Can testosterone injections cause hyperprolactinemia?

Testosterone Injections and Hyperprolactinemia

Testosterone injections can cause elevated prolactin levels, though this is not a common side effect and the relationship appears to be complex.

Relationship Between Testosterone and Prolactin

• Testosterone injections, particularly testosterone enanthate, can significantly increase prolactin levels with prolonged use (10 weeks) as demonstrated in animal studies 1
• The mechanism appears to involve changes in prolactin receptor signaling and upregulation of certain steroidogenic enzymes 1
• However, clinical evidence in humans shows that testosterone replacement therapy generally has a neutral effect on macroprolactin content in men with pre-existing macroprolactinemia 2

Clinical Implications

• Hyperprolactinemia can cause hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion, which affects testosterone production 3
• This creates a potential feedback loop where testosterone therapy could theoretically affect prolactin levels, which in turn could affect testosterone production 3
• Symptoms of hyperprolactinemia in men include decreased libido, erectile dysfunction, diminished ejaculate volume, and oligospermia 3

Monitoring Recommendations

• When initiating testosterone replacement therapy, baseline blood tests should include PSA and hematocrit/hemoglobin levels, but prolactin is not routinely included in standard monitoring protocols 4
• Follow-up visits should occur at 1-2 months after initiation to assess efficacy, with subsequent monitoring at 3-6 month intervals for the first year and yearly thereafter 4
• If symptoms of hypogonadism persist despite adequate testosterone replacement, checking prolactin levels may be warranted 5

Diagnostic Approach for Elevated Prolactin

• If elevated prolactin is detected in a patient on testosterone therapy:
  • Confirm the elevation with repeat measurement to ensure it's not spurious 5
  • Consider other common causes of hyperprolactinemia, particularly medications such as antipsychotics, antidepressants, and antihypertensives 6
  • Persistently high prolactin levels warrant referral to an endocrinologist 5
  • Consider pituitary MRI if prolactin remains significantly elevated 5

Management of Testosterone-Related Hyperprolactinemia

• If hyperprolactinemia is confirmed and symptomatic:
  • Consider adjusting the testosterone dosing regimen to minimize fluctuations in serum testosterone levels 4
  • Transdermal testosterone preparations may be preferable as they produce more stable serum testosterone concentrations compared to injections 4
  • Injectable testosterone preparations are associated with fluctuating serum testosterone levels with peaks and valleys 4
  • For persistent hyperprolactinemia, dopamine agonist therapy (bromocriptine or cabergoline) is the first-line treatment 7

Caveats and Pitfalls

• The prevalence of clinically significant hyperprolactinemia in men with erectile dysfunction is relatively low (0.76%) 7
• Some apparent hyperprolactinemia may be due to macroprolactins, which are biologically inactive variants that can cause false positive results in standard assays 7
• When evaluating a patient with both testosterone deficiency and elevated prolactin, it's important to determine which condition is primary, as hyperprolactinemia itself can cause hypogonadism 3
• Testosterone therapy should be used cautiously in men with congestive heart failure or renal insufficiency due to potential fluid retention 4