Version May 2024
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HIGH PROLACTIN OVERVIEW — The pituitary is a small gland in the middle of the head just below the brain (figure 1). The pituitary contains lactotroph cells that produce prolactin, the hormone that stimulates lactation (production of breast milk).
Prolactinomas (also called "prolactin-producing adenomas" or "lactotroph adenomas") are benign (non-cancerous) tumors of the pituitary gland that produce prolactin, thereby causing higher than normal blood prolactin concentrations. They can cause symptoms, either when the high blood prolactin concentration interferes with the function of the ovaries or testicles or, less commonly, when the adenoma grows large enough to compress the pituitary gland or nearby structures in the head, such as the nerves to the eyes.
Prolactinomas occur in both males and females but are more commonly diagnosed in female who are less than 50 years than in older females or males.
Prolactinomas can usually be treated successfully with medication alone. Medication lowers the prolactin level in the blood substantially, often to normal, and also usually reduces adenoma size. However, a minority of these adenomas do not respond to medication and must be treated with surgery or, less commonly, radiation therapy.
CAUSES OF HIGH PROLACTIN — Prolactinomas develop when one of the normal prolactin-producing cells in the pituitary gland develops a mutation. The mutation allows the cell to divide repeatedly, resulting in a large number of cells that produce an excessive amount of prolactin. Approximately 10 percent produce growth hormone as well as prolactin.
Most prolactinomas occur sporadically, but rarely, they occur in families as part of a condition called the multiple endocrine neoplasia type 1 (MEN1) syndrome.
Most prolactinomas remain small, less than 1 centimeter (0.4 inches) in diameter; these are called microadenomas. A minority grow larger, occasionally to several centimeters, and are called macroadenomas.
SYMPTOMS — The symptoms of prolactinomas fall into two categories: those that result from elevated blood prolactin levels, and those that result from compression of the normal pituitary and surrounding tissues.
Symptoms caused by elevated blood prolactin — Elevated blood prolactin interferes with the secretion of the hormones from the pituitary gland that control the function of the ovaries in females and the testicles in males. Therefore, it causes symptoms in premenopausal females and in males, but not in females who have already been through menopause, since their ovaries have already stopped functioning.
Females — When a high blood prolactin concentration interferes with the function of the ovaries in a premenopausal female, secretion of estradiol (the main female sex hormone [estrogen] in females) decreases. Symptoms include irregular or absent menstrual periods, infertility, menopausal symptoms (hot flashes and vaginal dryness), and, after several years, osteoporosis (thinning and weakening of the bones). High prolactin levels can also cause milk discharge from the breasts.
Males — When a high blood prolactin concentration interferes with the function of the testicles, the production of testosterone (the main male sex hormone) and sperm production decrease. Low testosterone causes decreased energy, sex drive, muscle mass and strength, and blood count (anemia). If levels remain low for several years, bone strength may decrease (osteoporosis). High levels of prolactin in the blood also cause difficulty in getting an erection, as well as breast tenderness and enlargement.
Symptoms caused by compression of surrounding tissue — Large adenomas can cause symptoms by pressing on nearby structures in the head. Pressure on nerves to the eyes can impair vision, especially peripheral (side) vision. Pressure on the normal pituitary gland can decrease production of the hormones that stimulate the thyroid gland and adrenal glands, leading to underactivity of the those glands. Pressure can also cause headaches.
DIAGNOSIS OF PROLACTINOMA — A prolactinoma is diagnosed based on an elevated blood level of prolactin and evidence of a mass in the pituitary gland, as seen by magnetic resonance imaging (MRI). Because other conditions can cause an elevated prolactin level, those potential causes must be evaluated as well.
Measurement of prolactin — The prolactin level can be measured in a single blood sample. The result can range from slightly elevated to a thousand times the upper limit of normal. In general, larger adenomas cause higher prolactin levels.
Magnetic resonance imaging (MRI) — MRI is the best test for identifying masses in or near the pituitary gland, although MRI cannot determine if the mass is a pituitary adenoma or another abnormality. Furthermore, some small adenomas (microadenomas) cannot be detected by MRI, and not all adenomas secrete prolactin or other hormones.
Evaluating other causes — Some of the medications that are used to treat psychiatric conditions can cause high blood prolactin levels. Other causes of high prolactin include high doses of female sex hormones (estrogens) and underactivity of the thyroid gland (hypothyroidism).
PROLACTINOMA TREATMENT OPTIONS — The goals of treatment are to lower the level of prolactin in the blood to normal and to decrease the size of a large adenoma, especially if it is compressing surrounding structures. It is important that the clinician and patient discuss the possible benefits and risks of treatment.
Not all prolactinomas require treatment. If the tumor is large or causing symptoms, it should probably be treated, but if it is small and is not causing symptoms, it does not need to be treated.
When treatment is necessary, most prolactinomas respond well to therapy with medications called dopamine agonists. If an adenoma does not respond to any of these medications or if the medication causes intolerable side effects, other treatments should be considered.
