Functional hypothalamic amenorrhea (FHA) is the most common cause of secondary amenorrhea in women of reproductive age. FHA is predominantly caused by stress, decreased caloric intake, excessive exercise, or a combination thereof. These physical, psychological, and metabolic stressors cause aberration in the pulsatile release of gonadotropin-releasing hormone (GnRH) and subsequently impair function of the hypothalamic–pituitary–ovarian (HPO) axis. Various neurotransmitters acting in the central nervous system are involved in control of the HPO axis and of these, kisspeptin is one of the most important. Corticotropin-releasing hormone (CRH), also inhibits the pulsatile secretion of GnRH and also acts as an intermediary between stress factors and the reproductive system. One of the main ongoing concerns in patients with FHA is chronic hypoestrogenism, a condition, which is associated with sexual dysfunction and infertility. It may also lead to osteoporosis, and predispose to neurodegenerative and cardiovascular diseases.

Treatment of FHA requires the elimination of causative factors, however, making the necessary lifestyle changes is not always easy to initiate and maintain. Broadening our knowledge of the complex neural mechanisms regulating reproductive function in which kisspeptin plays a key role can help in the development of new treatment options such as the potential of kisspeptin receptor agonists for patients with FHA.

功能性下丘脑性闭经 (FHA) 是育龄妇女继发性闭经的最常见原因。FHA 主要由压力、热量摄入减少、过度运动或其组合引起。这些身体、心理和代谢应激源会导致促性腺激素释放激素 (GnRH) 的脉冲释放失常，并随后损害下丘脑-垂体-卵巢 (HPO) 轴的功能。作用于中枢神经系统的各种神经递质都参与 HPO 轴的控制，其中，kisspeptin 是最重要的一种。促肾上腺皮质激素释放激素 (CRH) 也抑制 GnRH 的脉动分泌，并且还充当压力因素和生殖系统之间的中介。FHA 患者持续关注的主要问题之一是慢性雌激素不足，这种情况与性功能障碍和不育有关。它还可能导致骨质疏松症，并易患神经退行性和心血管疾病。

FHA 的治疗需要消除致病因素，但是，进行必要的生活方式改变并不总是容易开始和维持。拓宽我们对调节生殖功能的复杂神经机制的了解，其中 kisspeptin 起着关键作用，有助于开发新的治疗方案，例如 Kisspeptin 受体激动剂对 FHA 患者的潜力。