Etiology of Central (Hypogonadotropic) Female Hypogonadism: Genetic, Organic and Functional Causes

Abstract

Central (hypogonadotropic) hypogonadism (CH) can be mentioned among the causes of menstrual and fertility problems in women. This clinical syndrome is characterized by decreased sex steroid secretion due to the impairment of basal and/or impulse secretion of gonadotropins. It can be congenital or acquired, organic or functional (i.e. without visible anatomic damages of the hypothalamo-hypophyseal area), isolated or combined with other pituitary hormone deficits (hypopituitarism). All causes of central female hypogonadism can be conditionally divided into some subgroups: genetic factors (lead to congenital CH), organic factors (lead to acquired CH), and idiopathic (lead functional CH). Congenital CH can be caused by genes that control ontogenesis and migration of GnRH neurons, regulate secretion of GnRH and provide its’ biological effects on gonadotropins. The potential organic causes of CH include pituitary tumors and some other types of tumors with similar localization, consequences of surgical or radiation intervention in connection with these tumors, brain injury as well as autoimmune, infiltrative and other rare diseases. Classical risk factors for functional CH include stress, excessive physical exercises and critically low body mass, however, variety of hormonal changes (including metabolic hormones) was observed and genetic predisposition was also shown for these patients. It is very important to understand complex pathogenetic factors that will help to improve diagnosis of this rare disease.