Understanding High Prolactin: Health Implications and Next Steps

Prolactin, a hormone primarily known for its role in lactation, is involved in numerous physiological processes, from reproductive health to immune function. However, when prolactin levels become elevated, it can signal a variety of health issues that require careful attention. 

Hyperprolactinemia can lead to symptoms such as infertility, menstrual irregularities, and bone loss. Understanding the causes and implications of high prolactin levels is essential for accurate diagnosis and effective management, ensuring individuals receive the appropriate care and treatment.

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What Is Prolactin?

Prolactin is a hormone primarily produced by the anterior pituitary gland, a pea-sized endocrine gland located at the base of the brain. The central nervous system, immune system, uterus, and mammary glands can also produce prolactin. (2) 

Prolactin is involved in hundreds of physiological processes that maintain homeostasis in the body, including regulating the immune system, salt and water balance, and blood vessel formation. It is best known, however, for its role in breast tissue development and milk production. (16)

Various factors regulate prolactin synthesis and release. The hypothalamus, a region of the brain that coordinates the endocrine system, secretes prolactin-inhibiting factors (PIF) and prolactin-releasing factors (PRF). Dopamine is the predominant PIF, acting to inhibit prolactin secretion. PRFs that stimulate prolactin synthesis include (but are not limited to) thyrotropin-releasing hormone (TRH), serotonin, and estrogen. Nipple stimulation, stress, high-protein meals, and exercise can also cause transient increases in prolactin levels. (2, 18) 

Prolactin levels are normally low in people assigned male at birth and people assigned female at birth who are not pregnant or breastfeeding. Prolactin levels naturally increase during pregnancy and breastfeeding. (30) 

In general, normal values for serum prolactin are: 

• People assigned male at birth: less than 20 ng/mL
• Non-pregnant or breastfeeding people assigned female at birth: less than 25 ng/mL
• People who are pregnant or breastfeeding: 80-400 ng/mL

Causes of High Prolactin Levels

Hyperprolactinemia is a condition defined by higher-than-normal prolactin levels in the blood. While it can occur in both men and women, it typically affects people assigned female at birth under the age of 40. (20) 

In pregnancy, elevated prolactin prepares the mammary glands for milk production. During breastfeeding, prolactin levels remain high to maintain milk supply in response to the infant's suckling, ensuring adequate nutrition for the baby. (36)

Other physiologic causes of hyperprolactinemia include:

• Physical and emotional stress
• Exercise
• Hypoglycemia (low blood sugar)
• High-protein diet

The most common cause of hyperprolactinemia is prolactinoma, a benign prolactin-releasing pituitary tumor. Prolactinomas are classified by size as microadenoma (less than 10 mm in diameter) or macroadenoma (10 mm or larger in diameter).

Other medical conditions that carry the potential to cause hyperprolactinemia include (18, 30):

• Hypothyroidism (underactive thyroid)
• Kidney disease
• Shingles (a painful, blistering rash caused by a reactivation of the chickenpox virus), especially when the rash is located on the chest
• Polycystic ovary syndrome (PCOS)
• Cushing's syndrome (caused by excess cortisol)
• Nelson syndrome (a rare disorder in some patients with Cushing's disease caused by surgical removal of both adrenal glands)

Chest wall injuries, such as fractures of the ribs or breastbone, can lead to hyperprolactinemia by abnormally triggering the suckling reflex, which naturally stimulates prolactin release (18). 

Medications can induce hyperprolactinemia by interfering with dopamine's inhibitory effect on prolactin secretion or by directly stimulating prolactin release. Examples include: 

• Calcium channel blockers, reserpine, and methyldopa, which are used to treat high blood pressure
• Antipsychotic medications, including risperidone, haloperidol, phenothiazines, and butyrophenones
• Metoclopramide, used to treat nausea and vomiting
• Histamine type 2 receptor antagonists (H2RA), such as famotidine, used to treat heartburn and gastroesophageal reflux disease (GERD)
• Estrogen-containing medications
• Opioid pain-relieving drugs
• Antidepressant medications

Symptoms and Health Implications

Signs and symptoms of hyperprolactinemia in men and women include (19, 20):

• Infertility
• Low libido
• Bone loss
• Galactorrhea (spontaneous expression of breastmilk unrelated to pregnancy or breastfeeding)

Female-specific symptoms of hyperprolactinemia include (19, 20): 

• Irregular periods
• Amenorrhea (absence of menstrual periods)
• Vaginal dryness

Men may also present with (19, 20): 

• Erectile dysfunction
• Gynecomastia (breast enlargement)
• Low testosterone

Hyperprolactinemia is not life-threatening, but it can contribute to other hormonal imbalances, which can increase the risk of infertility and osteoporosis. Elevated prolactin levels inhibit the secretion of gonadotropin-releasing hormone (GnRH), leading to decreased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This disruption impairs ovulation in women and spermatogenesis in men, leading to infertility (34). Additionally, reductions in estrogen and progesterone, resulting from suppressed GnRH, can lead to decreased bone density and an increased risk of osteoporosis.

