Hyperprolactinemia

Last Updated: April 3, 2024

Hyperprolactinemia is simply an elevated level of prolactin in the blood. Prolactin is the hormone responsible for stimulating milk production during pregnancy and breastfeeding (and levels are naturally high during these times), but when it is inappropriately elevated, it affects reproductive hormones and can lead to infertility.

What is hyperprolactinemia?

Hyperprolactinemia is an elevated level of prolactin in the blood. Prolactin is a hormone that is secreted by the anterior pituitary gland and is important for breast tissue development and for regulating lactation. Hyperprolactinemia occurs when there is too much prolactin being produced, which can be the result of a tumor in the pituitary gland (a prolactinoma) or of a disruption of the mechanisms the body uses to control prolactin production.[1]

What are the main signs and symptoms of hyperprolactinemia?

The symptoms of hyperprolactinemia are often related to the suppression of gonadotropin releasing hormone (GnRH) by prolactin rather than to the raised level of prolactin itself. GnRH stimulates the pituitary gland to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). In women, they are important for the production of estrogen and progesterone by the ovaries. In men, FSH and LH are important for testosterone production.[2] If GnRH levels are low, LH and FSH will not be released, and estrogen and progesterone will not be produced.

As a result, women with hyperprolactinemia may present with infertility, amenorrhea (cessation of menstrual periods), or a low libido. Because a high level of prolactin suppresses estrogen production, symptoms of hyperandrogenism (excessive testosterone and other androgens) may also occur in women. These include hirsutism (abnormal hair growth, often around the mouth and chin), acne, and even decreased bone density.[3][2]

In men, hyperprolactinemia may cause erectile dysfunction, infertility, low libido, and gynecomastia. Other less-specific symptoms could include fatigue and a loss of muscle mass.[3][2]

The most well known function of prolactin is in lactation — in other words, milk production. Since prolactin triggers lactation, a possible symptom of hyperprolactinemia in both men and women is galactorrhea (the abnormal production of milk in the breast tissue). Galactorrhea is more common in young women and is often absent in men and postmenopausal women with hyperprolactinemia.[3][2]

Because of the location of the pituitary gland, a large prolactinoma (prolactin-producing tumor) can result in neurological symptoms like visual disturbances, headaches, and seizures.[3][2]

How is hyperprolactinemia diagnosed?

A blood test can be done to check prolactin levels. A prolactin level of 20 to 25 nanograms per milliliter (ng/ml) is considered normal. A level of up to 50 ng/ml may be a normal fluctuation. With a prolactinoma, the level usually exceeds 250 ng/ml. A diagnosis of hyperprolactinemia requires two tests that both show a clearly elevated prolactin level.[2]

It is important to remember that prolactin levels fluctuate throughout the day and are higher in the afternoon than in the morning. The blood sample should be taken while fasting and about 2 hours after waking in the morning. In the case of a slightly elevated prolactin level, the sample should be repeated. Some conditions that may cause elevated prolactin levels are seizures or trauma, excessive exercise, and certain medications, such as antipsychotics (e.g., risperidone), antidepressants (e.g., paroxetine), and antihypertensives (e.g., verapamil).[3]

If a prolactinoma is suspected as the cause of hyperprolactinemia, an MRI scan is the preferred imaging modality to look for the tumor.[2]

What are some of the main medical treatments for hyperprolactinemia?

The initial treatment for hyperprolactinemia is a type of medication called a dopamine agonist. An agonist produces the same effect on the receptors as the original molecule, so a dopamine agonist will have the same effect on the body as dopamine. Dopamine is part of the hypothalamic-pituitary-adrenal axis (HPA axis). Dopamine is produced in the hypothalamus, and higher levels of dopamine decrease the production of prolactin by the anterior pituitary gland.[2]

The two most commonly prescribed dopamine agonists are bromocriptine and cabergoline. Side effects include nausea, vomiting, dizziness, fainting, and constipation. These are more common in the initiation phase and often subside over time. A newer agent called quinagolide, which seems to have fewer side effects, is available in certain countries outside of the USA.[2]

In cases of large prolactinomas or when a person is unable to tolerate the medications, a surgical procedure may be done to remove the tumor.[3]

Have any supplements been studied for hyperprolactinemia?

