The crosstalk between female hormones and the vaginal microbiome

The gut and genital tract microflora of females are complex biological ecosystems that are in continuous communication with each other. The bacteria that colonise the vagina evolved through translocation of bacteria from the gut to the vagina, or through mother-to-child transfer during delivery. The vaginal microbiome is composed of over 200 species and is unique to each female, as it differs depending on genes, age, hygiene, dietary habits, ethnicity and use of lubricants or medications.^1,2   The overall health of the vagina depends on several factors, namely a healthy balance of the hormones oestrogen and progesterone, good quality connective tissue and a robust and diverse balance of beneficial bacteria that reside in the genital area, which make up the vaginal microbiome.³

The normal vaginal microflora consists of Lactobacillus bacteria that emerge from the gut. This includes L. crispatus, L. gasseri, L.rhamnosus, L. salivarius, and L. plantarum with some Bifidobacterium species.[i] These strains produce lactic acid, which maintain the vaginal pH to be within the required 3.5-4.5. This acidity is essential to prevent opportunistic bacteria from proliferating uncontrollably. Lactobacillus strains also exert a natural antimicrobial and anti-inflammatory effect, which keeps foreign bacteria at bay. Other commensal anaerobic species with great propensity to becoming pathogens, especially when Lactobacilli are depleted, include Gardnerella, Prevotella, Megasphaera, Atopobium, Streptococcus, Mobiluncus, Mycoplasma and Peptoniphilus. When in high levels, these strains may contribute to vaginal infections such as bacterial vaginosis (BV).⁴  

Pathogenic infections within the gut e.g. Escherichia coli (E. coli) and Candida strains (mostly Candida albicans) are thought to directly affect bacterial composition of the vagina due to their ability to translocate to the vagina and multiply.⁵ 

Oestrogen is particularly important to promote healthy epithelial and connective tissues of the vagina, and fluctuations in oestrogen levels have their part to play in the lubrication and bacterial balance of the vagina. The vaginal microbiome evolves over a women’s lifetime due to the natural ebb and flow of oestrogen. 

During childhood, the vagina has a more alkaline pH and is predominantly colonised by cutaneous and faecal microorganisms, but hormonal changes in puberty cause the pH to decrease, becoming more acidic, which allows Lactobacillus species to proliferate.⁶ The vaginal microbiome also changes during pregnancy, showing reduced richness and diversity becoming more Lactobacillus-dominated strains due to oestrogen affecting the thickness of vaginal mucosa. This change may be a contributing factor to an increased risk of vulvovaginal candidiasis during pregnancy.⁷ Many causes of idiopathic infertility are now thought to be related to microbial etiologies, as a non-optimal vaginal microbiome carries an increased risk of UTI’s, STI’s and pelvic inflammatory disease.⁸

During the menopause, there are significant changes to the vaginal microbiome^,2 as oestrogen levels drop, we see a reduction in Lactobacilli, leading to colonisation with cutaneous microorganisms, including Staphylococcus, which can increase the pH^.9,10 The combination of low oestrogen and a reduction in Lactobacilli strains can contribute to symptoms such as vulvovaginal atrophy, vaginal dryness and infections such as vulvovaginal candidiasis and bacterial vaginosis.^11,12

Vaginal infections are common in women from their teenage years through to menopause. It’s estimated that around 75% of women experience vulvovaginal candidiasis within their lifetime,¹³ and ²⁹. 2% will have an occurrence of bacterial vaginosis.¹⁴ Unfortunately, women who have hormonal imbalances are prime targets for reoccurring vaginal infections. The menstrual cycle alone can contribute to changes within the vaginal microbiome. For example, the pH of the vagina can increase during menses due to menstrual blood being slightly alkaline, which contributes to changes in the vaginal microbiome and increased susceptibility to infections during that time.¹⁵

