Does fezolinetant affect hormone levels?

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Prescribing Information including BOXED WARNING

In clinical trials, fezolinetant was associated with a transient decrease in luteinizing hormone (LH) levels, but had no significant impact on follicular stimulating hormone (FSH), sex hormone binding globulin (SHBG), estradiol, (free) testosterone, estrone, dehydroepiandriosterone (DHEA) or androstenedione in postmenopausal women

Change in serum concentrations of gonadotrophins, sex hormones and SHBG from baseline to selected visits were pre-specified pharmacodynamic assessments in the Phase 3 SKYLIGHT 1, 2, and 4 trials, and in Phase 1 and 2 studies.^1–3
In postmenopausal women, fezolinetant was associated with a transient decrease in LH levels three hours post-dose in all treatment groups across the 12-week clinical studies.^1–4 The decrease and prolonged LH recovery appeared to be dose-related and recovered to baseline levels within 24 hours of dosing.³

The following information is from a Phase 1 study in 24 premenopausal women:

LH: Fezolinetant significantly delayed the LH surge compared with placebo (p < 0.01 for 60 and 180 mg doses).³ Two women from the 60 mg and 180 mg dosing groups did not experience an LH surge at all over the 21-day dosing period. For two other women in the 60 mg dosing group, the delayed LH surge coincided with the final dosing day. Fezolinetant caused LH levels at surge to rapidly decline by 61% to 76% at four hours with recovery at six hours post-dosing. The transient decline in LH was not shown to have an effect on estradiol levels.¹
FSH: A midcycle FSH surge was not apparent in premenopausal women administered fezolinetant.³
Estradiol: Fezolinetant dose-dependently delayed the rise in estradiol in the follicular phase, delaying ovulation.³ This corresponded with the delay in the LH surge. The inhibition of LH secretion, but not FSH, allowed continuation of estradiol secretion from granulosa cells, enabling estradiol levels to remain above the 110 pmol/L threshold considered relevant for the appearance of menopausal-like adverse events.
Progesterone: Progesterone levels were dose-dependently inhibited by fezolinetant in the luteal phase.³
Menstrual cycle lengths were significantly prolonged compared with pretreatment cycles in the 60 and 180 mg groups (p < 0.05) but recovered to pretreatment lengths following termination of fezolinetant.³
The physiological changes matched the effect that fezolinetant had on the hypothalamic-pituitary-gonadal axis by selective modulation of sex hormones and gonadotrophins; reduced endometrial thickening and follicle maturation, and a delay in ovulation and menstrual cycle.³
An 84-day follow-up period showed recovery of the normal menstrual pattern once treatment with fezolinetant ended.¹

Data on file.
Fraser GL, Lederman S, Waldbaum A, et al. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020;27(4):382-392. https://dx.doi.org/10.1097/GME.0000000000001510.
Fraser GL, Ramael S, Hoveyda HR, Gheyle L, Combalbert J. The NK3 Receptor Antagonist ESN364 Suppresses Sex Hormones in Men and Women. J Clin Endocrinol Metab. 2016;101(2):417-426. https://dx.doi.org/10.1210/jc.2015-3621.
Depypere H, Timmerman D, Donders G, et al. Treatment of Menopausal Vasomotor Symptoms With Fezolinetant, a Neurokinin 3 Receptor Antagonist: A Phase 2a Trial. J Clin Endocr Metab. 2019;104(12):5893-5905. https://dx.doi.org/10.1210/jc.2019-00677.