Fertility, Menopause, and the Vaginal Microbiome: A Life Course View of Bacterial VaginosisFertility, Menopause, and the Vaginal Microbiome: A Life Course View of Bacterial VaginosisFertility, Menopause, and the Vaginal Microbiome: A Life Course View of Bacterial VaginosisFertility, Menopause, and the Vaginal Microbiome: A Life Course View of Bacterial Vaginosis
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Fertility, Menopause, and the Vaginal Microbiome: A Life Course View of Bacterial Vaginosis

Categories
  • Articles
  • Fertility
  • Microbiome
Tags
  • fertility
  • pregnancy
  • womens health

 

As practitioners we are all literate in the importance of the gut microbiome and how its dysregulation can lead to a myriad of imbalances and symptoms. In health, the gut microbiome is as diverse as it is complex largely due to its sensitivity to stressors, antibiotics, toxins and diet.

The vaginal microbiome shares these sensitivities, and it too plays a vital role in systemic and reproductive health. Unlike the gut however, the vaginal microbiome in health is comprised mainly of Lactobacillus species. There can also be both cross talk and translocation between the two sites.

When we consider the various body systems, they all have a role in vaginal health, we have influences from the nervous system, structure from the muscular system, endocrine of course, transport (when we consider blood supply and lymph) and a strong immunoregulatory role. There is an abundance of antimicrobial peptides found in the vagina i.e. beta defensin, calprotectin, lactoferrin (Mendez-Figueroa & Anderson, 2011) along with cytokines such as IL1alpha, IL 6 and TNF-α (Passmore et al., 2016).

The Role of pH, Oestrogen, and the Menstrual Cycle

As mentioned, it is primary Lactobacillus bacteria that maintain a healthy vaginal environment. As the name infers, these Lactobacilli produce lactic acid by utilising carbohydrates fermentatively, which helps maintain a low vaginal pH (around 4.5 or lower), creating an acidic environment that protects against pathogens. If pH shifts above 4.5 to a more alkaline environment this is when trouble can start and the opportunity for anaerobic bacteria to proliferate increases.

It is vital to also understand the role of oestrogen and the impact of menstruation (or lack thereof) on vaginal health, however. Blood is alkaline so length and indeed heaviness of the menstrual bleed can impact when symptoms may wax and wane.

Oestrogen has several roles; it supports proliferation of vaginal epithelial cells by binding to oestrogen receptors in vaginal tissue (Buchanan et al., 1998). The epithelial surface can contain up to forty layers and this structure can be reflective of oestrogen levels.  The vagina is a mucous membrane, and its tissue should be moist. Oestrogen is a natural lubricant and helps to keep the vaginal tissue elastic and thick. Additionally, oestrogen stimulates secretory activity in the Bartholin’s glands, particularly around ovulation, contributing to increased vaginal lubrication during the fertile window. Oestrogen also increases the secretion of glycogen which is fuel for protective Lactobacillus bacterial which maintain vaginal pH (Amabebe & Anumba, 2018).

Bacterial Vaginosis

There are significant variations during different stages of a woman’s life such as puberty, reproductive years, pregnancy, and menopause. This article will discuss both reproduction and menopause with a specific focus on Bacterial Vaginosis (BV).

BV is one of the most common vaginal microbiome disorders. It is unfortunately associated with infertility, sexually transmitted infections (STIs) and pelvic inflammatory disease (PID), (Chen et al., 2021). It can also be asymptomatic which makes screening especially important in the context of fertility. That said, healthy women may also carry one of the main microbes involved Gardnerella vaginalis so merely the presence of this microbe does not always indicate BV infection (Krohn et al., 1989).

Symptoms of BV

BV is characterized by a loss of Lactobacilli dominance and an overgrowth of anaerobic bacteria such as Gardnerella vaginalis, Prevotella bivia, and Atopobium vaginae and as noted can be completely asymptomatic.

Along with unusual discharge- typically thin or watery, and grey or green in colour- the most common symptom reported is odour which is often described as ‘fish like’. This odour may get stronger after intercourse. This could be due to the alkalinity of semen which can react with vaginal discharge creating a more pungent odour.  The fish odour properties of a typical BV discharge can also be linked to the conversion of trimethylamine oxide (TMAO) to trimethylamine (TMA) by bacteria in the vagina (Cruden & Galask, 1988).  These amines then raise the vaginal pH to further enhance the growth of microbes such as Gardnerella vaginalis.