There are mixed results when investigating the effects of hormonal contraceptives on the vaginal microbiome. Some studies have found that hormonal contraceptive use can alter the microbiome in a negative way, increasing the risk of sexually transmitted diseases, bacterial vaginosis and overgrowths of Candida albicans.^16,17 Progestin-only contraceptives have been found to reduce overall abundance of Lactobacillus species.¹⁸ However, other studies found that combined oral contraceptives can increase the abundance of Lactobacillus species, while reducing growth of pathogenic species.¹⁹ 

The oral contraceptive pill can reduce the diversity and abundance of the gut microbesiome,²⁰ as well as deplete nutrients needed for hormones, structure, and immune function, including B vitamins, vitamin C, E, zinc, selenium, and magnesium.²¹ The depletion of these essential nutrients, especially folate, vitamin B6, zinc and vitamin E,²² alongside changes within the gut, may play a role in the development of more severe and recurrent vaginal infections.²³ This may indicate a need for women using contraception to take a probiotic supplement alongside additional nutrients.

Other common causes of vaginal microbiome disruption include:

• Diet (high glycaemic load & low nutritional density)
• Smoking
• Exposure to synthetic chemicals, toiletries, and fragrances that disrupt vaginal bacteria and pH
• Changes in vaginal pH as a result of exposure to semen
• Vaginal douching
• Medications: Oral Contraceptive Pill (OCP), Hormone Replacement Therapy (HRT), steroids,²⁴ and antibiotics.
• Chronic stress can increase the pH of the vaginal microbiome and raise inflammation.²⁵

Both oral and topical probiotics can support the vaginal microbiome by secreting antimicrobial peptides such as lactic acid, hydrogen peroxide, and bacteriocin, which maintain the vaginal acidic pH, making it more difficult for pathogens to establish themselves.²⁶ Additionally, probiotic supplementation may have indirect effects on the vaginal microbiome through alteration of the estrobolome. This collection of bacteria can influence circulating oestrogen levels through the secretion of enzymes such as beta-glucuronidase which deconjugates oestrogens into their active forms.²⁷

As vaginal dysbiosis is associated with increased risk of certain symptoms and conditions, you may consider a probiotic in women who suffer with recurrent thrush, BV, or urinary tract infections (UTIs), currently on birth control, planning pregnancy, or going through the menopause. 

There are a few key strains that can be particularly beneficial for maintaining female health:

• Lactobacillus rhamnosus – Has anti-microbial properties against S.aureus and E.coli, ²⁸²⁹ helping to restore vaginal pH and control bacterial vaginosis.³⁰ In one study, after 28 days of daily oral supplementation of Lactobacillus rhamnosus resulted in an increase in vaginal Lactobacilli and a significant decrease in yeast and coliforms.³¹
• Lactobacillus crispatus – Is representative of a healthy vaginal microflora, due to being the dominant species of the vaginal microbiota.³² It offers protection against Candida albicans, especially against Candida translocation,33 as well as a Chlamydia, Bacterial Vaginosis and UTIs.³⁴ It is also associated with lower risk of pre-term birth.³⁵
• Lactobacillus salivarius – Produces antimicrobial peptides that can reduce growth of urogenital pathogens, including Candida albicans, but also Enterococcus faecalis and Neisseria gonorrhoeae.^36,37
• Lactobacillus gasseri – Is a strong producer of lactic acid which helps to inhibit the growth of E.coli and Candida albicans adhesion.³⁸ Supplementation of Lactobacillus gasseri daily in women aged 20-38yrs for 6 months significantly reduced PMS symptoms, including improved emotional wellbeing.³⁹ Supplementation has also shown to result in a significant decrease in endometriotic lesions via activation of NK cells. ⁴⁰
• Lactobacillus acidophilus (LA02) - An in vivo study combining Lactobacillus acidophilus (LA02) with Lactobacillus fermentum (LF10) in a slow-release effervescent tablet was shown to significantly reduce recurrence of vulvovaginal candidiasis infection by 72.4% 7 months after treatment.²³
• Lactobacillus fermentum (LF10) - L. fermentum antimicrobial actions have been attributed to its ability to produce a bacteriocin-like compound,24 and antimicrobial peptide fermenticin HV6b.²⁵ In vitro studies suggested that L. fermentum was an excellent candidate for adhesion to the vaginal epithelium and can produce a biofilm on the surface of epithelial cells. Interaction with mucin allows the Lactobacilli to remain within the mucus layers, thereby contributing to the formation of multi-species biofilms.^26,27 In a recent study, the growth and virulence of Escherichia coli and Gardnerella vaginalis were inhibited by the L. fermentum^.28 It has also been shown to inhibit C. albicans and C. glabrata growth,²⁹ and reduce growth of Bacteroides, G. vaginalis, Mobiluncus, Staphylococcus spp., and Streptococcus spp.³⁰

