Ovarian Lifecycle

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  • Thyroid Treatment
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Treatment Options: Prolactin Treatment
Treatment  |   Medications

When hyperprolactinemia should be treated
The overwhelming majority of patients with excess circulating prolactin concentrations can be effectively treated with medication alone (often Bromocriptine). Surgical excision of pituitary prolactinomas (tumors of lactotrophs, the prolactin producing cells of the pituitary gland) is currently reserved for large symptomatic tumors, patients noncompliant with medical treatment (the use of medication for treatment) or for tumors that have failed to respond to medical management. When surgery is recommended, it is usually performed as a "transsphenoidal microsurgical resection" (with a small incision made under the upper lip) which has minimal cosmetic consequences and fewer major complications than a craniotomy (opening of the skull).

Treatment depends on the fertility goals of the couple, the reason for the excess prolactin, and the woman’s symptoms.

pregnancy is not desired,
the radiologic exam demonstrates either no tumor or a microadenoma (prolactinoma less than 1 cm diameter),
there is either no galactorrhea or the presence of milk is not bothersome to the patient, and
the patient does not have a low circulating estrogen concentration

Then she can reasonably consider "no active treatment." That is, she can consider continuing without medication, have her blood levels of prolactin checked 1-2 times a year for a few years, and recheck the radiologic exam every 1-2 years for a few years to confirm that a tumor is not rapidly growing.

pregnancy is not desired but,
the patient has bothersome galactorrhea

Normalizing the prolactin concentrations with medication usually effectively treats this. There are women who will continue to experience galactorrhea with normal prolactin concentrations, but the mechanism for this is not usually clear. Most likely the galactorrhea is due to the "most bioactive forms of prolactin" comprising a greater than normal percentage of the total amount of immunoreactive prolactin (the amount detected in the assays). Also, this may be due to an increase in breast cell receptors for prolactin.

pregnancy is not desired but,
the patient has a low circulating estrogen concentration

treatment for the low estrogen should be provided. Medical management of the excess prolactin to bring it into the normal range will generally correct the estrogen abnormality. If medical management of the excess prolactin is not desired, then estrogen replacement should be strongly recommended (if not otherwise contraindicated) to protect the woman from the harmful effects associated with a lack of estrogen (such as osteoporosis and heart disease). Birth control pills or traditional hormone replacement medication (such as Premarin and Provera) can be given.

pregnancy is desired,

an attempt to correct the ovulatory dysfunction associated with excess prolactin concentrations should be initiated. Usually medication to reduce the prolactin concentration is most effective and all that is required. Prolactin secretion from the pituitary gland is inhibited by dopamine and medications that act similar to dopamine (dopamine agonists). The response to the medication usually results in improvement of ovulation within 1-2 months of normalization of prolactin.

a woman becomes pregnant while taking medication for excess prolactin (such as Bromocriptine),

the physician usually discontinues the medicine during the pregnancy. One exception can be when there is a history of a large symptomatic tumor (macroadenoma). Prolactin levels generally increase and tumor growth may occur in high estrogen states (like pregnancy). In the early 1980s, a metaanalysis of the available literature reported that of 275 women with pituitary prolactinomas, 215 women had microadenomas and less than 1% of these had either visual changes or radiologic evidence of tumor growth during pregnancy (5% did have headaches), and 60 women had macroadenomas with 20% of these having visual changes or radiologic evidence of growth. Therefore, the need for treatment in pregnancy is uncommon.

Prolactin is the hormone primarily responsible for breast milk production during pregnancy and lactation, with circulating levels of prolactin typically increasing up to 10 fold by the end of pregnancy.

The size of a prolactinoma generally decreases with medical treatment. In microadenomas, reports demonstrate that 75% of patients treated with medication have a reduction in size and 40% have complete disappearance of the tumor. In macroadenomas, reports demonstrate that up to 90% have a reduction in size and most of these also have rapid relief of any symptoms (such as vision abnormalities).

