Hypogonadotropin hypogonadism (HH) is a group of diseases caused by a lack or decrease of hypothalamic gonadotropin-releasing hormone (GnRH) or pituitary gonadotropin secretion. HH causes decreased sex hormone synthesis, delayed or absent puberty in preadolescent children, and hypogonadism and/or infertility in adult patients. The etiologies of HH are usually classified as congenital and acquired. Congenital HH patients are characterized by GnRH secretion disorder and can be divided into idiopathic hypogonadotropin-induced hypogonadism (IHH) and HH associated with olfactory dysfunction (Kallmann syndrome). The incidence of this disease is about 1-10 per 100,000 live births, among which about 2/3 are patients with Kallmann syndrome . Mutations of multiple gene loci including kal-1, FGR1 and GNRHR are related to the occurrence of diseases. Acquired HH is often one of the manifestations of hypothalamic-pituitary axis with trauma, tumor and other substantial lesions.
HH usually has three treatment options: 1. Sex hormone replacement therapy: i.e., testosterone replacement therapy, or estrogen-progesterone sequential therapy. Alternative therapy is suitable for hypogonadism caused by various reasons, which can enable patients to acquire and maintain secondary sexual characteristics, but its disadvantage is that it cannot induce gametes and achieve reproductive function. 2. Gonadotropin therapy: human chorionic gonadotropin (hCG) combined with human menopausal gonadotropin (HMG) or hCG combined with follicle stimulating hormone (FSH) is usually used. Suitable for patients with hypothalamic or pituitary lesions, can promote the synthesis of gonadal hormones, so that patients obtain and maintain secondary sexual characteristics, while inducing the maturation of germ cells, to achieve reproductive function. 3.GnRH pulse therapy: currently, most GnRH analogs are given by programmable and portable miniature pumps in a continuous pulse mode, which causes the pituitary gland to produce nearly normal gonadotropin pulse, thus inducing gonad development, producing sex hormones and promoting the maturation of germ cells. Most men need treatment for at least two years to maximize testicular volume and sperm production. For patients with HH caused by hypothalamic lesions, this treatment is the closest to normal physiological status, but only for patients with normal pituitary function.