MEDICATIONS TO TREAT PROLACTINOMAS — A dopamine agonist is the best first treatment for a prolactinoma of any size. Two dopamine agonists are currently available for this purpose in the United States, cabergoline and bromocriptine; another one, quinagolide, is also available in other countries.
●Bromocriptine – Bromocriptine has been used for many years to treat prolactinomas. It is taken twice a day. While it is usually very effective in lowering blood prolactin levels, it can cause side effects, including dizziness, nausea, and nasal stuffiness. Many of the side effects can be avoided by taking the medication with meals or at bedtime and by starting with a very low dose.
●Cabergoline – Cabergoline is taken once or twice a week and is much less likely to cause nausea compared with other dopamine agonists. It may be effective for treating prolactinomas that are resistant to bromocriptine. For all these reasons, cabergoline is the best first choice.
Effectiveness of dopamine agonists — Dopamine agonists are very effective for decreasing prolactin levels and the size of most prolactinomas. Cabergoline, which appears to be the most effective dopamine agonist, lowers prolactin levels in approximately 90 percent of people who have prolactinomas, often to a normal level. It also usually decreases the size of micro- and macroadenomas to normal. Prolactin levels usually fall within the first two to three weeks of treatment, but detectable decreases in adenoma size take more time, usually several weeks to months. When the adenoma affects vision, improvement in vision may begin within days of starting treatment.
If the prolactin level decreases to normal or near-normal levels, the symptoms caused by the elevated prolactin are reversed. The upper normal value for serum prolactin in most laboratories is approximately 20 ng/mL (20 mcg/L SI units). In premenopausal females, ovarian function returns, estradiol levels increase, menstrual periods return to normal, and fertility returns. In males, testicular function returns, causing an increase in energy, sex drive, muscle mass, blood count, and bone calcium. The ability to have an erection returns and, eventually, breast enlargement regresses.
Side effects of drug therapy — The most common side effects of dopamine agonists are nausea, lightheadedness after standing, and mental fogginess. These side effects are most likely to occur when treatment first begins and when the dose is increased. They can be minimized by starting with a small dose, increasing the dose slowly if needed, using small doses more frequently, and taking the drug with food or at bedtime. Females who still have trouble tolerating their medication may try taking the pills intravaginally (by inserting them into the vagina) rather than by mouth. This might decrease or prevent nausea.
Cabergoline has been associated with valvular heart disease in people with Parkinson disease who took much larger doses than those typically used to treat prolactinomas. So far, the lower doses used to treat high blood prolactin are not known to cause heart valve defects. However, experts recommend using the lowest dose of cabergoline necessary to lower prolactin to normal; they also recommend doing ultrasound (echocardiogram) of the heart valves in people with prolactinomas who need higher than usual doses of cabergoline. Heart valve problems have not been seen in people taking bromocriptine, even in high doses.
Treatment with dopamine agonists, even at appropriate doses, increases the risk of impulse control disorders, such as pathologic gambling or compulsive sexual behavior, shopping, or eating. Decreasing or discontinuing the dopamine agonist quickly resolves these behaviors in nearly all cases.
How long is medication needed? — If the prolactin level remains normal and no tumor is seen on magnetic resonance imaging (MRI) for two or more years, a trial period without medication can be considered. However, the high prolactin level often recurs after the medication is stopped. Monitoring of the prolactin level and, less frequently, the size of the pituitary, should continue during this time. If the prolactin levels begin to rise or the adenoma grows in size, a dopamine agonist should be resumed.
If the dopamine agonist is not effective in lowering the prolactin level, or if the person cannot tolerate the side effects, surgery to attempt to remove the adenoma may be considered. (See 'Surgery for prolactinoma' below.)
Considerations specific to females
Drug therapy and menopause — Females who have microadenomas usually do not have to continue taking dopamine agonists after menopause. After menopause, there is no longer a concern about irregular or absent periods. The prolactin is usually measured a few months after treatment is stopped to be sure that it is not substantially higher than before treatment. This is usually done once per year for a few years and less often thereafter. Females who have macroadenomas should continue taking dopamine agonists after menopause to keep the size of the adenoma from increasing.
Estradiol and progestin — Estradiol, in combination with a progestin, is a treatment option for females who have small prolactinomas, especially females who have intolerable side effects when taking dopamine agonists and those who do not want to become pregnant.
The rationale for estradiol treatment is that the only known harmful effect of an elevated blood prolactin in a female is decreased ovarian function, including diminished secretion of estradiol. Estradiol doses and regimen are discussed in a separate topic review. (See "Patient education: Menopausal hormone therapy (Beyond the Basics)".)
The prolactin concentration should be monitored periodically because of the small chance that the adenoma could grow. Estradiol and progestin treatment are not recommended as the only treatment in females with macroadenomas (>1 cm).
Becoming pregnant — A female who has a prolactinoma and wants to get pregnant can usually do so with little risk to herself or her developing child. However, the female should speak with an endocrinology specialist before attempting to become pregnant. Issues to address include which treatment is best before trying to conceive, when to discontinue dopamine agonist treatment, the chance that the adenoma will grow during pregnancy, what would be done if it does grow, and whether or not breastfeeding is advisable. These considerations are influenced greatly by whether the adenoma was less than 1 cm (microadenoma) or greater than 1 cm (macroadenoma) prior to treatment:
●Microadenomas rarely increase in size during the course of pregnancy. The best treatment to restore fertility in females with a microadenoma is a dopamine agonist.