Vitamin B6 (pyridoxine) has been used as a supplement to reduce prolactin levels. A trial of 60 women of reproductive age showed that 300 mg of vitamin B6 taken in 3 separate doses daily reduced prolactin similarly to cabergoline.[4]

Vitamin B6 has also been suggested as a treatment for hyperprolactinemia caused by antipsychotic medications (like risperidone or haloperidol) and may effectively reduce prolactin levels and improve symptoms of hyperprolactinemia in people who take these medications.[5][6]

Low vitamin D levels are more common in women with hyperprolactinemia and prolactinoma (a prolactin-producing tumor) than in women without hyperprolactinemia. This association might not be causal; however, a low vitamin D level combined with an elevated prolactin level can lead to a decrease in bone density, especially in postmenopausal women.[7][8] With this in mind, a vitamin D supplement is useful in certain patients with hyperprolactinemia. It is best to check the vitamin D level before starting supplementation.

How could diet affect hyperprolactinemia?

There is no specific dietary recommendation for people with hyperprolactinemia. However, people with overweight and obesity may have higher prolactin levels,[9][10] so a diet that helps achieve and maintain a healthy body weight could reduce prolactin levels.

Certain foods may increase prolactin levels and should be avoided by people with hyperprolactinemia. (These foods are also often recommended to breastfeeding women to help improve milk supply.) They include fennel[11] and fenugreek[12] These two herbs — as well as basil, oats, and milk thistle — have been used historically for this purpose, but their true impact on prolactin levels remains uncertain.[13]

Are there any other treatments for hyperprolactinemia?

Extracts of the plant known as chaste tree (Vitex agnus-castus) have been studied as a possible remedy for hyperprolactinemia. This extract seems to improve premenstrual mastodynia (breast pain) and reduces prolactin levels during the premenstrual phase.[14] A small study done in 2020 found that Vitex agnus-castus was as effective as bromocriptine for reducing prolactin levels.[15] The use of chaste tree as a treatment for mild hyperprolactinemia has been supported by a 2023 review,[16] but more controlled studies are needed to verify these findings.

Mucuna pruriens is another herbal remedy that is sometimes recommended for treating hyperprolactinemia and infertility in men. It has been shown to decrease prolactin levels while also increasing testosterone levels. The prolactin-lowering property is likely because of the increase of dopamine and L-dopa, both of which work to inhibit prolactin release from the pituitary gland.[17][18][19]

What causes hyperprolactinemia?

Hyperprolactinemia is not always abnormal. High prolactin levels are expected during pregnancy and breastfeeding.

Certain medications, especially those used in psychiatric disorders, are expected to raise prolactin levels, although in some cases they may not cause symptoms of hyperprolactinemia. In those people who do experience symptoms, the treating doctor may decide to change the type of medication. Aripiprazole, a medication that is used to treat schizophrenia and bipolar mood disorder, is the best option in these cases.[20] Additional medications may also be added to reduce the prolactin levels.

Hypothyroidism can also cause hyperprolactinemia, and a thyroid function test should be included as part of the work up when assessing a high prolactin level. Other disorders of the pituitary gland, such as Cushing’s disease, might raise prolactin, as might chronic kidney and liver disorders.[3]

In some cases, the cause is never found. This is referred to as idiopathic hyperprolactinemia.[2] Sometimes this diagnosis can be explained by macroprolactin, a type of prolactin molecule that is larger and bound to immunoglobulins. It does not bind as easily to prolactin receptors in the body as prolactin does, so it usually will not cause the common symptoms of hyperprolactinemia, but testing will still show a high prolactin level when macroprolactin is elevated. Asymptomatic hyperprolactinemia caused by macroprolactin does not require treatment. Testing for this molecule is possible but it is difficult and expensive and so is not always an option.[21][22]

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References
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