From the Guidelines
Testosterone replacement therapy for hypogonadism significantly reduces fertility in men, and therefore, should be avoided in those pursuing or planning to pursue family building in the near future. When exogenous testosterone is administered, it suppresses the hypothalamic-pituitary-gonadal axis through negative feedback, leading to decreased production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), as stated in the 2024 AUA/ASRM guideline 1. This suppression results in reduced testicular testosterone production and decreased sperm production, often causing oligospermia (low sperm count) or azoospermia (no sperm).
The guideline recommends human chorionic gonadotropin (hCG) injections as the first-line treatment for idiopathic hypogonadotropic hypogonadism (IHH) to restore testosterone production and spermatogenesis 1. The treatment typically involves hCG injections (500-2500 IU, 2-3 times weekly) followed by FSH injections when indicated. For men with hypogonadism who wish to preserve fertility, alternative treatments such as hCG injections or combination therapy with FSH should be considered.
Key points to consider:
- Exogenous testosterone therapy inhibits intratesticular testosterone production and suppresses spermatogenesis, impairing fertility 1.
- The time course of recovery of sperm to the ejaculate after cessation of testosterone therapy may be prolonged, ranging from months to 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.
- For patients with non-obstructive azoospermia, pharmacologic manipulation with selective estrogen receptor modulators, aromatase inhibitors, and gonadotropins may be considered prior to surgical intervention 1.
From the FDA Drug Label
During treatment with large doses of exogenous androgens, including testosterone gel, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions (5. 8)]. Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see Drug Abuse and Dependence (9.2)]. With either type of use, the impact on fertility may be irreversible.
Testosterone replacement therapy for hypogonadism may reduce fertility in some men, as it can suppress spermatogenesis through feedback inhibition of the hypothalamic-pituitary-testicular axis.
- Reduced fertility is observed in some men taking testosterone replacement therapy.
- Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids.
- The impact on fertility may be irreversible 2 2.
From the Research
Effects of Testosterone Replacement Therapy on Fertility
- Testosterone replacement therapy (TRT) can lead to male infertility due to negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis 3, 4.
- The suppression of spermatogenesis caused by TRT is generally reversible, but the recovery period can vary among patients 4, 5.
- Alternative treatment options, such as clomiphene citrate, exogenous gonadotropins, and aromatase inhibitors, can be used to preserve fertility in hypogonadal men 6, 7.
Alternative Treatment Options
- Clomiphene citrate can stimulate endogenous testosterone production and improve sperm parameters and fertility, making it a potential alternative to TRT for men seeking to preserve fertility 6, 7.
- Exogenous gonadotropins and gonadotropin-releasing hormone can also induce spermatogenesis, but their use may be limited by practicality and safety concerns 6.
- Aromatase inhibitors may have limited use due to potential side effects, such as osteopenia 6.
Considerations for Treatment
- The choice of treatment for hypogonadism should take into account the patient's desire to preserve fertility, as well as the potential risks and benefits of each treatment option 4, 6, 7.
- Healthcare providers should be aware of the potential effects of TRT on fertility and discuss alternative treatment options with patients who wish to preserve their fertility 3, 4, 6.