Central Clinical School, Monash University, Carlton, VIC, Australia.
Melbourne Sexual Health Centre, Alfred Health, Carlton, VIC, Australia.
Front Cell Infect Microbiol. 2021 Nov 12;11:732423. doi: 10.3389/fcimb.2021.732423. eCollection 2021.
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.
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.
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.
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.
激素避孕和绝经激素治疗（MHT）中的外源性性激素被用于计划生育和管理绝经症状，而没有考虑它们对阴道微生物群的影响。这在很大程度上是因为它们的使用早于我们对阴道微生物组对人类健康重要性的认识。我们进行了一项系统评价（PROSPERO：CRD42018107730），以确定外源性性激素（按含有雌激素或仅含孕激素的避孕类型以及 MHT 分层）对阴道微生物群的影响，这是通过分子方法来衡量的。
检索了 Embase、PubMed 和 Medline 数据库，以获取截至 2020 年 12 月 1 日发表的相关文献。符合条件的研究报告了特定外源性性激素对阴道微生物群的影响，使用的是分子方法。提取并总结了每种避孕类型或 MHT 对阴道微生物群的“阳性”、“阴性”或“中性”影响的数据。阳性效应反映了与对照组相比，外源性性激素暴露与乳杆菌丰度增加、阴道微生物群组成发生变化或维持最佳状态、细菌多样性降低（具体反映为低多样性最佳微生物群状态）相关。如果外源性性激素对阴道微生物群产生相反的影响（即乳杆菌减少，非最佳微生物群状态），则将其指定为对阴道微生物群有负面影响。当未发现显著变化时，则认为是中性/不确定。
我们确定了 29 篇报告外源性性激素对阴道微生物群影响的手稿；25 篇研究激素避孕，4 篇研究 MHT。含有雌激素的避孕方法，特别是含有雌激素和孕激素的复方避孕药，对阴道微生物群的组成有积极影响。仅含孕激素的避孕方法，特别是醋酸甲羟孕酮，对微生物群的影响较为复杂。在使用 MHT 的绝经后妇女中，局部应用外源性雌激素与乳杆菌的患病率增加有关。
我们的研究结果表明，含有雌激素的化合物可能促进最佳的阴道微生物群，这可能具有临床应用价值。仅含孕激素的避孕方法对阴道微生物群的影响不太清楚；需要更多的数据来确定仅含孕激素的避孕药如何导致不良的生殖和性健康结局。
