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]
Frequently asked questions
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]
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]
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]
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]
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.
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]
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]
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]
The HPA axis is a neuroendocrine system that involves multiple pathways, hormones, and regulatory processes that keep certain hormones at the appropriate level. The main function of the HPA axis is to regulate the stress response in the body, and it has multiple different feedback loops that regulate physiological responses to various stressors.[23]
Prolactin is regulated by the HPA axis and also acts to regulate other hormones involved in the system. For example, a high prolactin level will slow down further prolactin production and will also inhibit gonadotropin-releasing hormone (GnRH) production. Progesterone and dopamine will inhibit prolactin production, while estrogen will increase it.[1]
In hypothyroidism, the thyroid fails to produce sufficient thyroid hormones, and the levels of thyroxine (T4) and sometimes triiodothyronine (T3) are too low. Because of this, the body’s feedback mechanisms try to stimulate the thyroid gland by producing more thyrotropin-releasing hormone (TRH). TRH triggers the release of thyroid-stimulating hormone (TSH) from the anterior pituitary gland. The action of TRH on the anterior pituitary gland also triggers the release of more prolactin, so prolactin levels increase with TRH levels and TSH levels in hypothyroidism. This does not happen in every case of hypothyroidism; however, it is worth testing for hypothyroidism as a possible cause of hyperprolactinemia.[24][25]
PCOS is characterized by hyperandrogenism (excessive testosterone and other androgens), anovulatory cycles (menstrual cycles where an egg is not released), and ovarian cysts seen on ultrasound. The commonly used Rotterdam criteria require that two of these three criteria be present to diagnose PCOS.[26]
Hyperprolactinemia might also result in symptoms of hyperandrogenism and could cause infertility and anovulation. Because of this similarity, doctors in the 1950s started investigating the possibility that PCOS might cause hyperprolactinemia. Studies done at the time showed overlapping symptoms, and blood tests supported the link, so it was quite a convincing hypothesis.
However, modern science and technology have improved our diagnostic abilities when it comes to hyperprolactinemia. In studies done prior to the 2000s, blood tests could not measure macroprolactin, and MRI scans could only pick up large prolactinomas (prolactin-producing tumors). Modern testing can see prolactinomas under even 3 mm in diameter. Macroprolactin can be tested for when the cause of hyperprolactinemia remains uncertain. These two tests explained the raised prolactin levels in many cases that had previously been attributed to PCOS.
Recent studies show that these two are likely separate entities, and people with PCOS who have high prolactin levels should undergo further testing to find a cause for the hyperprolactinemia. While more studies are needed to confirm these findings, current evidence suggests that PCOS is most likely not a cause of hyperprolactinemia.[21][27]
It is also worth noting that new diagnostic tools also helped several people misdiagnosed with PCOS. In some cases, the symptoms attributed to PCOS were in fact caused by hyperprolactinemia, so hyperandrogenism and infertility could be successfully treated with cabergoline.[21]
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