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.

Autor:	Gaspard U; From the Department of Obstetrics and Gynecology, University of Liège, Liège, Belgium., Taziaux M; Estetra SRL, Mithra Pharmaceuticals, Liège, Belgium., Jost M; Estetra SRL, Mithra Pharmaceuticals, Liège, Belgium., Coelingh Bennink HJT; Pantarhei Bioscience, Zeist, the Netherlands., Utian WH; Case Western Reserve University School of Medicine, Cleveland, OH., Lobo RA; Columbia University Medical Center, New York, NY., Foidart JM
Jazyk:	angličtina
Zdroj:	Menopause (New York, N.Y.) [Menopause] 2023 May 01; Vol. 30 (5), pp. 480-489. Date of Electronic Publication: 2023 Feb 20.
DOI:	10.1097/GME.0000000000002167
Abstrakt:	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. Competing Interests: 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. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)
Databáze:	MEDLINE
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