With vaginal infections being so common in women, it is encouraging to see the potential of probiotic supplementation in supporting women and reducing risk of both symptoms and infections. 

It’s important to note the bi-directional relationship between the microbiome and oestrogen, which emphasises the need to consider both areas in supporting female health. The natural shifts in oestrogen over a woman’s lifetime can influence both the structure and microbiome of the vagina, which have an overall effect on female health. 

1. Barrientos-Durán A, Fuentes-López A, de Salazar A, Plaza-Díaz J, García F. Reviewing the Composition of Vaginal Microbiota: Inclusion of Nutrition and Probiotic Factors in the Maintenance of Eubiosis. Nutrients 2020, Vol 12, Page 419. 2020;12(2):419. doi:10.3390/NU12020419
2. Muhleisen AL, Herbst-Kralovetz MM. Menopause and the vaginal microbiome. Maturitas. 2016;91:42-50. doi:10.1016/J.MATURITAS.2016.05.015
3. Wessels JM, Felker AM, Dupont HA, Kaushic C. The relationship between sex hormones, the vaginal microbiome and immunity in HIV-1 susceptibility in women. Dis Model Mech. 2018;11(9). doi:10.1242/DMM.03514
4. Amabebe E, Anumba DOC. The vaginal microenvironment: The physiologic role of Lactobacilli. Front Med (Lausanne). 2018;5(JUN):181. doi:10.3389/FMED.2018.00181/BIBTEX
5. Vásquez A, Ahrné S, Jeppsson B, Molin G, Molin R. Oral administration of Lactobacillus and Bifidobacterium strains of intestinal and vaginal origin to healthy human females: Re-isolation from faeces and vagina. Published online 2009. doi:10.1080/08910600510031376
6. Auriemma RS, Scairati R, del Vecchio G, et al. The Vaginal Microbiome: A Long Urogenital Colonization Throughout Woman Life. Front Cell Infect Microbiol. 2021;11:613. doi:10.3389/FCIMB.2021.686167/BIBTEX
7. Gupta P, Singh MP, Goyal K. Diversity of Vaginal Microbiome in Pregnancy: Deciphering the Obscurity. Front Public Health. 2020;8:326. doi:10.3389/FPUBH.2020.00326/BIBTEX
8. Chopra C, Kumar V, Kumar M, Bhushan I. Role of vaginal microbiota in idiopathic infertility: a prospective study. Microbes Infect. 2024;26(4). doi:10.1016/J.MICINF.2024.105308
9. Oliveira NS de, Lima ABF de, Brito JCR de, Sarmento ACA, Gonçalves AKS, Eleutério JJr. Postmenopausal Vaginal Microbiome and Microbiota. Frontiers in Reproductive Health. 2022;0:112. doi:10.3389/FRPH.2021.780931
10. Clabaut M, Suet A, Racine P-J, et al. Effect of 17β-estradiol on a human vaginal Lactobacillus crispatus strain. Scientific Reports |. 123AD;11:7133. doi:10.1038/s41598-021-86628-x
11. Kim J-M, Park YJ. Probiotics in the Prevention and Treatment of Postmenopausal Vaginal Infections: Review Article. J Menopausal Med. 2017;23(3):139. doi:10.6118/JMM.2017.23.3.139
12. Oliveira NS de, Lima ABF de, Brito JCR de, Sarmento ACA, Gonçalves AKS, Eleutério JJr. Postmenopausal Vaginal Microbiome and Microbiota. Frontiers in Reproductive Health. 2022;0:112. doi:10.3389/FRPH.2021.780931
