Kisspeptin and neurokinin B analogs use in gynecological endocrinology: where do we stand?

BACKGROUND: Recent studies have found that kisspeptin/neurokinin B/dynorphin neurons (KNDy neurons) in the infundibular nucleus play a crucial role in the reproductive axis. Analogs, both agonists and antagonists, of kisspeptin and neurokinin B (NKB) are particularly important in explaining the physiological role of KNDy in the reproductive axis in animals. The use of kisspeptin and NKB analogs has helped elucidate the regulators of the hypothalamic reproductive axis. PURPOSE: This review describes therapeutic uses of Kiss-1 and NKB agonists, most obviously the use of kisspeptin agonists in the treatment for infertility and the induction of ovulation. Kisspeptin antagonists may have potential clinical applications in patients suffering from diseases associated with enhanced LH pulse frequency, such as polycystic ovary syndrome or menopause. The inhibition of pubertal development using Kiss antagonists may be used as a therapeutic option in precocious puberty. Kisspeptin antagonists have been found capable of inhibiting ovulation and have been proposed as novel contraceptives. Hypothalamic amenorrhea and delayed puberty are conditions in which normalization of LH secretion may potentially be achieved by treatment with both kisspeptin and NKB agonists. NKB antagonists are used to treat vasomotor symptoms in postmenopausal women, providing rapid relief of symptoms while supplanting the need for exogenous estrogen exposure. CONCLUSIONS: There is a wide spectrum of therapeutic uses of Kiss-1 and NKB agonists, including the management of infertility, treatment for PCOS, functional hypothalamic amenorrhea or postmenopausal vasomotor symptoms, as well as contraceptive issues. Nevertheless, further research is needed before kisspeptin and NKB analogs are fully incorporated in clinical practice.