Can testosterone replacement therapy (TRT) cause pituitary problems?

From the Guidelines

Testosterone replacement therapy (TRT) can potentially cause pituitary problems through a mechanism called negative feedback suppression, but this suppression is generally reversible and considered a normal physiological response rather than a pathological problem. When external testosterone is administered, the body detects elevated testosterone levels in the bloodstream, which signals the pituitary gland to reduce its production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) 1. This suppression can lead to decreased pituitary function while on TRT, but it is expected to be reversible upon discontinuation of therapy.

Common TRT formulations include testosterone cypionate or enanthate injections (typically 100-200mg weekly or biweekly), transdermal gels (AndroGel, Testim, 50-100mg daily), or pellet implants (inserted every 3-6 months) 1. The pituitary suppression is considered a normal physiological response rather than a pathological problem. However, prolonged use may lead to testicular atrophy and potentially make recovery of natural testosterone production more difficult if TRT is discontinued.

Patients on TRT should have regular monitoring of hormone levels, including testosterone, estradiol, LH, and FSH, to ensure appropriate dosing and to watch for any unexpected pituitary issues 1. If fertility is a concern, additional medications like HCG (human chorionic gonadotropin) may be prescribed alongside TRT to maintain testicular function. The annual cost in 2016 per beneficiary for TRT was $2135.32 for the transdermal and $156.24 for the intramuscular formulation, according to paid pharmaceutical claims provided in the 2016 Medicare Part D Drug Claims data 1.

Some key points to consider when evaluating the potential for pituitary problems with TRT include:

• The mechanism of negative feedback suppression and its potential impact on pituitary function
• The reversibility of pituitary suppression upon discontinuation of TRT
• The importance of regular monitoring of hormone levels to ensure appropriate dosing and detect any unexpected pituitary issues
• The potential for prolonged use to lead to testicular atrophy and impact recovery of natural testosterone production
• The consideration of additional medications like HCG to maintain testicular function if fertility is a concern.

Overall, while TRT can potentially cause pituitary problems, the suppression is generally reversible and considered a normal physiological response. Regular monitoring and consideration of individual patient factors can help minimize the risks associated with TRT.

From the FDA Drug Label

Increased pituitary weight was seen in both sexes. During treatment with large doses of exogenous androgens, including testosterone gel 1.62%, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis

Testosterone replacement therapy (TRT) may cause pituitary problems due to feedback inhibition of the hypothalamic-pituitary-testicular axis, which can lead to suppression of spermatogenesis. Additionally, increased pituitary weight has been observed in animal studies. However, the clinical significance of these findings in humans is unclear. 2

• Key points:
  • Feedback inhibition of the hypothalamic-pituitary-testicular axis
  • Suppression of spermatogenesis
  • Increased pituitary weight (observed in animal studies) However, these findings do not provide clear evidence of pituitary problems in humans. Therefore, caution is advised when using TRT, and patients should be monitored for any potential adverse effects on the pituitary gland.

From the Research

Testosterone Replacement Therapy and Pituitary Problems

• Testosterone replacement therapy (TRT) may cause pituitary problems due to its effect on gonadotropin secretion 3.
• The administration of testosterone can slow down LH pulse frequency in men, which may be caused by an effect on the hypothalamic GnRH pulse generator or a direct action on the pituitary 3.
• A study found that testosterone administration suppressed the mean serum LH level to about 50% of the value during GnRH alone and suppressed the mean serum FSH level to about 30% of the value during GnRH alone 3.

Mechanism of Action

• The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol 4.
• Administration of testosterone or estradiol resulted in decreased mean levels of biologically and immunologically active LH and FSH, while administration of dihydrotestosterone did not alter gonadotropin secretion 4.

Clinical Implications

• The use of testosterone replacement therapy may be associated with cardiovascular risks, although the evidence is still controversial 5.
• The pharmacology of testosterone replacement therapy preparations is complex, and the choice of formulation depends on various factors, including patient participation 6.
• A study found that biweekly injections of 200 mg testosterone cypionate resulted in wide variations in circulating androgen levels, from high to elevated shortly after injection, declining to basal by days 13 to 14 7.