From the Guidelines
Elevated prolactin levels can be caused by various factors, including medications, pituitary tumors, physiological conditions, and certain diseases. The most common causes of hyperprolactinemia include medications such as antipsychotics, certain antidepressants, and anti-nausea drugs, as well as pituitary tumors, especially prolactinomas, which directly produce excess prolactin 1. Physiological conditions like pregnancy, breastfeeding, and nipple stimulation naturally increase prolactin levels, as seen in breastfeeding women where prolactin remains elevated and breastfeeding bouts trigger acute increases in both prolactin and oxytocin 1. Other causes include hypothyroidism, which can elevate prolactin due to decreased thyroid hormone leading to increased TRH, chronic kidney disease, and liver cirrhosis, which may cause hyperprolactinemia due to decreased clearance of prolactin 1. Stress, both physical and psychological, can temporarily raise prolactin levels, and chest wall injuries or surgeries that irritate the chest wall nerves can trigger prolactin release 1. Understanding the specific cause of hyperprolactinemia is crucial for appropriate management, which may include medication adjustment, dopamine agonists like cabergoline or bromocriptine for prolactinomas, or treating underlying conditions, with cabergoline being the dopamine agonist of choice given its superior effectiveness and lower adverse effect profile 1. It is also important to assess baseline macroprolactin levels where serum prolactin is found to be mildly or incidentally elevated to distinguish between monomeric prolactin and macroprolactin, which has low biological activity 1. In summary, the causes of elevated prolactin levels are diverse and require careful evaluation to determine the underlying cause and appropriate treatment. Some key points to consider include:
- Medications as a common cause of hyperprolactinemia
- Physiological conditions like pregnancy and breastfeeding
- Pituitary tumors, especially prolactinomas
- Hypothyroidism and chronic diseases like kidney disease and liver cirrhosis
- Stress and chest wall injuries as potential triggers
- The importance of distinguishing between monomeric prolactin and macroprolactin
- Cabergoline as the preferred dopamine agonist for treating prolactinomas due to its effectiveness and safety profile 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 is associated with higher levels of prolactin elevation than other antipsychotic agents. RISPERIDONE has been shown to elevate prolactin levels in children and adolescents as well as in adults.
Elevated prolactin levels can be caused by RISPERIDONE, as it antagonizes dopamine D2 receptors, leading to an increase in prolactin levels. This elevation can persist during chronic administration of the drug.
- Key factors that contribute to elevated prolactin levels include:
- Dopamine D2 receptor antagonism: RISPERIDONE's mechanism of action, which leads to an increase in prolactin levels.
- Chronic administration: The elevation of prolactin levels persists during long-term use of the drug.
- Dose-dependent increases: Elevated prolactin levels are generally greater in females than in males across indications, and increases are dose-dependent. 2 2
From the Research
Causes of Elevated Prolactin Levels
Elevated prolactin levels can be caused by various physiological and pathological conditions. Some of the main causes include:
- Pregnancy and lactation, which are physiological conditions that can lead to high prolactin levels 3
- Pituitary tumors, such as micro- or macroprolactinoma, which can produce excessive amounts of prolactin or disrupt the normal delivery of dopamine from the hypothalamus to the pituitary 4
- Medications, including:
- Anti-psychotics, such as typical antipsychotics and some atypical antipsychotics like risperidone 5, 6
- Antidepressants with serotoninergic activity, such as selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAO-I), and some tricyclics 6
- Prokinetics, opiates, estrogens, anti-androgens, anti-hypertensive drugs, H2-receptor antagonists, anti-convulsivants, and cholinomimetics 6
- Idiopathic hyperprolactinemia, which accounts for 30-40% of cases and may be caused by macroprolactinemia, a condition in which most circulating prolactin forms large protein complexes 4, 7
- Other pathological conditions, such as hypothalamic and pituitary diseases, and iatrogenic conditions 3
Physiological Conditions
Physiological conditions that can lead to elevated prolactin levels include:
- Pregnancy, which is a normal condition that can cause high prolactin levels 4, 3
- Lactation, which is also a normal condition that can cause high prolactin levels 4, 3
Pathological Conditions
Pathological conditions that can lead to elevated prolactin levels include: