Family doctor

What is it and what does it do?

Prolactin is a hormone. A hormone is a chemical substance, which is secreted by an endocrine gland, and is transported to another part of the body (the "target tissue") where it has an effect. Hormones act at the target tissue by binding to a receptor site on the responding cells. The body's endocrine system uses hormones to convey information and control many of the day to day functions.

Prolactin is produced primarily in the front part of the pituitary gland. This gland is known as the "master gland" because it controls a range of other endocrine organs. The pituitary gland is about the size of a pea and is situated near the middle of the brain.

Prolactin is produced in both men and women. Prolactin is secreted periodically by the pituitary throughout the day and night. The secretion of prolactin is increased by a number of external stimuli including stress, breast-feeding and sexual activity.

In women, the breast is the predominant prolactin target tissue. Prolactin has the effect of stimulating the breast to produce breast milk in late pregnancy and sustaining milk production after birth. To have this effect on the breast, other hormones such as oestrogen also need to be present.

Prolactin is also normally produced in men but appears to have no specific role in males. High prolactin levels have the effect of suppressing the hormones responsible for the normal functioning of the ovaries and testes. High prolactin levels can therefore lead to menstrual irregularity and/or fertility problems.

What controls prolactin production?

A neurotransmitter substance called dopamine controls the release of prolactin from the pituitary gland. Dopamine has the effect of inhibiting the secretion of prolactin from the pituitary gland. Other prolactin releasing factors exist that can stimulate prolactin secretion. These include serotonin and thyroid releasing hormones. The drugs available to treat high prolactin levels either mimic the inhibitory effect of dopamine or block the stimulating effect of serotonin (see under treatment).

How do you know if there is a problem with prolactin?

Prolactin can be measured in the blood. Your doctor may arrange a blood test to check on the blood prolactin level for a range of reasons.

A common reason for measuring blood prolactin is the presence of an unexpected milk-like discharge from the breast. This is a condition known as galactorrhoea. Galactorrhoea can appear in both women and men. Your doctor may also measure the blood prolactin level if a woman has irregular or infrequent periods, or if periods have stopped. Measurements can be done if there has been difficulty conceiving or if there is a suspicion of problems with the pituitary gland.

The prolactin level in the blood is usually 30-600 mIU/l. This value may vary from laboratory to laboratory and is lower in males. If your blood level of prolactin is higher than normal this is known as hyperprolactinaemia.

What causes hyperprolactinaemia (elevated blood prolactin levels)?

Firstly, if the prolactin level is only mildly raised your doctor may simply want to remeasure this again. The stress of the blood test in some people is enough to raise the blood prolactin levels. High prolactin levels are quite normal in pregnancy and if the patient is breast-feeding. Prolactin levels usually return to the normal range within 6 months of the completion of nursing.

Many different types of drugs can elevate blood prolactin levels such as antidepressant medication, opiate drugs and painkillers. Often these medications interfere with the dopamine inhibition of prolactin release. Oestrogen use (as in the use of the contraceptive pill) and the withdrawal of the oral contraceptive pill may also cause a modest elevation in blood prolactin levels in some individuals.

The most important consideration in a patient with hyperprolactinaemia is the possibility of a benign prolactin-secreting tumour of the pituitary gland. This is diagnosed usually by a MRI scan of the pituitary area. Tumours of the pituitary gland associated with hyperprolactinaemia are due to benign over-growths of the prolactin producing cells in the gland. These growths are not malignant or cancerous and either remain stable in size or grow in size very slowly (see below).

Pituitary prolactin producing tumours ("adenomas") are divided into two different "types" by size. Microprolactinomas are the smaller prolactin producing tumours (less than 10 mm in diameter). Macroprolactinomas are the larger prolactin producing tumours (greater than 10 mm in diameter). The larger the tumour, the higher the blood prolactin level so that prolactin levels greater than 6000 mIU/L are usually associated with macroprolactinomas. The exact cause of these tumours is unknown but may be to due some genetic disruption within the pituitary gland.