13. van Riel SJJM, Lardenoije CMJG, Oudhuis GJ, Cremers NAJ. Treating (Recurrent) Vulvovaginal Candidiasis with Medical-Grade Honey—Concepts and Practical Considerations. Journal of Fungi. 2021;7(8). doi:10.3390/JOF7080664
14. Koumans EH, Sternberg M, Bruce C, et al. The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. 2007;34(11):864-869. doi:10.1097/OLQ.0B013E318074E565
15. Lin YP, Chen WC, Cheng CM, Shen CJ. Vaginal pH Value for Clinical Diagnosis and Treatment of Common Vaginitis. Diagnostics. 2021;11(11). doi:10.3390/DIAGNOSTICS11111996
16. Achilles SL, Austin MN, Meyn LA, Mhlanga F, Chirenje ZM, Hillier SL. Impact of contraceptive initiation on vaginal microbiota. Am J Obstet Gynecol. 2018;218(6):622.e1. doi:10.1016/J.AJOG.2018.02.017
17. Balle C, Konstantinus IN, Jaumdally SZ, et al. Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial. Nature Communications 2020 11:1. 2020;11(1):1-15. doi:10.1038/s41467-020-19382-9
18. Song SD, Acharya KD, Zhu JE, et al. Daily Vaginal Microbiota Fluctuations Associated with Natural Hormonal Cycle, Contraceptives, Diet, and Exercise. mSphere. 2020;5(4). doi:10.1128/MSPHERE.00593-20/SUPPL_FILE/MSPHERE.00593-20-ST001.DOCX
19. Gupta K, Hillier SL, Hooton TM, Roberts PL, Stamm WE. Effects of Contraceptive Method on the Vaginal Microbial Flora: A Prospective Evaluation. J Infect Dis. 2000;181(2):595-601. doi:10.1086/315267
20. Mihajlovic J, Leutner M, Hausmann B, et al. Combined hormonal contraceptives are associated with minor changes in composition and diversity in gut microbiota of healthy women. Environ Microbiol. 2021;23(6):3037-3047. doi:10.1111/1462-2920.15517
21. Oral contraceptives and changes in nutritional requirements - PubMed. Accessed March 17, 2022. https://pubmed.ncbi.nlm.nih.gov/23852908/
22. Neggers YH, Nansel TR, Andrews WW, et al. Dietary Intake of Selected Nutrients Affects Bacterial Vaginosis in Women. J Nutr. 2007;137(9):2128-2133. doi:10.1093/JN/137.9.2128
23. Sustr V, Foessleitner P, Kiss H, Farr A. Vulvovaginal Candidosis: Current Concepts, Challenges and Perspectives. Journal of Fungi. 2020;6(4):1-14. doi:10.3390/JOF6040267
24. Reid G. Has knowledge of the vaginal microbiome altered approaches to health and disease? F1000Res. 2018;7. doi:10.12688/F1000RESEARCH.13706.1
25. Amabebe E, Anumba DOC. The Vaginal Microenvironment: The Physiologic Role of Lactobacilli. 2018;5(JUN):181. doi:10.3389/FMED.2018.00181
26. Delgado-Diaz DJ, Tyssen D, Hayward JA, Gugasyan R, Hearps AC, Tachedjian G. Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota. Front Cell Infect Microbiol. 2020;9:446. doi:10.3389/FCIMB.2019.00446/BIBTEX
27. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017;103:45-53. doi:10.1016/J.MATURITAS.2017.06.025
28. Mogna L, Deidda F, Nicola S, Amoruso A, del Piano M, Mogna G. In Vitro Inhibition of Klebsiella pneumoniae by Lactobacillus delbrueckii Subsp. delbrueckii LDD01 (DSM 22106): An Innovative Strategy to Possibly Counteract Such Infections in Humans? J Clin Gastroenterol. 2016;50:S136-S139. doi:10.1097/MCG.0000000000000680