Patients with hyperprolactinemia due to prolactinoma may face additional health concerns. If untreated, prolactinomas can grow large enough to compress the optic nerve. The first symptom of optic nerve compression is often a loss of peripheral vision. Larger prolactinomas can also impair the production of other pituitary hormones, resulting in various hormonal imbalances and endocrine disorders. (32) 

Diagnosis and Evaluation

Follow this step-by-step protocol to diagnose hyperprolactinemia: 

Step 1: Clinical Evaluation

Suspect hyperprolactinemia in any patient with galactorrhea or any of the other following symptoms:

• Infertility
• Decreased libido
• Delayed puberty
• Erectile dysfunction or gynecomastia in males
• Menstrual irregularities or amenorrhea in females

Step 2: Measure Serum Prolactin

Elevated serum levels of prolactin are diagnostic for hyperprolactinemia. Patients should have blood drawn in the morning after an overnight fast. False positives can be caused by excessive venipuncture stress, recent food consumption, and recent exercise. (31)  

The following prolactin tests are available to order through Rupa Health:

• Prolactin by Access Med Labs
• Prolactin by Access LabCorp Draw
• Prolactin by Boston Heart Diagnostics

Step 3: Testing for Underlying Cause

Additional blood tests, including a pregnancy test, thyroid and renal function tests, and morning cortisol, can be ordered to rule out pregnancy, hypothyroidism, kidney disease, and Cushing's syndrome. For example:

• hCG, Total by Access Med Labs
• Comprehensive Thyroid Panel w/ Antibodies by Precision Point
• Comprehensive Metabolic Panel by Access Med Labs
• Cortisol by Access LabCorp Draw

Pituitary imaging via gadolinium-enhanced magnetic resonance imaging (MRI) is needed to diagnose prolactinomas, which should be highly suspected with prolactin levels greater than 200 ng/mL.

If drug-induced hyperprolactinemia is suspected, consider retesting serum prolactin three days after the patient has discontinued the medication. Normalized prolactin levels confirm this diagnosis. Note that discontinuing medications may not be safe or feasible in all cases.

Step 4: Additional Testing to Assess Reproductive Health

Testing hormonal levels may be recommended for patients with reproductive health concerns. Hormones typically included in a comprehensive sex hormone panel include LH, FSH, estradiol, progesterone, and testosterone. Examples include:

• Female Hormone Panel by Precision Point
• Male Hormone Panel by Precision Point

Treatment and Management

Successfully lowering prolactin levels is dependent on addressing the underlying cause. Examples include: 

• Medication-Induced: Patients who are asymptomatic may not require active treatment. If possible, your doctor can switch you to an alternative medication that doesn't increase prolactin levels. Never stop a medication without your doctor's advice. 
• Hypothyroidism: Synthetic thyroid hormone, called levothyroxine, is the first-line recommended medication for treating hypothyroidism.
• Prolactinoma: Dopamine agonist medications, such as bromocriptine or cabergoline, suppress prolactin synthesis and release and cause shrinkage of the tumor. Surgical removal may be recommended for large prolactinomas or those that don't respond to medication. (42) 

Lifestyle modifications can complement medical interventions to lower prolactin, support overall hormonal balance, and enhance fertility:

• Limit Alcohol Consumption: Alcohol increases prolactin levels by stimulating the proliferation of prolactin-producing cells.
• Eat a Healthy Diet: The nutrient-rich, antioxidant, and anti-inflammatory properties of the Mediterranean diet explain its association with improved conception rates in couples facing infertility, as well as enhanced sperm and egg quality. 
• Reduce Stress Levels: Mind-body therapies modulate the body's stress signaling axis to reduce cortisol levels and perceived stress. Prioritizing sleep, engaging in gentle exercise, and taking adaptogenic herbs can also help manage stress levels. 

There is research to support that the following supplements can reduce prolactin levels:

• Vitamin B6: 300 mg twice daily
• Vitex agnus-castus (chasteberry): 40 drops of tincture or 20-40 mg of standardized extract daily (33) 

Patients should regularly follow up with their doctors to monitor prolactin levels and treatment plan efficacy. Per hyperprolactinemia treatment guidelines:

• Serum prolactin should be remeasured one month after starting dopamine agonist therapy and periodically thereafter to guide dose titration. Once prolactin levels have normalized, they should be remeasured every 4-6 months.
• Repeat imaging should be performed when treating prolactinomas (3-6 months and one year after initiating treatment for macroadenomas and microadenomas, respectively).

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Key Takeaways

• Hyperprolactinemia is characterized by elevated prolactin levels. It can arise from various causes, including pituitary tumors, medications, stress, and physiological conditions like pregnancy and breastfeeding. 
• Accurate diagnosis involves a thorough medical history, blood tests, and imaging studies.
• The prognosis for hyperprolactinemia is very good. Treatment options range from medication to manage prolactin levels, surgery for larger tumors, and addressing underlying conditions. 
• Patients experiencing persistent symptoms of hyperprolactinemia should seek medical advice to prevent complications like infertility and osteoporosis. Regular health check-ups and adherence to personalized treatment plans play a vital role in managing this condition effectively.