In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 9 ( 2021-08-18), p. e3519-e3532
Abstract:
Polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder characterized by hyperandrogenism, is the leading cause of anovulatory infertility. Objective This proof-of-concept study evaluated clinical efficacy and safety of the neurokinin 3 (NK3) receptor antagonist fezolinetant in PCOS. Methods This was a phase 2a, randomized, double-blind, placebo-controlled, multicenter study (EudraCT 2014-004409-34). The study was conducted at 5 European clinical centers. Women with PCOS participated in the study. Interventions included fezolinetant 60 or 180 mg/day or placebo for 12 weeks. The primary efficacy end point was change in total testosterone. Gonadotropins, ovarian hormones, safety and tolerability were also assessed. Results Seventy-three women were randomly assigned, and 64 participants completed the study. Adjusted mean (SE) changes in total testosterone from baseline to week 12 for fezolinetant 180 and 60 mg/day were −0.80 (0.13) and −0.39 (0.12) nmol/L vs −0.05 (0.10) nmol/L with placebo (P & lt; .001 and P & lt; .05, respectively). Adjusted mean (SE) changes from baseline in luteinizing hormone (LH) for fezolinetant 180 and 60 mg/d were −10.17 (1.28) and −8.21 (1.18) vs −3.16 (1.04) IU/L with placebo (P & lt; .001 and P = .002); corresponding changes in follicle-stimulating hormone (FSH) were −1.46 (0.32) and −0.92 (0.30) vs −0.57 (0.26) IU/L (P = .03 and P = .38), underpinning a dose-dependent decrease in the LH-to-FSH ratio vs placebo (P & lt; .001). Circulating levels of progesterone and estradiol did not change significantly vs placebo (P & gt; .10). Fezolinetant was well tolerated. Conclusion Fezolinetant had a sustained effect to suppress hyperandrogenism and reduce the LH-to-FSH ratio in women with PCOS.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/clinem/dgab320
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2021
detail.hit.zdb_id:
2026217-6
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