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 [1]. 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.