Hormonal Treatment of Male Infertility: Gonadotropins and Beyond

Treatment of male infertility has become one of the hottest topics of research in endocrinology and andrology. A significant proportion of the causes of male infertility can now be treated: obstructive azoospermia, infections, and, to a certain extent, varicocele are known factors for sub- or infertility which can be improved through various types of treatment. Hormone therapy has been used for hypogonadotropic hypogonadism (HH), whether congenital or acquired. In these patients, exogenous hCG, LH, and FSH are given to induce fertility and stimulate testicular steroidogenesis. The administration of exogenous gonadotropins can restore spermatogenesis, albeit not to normal levels, in most cases of HH-associated azoospermia, but recent evidence suggests that other conditions involving reduced germ cell output might also benefit. In some cases of idiopathic oligoasthenoteratozoospermia (OAT), gonadotropin administration improved sperm quality and parameters, although the changes were of uncertain clinical significance. More convincing evidence has emerged on the effect of FSH administration on nonconventional sperm parameters, including chromatin condensation and DNA fragmentation, suggesting a possible adjuvant use in assisted reproduction techniques (ART). Areas of active research include the identification of the best or individualized doses and regimen to administer gonadotropins. Recent advances in genome research have also paved the way for new approaches to the hormonal treatment of idiopathic OAT. Polymorphisms in the FSH receptor have been investigated as a contributing pathogenic factor but also as a predictor of response to treatment. Genetic variants might explain why not all men respond in the same way to gonadotropin administration. There is no rationale for the use of hormone treatment in men with elevated gonadotropins, and such treatment is mostly unsuccessful. Other drugs acting on hormonal homeostasis have also been used to treat male infertility, including aromatase inhibitors and antiestrogens. The evidence for their use is far from definitive, although some possible factors predictive of a positive response have been identified. Tailored therapy, genetic profiling, and new drugs with slower absorption rates have shown promising results, and recent evidence suggests that hormone therapy may also benefit men with oligozoospermia and normal concentrations of FSH and LH.