A multicenter, randomized, placebo-controlled study to select the minimum effective dose of estetrol in postmenopausal participants (E4Relief): part 2-vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life
- PMID: 36809193
- PMCID: PMC10155698
- DOI: 10.1097/GME.0000000000002167
A multicenter, randomized, placebo-controlled study to select the minimum effective dose of estetrol in postmenopausal participants (E4Relief): part 2-vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life
Abstract
Objective: A phase 2 study showed that 15 mg estetrol (E4) alleviates vasomotor symptoms (VMS). Here, we present the effects of E4 15 mg on vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life.
Methods: In a double-blind, placebo-controlled study, postmenopausal participants (n = 257, 40-65 y) were randomized to receive E4 2.5, 5, 10, or 15 mg or placebo once daily for 12 weeks. Outcomes were the vaginal maturation index and maturation value, genitourinary syndrome of menopause score, and the Menopause Rating Scale to assess health-related quality of life. We focused on E4 15 mg, the dose studied in ongoing phase 3 trials, and tested its effect versus placebo at 12 weeks using analysis of covariance.
Results: Least square (LS) mean percentages of parabasal and intermediate cells decreased, whereas superficial cells increased across E4 doses; for E4 15 mg, the respective changes were -10.81% ( P = 0.0017), -20.96% ( P = 0.0037), and +34.17% ( P < 0.0001). E4 15 mg decreased LS mean intensity score for vaginal dryness and dyspareunia (-0.40, P = 0.03, and -0.47, P = 0.0006, respectively); symptom reporting decreased by 41% and 50%, respectively, and shifted to milder intensity categories. The overall Menopause Rating Scale score decreased with E4 15 mg (LS mean, -3.1; P = 0.069) and across doses was associated with a decreasing frequency and severity of VMS ( r = 0.34 and r = 0.31, P < 0.001).
Conclusions: E4 demonstrated estrogenic effects in the vagina and decreased signs of atrophy. E4 15 mg is a promising treatment option also for important menopausal symptoms other than VMS.
Trial registration: ClinicalTrials.gov NCT04209543 NCT02834312.
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.
Conflict of interest statement
Financial disclosure/conflicts of interest: M.T. and M.J. are employees, U.G. and J.-M.F. are consultants, and W.H.U. and R.A.L. are members of the Scientific Advisory Board of Mithra Pharmaceuticals. W.H.U. received funding from Pharmavite, Los Angeles. H.J.T.C.B. is president and CEO of Pantarhei Bioscience.
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References
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- Portman DJ Gass ML, Vulvovaginal Atrophy Terminology Consensus Conference Panel . Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and The North American Menopause Society. Menopause 2014;21:1063–1068. doi: 10.1097/GME.0000000000000329 - DOI - PubMed
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