BV is associated with low oestrogen states both in menses and life cycle i.e. menopause or premature ovarian failure and can be more common after the bleed stage of a cycle where Gardnerella vaginalis can proliferate, this is why it can present in recurrent pattens with shifts in pH and microbiome status also triggering relapse or chronicity.

BV Across the Lifecycle
Reproductive Years & Fertility

The age cohort most at risk of BV are females of reproductive age and indeed BV is the most common vaginal infection in this group (Peebles et al., 2019).  It is associated with a litany of obstetric complications such preterm labour, low birth weight, post-partum endometritis, and miscarriage.

BV is a risk factor for transmission of HIV and other STIs. It also may be considered an STI in its own right and is sometimes discussed in that context. The burden of BV in the setting of fertility and reproduction is certainly a heavy one with sometimes serious consequences.

Menopause

The burden in menopause is less grave but symptoms can impact a woman’s quality of life, and these women may be numerous with prevalence estimates varying from 2.0 to 57.1% (Stewart et al., 2022).

An oestrogen deficient menopausal state can result in an elevated pH and a reduction in Lactobacillus bacteria. This is the perfect environment for BV associated bacteria to proliferate. Even if BV is not present the microbiota of females of menopausal age versus reproductive is quite different.

Given that oestrogen supports vaginal structure, tissue health and levels of collagen and elastin, with its decline comes atrophy and other symptoms. They include vaginal dryness, burning, and irritation as well as dysuria and dyspareunia. Vaginal atrophy is now termed Genitourinary Syndrome of Menopause (GSM). Differentiating between GSM and BV can be challenging due to symptom overlap, but pH testing, microscopy, and clinical history help guide diagnosis.

Interestingly, obese postmenopausal women may have lower rates of BV compared to non-obese postmenopausal women, potentially due to increased vaginal glycogen (Daubert et al., 2021). This does not appear to bear out in women of reproductive age where in fact obesity may increase risk of BV (Brookheart et al., 2019).

Post menopausal women receiving oestrogen replacement therapy may have a lower propensity for overgrowth of anaerobic bacteria with studies suggesting lower incidences of BV in this cohort than those not treated with HRT (Heinemann & Reid, 2005).

Therapeutic Considerations and Functional Supports

Biofilms can be a barrier to treatment and are a huge consideration with BV. Gardnerella vaginalis can happily ‘scaffold’ itself in situ, protected, and re-emerge when conditions are more favourable (Crucitti, 2017). The use of N-Acetyl-L-Cysteine or other biofilm disrupting agents can help breakdown these structures and improve treatment outcomes.

Probiotics and restoration of Lactobacillus bacteria are key, in particular Lactobacillus crispatus as a strong lactic acid producer. It’s dominance in the vaginal microbiome has been associated with an increase in successful conception (Sirota et al., 2014) and so use of targeted probiotics may support both BV remission and fertility.

Prebiotics if the goal is to restore protective Lactobacillus then it makes sense to also provide substrate. Vaginal applications containing both glycogen and lactic acid are available over the counter and of course oral intake of inulin, FOS or GOS can also be recommended.

Support pharmaceutical efficacy, although some strains can be resistant to Metronidazole there may be a susceptibility to Clindamycin, of course use should be considered in light of the clinical findings and may be less useful in menopause than fertility.

Anti microbials are an alternative to antibiotics and indeed should be first line treatment depending on clinical picture. Allicin may show greater efficacy than Metronidazole in treating BV with lower harm potential and fewer detrimental effects on the microbiome.

Epithelial support is key for menopausal women in particular. Sea buckthorn is a rich source of omega-7 (palmitoleic acid) which plays an important role in mucous membrane health, it is also anti-inflammatory and antioxidant rich which supports collagen production. It improves the integrity of the vaginal epithelium in patients unable to use oestrogen treatment for GSM (Larmo et al., 2014).

Oestrogen therapy is potentially beneficial for both fertility and the management of BV in GSM and may support increase glycogen availability and epithelial integrity.

Clinical Takeaway

Understanding the complex interplay between hormones, immunity, microbiome composition, and lifestyle is key to addressing BV comprehensively. As always: test, don’t guess—lab testing and patient history should guide supports. As functional and integrative practitioners, recognizing microbiome transitions across the life course empowers us to intervene with greater precision and impact.

