Management of hyperprolactinemia
Lactotroph adenomas (prolactinomas)
INDICATIONS FOR TREATMENT
- existing or impending neurologic symptoms (such as visual impairment or headache) due to the large size of a lactotroph adenoma, and
- hypogonadism or other symptoms due to hyperprolactinemia, such as galactorrhea.
- in women with mild hyperprolactinemia and normal cycles who are trying to conceive as they may have subtle luteal phase dysfunction
OVERVIEW OF DOPAMINE AGONISTS
A dopamine agonist drug should usually be the first treatment for patients with hyperprolactinemia of any cause, including lactotroph adenomas (prolactinomas) of all sizes, because these drugs decrease serum prolactin concentrations and decrease the size of most lactotroph adenomas
Choice of drug —
- For most patients with hyperprolactinemia, cabergoline is our first choice, and bromocriptine is our second.
- Pergolide had been used for Parkinson disease and hyperprolactinemia, but it was withdrawn à concerns about valvular heart disease.
- Quinagolide is available in some countries, but not the United States
●Cabergoline –
- first choice because of its efficacy and favorable side-effect profile
- an ergot dopamine agonist that is administered once or twice a week and
- Dopamine agonists decrease prolactin secretion and reduce the size of the lactotroph adenoma in more than 90 percent of patients.
- For patients with lactotroph macroadenomas, no matter how large or how severe the neurologic consequences à recommend initial treatment with a dopamine agonist. Dosing is the same as that for microadenomas
- Cabergoline may be superior to bromocriptine in decreasing the serum prolactin concentration
- has much less tendency to cause nausea than bromocriptine
- may also be effective in patients resistant to bromocriptine
- At the high doses used for the treatment of Parkinson disease, cabergoline is associated with an increased risk of valvular heart disease
- but at the lower doses generally used for the treatment of hyperprolactinemia, cabergoline does not appear to be associated with this risk.
recommend cabergoline as the initial choice of dopamine agonists in most circumstances because it is most likely to be effective and least likely to cause side effects
Because of the association between high-dose cabergoline use for Parkinson disease and valvular heart disease, we suggest using the lowest dose of cabergoline necessary to lower prolactin to normal
For patients who require higher than usual doses of cabergoline (eg, greater than 2 mg per week), we suggest cardiac ultrasonography every two years
If bromocriptine is used first and the patient cannot tolerate it or serum prolactin concentrations do not normalize, we suggest switching to cabergoline
In women with lactotroph microadenomas seeking fertility whose serum prolactin concentrations do not normalize with dopamine agonist therapy (and who therefore do not ovulate), we suggest ovulation induction with clomiphene citrate or gonadotropin therapy
Bromocriptine –
- given twice a day to have optimal therapeutic effect
- more likely to cause nausea than cabergoline.
Actions of bromocriptine are:
1. Decreases prolactin release from pituitary and is a strong antigalactopoietic.
2. Increases GH release in normal individuals, but decreases the same from pituitary tumours that cause acromegaly.
3. Has levodopa like actions in CNS- antiparkinsonian and behavioural effects.
4. Produces nausea and vomiting by stimulating dopaminergic receptors in the CTZ.
5. Hypotension- due to central suppression of postural reflexes and weak peripheral a adrenergic blockade.
6. Decreases gastrointestinal motility.
The therapeutic efficacy of dopamine agonists may be blunted by the concurrent use of drugs known to raise serum prolactin concentrations, including neuroleptic drugs, metoclopramide, domperidone, methyldopa, verapamil, and cimetidine.
Time course of clinical response —
- The fall in serum prolactin à within the first two to three weeks of therapy.
- The decrease in adenoma size can, in many patients, be detected by imaging within six weeks after initiation of treatment
- Following the decrease in serum prolactin and adenoma size in patients with macroadenomas à visual and pituitary function often return to normal.
- Vision usually begins to improve within days after the initiation of treatment
- There is recovery of menses and fertility in women and of testosterone secretion, sperm count, and erectile function in men
Adverse effects —
- nausea, postural hypotension, and mental fogginess.
- Less common side effects include nasal stuffiness, depression, Raynaud phenomenon, alcohol intolerance, and constipation.
- Nausea appears to be more common with bromocriptine than cabergoline.
