The roles of aromatase inhibitors in treating hypogonadism and male infertility

Testis is an organ with both endocrine and exocrine functions. The former stands for testosterone release, and the latter represents sperm production. Spermatogenesis is a process highly depending on adequate supply of testosterone by the Leydig cells of the testis. In men at the reproductive age, more than 90% of testosterone produced is used for spermatogenesis. In men with diminished testosterone secretion in testis, or hypogonadism, the spermatogenesis process is impaired. Testosterone can be converted into estradiol through the catalyzation of aromatase, a cytochrome P450 enzyme presented in the peripheral tissue. Blocking the activity of aromatase causes an elevation of serum testosterone and a decrease of serum estradiol levels. These effects result in an increase of testosterone-to-estradiol ratio. Infertile males with dysfunction of spermatogenesis may demonstrate a low testosterone-to-estradiol ratio. Studies have shown that aromatase inhibitors (AIs) are beneficial to treat patients with impaired spermatogenesis, by demonstrating improvement of the semen parameters in men with oligoasthenoteratozoospermia. Besides, AIs can also be applied in other health issues, such as hypogonadism-related erectile dysfunction, short statue, depression, or male breast cancer. There are two different types of AIs: steroidal and nonsteroidal. Steroidal AI (e.g., testolactone) is an irreversible, but weaker inhibitors, while nonsteroidal AIs (e.g., letrozole and anastozole) are potent reversible inhibitors. Both types of AIs demonstrate plausible effects to improve semen parameters. In this review, the physiological action of aromatase and the indications of AIs treatment are discussed in detail, especially focusing on the function of spermatogenesis in infertile men.