The selective estrogen receptor modulator ospemifene appears to improve the vaginal microbiome of postmenopausal women with vulvovaginal atrophy (VVA), according to results from a small Italian case-control study in the journal Menopause.
The study sheds microbiological light on the mechanisms of ospemifene and low-dose systemic hormone therapy, which are widely used to treat genitourinary symptoms. Both had a positive effect on vaginal well-being, likely by reducing potentially harmful bacteria and increasing health-promoting acid-friendly microorganisms, writes a group led by M. Cristina Meriggiola, MD, PhD, of the gynecology and physiopathology of human reproduction unit at the University of Bologna, Italy.
VVA occurs in about 50% of postmenopausal women and produces a less favorable, less acidic vaginal microbiome profile than that of unaffected women. "The loss of estrogen leads to lower concentrations of Lactobacilli, bacteria that lower the pH. As a result, other bacterial species fill in the void," explained Stephanie S. Faubion, MD, MBA, director of the Mayo Clinic Center for Women's Health in Jacksonville, Fla., and medical director of the North American Menopause Society.
Added Tina Murphy, APN, a NAMS-certified menopause practitioner at Northwestern Medicine Orland Park in Illinois, "When this protective flora declines, then pathogenic bacteria can predominate the microbiome, which can contribute to vaginal irritation, infection, UTI's, dyspareunia, and discomfort. Balancing and restoring the microbiome can mitigate the effects of estrogen depletion on the vaginal tissue and prevent the untoward effects of the hypoestrogenic state." While ospemifene and hormone therapy are common therapies for the genitourinary symptoms of menopause, the focus has been on their treatment efficacy, not their effect on the microbiome profile, added Dr. Faubion. Only about 9% of women with menopause-related genitourinary symptoms receive prescription treatment, she added.
Of 67 eligible postmenopausal participants in their mid-50s enrolled at a gynecology clinic from April 2019 to February 2020, 39 were diagnosed with VVA and 28 were considered healthy controls. In the atrophic group, 20 were prescribed ospemifene and 19 received hormone treatment.
Only those women with VVA but no menopausal vasomotor symptoms received ospemifene (60 mg/day); symptomatic women received hormone therapy according to guidelines.
The researchers calculated the women's vaginal health index (VHI) based on elasticity, secretions, pH level, epithelial mucosa, and hydration. They used swabs to assess vaginal maturation index (VMI) by percentages of superficial, intermediate, and parabasal cells. Evaluation of the vaginal microbiome was done with 16S rRNA gene sequencing, and clinical and microbiological analyses were repeated after 3 months.
The vaginal microbiome of atrophic women was characterized by a significant reduction of benign Lactobacillus bacteria (P = .002) and an increase of potentially pathogenic Streptococcus (P = .008) and Sneathia (P = .02) bacteria.
The vaginal microbiome of women with VVA was depleted, within the Lactobacillus genus, in the L. crispatus species, a hallmark of vaginal health that has significant antimicrobial activity against endogenous and exogenous pathogens.
Furthermore, there was a positive correlation between the VHI/VMI and Lactobacillus abundance (P = .002 and P = 0.035, respectively).
While the lactic acid–producing Lactobacillus and Bifidobacterium genera were strongly associated with healthy controls, the characteristics of VVA patients were strongly associated with Streptococcus, Prevotella, Alloscardovia, and Staphylococcus.
Both therapeutic approaches effectively improved vaginal indices but by different routes. Systemic hormone treatment induced changes in minority bacterial groups in the vaginal microbiome, whereas ospemifene eliminated specific harmful bacterial taxa, such as Staphylococcus (P = .04) and Clostridium (P = .01). Both treatments induced a trend in the increase of beneficial Bifidobacteria.
A 2022 study reported that vaginal estradiol tablets significantly changed the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but the reductions in bothersome symptoms were similar.
"Areas for future study include the assessment of changes in the vaginal microbiome, proteomic profiles, and immunologic markers with various treatments and the associations between these changes and genitourinary symptoms," Dr. Faubion said. She added that, while there may be a role at some point for oral or topical probiotics, "Thus far, probiotics have not demonstrated significant benefits."
Meanwhile, said Ms. Murphy, "There are many options available that may benefit our patients. As a provider, meeting with your patient, discussing her concerns and individual risk factors is the most important part of choosing the correct treatment plan."
The authors call for further studies to confirm the observed modifications of the vaginal ecosystem. In the meantime, Dr. Meriggiola said in an interview, "My best advice to physicians is to ask women if they have this problem. Do not ignore it; be proactive and treat. There are many options on the market for genitourinary symptoms – not just for postmenopausal women but breast cancer survivors as well."
Dr. Meriggiola's group is planning to study ospemifene in cancer patients, whose quality of life is severely affected by VVA.
This study received no financial support. Dr. Meriggiola reported past financial relationships with Shionogi Limited, Teramex, Organon, Italfarmaco, MDS Italia, and Bayer. Coauthor Dr. Baldassarre disclosed past financial relationships with Shionogi. Ms. Murphy disclosed no relevant conflicts of interest with respect to her comments. Dr. Faubion is medical director of the North American Menopause Society and editor of the journal Menopause.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
Lead image: Shionogi, Inc.
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Cite this: Ospemifene and HT Boost Vaginal Microbiome in Vulvovaginal Atrophy - Medscape - Feb 01, 2023.