29. Mogna L, del Piano M, Deidda F, et al. Assessment of the in vitro inhibitory activity of specific probiotic bacteria against different Escherichia coli strains. J Clin Gastroenterol. 2012;46(SUPPL. 1). doi:10.1097/MCG.0b013e31826852b7
30. Rossi A, Rossi T, Bertini M, Caccia G. The use of Lactobacillus rhamnosus in the therapy of bacterial vaginosis. Evaluation of clinical efficacy in a population of 40 women treated for 24 months. Arch Gynecol Obstet. 2010;281(6):1065-1069. doi:10.1007/S00404-009-1287-6
31. Reid G, Charbonneau D, Erb J, et al. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 2003;35(2):131-134. doi:10.1016/S0928-8244(02)00465-0
32. de Almeida MO, Carvalho R, Aburjaile FF, et al. Characterization of the first vaginal Lactobacillus crispatus genomes isolated in Brazil. PeerJ. 2021;9. doi:10.7717/PEERJ.11079
33. Wang S, Wang Q, Yang E, Yan L, Li T, Zhuang H. Antimicrobial compounds produced by vaginal Lactobacillus crispatus are able to strongly inhibit Candida albicans growth, hyphal formation and regulate virulence-related gene expressions. Front Microbiol. 2017;8(APR):564. doi:10.3389/FMICB.2017.00564/BIBTEX
34. Nardini P, Nãhui Palomino RA, Parolin C, et al. Lactobacillus crispatus inhibits the infectivity of Chlamydia trachomatis elementary bodies, in vitro study. Sci Rep. 2016;6. doi:10.1038/SREP29024
35. Tabatabaei N, Eren AM, Barreiro LB, et al. Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study. BJOG. 2019;126(3):349-358. doi:10.1111/1471-0528.15299
36. Dover SE, Aroutcheva AA, Faro S, Chikindas ML. NATURAL ANTIMICROBIALS AND THEIR ROLE IN VAGINAL HEALTH: A SHORT REVIEW. Int J Probiotics Prebiotics. 2008;3(4):219. Accessed February 16, 2022. /pmc/articles/PMC2908489/
37. Ocaña VS, De Ruiz Holgado AAP, Nader-Macías ME. Characterization of a Bacteriocin-Like Substance Produced  by a Vaginal Lactobacillus salivarius Strain. Appl Environ Microbiol. 1999;65(12):5631. doi:10.1128/aem.65.12.5631-5635.1999
38. The role of lactic acid production by probiotic Lactobacillus species in vaginal health | Elsevier Enhanced Reader. Accessed February 17, 2022. https://reader.elsevier.com/reader/sd/pii/S0923250817300839?token=5D284F82D505F23E7A0A0D976FEB366381F8DA94DC02E82BBEAF97C2CF1FD78F2A912FB3C49BD5B7262239C6A4576993&originRegion=eu-west-1&originCreation=20220217122446
39. Nishida K, Sawada D, Yasui T, Kuwano Y, Rokutan K. Daily intake of Lactobacillus gasseri CP2305 ameliorates psychological premenstrual symptoms in young women: A randomized, double-blinded, placebo-controlled study. J Funct Foods. 2021;80:104426. doi:10.1016/J.JFF.2021.104426
40. Itoh H, Sashihara T, Hosono A, Kaminogawa S, Uchida M. Lactobacillus gasseri OLL2809 inhibits development of ectopic endometrial cell in peritoneal cavity via activation of NK cells in a murine endometriosis model. Cytotechnology. 2011;63(2):205. doi:10.1007/S10616-011-9343-Z