Hypothalamic-Pituitary-Gonadal Axis Disorders Impacting Fertility in Both Sexes and the Potential of Kisspeptin-Based Therapies to Treat Them

Impaired function of the hypothalamic-pituitary-gonadal (HPG) axis can lead to a vast array of reproductive disorders some of which are inherited or acquired, but many are of unknown etiology. Among the clinical consequences of HPG impairment, infertility is quite common. According to the latest report from the World Health Organization, the global prevalence of infertility during a person’s lifetime is a staggering 17.5% which translate into 1 out of every 6 people experiencing it. In both sexes, infertility is associated with adverse health events, and if unresolved, infertility can cause substantial psychological stress, social stigmatization, and economic strain. Even though significant advances have been made in the management and treatment of infertility, low or variable efficacy of treatments and medication adverse effects still pose a significant problem. However, the discovery that in humans inactivating mutations in the gene encoding the kisspeptin receptor (Kiss1R) results in pubertal failure and infertility has expanded our understanding of the mechanisms underlying the neuroendocrine control of reproduction, opening up potential new therapies for the treatment of infertility disorders. In this chapter we provide an overview of common infertility disorders affecting men and women, their recommended treatments, and the potential of kisspeptin-based pharmacotherapies to treat them.