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

Effects of Hyperprolactinemia

Elevated prolactin levels (hyperprolactinemia) cause hypogonadism, menstrual disturbances, galactorrhea, infertility, and bone density loss, with symptoms varying based on severity and duration of the condition. 1

Clinical Manifestations of Hyperprolactinemia

Reproductive System Effects

• Hypogonadism: Hyperprolactinemia disrupts normal gonadal function by:
  • Interfering with GnRH pulsatility at the hypothalamic level
  • Causing oligomenorrhea or amenorrhea in women
  • Leading to erectile dysfunction in men 2, 3
• Menstrual Disturbances:
  • Oligomenorrhea (cycles >35 days)
  • Amenorrhea (no bleeding >6 months)
  • Decreased libido 1, 2
• Infertility: Due to disruption of normal ovulation and gonadal function 2
• Galactorrhea: Abnormal milk secretion not associated with pregnancy or breastfeeding 1, 4

Bone Health Effects

• Osteopenia and Osteoporosis: Untreated hyperprolactinemia leads to:
  • Decreased bone mineral density
  • Increased fracture risk
  • Long-term skeletal complications due to hypogonadism 1, 2, 5

Tumor-Related Effects (if caused by prolactinoma)

• Mass effects: Larger tumors (macroprolactinomas ≥10mm) may cause:
  • Headaches
  • Visual field defects
  • Pituitary dysfunction affecting other hormones 2, 5

Pathophysiology

Hyperprolactinemia affects the body through several mechanisms:

1. Disruption of hypothalamic-pituitary-gonadal axis:

   • Inhibits GnRH secretion from hypothalamus
   • Reduces LH and FSH secretion
   • Results in decreased estrogen/testosterone production 3

2. Direct effects on breast tissue:

   • Stimulates mammary gland development
   • Promotes milk production even outside of normal lactation 6

3. Medication-induced hyperprolactinemia:

   • Most commonly caused by antipsychotics that block dopamine receptors
   • Can also result from antidepressants, antihypertensives, and GI motility drugs 4
   • Dopamine normally inhibits prolactin secretion; blocking dopamine receptors increases prolactin 6

Common Causes of Hyperprolactinemia

1. Physiological causes:

   • Pregnancy
   • Lactation
   • Stress
   • Sleep
   • Sexual intercourse 2

2. Pathological causes:

   • Prolactinomas (micro <10mm or macro ≥10mm)
   • Medications (especially antipsychotics)
   • Hypothyroidism
   • Chronic renal failure
   • Idiopathic (30-40% of cases) 4, 2

Treatment Considerations

When hyperprolactinemia is identified, treatment should focus on:

• Normalizing prolactin levels
• Restoring gonadal function
• Reducing tumor size (if present)
• Preventing long-term complications like osteoporosis 1, 5

Dopamine agonists are the first-line treatment, with cabergoline generally preferred due to better efficacy and tolerability compared to bromocriptine 1, 7. Treatment goals include normalizing prolactin levels, restoring gonadal function, reducing tumor size, preserving pituitary function, and preventing osteoporosis 1.

Clinical Pitfalls and Caveats

• Medication review is essential: Many common medications can cause hyperprolactinemia and should be identified before pursuing extensive workup 4
• Pregnancy testing: Always rule out pregnancy as a cause of elevated prolactin
• Hypothyroidism screening: Check thyroid function as hypothyroidism commonly causes hyperprolactinemia 1
• Macroprolactin: Some laboratories may report falsely elevated prolactin due to macroprolactin, which has minimal biological activity
• Untreated consequences: Failure to diagnose and treat hyperprolactinemia can lead to long-term bone loss and persistent hypogonadism 2, 5

Regular monitoring of prolactin levels and periodic reassessment of the need for continued therapy are essential to prevent long-term complications of both the condition and its treatment 1.