Hyperprolactinemia refers to a continuous elevation of serum prolactin (PRL) levels greater than 25–30 μg/L caused by various factors.
Etiology and Pathogenesis
Hypothalamic Disorders
Conditions such as craniopharyngioma or inflammation can impair the secretion of prolactin-inhibiting factor (PIF), leading to elevated prolactin levels.
Pituitary Disorders
These represent the most common cause of hyperprolactinemia, with prolactinomas being the most frequent type. More than one-third of patients with hyperprolactinemia have pituitary microadenomas (with a diameter <1 cm). The empty sella syndrome can also cause elevated serum prolactin levels.
Primary Hypothyroidism
Increased thyrotropin-releasing hormone (TRH) levels in hypothyroidism stimulate prolactin secretion from the pituitary.
Idiopathic Hyperprolactinemia
This condition is characterized by elevated serum prolactin levels, typically ranging from 60–100 μg/L, without identified pituitary or central nervous system disorders. A subset of patients may develop pituitary microadenomas after several years.
Other Causes
Polycystic ovary syndrome (PCOS), autoimmune diseases, trauma (such as pituitary stalk disruption or injury), and prolonged use of antipsychotics, antidepressants, antiepileptics, antihypertensives, anti-ulcer drugs, and opioids may lead to mild or significant elevations in serum prolactin.
Clinical Manifestations
Menstrual Irregularities and Infertility
Over 85% of patients experience menstrual irregularities. Women of reproductive age may present with anovulation or a shortened luteal phase, resulting in scanty menstruation, infrequent periods, or even amenorrhea. Primary amenorrhea may occur in females before or during early adolescence, while secondary amenorrhea is more common in post-adolescent, reproductive-aged women. Anovulation often leads to infertility.
Abnormal Lactation
This is a hallmark clinical feature of hyperprolactinemia. Approximately two-thirds of patients with amenorrhea-galactorrhea syndrome have hyperprolactinemia, and one-third of these cases are caused by pituitary microadenomas. Lactation usually presents as bilateral discharge, which may be spontaneous or expressible, appearing as non-bloody, milky, or clear fluid.
Tumor Compression Symptoms
Significant enlargement of pituitary adenomas may lead to cerebrospinal fluid obstruction and compression of adjacent brain tissue or the optic nerve. Symptoms include headaches, blurred vision, vomiting, visual field defects, and oculomotor nerve palsy.
Low Estrogen State
Suppression of pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion results in a state of low estrogen. Symptoms may include vaginal mucosal thinning or atrophy, decreased secretions, and diminished libido.
Diagnosis
Clinical Symptoms
Hyperprolactinemia should be suspected in individuals presenting with menstrual irregularities, infertility, galactorrhea, amenorrhea, or delayed puberty.
Blood Tests
Serum prolactin levels exceeding 25–30 μg/L confirm the diagnosis of hyperprolactinemia. Blood sampling is most accurate between 9:00 a.m. and 12:00 p.m., minimizing stress before testing.
Imaging Studies
Serum prolactin levels >100 μg/L warrant magnetic resonance imaging (MRI) of the pituitary gland to identify the presence of microadenomas or macroadenomas.
Funduscopic Examination
Pituitary adenomas may invade or compress the optic chiasm, causing optic disc edema or visual field defects. Funduscopic and visual field examinations help assess the size and location of pituitary adenomas, particularly in pregnant individuals.
Treatment
Treatment requires an accurate determination of the causative factor and timely intervention. Treatment modalities include pharmacologic therapy, surgery, and radiotherapy.
Pharmacologic Therapy
Bromocriptine Mesylate
This polypeptide-derived ergot alkaloid acts as a dopamine receptor agonist, effectively lowering prolactin levels. Bromocriptine suppresses prolactin elevation caused by functional or tumor-related causes. After bromocriptine treatment, tumor volume reduction may restore menstruation and fertility in women with amenorrhea and galactorrhea.
During treatment of pituitary microadenomas, the dosage is typically titrated as follows:
- Week 1: 1.25 mg, once per evening.
- Week 2: 1.25 mg, twice daily.
- Week 3: 1.25 mg in the morning and 2.5 mg in the evening.
- After week 4: 2.5 mg, 2–3 times daily for a three-month treatment course.
Common side effects include nausea, headache, dizziness, fatigue, drowsiness, constipation, and orthostatic hypotension, which usually subside within a few days of treatment. The new long-acting bromocriptine injection reduces gastrointestinal side effects. A dose of 50–100 mg is injected every 28 days, with an initial dose of 50 mg. Cabergoline and α-dihydroergocryptine mesylate, next-generation selective dopamine D2 receptor agonists, are alternatives to bromocriptine. Cabergoline is initiated at 0.25 mg, orally, twice weekly. However, insufficient safety data exist regarding their use during pregnancy.
Quinagolide
Quinagolide is a potent dopamine D2 receptor agonist. It is often prescribed for patients intolerant to bromocriptine side effects. The initial dose is 25 μg per day for three days, followed by an incremental increase of 25 μg every three days until prolactin levels are effectively controlled.
Vitamin B6
A dose of 20–30 mg, taken orally three times daily, may act synergistically when combined with bromocriptine.
Surgical Therapy
If pituitary tumors cause significant compression or neurological symptoms or if pharmacologic therapy proves ineffective, surgical removal of the tumor may be considered. Short-term bromocriptine use before surgery may shrink the tumor and reduce intraoperative bleeding, improving surgical outcomes.
Radiotherapy
Radiotherapy is reserved for patients unable or unwilling to undergo pharmaceutical or surgical treatments. Although effective, its delayed efficacy and risk of complications—such as hypopituitarism, optic nerve injury, or secondary tumor formation—need consideration.