What can cause a mild elevation in prolactin levels, also known as hyperprolactinemia?

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From the Guidelines

Mild elevation in prolactin can be caused by various factors, including medications, physiological conditions, and medical conditions, with medications being one of the most common causes in adults, as reported in a 2024 study published in Nature Reviews Endocrinology 1.

Causes of Mild Elevation in Prolactin

Mild elevation in prolactin (hyperprolactinemia) can be caused by several factors, including:

  • Medications, such as antipsychotics, certain antidepressants, metoclopramide, and some antihypertensives, which can stimulate prolactin secretion or antagonize inhibitory dopaminergic tone 1
  • Physiological conditions, such as pregnancy, breastfeeding, and stress, which can naturally increase prolactin levels
  • Medical conditions, including hypothyroidism, chronic kidney disease, liver cirrhosis, and polycystic ovary syndrome, which can cause mild elevations in prolactin levels 1
  • Other factors, such as sleep disruption, intense exercise, and nipple stimulation, which may also temporarily elevate prolactin levels

Importance of Baseline Macroprolactin Levels

According to a 2024 consensus guideline published in Nature Reviews Endocrinology, baseline macroprolactin levels should be assessed where serum prolactin is found to be mildly or incidentally elevated 1. This is because macroprolactin, a form of prolactin with low biological activity, can circulate in the blood and may be present in individuals with hyperprolactinemia.

Clinical Implications

If you have unexplained elevated prolactin, it's essential to review your medication list with your healthcare provider and consider underlying medical conditions that might require treatment. Additionally, prompt and appropriate secondary analysis should be undertaken to detect the possible presence of macroprolactin in the initial investigation of asymptomatic individuals with hyperprolactinemia 1.

From the FDA Drug Label

As with other drugs that antagonize dopamine D2 receptors, RISPERIDONE elevates prolactin levels and the elevation persists during chronic administration.

  • Risperidone can cause a mild elevation in prolactin levels due to its dopamine D2 receptor antagonism properties 2.

From the Research

Causes of Mild Elevation in Prolactin

  • Antipsychotic medications, particularly first-generation antipsychotics, can cause hyperprolactinemia due to their ability to block dopamine activity at the level of the dopamine type 2 receptor (D2R) 3, 4, 5, 6
  • The risk of hyperprolactinemia is higher with certain antipsychotics, such as risperidone, sulpiride, and amisulpride 5, 6
  • Metformin can cause a mild reduction in prolactin levels, but may also contribute to a mild elevation in some cases 4
  • Other factors, such as stress, renal failure, or hypothyroidism, can also contribute to hyperprolactinemia 7
  • Herbal supplements, such as chamomile, Peony-Glycyrrhiza decoction, and shakuyaku-kanzo-to, may have some effect on prolactin levels, but the evidence is limited 4

Factors Influencing Prolactin Levels

  • Dose and duration of antipsychotic treatment can impact prolactin levels, with higher doses and longer treatment durations associated with greater increases in prolactin 5, 6
  • Individual variability in response to antipsychotics and other medications can also influence prolactin levels 4, 6
  • Presence of other medical conditions, such as pituitary adenomas or hypothyroidism, can affect prolactin levels and should be considered in the diagnosis and treatment of hyperprolactinemia 3, 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Treatments of psychiatric disorders, hyperprolactinemia and dopamine agonists.

Best practice & research. Clinical endocrinology & metabolism, 2022

Research

Guidance on the treatment of antipsychotic-induced hyperprolactinemia when switching the antipsychotic is not an option.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2021

Research

Hyperprolactinemia: pathophysiology and therapeutic approach.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2015

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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