Macroprolactinomas can grow large enough to interfere with nearby structures such as the nerves from the eyes and other areas of brain function. Rarely, other types of pituitary adenoma can cause hyperprolactinaemia, but not usually to the levels seen in those with macroprolactinomas.

Other medical conditions such as thyroid disease, polycystic ovary syndrome and shingles are also associated with modest degrees of hyperprolactinaemia.

Idiopathic hyperprolactinaemia is the term used for persistently elevated blood prolactin levels for which no cause is found.

What treatment is available for those with symptoms from a raised blood prolactin level?

A raised prolactin level without symptoms, or galactorrhoea without an elevation of prolactin may not necessarily require any treatment as long as the patient is not bothered by it, is menstruating regularly and fertility is not an issue. If the patient is symptomatic, has an absence of periods or wants to conceive, medical treatment (see below) could be considered.

Hyperprolactinaemia and galactorrhoea caused by medication usually responds to the withdrawal of these agents.

If hyperprolactinaemia is due to a pituitary tumour, the choice of treatment depends on the size of the tumour. Microadenomas have an excellent prognosis and do not need treatment if the patient is symptom free, menstruating regularly and fertility is not an issue. There is little evidence that these microadenomas progress to become macroadenomas. These patients need to have regular blood prolactin measurements and probably follow-up pituitary scans to ensure that the tumour does not grow (although this is unlikely).

Prolactin secreting macroadenomas usually need treatment as they may, on occasion, threaten vision and cause other pressure effects within the brain. Tablet treatment (as opposed to surgical treatment) is the management of choice. Such medical treatment can shrink these tumours and control their growth, and there is a high response rate. Several drugs are now available for this purpose. If medical treatment is unsuccessful, pituitary surgery can be considered.

Medical treatment

Dopamine agonists

This group of drugs act like naturally occurring dopamine to inhibit the secretion of prolactin from pituitary cells.

Bromocriptine

This has been used as a prolactin-suppressing agent since the 1970s. This is usually given as 1.25 mg (half a tablet) at bedtime for the first week. This is the treatment of choice for the treatment of prolactin-related infertility, as it is considered to be relatively safe in pregnancy. This dose can be increased slowly to a dose of 2.5 - 5 mg given twice a day with food to minimise side effects. Side effects include dizziness on standing (due to low blood pressure), nausea, and nasal stuffiness. Caution should be taken if taking other medicines for treatment of high blood pressure.

Lisuride

This is an alternative to bromocriptine and acts in a similar way. Again, low doses starting slowly should limit side effects. The starting dose is 0.1 mg daily increasing slowly after 1-2 weeks to a standard dose of 0.2 mg three times daily.

Cabergoline

This is very similar to bromocriptine but is longer acting with fewer side effects. If bromocriptine or lisuride are not suitable then this is a reasonable alternative. It is more expensive than the other agents and in New Zealand needs to be prescribed by a specialist. Experience with this drug in pregnancy is limited but appears safe in general experience to date.

Quinagolide (CV 205-502)

This is a second line treatment more potent then bromocriptine and is available on specialist recommendation only. It is used for those intolerant of bromocriptine-like medications.

Serotonin Antagonists

Serotonin acts to stimulate prolactin release. Serotonin antagonists act by blocking this effect of serotonin on prolactin secretion.

Metergoline

A serotonin antagonist with a short duration of action. This is no longer listed for use in New Zealand.

How can one tell if the treatment is working?

Treatment can be assessed by noting the restoration of menstrual periods, resolution of galactorrhoea, tumour shrinkage as assessed by scanning, and blood prolactin levels. Fertility may be restored even before menstruation occurs. If pregnancy is not desired then appropriate precautions need to be taken once treatment for raised prolactin begins.

Pregnancy

For those wishing to become pregnant, suppressive tablets are usually stopped once the pregnancy test is positive. Rarely (in those with large tumours), treatment may need to be continued during pregnancy to avoid pregnancy-related expansion of the adenoma. Specialist supervision may be needed for these patients. Interestingly, small pituitary microprolacinomas can sometimes disappear following pregnancy. Breast-feeding can usually continue normally in those wishing to breast-feed.