Strategies to Increase Testosterone in Men Seeking Fertility

Prevalence of testosterone deficiency is increasing in the adolescent and young adult male population. As the average paternal age rises, there is a significant population of men with hypogonadism seeking testosterone therapy wishing to achieve or maintain fertility potential. Identification of potential lifestyle modifications that may improve the testosterone deficiency is one of the initial interventions of the holistic strategy in treatment. This is followed by drug therapy; however, traditional testosterone therapy acts as a contraceptive by suppressing the hypothalamus-pituitary-gonadal (HPG) axis and therefore cannot be used as a treatment strategy. A solution has been the off-label use of selective estrogen receptor modulators, human chorionic gonadotropin (hCG), and anastrozole inhibitors to treat hypogonadal symptoms while increasing intratesticular testosterone, a necessity for spermatogenesis. Recently, a novel therapy, Natesto intranasal testosterone gel, has been shown to increase serum testosterone levels while maintaining semen parameters. This is hypothesized to be because of its short-acting properties having lesser effect on the HPG axis, in contrast to the long-acting properties of traditional testosterone therapy. It is important to differentiate hypogonadal men between those seeking to achieve or maintain fertility status because the drug therapy of choice differs. This can be accomplished by determining the levels of 17-hydroxyprogesterone (17-OHP), because it is a biomarker for intratesticular testosterone. Those with low 17-OHP may wish to initiate treatment with alternative therapies, whereas those with high 17-OHP may trial short-acting testosterone therapies. As the urologist's armamentarium continues to increase, better strategies to increase testosterone levels in men seeking fertility can be achieved.