Fezolinetant downregulates the activity of candy neurons in the hypothalamus, said Dr. Fraser in an interview. In turn, gonadotropin-releasing hormone (GNRH) pulse frequency is reduced, lowering luteinizing hormone (LH) levels. Since LH drives testosterone levels, this drops as well – a beneficial effect in PCOS, with its cardinal symptom of hyperandrogenism.
The double-blind, placebo-controlled study was conducted in Western Europe; 73 participants were randomized into three groups: 27 to a placebo group, 23 to a treatment group given 60 mg of fezolinetant once daily, and 23 to a treatment group given 180 mg of fezolinetant once daily. All groups received treatment for 12 weeks.
A total of 26 patients on placebo, 21 on 60-mg fezolinetant, and 17 on 180-mg fezolinetant completed the study. Patients who completed the study were included in the safety analysis, while all who took the study medication were included in the intent-to-treat analysis for primary and secondary outcome measures.
All participants had PCOS with hyperandrogenism, mean age was about 31 years, and about three quarters of enrollees were white, though local regulations restricted the collection of race and ethnicity data in some cases. One secondary outcome measure of the study was how fezolinetant affected the LH:FSH (follicle-stimulating hormone) ratio. “Patients with PCOS tend to have a very high GNRH [gonadotropin-releasing hormone] pulse frequency, which leads to a very high LH:FSH ratio,” said Dr. Fraser.