Is suppressed Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) expected in the setting of testosterone replacement therapy with significantly low FSH and LH levels?

From the Guidelines

Suppressed FSH and LH levels (FSH < 0.1, LH < 0.2) are an expected and normal finding in patients on testosterone replacement therapy (TRT), and no intervention is needed as this represents the body's natural feedback response to exogenous testosterone. When external testosterone is administered, the hypothalamic-pituitary-gonadal axis detects adequate or elevated testosterone levels in the bloodstream, which triggers negative feedback to shut down the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland, as noted in the context of testosterone therapy efficacy and safety evaluations 1. This suppression is reversible and will normalize if testosterone therapy is discontinued. However, patients should be aware that this suppression can lead to reduced or absent sperm production while on TRT, which may affect fertility. If fertility is desired while on testosterone therapy, additional medications like human chorionic gonadotropin (hCG) at doses of 500-1500 IU 2-3 times weekly may be considered to maintain testicular function, though this should be managed by a specialist. Regular monitoring of testosterone levels, complete blood count, and prostate-specific antigen is still recommended as part of routine TRT follow-up, but the suppressed gonadotropins themselves do not require correction. Key points to consider include:

• The natural feedback mechanism of the body in response to exogenous testosterone
• The potential impact on fertility due to suppressed FSH and LH levels
• The importance of regular monitoring during TRT
• The role of additional medications if fertility is a concern, as guided by specialist care.

From the FDA Drug Label

These men usually have low serum testosterone levels and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. These men have low testosterone serum levels but have gonadotropins in the normal or low range.

The expected FSH and LH levels in the setting of testosterone replacement are not explicitly stated in the provided drug label. However, it can be inferred that suppressed FSH and LH levels may occur as a result of testosterone replacement therapy, as the label mentions that men with hypogonadotropic hypogonadism have low testosterone serum levels and gonadotropins in the normal or low range. Given the information provided, FSH < 0.1 and LH < 0.2 may be considered low, but without explicit guidance from the label, it is difficult to determine if these levels are expected or not 2.

From the Research

Suppression of FSH and LH in Testosterone Replacement Therapy

• Testosterone replacement therapy is known to suppress the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) due to negative feedback mechanisms on the hypothalamic-pituitary-gonadal (HPG) axis 3.
• Studies have shown that exogenous testosterone replacement therapy can lead to variable suppression of LH secretion, with some men experiencing significant suppression while others may not 4.
• The level of suppression can depend on the formulation and dosage of testosterone used, with longer-acting formulations tend to cause greater suppression of FSH and LH compared to shorter-acting ones 5.

Expected Levels of FSH and LH Suppression

• In men with hypogonadotropic hypogonadism, testosterone replacement therapy can lead to a suppression of FSH levels from 2.8 IU/L to 1.1 IU/L and LH levels from 2.3 to 0.8 IU/L 6.
• FSH levels < 0.1 and LH levels < 0.2 are considered suppressed, which is expected in the setting of testosterone replacement therapy 6.
• The suppression of FSH and LH can be reversible, and the use of human chorionic gonadotropin, selective estrogen receptor modulators, or aromatase inhibitors may be used to stimulate endogenous testosterone production and preserve fertility 7.

Clinical Implications

• The suppression of FSH and LH can have clinical implications, including decreased semen parameters and possible infertility 5, 7.
• Monitoring of FSH and LH levels can be useful in assessing the adequacy of androgen replacement therapy and adjusting dosage as needed 6.
• Patient-centered decision making is paramount in selecting the optimal treatment option for hypogonadal men, taking into account factors such as safety, efficacy, cost-effectiveness, and side effects 3.