question: What is ESN364?
answer: systemic administration of an NK3R antagonist (ESN364) prolongs the LH interpulse interval in ovarectomized ewes and significantly lowers plasma LH and FSH concentrations in castrated nonhuman primates (Macaca fascicularis). Moreover, daily oral dosing of ESN364 throughout the menstrual cycle in M fascicularis lowered plasma estradiol levels in a dose-dependent manner, although nadir levels of estradiol were maintained well above menopausal levels. Nevertheless, estradiol levels during the follicular phase were sufficiently inhibited at all doses to preclude the triggering of ovulation as evidenced by the absence of the LH surge and failure of a subsequent luteal phase rise in plasma progesterone concentrations, consistent with the absence of normal cycle changes in the uterus. Apart from the point at surge, FSH levels were not altered over the course of the menstrual cycle. These effects of ESN364 were reversible upon cessation of drug treatment.
  
  ESN364 was well-tolerated and rapidly bioavailable with linear pharmacokinetics and no drug accumulation with repeated, daily oral administration. Drug treatment dose-dependently decreased basal LH, but not FSH, and consequently decreased estradiol and progesterone (in women) as well as testosterone (in men). The hormonal changes in women corresponded to delayed ovulation, decreased endometrial thickening, impeded follicular maturation, and prolongation of the menstrual cycle. Drug effects were rapidly reversible. Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women. These results suggest that ESN364 may offer therapeutic benefit in the treatment of women's health disorders with a mitigated risk of menopausal-like adverse events.