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Galactorrhea

by Ian M. Chapman, MBBS, PhD

Galactorrhea is lactation in men or in women who are not breastfeeding. It is generally due to a prolactin-secreting pituitary adenoma. Diagnosis is by measurement of prolactin levels and imaging tests. Treatment involves tumor inhibition with dopamine agonist drugs and sometimes removal or destruction of the adenoma.

Galactorrhea involves secretion of breast milk. For a discussion of nipple discharge in general, see Nipple Discharge.

Etiology

Galactorrhea is generally due to a prolactin-secreting pituitary adenoma (prolactinoma). Most tumors in women are microadenomas (< 10 mm in diameter), but a small percentage are macroadenomas (> 10 mm) when diagnosed. The frequency of microadenomas is much lower in men, perhaps because of later recognition. Nonfunctioning pituitary mass lesions also can increase prolactin levels by compressing the pituitary stalk and thus reducing the action of dopamine , a prolactin inhibitor.

Hyperprolactinemia and galactorrhea also may be caused by ingestion of certain drugs, including phenothiazines, other antipsychotics, certain antihypertensives (especially α-methyldopa), and opioids. Primary hypothyroidism can cause hyperprolactinemia and galactorrhea, because increased levels of thyroid-releasing hormone increase secretion of prolactin as well as thyroid-stimulating hormone (TSH). It is unclear why hyperprolactinemia is associated with hypogonadotropism and hypogonadism. For causes of hyperprolactinemia, Causes of Hyperprolactinemia.

Causes of Hyperprolactinemia

Cause

Example

Physiologic

Nipple stimulation in women

Pregnancy

Postpartum period

Stress

Food ingestion

Sexual intercourse in some women

Sleep

Hypoglycemia

Early infancy (up to 3 mo)

Hypothalamic disorders

Hypothalamic tumors

Nontumerous hypothalamic infiltration: Sarcoidosis, TB, Langerhans cell histiocytosis (Hand-Schüller-Chrisitan disease)

Postencephalitis

Idiopathic galactorrhea (presumed abnormality in dopamine secretion)

Head trauma

Pituitary disorders

Prolactin-secreting pituitary tumors

Tumors causing pituitary stalk compression

Surgical pituitary stalk section and other stalk lesions

Empty sella syndrome

Other endocrine disorders

Acromegaly

Cushing disease

Primary hypothyroidism

Disorders of other systems

Chronic renal failure

Liver disease

Ectopic production of prolactin: Bronchogenic carcinoma (not squamous cell; mostly small cell undifferentiated)

Hypernephroma

Chest wall lesions

Surgical scars

Trauma

Tumors

Herpes zoster

Pharmacologic

Antihypertensive drugs: Resperine, α-methyldopa, labetalol, atenolol, verapamil, clonidine

H 2 -antagonists (eg, ranitidine)

Oral contraceptives and estrogens

Opioids

Psychoactive drugs, eg, phenothiazines, tricyclic and some other antidepressants, butyrphenones (haloperidol), benzamides (metoclopramide, sulpiride)

Thyrotropin-releasing hormone

Data from Rebar RW: Practical evaluation of hormonal status. In Reproductive Endocrinology: Physiology, Pathophysiology and Clinical Management , edited by SSC Yen and RB Jaffe. Philadelphia, WB Saunders Company, 1978, p. 493.

Symptoms and Signs

Abnormal lactation is not defined quantitatively; it is milk release that is inappropriate, persistent, or worrisome to the patient. Spontaneous lactation is more unusual than milk released in response to manual expression. The milk is white. Women with galactorrhea commonly also have amenorrhea or oligomenorrhea. Women with galactorrhea and amenorrhea may also have symptoms and signs of estrogen deficiency, including dyspareunia, due to inhibition of pulsatile luteinizing hormone and follicle-stimulating hormone release by high prolactin levels. However, estrogen production may be normal, and signs of androgen excess have been observed in some women with hyperprolactinemia. Hyperprolactinemia may occur with other menstrual cycle disturbances besides amenorrhea, including infrequent ovulation and corpus luteum dysfunction.

Men with prolactin-secreting pituitary tumors typically have headaches or visual difficulties. About two thirds of affected men have loss of libido and erectile dysfunction.

Diagnosis

  • Prolactin levels

  • Thyroxine (T 4 ) and TSH levels

  • CT or MRI

Diagnosis of galactorrhea due to a prolactin-secreting pituitary adenoma is based on elevated prolactin levels (typically > 5 times normal, sometimes much higher) and decrease in lesion size in response to drug treatment. In general, prolactin levels correlate with the size of a pituitary tumor and can be used to follow patients over time. With a nonfunctioning pituitary mass, prolactin levels are not usually elevated > 3 to 4 times normal. A trial of dopamine agonist therapy can help distinguish between prolactin-secreting and nonfunctioning lesions; in both types of lesion, prolactin levels decrease after treatment, but prolactin-secreting lesions decrease in size, whereas nonfunctioning lesions do not.

