Testosterone plays several important roles in men. It is associated with sexual function, energy level, muscle and bone health, and metabolic fitness. When deficient, men with hypogonadism often present with expected symptoms of fatigue and sexual dysfunction. Exogenous testosterone is the primary treatment for symptomatic hypogonadism. However, exogenous testosterone exerts negative feedback on the hypothalamic-pituitary-gonadal axis, resulting in suppression of gonadotropic production by the anterior pituitary leading to diminished intratesticular testosterone production and significant reductions in spermatogenesis.

Such conflict between testosterone therapy and reproductive goals must be carefully managed by clinicians. The plenary “Second Opinion Cases: TRT and the Infertile Male” will examine the management of such challenging cases. We will explore 2 common scenarios.

Case 1: A 32-year-old male presents to clinic for infertility evaluation. His semen testing is normal. He reports low libido and mild erectile dysfunction. His testosterone level is 210 ng/mL with normal gonadotropins. His body mass index is normal. The patient is presented with options to treat symptomatic hypogonadism in a patient who desires intact fertility. Given the implications of testosterone replacement therapy on spermatogenesis, alternative options to treat hypogonadism must be utilized. There are 3 classes of medications that are used clinically in this scenario: selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and human chorionic gonadotropin (hCG). Data regarding use, dosing, and efficacy will be discussed.

Case 2: A 38-year-old male presents for infertility. He is in a 2-year relationship with his 37-year-old partner and they have been unsuccessful at pregnancy after 1 year of attempts. He has no prior children. His history is significant for using intramuscular testosterone cypionate 100 mg weekly for the past 3 years. He has no other significant medical history. He reports that his testosterone levels were below 300 ng/dL when he started, and he was not offered options other than testosterone or warned that it could affect his fertility. His semen analysis shows 0 sperm. The patient was counseled that age and duration of testosterone use predict the probability of sperm recovery. The use of hCG and SERM therapy will be discussed as well as predictive models for likelihood and timing of spermatogenic recovery.

SERMs occupy the estrogen receptors at the hypothalamus and anterior pituitary, reducing negative feedback and resulting in increased production of luteinizing hormone and follicle stimulating hormone. AIs block the peripheral conversion of testosterone to estrogen by inhibiting the enzyme aromatase, thereby raising testosterone levels. hCG shares an alpha-subunit with luteinizing hormone leading to activation of the luteinizing hormone receptors on the Leydig cells, leading to increased testosterone production. Specific dosage regimens are variable and not standardized, but all 3 classes of medications can maintain normal levels of testosterone production without impairing spermatogenesis. SERMs and AIs are given orally while hCG is given via subcutaneous or intramuscular injection.

The panelists will discuss each case in detail and present options for management for each patient. Importantly, most of the discussion will center around uses for medications which are off-label, as no Food and Drug Administration–approved therapy exists for male fertility.