives, and 4 investigating MHT. Oestrogen-containing contraception, particularly reflecting the combined oestrogen and progestin-containing contraceptive pill, had a positive effect on the composition of the vaginal microbiota. Progestin-only contraception, particularly reflecting depo-medroxyprogesterone acetate, had mixed effects on the microbiota. Among post-menopausal women using MHT, exogenous oestrogen applied topically was associated with increased prevalence of lactobacilli.

CONCLUSION

Our findings suggest that oestrogen-containing compounds may promote an optimal vaginal microbiota, which could have clinical applications. The impact of progestin-only contraceptives on the vaginal microbiota is less clear; more data is needed to determine how progestin-only contraceptives contribute to adverse reproductive and sexual health outcomes.

Address: Central Clinical School, Monash University, Carlton, VIC, Australia.; Melbourne Sexual Health Centre, Alfred Health, Carlton, VIC, Australia.; Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia.; Centre for Women's Infectious Diseases Research, The Royal Women's Hospital, Parkville, VIC, Australia.; Infection and Immunity, Murdoch Children's Research Institute, Parkville, VIC, Australia.; Family Planning NSW, Sydney, NSW, Australia.; Discipline of Obstetrics, Gynaecology and Neonatology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Life Sciences Discipline, Burnet Institute, Melbourne, VIC, Australia.; Department of Microbiology, Monash University, Clayton, VIC, Australia.; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.; Institute of Infectious Disease and Molecular Medicine and Department of Pathology, University of Cape Town, Cape Town, South Africa.; Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.

DOI: 10.3389/fcimb.2021.732423