What are the effects of hyperprolactinemia (elevated prolactin levels) on the body?

Effects of Elevated Prolactin on the Body

Elevated prolactin primarily disrupts reproductive function by inhibiting gonadotropin secretion through suppression of hypothalamic kisspeptin, leading to hypogonadism and its associated complications in both sexes. 1

Reproductive and Sexual Effects

In Women

• Menstrual dysfunction manifesting as amenorrhea or oligomenorrhea occurs due to prolactin's inhibition of the hypothalamic-pituitary-gonadal axis 1
• Galactorrhea (inappropriate breast milk production) develops in a significant proportion of affected women 2
• Infertility and anovulation result from disrupted ovulatory cycles, with approximately 15-20% of women undergoing infertility evaluation having hyperprolactinemia 3
• Luteal phase insufficiency can occur even with mild elevations, contributing to recurrent miscarriage 4

In Men

• Decreased libido and erectile dysfunction are the primary sexual manifestations 1, 5
• Hypogonadism develops through the same mechanism of gonadotropin suppression 3
• Gynecomastia may occur in some cases 5
• Impaired fertility can result from chronic, significant hyperprolactinemia 4

Long-Term Metabolic Consequences

Bone Health

• Osteopenia and osteoporosis develop as chronic complications due to prolonged hypogonadism and estrogen/testosterone deficiency 6, 7
• This represents a significant long-term morbidity concern requiring monitoring and management 6

Mass Effect Symptoms (When Caused by Prolactinoma)

Neurological Manifestations

• Visual field defects occur when macroadenomas compress the optic chiasm, with resolution achieved in 67% of patients treated with dopamine agonists 2
• Headaches are commonly reported, particularly with larger tumors 2
• Pituitary apoplexy can occur in rare cases with large tumors 2

Important Diagnostic Considerations

Macroprolactinemia

• 10-40% of patients with elevated prolactin have macroprolactinemia, a benign condition where large, biologically inactive prolactin complexes circulate 2, 1
• Among adults with macroprolactinemia, 20% still have galactorrhea, 45% have oligo-amenorrhea, and 20% have pituitary adenomas, indicating some may have concurrent true hyperprolactinemia 2
• Assessment for macroprolactin should be performed in cases of mild or incidental elevation, especially in asymptomatic patients 2, 8

The Hook Effect

• Approximately 5% of patients with macroprolactinomas show paradoxically normal or mildly elevated prolactin due to assay saturation at very high concentrations 2, 1
• Serial dilutions should be performed when large pituitary lesions are present with unexpectedly low prolactin levels 2

Common Pitfalls to Avoid

Secondary Causes Must Be Excluded

• Medications (particularly antipsychotics and antidepressants) are among the most common causes and act by blocking dopamine's inhibitory effect 1, 9, 5
• Primary hypothyroidism causes hyperprolactinemia in 43% of women and 40% of men through compensatory thyrotropin-releasing hormone hypersecretion 1
• Chronic kidney disease is associated with hyperprolactinemia in 30-65% of adult patients due to increased secretion and reduced renal clearance 1, 9
• Severe liver disease can also cause elevation 1
• Stress can elevate prolactin up to five times the upper limit of normal 1, 8

Pituitary Stalk Compression

• Non-prolactin-secreting masses compressing the pituitary stalk interrupt dopaminergic inhibition, causing mild elevation typically <100 μg/L 1
• This must be distinguished from true prolactinomas, where levels generally exceed 4,000 mU/L in children and adolescents and correlate with tumor size 1