From the Guidelines
Men undergoing testosterone replacement therapy (TRT) who wish to maintain fertility should not be prescribed exogenous testosterone therapy.
Fertility Maintenance Protocol
To maintain fertility in men undergoing TRT, the following protocol can be used:
- Human chorionic gonadotropin (hCG) is the usual first-line drug for the treatment of idiopathic hypogonadotropic hypogonadism (IHH) for restoration of testosterone production and spermatogenesis 1.
- hCG injections (500-2500 IU, 2-3 times weekly) can be used to stimulate testosterone production, followed by FSH injections when indicated, after testosterone levels are normalized on hCG 1.
- Aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs), or a combination thereof can be used for infertile men with low serum testosterone to increase endogenous testosterone production and improve spermatogenesis 1.
Important Considerations
- Exogenous testosterone administration provides negative feedback to the hypothalamus and pituitary gland, which can result in inhibition of gonadotropin secretion and suppression of spermatogenesis 1.
- Recovery of sperm to the ejaculate after cessation of testosterone therapy can be prolonged and may take months or rarely years 1.
- Clinicians should counsel patients about the potential negative effects of exogenous testosterone therapy on spermatogenesis and the time course required for resumption of spermatogenesis after cessation 1.
From the Research
Protocol for Maintaining Fertility in Men Undergoing TRT
To maintain fertility in men undergoing testosterone replacement therapy (TRT), several protocols can be considered:
- The use of human chorionic gonadotropin (hCG) therapy, which can help re-establish or maintain spermatogenesis in hypogonadal men 2, 3, 4
- The off-label use of selective estrogen receptor modulators, hCG, and anastrozole inhibitors to treat hypogonadal symptoms while increasing intratesticular testosterone, a necessity for spermatogenesis 3
- The use of Natesto intranasal testosterone gel, which has been shown to increase serum testosterone levels while maintaining semen parameters due to its short-acting properties having lesser effect on the HPG axis 3
- Determining the levels of 17-hydroxyprogesterone (17-OHP) to differentiate hypogonadal men between those seeking to achieve or maintain fertility status, and choosing the appropriate drug therapy accordingly 3
- The usage of ancillary medications instead of or after testosterone administration to help maintain fertility in hypogonadal patients 5
- Strategies to mitigate the risk of causing iatrogenic infertility when men require TRT, such as hypothalamic-pituitary-gonadal (HPG) axis reset in hypergonadotrophic, hypogonadal infertile men who are planning sperm retrieval procedures 6