Treating hyperprolactinemia means restoring the gonadal axis and stopping galactorrhea while preserving bone density, and — when a prolactinoma is present — shrinking the tumour. Because the cause changes what is done, the first question after diagnosis is which of the causes is responsible.
Aims of treatment and who needs it
Treatment of hyperprolactinemia is aimed at normalising the final effect of hyperprolactinemia on the gonadal system and on galactorrhea, and also at preserving bone density.
Not every raised level needs treatment. A patient with a microadenoma or idiopathic hyperprolactinemia, non-bothersome galactorrhea and normal estrogen or testosterone levels can simply be followed with periodic prolactin measurement. A similar patient with amenorrhea who is not interested in fertility can be managed with estrogen replacement rather than a prolactin-lowering drug.
Dopamine agonists
Regardless of the etiological cause of hyperprolactinemia, the use of a dopamine agonist will help to reduce the level of hyperprolactinemia. For prolactinomas specifically, dopamine agonists are the first-line treatment: they normalise prolactin, restore gonadal function, stop galactorrhea, and reduce tumour size by more than 50% in 80-90% of patients.
Cabergoline is the preferred dopamine agonist, because its long half-life allows once- or twice-weekly dosing, and it is both more effective and better tolerated than bromocriptine. Bromocriptine and quinagolide are alternatives where cabergoline is unavailable. Cabergoline is usually started at 0.25-0.5 mg per week, and bromocriptine at 1.25 mg per day; taking the dose at bedtime with food and increasing it slowly reduces nausea, dizziness and postural hypotension, which are the most common early adverse effects.
A few adverse effects matter beyond the early nausea and dizziness. Dopamine agonists can cause impulse control disorders — compulsive buying, gambling, hypersexuality and mood change — which are uncommon but are a reason to stop or reduce the drug. Long-term or high-dose cabergoline (more than 2 mg per week) can cause cardiac valve changes, so baseline echocardiography is considered when such treatment is planned. In a large prolactinoma, rapid tumour shrinkage can open a path for cerebrospinal fluid and cause CSF rhinorrhea, which needs surgical repair.
Withdrawing the dopamine agonist
Long-term dopamine agonist treatment is not always permanent. When prolactin has been normal for at least two years, the maintenance dose is low, and the tumour has shrunk substantially, the agonist can be withdrawn and prolactin rechecked; roughly 20-30% of patients remain in remission. If hyperprolactinemia recurs, it usually responds to restarting the agonist.
Surgery
Transsphenoidal surgery, which reaches the pituitary through the sphenoid sinus, is used mainly when a dopamine agonist is resisted or not tolerated. It is the treatment of choice when the hyperprolactinemia comes from stalk compression by a tumour that does not itself secrete prolactin, because such a tumour will not shrink with a dopamine agonist. It is also used for rapidly progressive visual loss or pituitary apoplexy (sudden haemorrhage or infarction of the pituitary), and to repair CSF rhinorrhea.
In experienced hands, remission rates are high for microprolactinomas, up to about 90%, and lower for macroprolactinomas. Radiotherapy is reserved for the rare macroadenoma that is not controlled by either medical or surgical treatment.
Prolactinoma in pregnancy
In a woman who becomes pregnant while taking a dopamine agonist for a microprolactinoma or a small macroprolactinoma, the drug is usually stopped once pregnancy is confirmed, and symptomatic tumour growth during pregnancy is uncommon in these groups. A large macroprolactinoma carries a higher risk of growth during pregnancy, so it may need to be shrunk with medical therapy or debulked surgically before conception.
When the cause is a drug
Not every raised level comes from a tumour. In the case of patients who have hyperprolactinemia due to the side effect of drugs, changing the drug or titrating its dose can help to reduce the hyperprolactinemia. Switching to a drug in the same class that does not raise prolactin, and checking the prolactin again, is the practical way to confirm that the drug was responsible; the level usually falls within a short time once the offending drug is withdrawn. An antipsychotic cannot always be stopped, and the partial dopamine agonist aripiprazole can be used to attenuate antipsychotic-induced hyperprolactinemia.