Cabergoline is more effective in decreasing blood prolactin levels and adenoma size than bromocriptine. Neither cabergoline nor bromocriptine appears to increase the risk of miscarriage or birth defects when taken to restore fertility and discontinued early in pregnancy, but more information supports the safety of bromocriptine during pregnancy.
Dopamine agonist treatment should be discontinued as soon as pregnancy is diagnosed. There is insufficient information about the safety of these medications during later stages of pregnancy.
If dopamine agonists do not lower prolactin sufficiently to restore ovarian function, other medications, such as clomiphene citrate or gonadotropins, may be recommended to induce ovulation. Once the female becomes pregnant, the dopamine agonist should be discontinued. (See "Patient education: Ovulation induction with clomiphene or letrozole (Beyond the Basics)".)
During the course of the pregnancy, it is possible for the prolactinoma to increase in size. To monitor for an increase in size, the female should let her health care provider know if she develops new or worsening headaches or changes in vision.
●Macroadenomas may increase in size during the course of pregnancy. Signs that the adenoma is growing include new or worsening headaches or changes in vision.
If vision worsens, the female should see an ophthalmologist (eye doctor) and have a visual field test to evaluate peripheral vision. An MRI may be recommended to determine if the prolactinoma has grown. If so, bromocriptine or cabergoline is usually recommended to decrease the size. There is little information about the effect of either medication on the fetus during the second and third trimesters; however, the available information suggests that neither harms the fetus. If necessary, surgery to remove the adenoma can be performed during the second trimester.
If the adenoma was greater than 2 cm in diameter or was affecting vision prior to treatment, surgery should be considered before the female tries to become pregnant. Surgery is recommended because growth of the adenoma during pregnancy can potentially interfere with vision. If the prolactin level remains high following surgery, a dopamine agonist may be recommended to restore fertility. Alternatively, if the adenoma is very sensitive to cabergoline or bromocriptine, a low dose can be continued during the entire pregnancy or it can be administered only if the adenoma increases sufficiently to cause visual symptoms during the pregnancy. (See 'Surgery for prolactinoma' below.)
Breastfeeding — If a female wishes to breastfeed, she should not resume dopamine agonist treatment until breastfeeding is completed, because lowering the prolactin could decrease lactation and because the infant could be exposed to the medication in the milk. If there was an increase in the size of the adenoma during pregnancy sufficient to cause visual symptoms, most experts recommend that the female not breastfeed, so that she may restart dopamine agonist treatment immediately after delivery.
SURGERY FOR PROLACTINOMA — Surgery is an option when dopamine agonists are ineffective or not tolerated. Surgery may also be the best choice for a female with very large macroadenoma that is not entirely responsive to dopamine agonists who wants to become pregnant.
During surgery, a small incision is made in the nose (figure 2). The incision is extended through the sphenoid sinus, allowing the surgeon to visualize and remove the adenoma. Most experienced pituitary neurosurgeons now perform this procedure using an endoscope (a thin, lighted tube with a camera).
Surgery can often reduce the blood prolactin concentration, sometimes to normal. This is more likely for a microadenoma than a macroadenoma. Even if the prolactin is lowered to within the normal range shortly after surgery, the level may become elevated in the next several years. Potential side effects of surgery include worsening of vision, hemorrhage, and meningitis, which are all uncommon, and hormonal deficiencies. The risk of complications is less when the procedure is performed by a surgeon who specializes in pituitary surgery and has performed many operations on the pituitary gland.
Radiation therapy — Radiation therapy can shrink prolactinomas and lower blood prolactin levels, but these effects usually take several years. Therefore, radiation is uncommonly used as treatment of macroadenomas, and when it is, it is used to prevent regrowth of substantial residual tissue that could not be removed during surgery of a macroadenoma that is not responsive to dopamine agonists.
The possible side effects of radiation treatment include temporary nausea, fatigue, loss of taste and smell, and loss of hair on specific parts of the scalp. Approximately half of all people who receive pituitary radiation therapy develop pituitary hormone deficiencies within 10 years.
WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Prolactinoma (The Basics)
Patient education: Pituitary adenoma (The Basics)
Patient education: Panhypopituitarism (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Menopausal hormone therapy (Beyond the Basics)
Patient education: Ovulation induction with clomiphene or letrozole (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Causes of hyperprolactinemia
Causes, presentation, and evaluation of sellar masses
Clinical manifestations and evaluation of hyperprolactinemia
Management of lactotroph adenoma (prolactinoma) before and during pregnancy
Pituitary incidentalomas
Management of hyperprolactinemia
The following organizations also provide reliable health information.
●National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
●National Institute of Diabetes and Digestive and Kidney Disorders
●Hormone Health Network
(http://www.hormone.org/diseases-and-conditions/pituitary/hyperprolactinemia)
●Pituitary Network Association
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