Researchers at the University of Colorado Anschutz tested a vaginal suppository built around 3-fluoro 6,4'-dihydroxyflavone, or 3F, as a nonhormonal way to repair menopausal vaginal tissue. In a preclinical menopause model, the molecule restored the vaginal epithelium and showed no evidence of systemic estrogenic activity. The work was published July 7 in Menopause and is aimed at genitourinary syndrome of menopause, a chronic condition that affects the vulva, vagina and urinary tract.
GSM, introduced in 2014 to replace vulvovaginal atrophy, covers a wider set of vulvovaginal, urinary and sexual symptoms linked to falling estrogen and androgen levels during the menopausal transition and after menopause. Dryness, painful intercourse and recurrent vaginal or urinary tract infections are common. AUA/SUFU/AUGS guidance does not set a consensus number of symptoms or physical signs for diagnosis, and urinary complaints can overlap with overactive bladder. Studies have put symptom rates at 50% to 70% of women with natural or medically induced menopause, while a 2021 review in Frontiers in Reproductive Health found a range of 27% to 84% in postmenopausal women.
The Menopause Society updated and expanded its 2013 GSM guidance in 2020. Evidence-based recommendations continue to place low-dose local vaginal estrogen as the most effective commonly used treatment for moderate to severe vaginal atrophy when nonhormonal measures are not enough. Many women and clinicians remain cautious about estrogen exposure, especially those with a history of breast cancer or concerns about hormone-sensitive cancers. 3F targets patients who cannot, do not want to, or are not advised to use hormones.
An earlier chemistry paper identified 3-fluoro, 6,4′-dihydroxyflavone as a potent estrogen-receptor agonist with increased estrogen-agonist potency. Senior author Steve Nordeen aimed to address the underlying cause of vaginal changes after menopause without relying on steroid hormones. The next step is support for human clinical trials.