From the Guidelines
Testosterone replacement therapy can significantly impact fertility in men, and it is not recommended for those interested in current or future fertility. The most recent and highest quality study, published in 2024, 1, highlights the negative effects of exogenous testosterone therapy on spermatogenesis, leading to impaired fertility. When external testosterone is introduced, the body's natural production is reduced, resulting in decreased sperm production. This occurs because testosterone replacement therapy suppresses the hormones FSH and LH, which stimulate sperm production in the testes.
The effect of testosterone replacement therapy on fertility can be temporary but may become permanent with long-term use. Common TRT medications, such as testosterone cypionate, enanthate, or topical gels, typically cause reduced sperm counts within months of starting treatment. According to the 2024 guideline, 1, for men interested in current or future fertility, clinicians should not prescribe exogenous testosterone therapy due to its inhibitory effects on spermatogenesis.
Instead, alternative treatments such as human chorionic gonadotropin (hCG) or clomiphene citrate may be considered to maintain fertility while addressing low testosterone symptoms. The 2021 guideline, 1, also supports the use of hCG, selective estrogen receptor modulators (SERMs), or aromatase inhibitors (AIs) for infertile men with low serum testosterone. However, the most recent study, 1, takes precedence, and its recommendations should be prioritized.
Some men may benefit from freezing sperm before starting TRT, and regular semen analysis can help monitor fertility status during treatment. The fertility impact varies between individuals, with some men maintaining fertility on TRT while others experience complete suppression of sperm production. It is essential for clinicians to counsel patients about the potential negative effects of testosterone replacement therapy on fertility and discuss alternative treatment options.
From the FDA Drug Label
At large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH) During exogenous administration of androgens, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH)
Testosterone replacement therapy can affect fertility. The use of exogenous androgens, such as testosterone enanthate and testosterone cypionate, can suppress spermatogenesis through feedback inhibition of pituitary follicle stimulating hormone (FSH) and luteinizing hormone (LH) 2, 3. This can lead to a decrease in fertility.
- Key points:
- Exogenous androgens can suppress spermatogenesis
- Feedback inhibition of pituitary FSH and LH can occur
- Testosterone replacement therapy may affect fertility
From the Research
Effects of Testosterone Replacement Therapy on Fertility
- Testosterone replacement therapy (TRT) can inhibit spermatogenesis, leading to male infertility 4, 5, 6, 7.
- Exogenous testosterone suppresses intratesticular testosterone production, which is essential for normal spermatogenesis 4.
- Studies have shown that most men experience a return of normal sperm production within 1 year after discontinuing TRT 4, 7.
Treatment Options for Hypogonadal Men
- Clomiphene citrate is a safe and effective therapy for men who desire to maintain future potential fertility 4, 5, 6.
- Human chorionic gonadotropin (hCG) therapy can also be used to stimulate spermatogenesis in men with hypogonadism 4, 5.
- Selective estrogen receptor modulators (SERMs) and gonadotropin therapy may be necessary for some men to recover spermatogenesis after cessation of TRT 7.
Recovery of Spermatogenesis
- The recovery period of spermatogenesis after cessation of TRT is highly variable among patients 5, 7.
- Factors such as baseline testicular function, duration of drug use, and age at cessation can influence the recovery of spermatogenesis 7.
- In some cases, drug cessation alone may not achieve spontaneous recovery, and hormonal stimulation or assisted reproductive techniques may be necessary 7.