Hypogonadotropic hypogonadism (HH), also known as secondary or central hypogonadism, as well as gonadotropin-releasing hormone deficiency or gonadotropin deficiency (GD), is a condition which is characterized by hypogonadism due to an impaired secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), by the pituitary gland in the brain, and in turn decreased gonadotropin levels and a resultant lack of sex steroid production.[1]

The type of HH, based on its cause, may be classified as either primary or secondary. Primary HH, also called isolated HH, is responsible for only a small subset of cases of HH, and is characterized by an otherwise normal function and anatomy of the hypothalamus and anterior pituitary. It is caused by congenital syndromes such as Kallmann syndrome, CHARGE syndrome, and gonadotropin-releasing hormone (GnRH) insensitivity. Secondary HH, also known as acquired or syndromic HH, is far more common than primary HH, and is responsible for most cases of the condition. It has a multitude of different causes, including brain or pituitary tumors, pituitary apoplexy, head trauma, ingestion of certain drugs, and certain systemic diseases and syndromes.[1]

Primary and secondary HH can also be attributed to a genetic trait inherited from the biologic parents. For example, the male mutations of the GnRH coding gene could result in HH. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis.

Examples of symptoms of hypogonadism include delayed, reduced, or absent puberty, low libido, and infertility.

Treatment of HH may consist of administration of either a GnRH agonist or a gonadotropin formulation in the case of primary HH and treatment of the root cause (e.g., a tumor) of the symptoms in the case of secondary HH. Alternatively, hormone replacement therapy with androgens and estrogens in males and females, respectively, may be employed.

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