The length of therapy with medication for excess prolactin is classically long term. There is a high incidence of recurrence after discontinuing medication for a macroadenoma so long term treatment is usually recommended. Women with a microadenoma can have continued normalization of prolactin after discontinuing the medication (about 10% if treated for 1 year and up to 20% if treated for 2 years) so that these women may try discontinuing the medicine to see whether they need it after 1-2 years.

Hyperprolactinemia: Medications
Bromocriptine readily crosses the placenta to enter the fetal circulation. Fetal prolactin production is suppressed but other fetal effects have not been recognized. In one study of over 1400 pregnancies in which bromocriptine was taken in early pregnancy, there was no increase in minor or major congenital abnormalities and no increase in reported spontaneous abortions (miscarriages). Nevertheless, to be prudent, asymptomatic patients with either microadenomas or macroadenomas should discontinue bromocriptine during pregnancy and restart the medicine only if symptoms develop or rapid tumor growth is demonstrated. Pregnant patients with macroadenomas or symptomatic microadenomas should have regular (some say monthly) visual field and neurologic exams.

Bromocriptine was developed in 1967 and is FDA approved. Side effects are not uncommon and can lead to intolerance to the medication, including

  • orthostatic hypotension in up to 15% of patients, which may result in "nausea or vomiting" as well as "dizziness and faintness" immediately after standing up.
  • headache
  • fatigue, or
  • altered bowel activity (constipation or diarrhea).

These side effects are usually transient so that most physicians will initiate treatment at a low dose (such as 2.5 mg) taken only at night (so you are asleep during the symptomatic time period). The dose can then be increased at weekly intervals to the dosage determined to be effective (generally 2.5 mg twice a day). Bloodwork for prolactin is usually determined about 3-4 weeks after a change in dosage, until the prolactin concentration is within the normal range. Then bloodwork can be checked less regularly, say every 6-12 months until proven stable and then even less often.

If the woman is very uncomfortable due to the symptoms of oral Bromocriptine, vaginal administration (tablet placed deep in vagina) allows for excellent absorption, much fewer side effects, and typically only daily dosing (since therapeutic levels continue for greater than 24 hours).

There are other dopamine agonist medications that do not have the same side effects.

Pergolide (permax) is another dopamine receptor agonist that is occasionally used as an alternative to bromocriptine. Administration is oral, and pergolide is much more potent than bromocriptine on a mg to mg basis (up to 1,000 times more potent). Adequate doses of pergolide (50-150 mcg a day) are lower than those of bromocriptine. As with bromocriptine, women taking pergolide may experience orthostatic hypotension so they are often started at low doses and increased to a therapeutic dose over a several week period of time. Additionally, nervous system complaints including hallucinations and dyskinesia (difficulty in performing voluntary movements) were severe enough to cause discontinuation of treatment in up to 15% of women.

Cabergoline (dostinex) is a dopamine receptor agonist that has a longer half life than bromocriptine ( dosing is only twice a week). Clinical trials of high quality (randomized double blinded prospective studies) comparing cabergoline to both placebo and bromocriptine (in terms of their ability to suppress prolactin in women) demonstrated efficacy. Compared to bromocriptine (in an eight week trial), cabergoline (0.5 mg twice weekly) normalized prolactin in 77% of hyperprolactinemic women compared to 59% of those treated with bromocriptine (2.5 mg twice a day). In over 900 hyperprolactinemic women taking cabergoline the adverse (side) effects were considered predominantly mild or moderate, including gastrointestinal complaints (nausea, constipation, abdominal pain), nervous system complaints (headache and dizziness), fatigue, depression, and orthostatic hypotension. Cabergoline is discontinued in about 2% of users, with the most common reasons for discontinuing cabergoline being headaches, nausea and vomiting. Usual starting doses of cabergoline are 0.25 mg twice a week and increased by .25 mg (to maximum of 1 mg) as needed.

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