Context Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause. Objective We aimed to assess efficacy/safety of fezolinetant for treatment of moderate-to-severe VMS associated with menopause. Methods In this double-blind, placebo-controlled, 12-week (W) phase 3 trial with a 40W active treatment extension (NCT04003142; SKYLIGHT 2) women aged 40–65 years with minimum average 7 moderate-to-severe VMS/day were randomized to 12 weeks’ once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to W4 and W12 in VMS frequency and severity. Safety was also assessed. Results Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, –1.82 (0.46; P < .001); 45 mg, –2.55 (0.46; P < .001); W12: 30 mg, –1.86 (0.55; P < .001); 45 mg, –2.53 (0.55; P < .001). For VMS severity, W4: 30 mg, –0.15 (0.06; P<.05); 45 mg, –0.29 (0.06; P < .001); W12: 30 mg, –0.16 (0.08; P <.05); 45 mg, –0.29 (0.08; P < .001). Improvement in VMS frequency and severity was observed by W1; maintained through W52. Serious TEAEs were infrequent; these were reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively. Conclusions Daily fezolinetant 30 mg and 45 mg were efficacious and well-tolerated for treating moderate-to-severe VMS associated with menopause.

Estrogens are known to act selectively on some components of memory, exerting beneficial effects on cognitive performances. However, there are few data on the long-term effect of the lack of estrogen in postmenopausal women. Therefore, we investigated attentive and verbal memory performances in physiological and surgical menopause, drawing attention to the impact of age at menopause, and we compared a well-known aging and estrogen-dependent index, the entity of bone mass loss to memory functioning. No significant differences were found in the mean scores of attentive and psychomotor performances between physiological and surgical menopause, whereas a lower number of recalled words (recency effect = PS2) was found in surgical menopause (p < 0.001) in comparison to physiological menopause. In addition, both the age at the time of ovariectomy (r = 0.47; p = 0.014) and the years since surgery (r = –0.64; p = 0.000) correlated to short-term verbal memory performance (PS2) with better scores when surgery occurred later in women’s lives. Surgical menopause is able to affect short-term verbal memory more than physiological menopause and seems to represent a critical negative event within the female brain, in particular when it occurs prematurely.

SKYLIGHT 4 (Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause) demonstrates the 52-week safety and tolerability of fezolinetant and its use for the treatment of vasomotor symptoms associated with menopause.