Why is it necessary to check prolactin (Prolactin) levels in males with low testosterone (Hypogonadism)?

Why Prolactin Should Be Checked in Males with Low Testosterone

Serum prolactin levels should be measured in patients with low testosterone levels combined with low or low/normal luteinizing hormone (LH) levels to screen for hyperprolactinemia, which can indicate the presence of pituitary tumors such as prolactinomas. 1

Diagnostic Algorithm for Low Testosterone

When evaluating a male with low testosterone, a systematic approach is necessary:

1. Confirm low testosterone with at least two morning measurements showing levels consistently <300 ng/dL 1
2. Measure LH levels to determine the etiology of testosterone deficiency 1
   • High LH = primary hypogonadism (testicular failure)
   • Low/normal LH = secondary hypogonadism (hypothalamic-pituitary disorder)
3. Check prolactin levels if LH is low or low/normal 1

Why Prolactin Testing is Necessary

• Hyperprolactinemia directly affects the hypothalamic-pituitary-gonadal axis:

  • Inhibits gonadotropin-releasing hormone (GnRH) pulsatile secretion
  • Reduces LH, FSH, and testosterone production
  • Results in hypogonadism even when the testes are normal 2

• Elevated prolactin may indicate pituitary tumors:

  • Prolactinomas are the most common functioning pituitary tumors
  • Non-secreting adenomas may also be present 1
  • Men with prolactinomas more frequently present with macroadenomas than microadenomas 2

• Hyperprolactinemia can cause erectile dysfunction independent of testosterone levels:

  • Recent research shows prolactin directly impairs erectile function by suppressing the PI3K-Akt-eNOS pathway 3
  • This explains why some men with normal testosterone but elevated prolactin still experience erectile dysfunction 3

Clinical Significance and Management

• If prolactin is elevated:

  • Repeat measurement to ensure the elevation is not spurious 1
  • Persistently high levels warrant referral to an endocrinologist 1
  • Consider pituitary MRI, especially if testosterone <150 ng/dL with low/normal LH 1

• Treatment of hyperprolactinemia:

  • Dopamine agonists (bromocriptine, cabergoline) are first-line treatments 2, 4
  • Cabergoline is often preferred due to higher response rates and fewer side effects 4
  • Treatment can restore normal testosterone levels and improve fertility 5

Important Clinical Considerations

• Hyperprolactinemia is present in:

  • Approximately 16% of patients with erectile dysfunction 2
  • About 11% of men with oligospermia 2

• Clomiphene can be effective:

  • For persistent hypogonadism in males with prolactinomas under dopamine agonist treatment
  • Can restore normal testosterone levels and improve sperm motility 5

• Common pitfalls to avoid:

  • Failing to check prolactin in men with low testosterone and low/normal LH
  • Ignoring prolactin levels when testosterone is only moderately reduced
  • Not repeating prolactin measurement to confirm persistent elevation
  • Missing the opportunity to identify potentially treatable pituitary tumors 1

• Men with total testosterone levels <150 ng/dL and low/normal LH should undergo pituitary MRI regardless of prolactin levels, as non-secreting adenomas may be present 1