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Testosterone treatment of male hypogonadism

Testosterone treatment of male hypogonadism
Hypogonadism in a male refers to a decrease in either of the two major functions of the testes: sperm production or testosterone production. These abnormalities can result from disease of the testes (primary hypogonadism) or disease of the pituitary or hypothalamus (secondary hypogonadism).
The use of testosterone to treat male hypogonadism, primary or secondary, is reviewed here. The clinical manifestations and diagnosis of male hypogonadism are discussed elsewhere. (See "Clinical features and diagnosis of male hypogonadism".)


The following principles should guide testosterone therapy:

Testosterone should be administered only to a man who is hypogonadal, as evidenced by clinical symptoms and signs consistent with androgen deficiency and a distinctly subnormal serum testosterone concentration. In comparison, increasing the serum testosterone concentration in a man who has symptoms suggestive of hypogonadism but whose testosterone concentration is already normal will not relieve those symptoms. (See "Clinical features and diagnosis of male hypogonadism".)
Testosterone can be replaced satisfactorily whether the testosterone deficiency is due to primary or secondary hypogonadism.
The principal goal of testosterone therapy is to restore the serum testosterone concentration to the normal range. It is not yet known if restoring the normal circadian rhythm of testosterone is important.
The role of testosterone replacement to treat the decline in serum testosterone concentration that occurs with increasing frequency above age 60 in the absence of identifiable pituitary or hypothalamic disease is uncertain.

Choosing among the different testosterone preparations requires an understanding of their pharmacokinetics. Native testosterone is absorbed well from the intestine, but it is metabolized so rapidly by the liver that it is virtually impossible to maintain a normal serum testosterone concentration in a hypogonadal man with oral testosterone. The solutions to this problem that have been developed over many years involve modifying the testosterone molecule, changing the method of testosterone delivery, or both. The following testosterone preparations are currently available or are under development for treating testosterone deficiency:

Alkylated androgens — Decades ago, investigators discovered that adding an alkyl group in the 17-alpha position of the testosterone molecule retarded its catabolism by the liver . Since that time, several 17-alkylated androgens (eg, methyltestosterone) have been available for oral use. Many endocrinologists who treat male hypogonadism think that these preparations are not fully effective in producing virilization, although no studies have tested these observations. In addition, several reports have described hepatic side effects with these preparations, including cholestatic jaundice, a hepatic cystic disease called peliosis hepatis, and hepatoma . For both of these reasons, and because better preparations are available, the 17-alkylated androgens should generally not be used to treat testosterone deficiency.