Why is serum prolactin slightly elevated in patients with Polycystic Ovary Syndrome (PCOS)?

Why Serum Prolactin is Slightly Elevated in PCOS

Mild prolactin elevation in PCOS patients is not actually a feature of PCOS itself—when hyperprolactinemia is found, it represents a coexisting but distinct condition that requires separate investigation to identify the underlying cause. 1

The Evidence Against Prolactin Elevation Being Part of PCOS

The most definitive research demonstrates that PCOS patients without hyperprolactinemia have prolactin levels (12.1 ± 5.5 μg/L) that are statistically identical to women with insulin resistance who don't have PCOS (11.8 ± 4.9 μg/L). 1 This finding directly contradicts the premise that PCOS inherently causes prolactin elevation.

When Hyperprolactinemia Occurs in PCOS Patients

Approximately 16-37% of women presenting with PCOS will have elevated prolactin levels, but these elevations have identifiable causes separate from PCOS itself. 2, 1

The actual causes include:

• Pituitary adenomas (69% of hyperprolactinemic PCOS cases, with prolactin ranging 28.6-538 μg/L) 1
• Macroprolactinemia (59% of apparent hyperprolactinemia cases normalize after PEG precipitation) 2
• Medication effects (oral contraceptives, buspirone, tianeptine, antiepileptic drugs) 3, 1
• Idiopathic hyperprolactinemia (13% of cases with normal MRI) 2

Clinical Approach to Prolactin in PCOS

When evaluating PCOS patients, measure morning resting serum prolactin levels (not postictal), with values >20 μg/L considered abnormal. 3

If prolactin is elevated (>25 ng/mL):

1. Repeat measurement using PEG precipitation method to exclude macroprolactinemia 2
2. Obtain brain MRI to evaluate for pituitary adenoma 2
3. Review all medications that may affect prolactin levels 3
4. Rule out hypothyroidism as a contributing factor 3

Historical Context and Outdated Observations

Older studies from 1984 reported abnormal prolactin secretion in approximately 50% of PCOS patients, with correlations to DHEA-S and estrone levels. 4, 5 However, these studies predated modern understanding of macroprolactinemia and did not systematically exclude other causes of hyperprolactinemia. The contemporary evidence clearly establishes that these are coincidental findings rather than causative relationships. 1

Critical Pitfall to Avoid

Do not attribute hyperprolactinemia to PCOS itself. 1 The presence of elevated prolactin in a PCOS patient mandates investigation for pituitary pathology, macroprolactinemia, or medication effects. Failing to investigate can result in missed diagnoses of prolactinomas or other treatable conditions. 2, 1

Clinical implications:

• Menstrual disorders are more prevalent in PCOS patients with pituitary adenomas compared to those with normal prolactin 2
• Higher LH and LH/FSH ratios with lower estradiol levels characterize PCOS patients with normal prolactin 2
• Hyperprolactinemia and PCOS represent distinct endocrine entities that may coexist but require separate management 1