Serum gonadotropin and estradiol levels are either low or in the normal range in women with hyperprolactinemia. Primary hypothyroidism is easily ruled out by absence of elevated TSH.

High-resolution CT or MRI is the method of choice in identifying microadenomas. Visual field examination is indicated in all patients with macroadenomas and in any patient who elects drug therapy or surveillance only.

Treatment

  • Depends on sex, cause, symptoms, and other factors

The treatment of microprolactinomas is controversial. Asymptomatic patients who have prolactin levels < 100 ng/mL and normal CT or MRI results or who have only microadenomas can probably be observed; serum prolactin often normalizes within years. Patients with hyperprolactinemia should be monitored with quarterly measurement of prolactin levels and undergo sellar CT or MRI annually for at least an additional 2 yr. The frequency of sellar imaging can then be reduced if prolactin levels do not increase.

In women, indications for treatment include

  • Desire for pregnancy

  • Amenorrhea or significant oligomenorrhea (because of the risk of osteoporosis)

  • Hirsutism

  • Low libido

  • Troublesome galactorrhea

In men, galactorrhea itself is rarely troublesome enough to require treatment; indications for treatment include

  • Hypogonadism (because of the risk of osteoporosis)

  • Erectile dysfunction

  • Low libido

  • Troublesome infertility

The initial treatment is usually a dopamine agonist such as bromocriptine 1.25 to 5 mg po bid or the longer-acting cabergoline 0.25 to 1.0 mg po once/wk or twice/wk, which lower prolactin levels. Cabergoline is the treatment of choice because it appears to be more easily tolerated and more potent than bromocriptine. Women trying to become pregnant should switch to bromocriptine at least 1 mo before planned conception and stop bromocriptine use at the time of a positive pregnancy test result; long-term safety data are better established for bromocriptine than for cabergoline, although evidence for the safety of cabergoline is increasing. Exogenous estrogen can be given to women with a microadenoma who are clinically hypoestrogenic or have low estradiol levels. Exogenous estrogen is unlikely to cause tumor expansion. Quinagolide, a nonergot-derived dopamine agonist, is also an option for hyperprolactinemia. It is started at 25 mcg po once/day and titrated over 7 days up to the usual maintenance dose of 75 mcg once/day (maximum dose 600 mcg once/day).

Patients with macroadenomas generally should be treated with dopamine agonists or surgically but only after thorough testing of pituitary function and evaluation for radiation therapy. Dopamine agonists are usually the initial treatment of choice and usually shrink a prolactin-secreting tumor but will not shrink a nonfunctioning tumor causing pituitary stalk compression, although prolactin levels will decrease. If prolactin levels fall and symptoms and signs of compression by the tumor abate, no other therapy may be necessary. However, typically, larger, nonfunctioning lesions need additional treatment, usually surgery. Surgery or radiation therapy may be easier to do or yield better results after tumor shrinkage induced by a dopamine agonist. Although dopamine agonist treatment usually needs to be continued long-term, prolactin-secreting tumors sometimes remit, either spontaneously or perhaps aided by the drug therapy. Sometimes, therefore, dopamine agonists can be stopped without a recurrence of the tumor or a rise in prolactin levels; remission is more likely with microadenomas than macroadenomas. Remission is also more likely after pregnancy.

High doses of dopamine agonists, particularly cabergoline and pergolide, are thought to have caused valvular heart disease in some patients with Parkinson disease. It is not clear whether the lower doses of dopamine agonists used for hyperprolactinemia similarly increase the risk of valvular heart disease, but the possibility should be discussed with patients, and echocardiographic surveillance should be considered. The risk may be less with bromocriptine or quinagolide.

Radiation therapy should be used only in patients with progressive disease who do not respond to other forms of therapy. With irradiation, hypopituitarism often develops several years after therapy. Monitoring endocrine function and sellar imaging are indicated yearly for life.

Key Points

  • Galactorrhea is milk release that is inappropriate, persistent, or worrisome to the patient.

  • The most common cause is a pituitary tumor, but many drugs, and endocrine, hypothalamic, or other disorders may be responsible.

  • Measure prolactin levels and do CNS imaging to detect a causative tumor.

  • For microprolactinomas, give a dopamine agonist if certain troublesome symptoms are present.

  • For macroadenomas, give a dopamine agonist and consider surgical ablation or sometimes radiation therapy.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • No US brand name
  • REGLAN
  • HALDOL
  • No brand name
  • CALAN
  • TENORMIN
  • CATAPRES
  • ZANTAC
  • ESTRADERM, ESTROGEL, VIVELLE
  • PARLODEL

* This is a professional Version *