Molecular Effects of Topical Estrogen on Vaginal Granulation Tissue in Postpartum Women

Objective The aims of this study were to evaluate the biomolecular properties of vaginal and perineal granulation tissue in postpartum women and assess the potential impact of vaginal estrogen application. Methods We prospectively identified women referred to a subspecialty peripartum clinic between September 2016 and April 2018 who developed symptomatic perineal or vaginal granulation tissue. As part of routine clinical care, granulation tissue was excised from each participant by a urogynecologist and subjected to RNA extraction, real-time quantitative polymerase chain reaction, histologic evaluation, and immunohistochemistry. Serum steroid hormone levels were measured. Comparisons were made between participants who used topical vaginal estradiol (E2) and those who did not (non-E2 controls). Results Sixteen postpartum women were recruited for this pilot study. More than 30% of patients (n = 5, 31%) had used topical vaginal estradiol (E2) during their postpartum recovery. Histological appearance of granulation tissue evaluated by hematoxylin and eosin staining was similar in women treated with vaginal E2 and non-E2 controls. Both estrogen receptor α (ERα) and ERβ mRNA and ERα protein were readily detectable in the granulation tissue of E2-treated women. Although not statistically significant, participants who used topical E2 developed granulation tissue that exhibited local estrogen-responsive gene upregulation. Serum levels of estrone, E2, dehydroepiandrosterone, progesterone, and testosterone did not differ between vaginal E2-treated patients and controls. Conclusions Estrogen receptor α seems to be the predominant receptor mediating estrogen action in postpartum perineal and vaginal granulation tissue. Vaginal E2 use does not seem to affect serum levels of estrone, E2, dehydroepiandrosterone, progesterone, and testosterone in postpartum women.