This article was orignally written by Lynne Dalton for Pure & Natural practitioner magazine.

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References 

Amabebe, E., & Anumba, D. O. C. (2018). The vaginal microenvironment: The physiologic role of lactobacilli. Frontiers in Medicine, 5, 181. https://doi.org/10.3389/fmed.2018.00181

Brookheart, R. T., Lewis, W. G., Peipert, J. F., Lewis, A. L., & Allsworth, J. E. (2019). Association between obesity and bacterial vaginosis as assessed by Nugent score. American Journal of Obstetrics and Gynecology, 220(5), 476.e1–476.e11. https://doi.org/10.1016/j.ajog.2019.01.229

Buchanan, D. L., Kurita, T., Taylor, J. A., Lubahn, D. B., Cunha, G. R., & Cooke, P. S. (1998). Role of stromal and epithelial estrogen receptors in vaginal epithelial proliferation, stratification, and cornification. Endocrinology, 139(10), 4345–4352. https://doi.org/10.1210/endo.139.10.6241

Chen, X., Lu, Y., Chen, T., & Li, R. (2021). The female vaginal microbiome in health and bacterial vaginosis. Frontiers in Cellular and Infection Microbiology, 11, 631972. https://doi.org/10.3389/fcimb.2021.631972

Crucitti, T. (2017). Eve’s garden: Myths, legends and secrets unmasked. Research in Microbiology, 168, 773–781. https://doi.org/10.1016/j.resmic.2017.07.004

Cruden, D. L., & Galask, R. P. (1988). Reduction of trimethylamine oxide to trimethylamine by Mobiluncus strains isolated from patients with bacterial vaginosis. Microbial Ecology in Health and Disease, 1(2), 95–100. https://doi.org/10.3109/08910608809140187

Daubert, E., Weber, K. M., French, A. L., Seidman, D., Michel, K., Gustafson, D., et al. (2021). Obesity is associated with lower bacterial vaginosis prevalence in menopausal but not pre-menopausal women in a retrospective analysis of the Women’s Interagency HIV Study. PLOS ONE, 16(3), e0248136. https://doi.org/10.1371/journal.pone.0248136

Heinemann, C., & Reid, G. (2005). Vaginal microbial diversity among postmenopausal women with and without hormone replacement therapy. Canadian Journal of Microbiology, 51(9), 777–781. https://doi.org/10.1139/w05-070

Krohn, M. A., Hillier, S. L., & Eschenbach, D. A. (1989). Comparison of methods for diagnosing bacterial vaginosis among pregnant women. Journal of Clinical Microbiology, 27(6), 1266–1271. https://doi.org/10.1128/jcm.27.6.1266-1271.1989

Larmo, P. S., Yang, B., Hyssälä, J., Kallio, H. P., & Erkkola, R. (2014). Effects of sea buckthorn oil intake on vaginal atrophy in postmenopausal women: A randomized, double-blind, placebo-controlled study. Maturitas, 79(3), 316–321. https://doi.org/10.1016/j.maturitas.2014.07.010

Mendez-Figueroa, H., & Anderson, B. (2011). Vaginal innate immunity, alteration during pregnancy and its impact on pregnancy outcomes. Expert Review of Obstetrics & Gynecology, 6(6), 629–641. https://doi.org/10.1586/eog.11.63

Passmore, J. A., Jaspan, H. B., & Masson, L. (2016). Genital inflammation, immune activation and risk of sexual HIV acquisition. Current Opinion in HIV and AIDS, 11(2), 156–162. https://doi.org/10.1097/COH.0000000000000232

Peebles, K., Velloza, J., Balkus, J. E., McClelland, R. S., & Barnabas, R. V. (2019). High global burden and costs of bacterial vaginosis: A systematic review and meta-analysis. Sexually Transmitted Diseases, 46(5), 304–311. https://doi.org/10.1097/OLQ.0000000000000972

Sirota, I., Zarek, S. M., & Segars, J. H. (2014). Potential influence of the microbiome on infertility and assisted reproductive technology. Seminars in Reproductive Medicine, 32(1), 35–42. https://doi.org/10.1055/s-0033-1361821

Stewart, L. L., et al. (2022). Prevalence of bacterial vaginosis in postmenopausal women: A systematic review and meta-analysis. Sexual Health, 19(1), 17–26. https://doi.org/10.1071/SH21083

 

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