Effect of ospemifene on vaginal microbiome in postmenopausal women with vulvovaginal atrophy

Abstract

Objectives: This study aimed (i) to compare the vaginal microbiome profiles of women suffering from vulvovaginal atrophy with that of healthy postmenopausal women and to (ii) assess the effect of ospemifene and systemic hormone treatment on the composition of the vaginal microbiome.Methods: Sixty-seven postmenopausal women attending the Gynecology Clinic of Azienda Ospedaliero-Universitaria of Bologna (Italy) were enrolled. Of them, 39 received a diagnosis of atrophy and 28 were considered healthy controls. In the group of atrophic women, 20 were prescribed ospemifene and 19 received hormone treatment. The vaginal health index was calculated, and a vaginal swab was collected for the assessment of vaginal maturation index and the analysis of vaginal microbiome through 16S rRNA gene sequencing. Clinical/microbiological analyses were repeated after 3 months of treatment.Results: The vaginal microbiome of atrophic women was characterized by a significant reduction of Lactobacillus (P = 0.002) and an increase of Streptococcus (P = 0.008) and Sneathia (P = 0.02). A positive correlation between vaginal health index/vaginal maturation index and Lactobacillus abundance was found (P = 0.002 and P = 0.035, respectively). Both therapeutic approaches effectively improved vaginal indices. Systemic hormone treatment induced changes in minority bacterial groups of the vaginal microbiome, whereas ospemifene was able to eliminate specific bacterial taxa, such as Staphylococcus (P = 0.04) and Clostridium (P = 0.01). Both treatments induced a trend in the increase of bifidobacteria.Conclusions: The vaginal microbiome of atrophic women differs significantly from that of healthy postmenopausal women. Ospemifene may lead to a condition of vaginal health, likely characterized by the reduction of "potentially harmful" bacteria.

The Postmenopausal Vaginal Microbiome and Genitourinary Syndrome of Menopause

“…A higher VMI (reflective of more superficial cells and a thicker vaginal epithelium) has been associated with higher relative abundance of Lactobacillus spp. 21 Vaginal pH reliably increases as serum estradiol levels decrease in menopause. Lactobacillus species produce lactic acid, which may play an antimicrobial role to protect against pathogen colonization.…”

“…15 A comparison of people with VVA being treated with oral estrogen and the selective estrogen receptor modulator ospemifene showed that both had higher relative abundance of Lactobacillus than untreated participants. 21 Lastly, although not an randomized controlled trial, a comparison of people on tibolone therapy versus no treatment demonstrated that people on tibolone had a higher relative abundance of Lactobacillus. 25 Topical vaginal estrogen is also associated with a change in microbiome composition.…”

“…Vaginal maturation index (VMI) is a laboratory scoring of epithelial cell morphotypes, and is lower when the vaginal epithelium is thin and circulating estrogen is low. A higher VMI (reflective of more superficial cells and a thicker vaginal epithelium) has been associated with higher relative abundance of Lactobacillus spp 21 . Vaginal pH reliably increases as serum estradiol levels decrease in menopause.…”

“…In a study of 60 postmenopausal women treated with oral conjugated equine estrogen 0.3 mg daily, after 4 weeks of treatment the relative abundance of Gardnerella, Prevotella and Fannyhessea (previously known as Atopobium ) decreased and Lactobacillus increased 15 . A comparison of people with VVA being treated with oral estrogen and the selective estrogen receptor modulator ospemifene showed that both had higher relative abundance of Lactobacillus than untreated participants 21 . Lastly, although not an randomized controlled trial, a comparison of people on tibolone therapy versus no treatment demonstrated that people on tibolone had a higher relative abundance of Lactobacillus 25 …”

Is the vaginal microbiome a marker or an effector of vaginal health?

“…In this issue, Alvisi et al 12 made two comparisons of the vaginal microbiota: (1) between healthy postmenopausal controls (n = 28) and people with vulvovaginal atrophy (VVA) on examination (n = 39), and (2) between pretreatment and posttreatment samples among women with VVA who received either systemic hormonal therapy (HT) (n = 19) or ospemifene (n = 20). 13 The authors specifically excluded people with primarily urinary symptoms, which is why they did not use the term genitourinary syndrome of menopause. At baseline, they demonstrated significantly different alpha and beta diversity between healthy controls and people with VVA.…”