Does Hormone Replacement Therapy (HRT) suppress Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) in men?

From the Guidelines

Hormone replacement therapy (HRT) in men indeed suppresses luteinizing hormone (LH) and follicle-stimulating hormone (FSH) due to the negative feedback mechanism on the hypothalamus and pituitary gland. This suppression occurs because exogenous testosterone from HRT signals the body that sufficient testosterone levels are present, thereby reducing the need for the pituitary gland to produce LH and FSH, which are essential for stimulating the testes to produce testosterone and sperm [ 1 ].

Mechanism of Suppression

The degree of LH and FSH suppression depends on the dose and formulation of testosterone used in HRT. High doses of testosterone can lead to more significant suppression of LH and FSH, potentially resulting in reduced sperm production and infertility in men undergoing testosterone replacement therapy. This is a critical consideration for men who may wish to preserve their fertility while undergoing HRT.

Clinical Implications

For men concerned about fertility, alternative approaches such as human chorionic gonadotropin (hCG) therapy might be considered. hCG mimics the action of LH and can help maintain testicular function while providing the benefits of testosterone therapy [ 1 ]. It's essential to note that the suppression of LH and FSH by HRT is typically reversible when the therapy is discontinued. However, recovery of normal hormone levels and fertility may take several months to a year, emphasizing the need for careful consideration and planning before initiating HRT.

Evidence and Recommendations

The evidence from recent studies, such as the one published in the Annals of Internal Medicine [ 1 ], supports the use of testosterone therapy for improving sexual functioning and quality of life in men with low testosterone levels, although the effect sizes are small. However, the long-term efficacy and safety of testosterone therapy, including its effects on LH and FSH suppression, are areas that require further research. Given the current evidence, it is crucial for clinicians to weigh the benefits of HRT against potential risks, including the suppression of LH and FSH, and to closely monitor patients undergoing such therapy.

From the FDA Drug Label

During exogenous administration of androgens, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH). At large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH) 2 During exogenous administration of androgens, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH). At large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH) 3

Yes, Hormone Replacement Therapy (HRT) with testosterone can suppress Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) in men, particularly at large doses.

• LH is suppressed through feedback inhibition during exogenous administration of androgens.
• FSH is also suppressed at large doses of exogenous androgens, which can lead to suppression of spermatogenesis.

From the Research

Hormone Replacement Therapy (HRT) and its Effects on Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) in Men

• The administration of exogenous testosterone, a form of HRT, has been shown to suppress the production of LH and FSH in men 4, 5, 6, 7, 8.
• This suppression is due to the negative feedback mechanism involved in the hypothalamic-pituitary-gonadal axis, where high levels of testosterone inhibit the release of gonadotropin-releasing hormone (GnRH), leading to decreased production of LH and FSH 6, 8.
• The degree of suppression of LH and FSH varies depending on the dosage and formulation of testosterone used, with higher dosages and longer-acting formulations resulting in greater suppression 5, 8.
• Studies have shown that testosterone replacement therapy can lead to significant decreases in LH and FSH levels, with some men experiencing azoospermia or severe oligospermia as a result 4, 5, 8.
• The suppression of LH and FSH can have significant implications for fertility, and men who wish to preserve their fertility should be cautious when considering testosterone replacement therapy 4, 5, 7.

Key Findings

• A study published in 2020 found that testosterone replacement therapy led to marked suppression of gonadotropins in 5 out of 6 patients, resulting in hypogonadotropic hypogonadism 4.
• A 2021 study found that shorter-acting testosterone preparations resulted in less suppression of FSH and LH compared to longer-acting formulations 5.
• A 2006 study found that testosterone replacement led to a suppression of FSH and LH levels in men with hypogonadotropic hypogonadism, with a linear correlation between testosterone levels and gonadotropin levels 6.
• A 2022 study found that 73% of men treated with exogenous testosterone had at least one LH level <1 IU/ml during treatment, with intramuscular route, baseline LH, and estradiol levels being significant predictors of LH suppression 7.
• A 1990 study found that chronic testosterone administration resulted in parallel dose-dependent suppression of LH, FSH, and sperm production, with no significant adverse health effects detected 8.