From the Guidelines
Testosterone replacement therapy (TRT) typically causes a significant decrease in both Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels in the body. This decrease is due to the negative feedback mechanism triggered by exogenous testosterone administration, which suppresses the production of gonadotropin-releasing hormone (GnRH) by the hypothalamus, leading to a decrease in FSH and LH secretion by the pituitary gland 1.
When exogenous testosterone is administered, the hypothalamic-pituitary-gonadal axis detects the increased testosterone levels in the bloodstream, triggering this negative feedback mechanism. This suppression is dose-dependent and often leads to levels well below the normal reference range during standard TRT doses. The reduction in these hormones has important clinical implications, particularly regarding fertility, as FSH and LH are essential for sperm production and testicular function.
Key points to consider:
- The decrease in FSH and LH levels is a common effect of TRT, and it can lead to decreased sperm production and potentially reversible infertility.
- Men on TRT who wish to preserve fertility may require additional medications like human chorionic gonadotropin (hCG) or clomiphene citrate to help maintain FSH and LH levels.
- The use of aromatase inhibitors (AIs), hCG, selective estrogen receptor modulators (SERMs), or a combination thereof may be considered for infertile men with low serum testosterone, but testosterone monotherapy should not be prescribed for men interested in current or future fertility 1.
In clinical practice, it is essential to carefully evaluate the etiology of hypogonadism and consider the potential effects of TRT on FSH and LH levels, as well as fertility, before initiating treatment. TRT should be used with caution in men who wish to preserve fertility, and alternative treatments or adjunctive therapies should be considered to minimize the risk of infertility.
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)
When on testosterone replacement therapy, LH and FSH levels are suppressed due to feedback inhibition of the pituitary gland. This means that:
- LH levels will be decreased because exogenous testosterone inhibits the release of endogenous testosterone, which in turn reduces the production of LH.
- FSH levels will also be decreased, particularly at large doses of exogenous androgens, leading to suppression of spermatogenesis. 2
From the Research
Effects of Testosterone Replacement on FSH and LH Levels
- Testosterone replacement therapy (TRT) can suppress the secretion of luteinizing hormone (LH) due to the negative feedback mechanism involved in the hypothalamic-pituitary-gonadal axis 3.
- A study found that 73% of men on TRT had at least one LH level <1 IU/ml during treatment, but only 22% maintained suppressed LH levels throughout the treatment 3.
- Another study suggested that the suppression of LH secretion during testosterone treatment is greater in older men, and this effect may be related to changes in gonadotropin negative feedback regulation 4.
- Follicle-stimulating hormone (FSH) levels are also suppressed during TRT, with one study finding a linear correlation between FSH and LH levels and testosterone levels in men with hypogonadotropic hypogonadism 5.
- Testosterone administration can inhibit gonadotropin secretion by a direct effect on the human pituitary gland, independent of the hypothalamic GnRH pulse generator 6.
Factors Influencing FSH and LH Suppression
- The route of testosterone administration can influence LH suppression, with intramuscular administration associated with greater suppression than transdermal administration 3.
- Baseline LH levels and estradiol levels can also predict LH suppression during TRT 3.
- Age is a strong predictor of LH suppression during testosterone replacement, with older men experiencing greater suppression 4.
- The relationship between FSH and LH levels and testosterone levels can vary between individuals, and may be influenced by factors such as hypothalamic-pituitary disease or injury 5.
Clinical Implications
- The suppression of FSH and LH levels during TRT can have implications for testicular function and fertility 5.
- Monitoring of FSH and LH levels during TRT can help to assess the adequacy of androgen replacement and minimize the risk of testicular atrophy 3, 5.
- Further research is needed to fully understand the effects of TRT on FSH and LH levels and to optimize treatment strategies for men with hypogonadism 3, 4, 5, 6.