CONTEXT: 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. DESIGN: This was a phase 2a, randomized, double-blind, placebo-controlled, multicenter study (EudraCT 2014-004409-34). SETTING: The study was conducted at 5 European clinical centers. PATIENTS: Women with PCOS participated in the study. INTERVENTION: Interventions included fezolinetant 60 or 180 mg/d or placebo for 12 weeks. MAIN OUTCOME MEASURE: The primary efficacy endpoint was change in total testosterone. Gonadotropins, ovarian hormones, and safety/tolerability were also assessed. RESULTS:Seventy-three women were randomized, and 64 participants completed the study. Adjusted mean (SE) changes in total testosterone from baseline to week 12 for fezolinetant 180 and 60 mg/d were -0.80 (0.13) and -0.39 (0.12) nmol/L versus -0.05 (0.10) nmol/L with placebo (P<0.0001 and P<0.05, 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) versus -3.16 (1.04) IU/L with placebo (P<0.0001 and P=0.0022); corresponding changes in follicle-stimulating hormone (FSH) were -1.46 (0.32) and -0.92 (0.30) versus -0.57 (0.26) IU/L (P=0.0336 and P=0.3770), underpinning a dose-dependent decrease in the LH-to-FSH ratio versus placebo (P<0.001). Circulating levels of progesterone and estradiol did not change significantly versus placebo (P>0.1). Fezolinetant was well tolerated. CONCLUSIONS: Fezolinetant had a sustained effect to suppress hyperandrogenism and reduce the LH-to-FSH ra.
RCT Entities:
CONTEXT: 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. DESIGN: This was a phase 2a, randomized, double-blind, placebo-controlled, multicenter study (EudraCT 2014-004409-34). SETTING: The study was conducted at 5 European clinical centers. PATIENTS: Women with PCOS participated in the study. INTERVENTION: Interventions included fezolinetant 60 or 180 mg/d or placebo for 12 weeks. MAIN OUTCOME MEASURE: The primary efficacy endpoint was change in total testosterone. Gonadotropins, ovarian hormones, and safety/tolerability were also assessed. RESULTS: Seventy-three women were randomized, and 64 participants completed the study. Adjusted mean (SE) changes in total testosterone from baseline to week 12 for fezolinetant 180 and 60 mg/d were -0.80 (0.13) and -0.39 (0.12) nmol/L versus -0.05 (0.10) nmol/L with placebo (P<0.0001 and P<0.05, 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) versus -3.16 (1.04) IU/L with placebo (P<0.0001 and P=0.0022); corresponding changes in follicle-stimulating hormone (FSH) were -1.46 (0.32) and -0.92 (0.30) versus -0.57 (0.26) IU/L (P=0.0336 and P=0.3770), underpinning a dose-dependent decrease in the LH-to-FSH ratio versus placebo (P<0.001). Circulating levels of progesterone and estradiol did not change significantly versus placebo (P>0.1). Fezolinetant was well tolerated. CONCLUSIONS:Fezolinetant had a sustained effect to suppress hyperandrogenism and reduce the LH-to-FSH ra.
Authors: Christopher R McCartney; Rebecca E Campbell; John C Marshall; Suzanne M Moenter Journal: J Neuroendocrinol Date: 2022-01-26 Impact factor: 3.870