Galactorrhea is a relatively common problem that occurs in approximately 20 to 25 percent of women. Simply put, galactorrhea is the presence and discharge of milk in the breast of a non pregnant woman and some men. Lactation requires the presence of estrogen, progesterone and, most importantly, prolactin. Prolactin acts at the breast to promote milk secretion and at the ovaries to regulate the release of luteinizing hormone and follicle-stimulating hormone. Normal Lactation and Prolactin
Before lactation, the female breast is primed by estrogen, progesterone, growth hormone, insulin, thyroid hormone and glucocorticoids. These hormones aid in the growth of the ductal system and lobules, and in the development of secretory characteristics of the alveoli. Ironically, high levels of estrogen and progesterone also inhibit lactation at receptor sites in the breast tissue. The precipitous drop in the levels of these hormones after delivery, in the presence of an elevated prolactin level, facilitates lactation. Prolactin levels cycle and are highest during sleep. Levels in normal non-pregnant women range from 1 to 20 ng per mL (1 to 20 μg per L), depending on the laboratory, and may increase to as high as 300 ng per mL (300 μg per L) during pregnancy. Causes and Diagnosis The diagnosis of galactorrhea includes conditions affecting many different organ systems, with causes ranging from physiologic to malignant.
PHYSIOLOGIC CONDITIONS Galactorrhea may be considered physiologic. Pregnant women may lactate as early as the second trimester and may continue to produce milk for up to two years after cessation of breast-feeding. Fluctuating hormone levels, particularly during puberty or menopause, may also cause lactation. Nipple stimulation, commonly associated with repeated breast self-examinations or sexual activity, causes an increase in prolactin secretion.
NEOPLASTIC PROCESSES Although galactorrhea is not associated with breast cancer, it can be caused by neo-plastic processes in the brain and pituitary gland. Fortunately, most of these tumors are benign. Approximately 20 percent of women with galactorrhea have radiologically evident pituitary tumors.
HYPOTHALAMIC-PITUITARY DISORDERS Any disruption of the comunication between the pituitary and hypothalamus glands can result in increased prolactin secretion and milk production. Craniopharyngiomas and other tumors, infiltrative diseases, pituitary-stalk resection and empty-sella syndrome may disrupt the delivery of dopamine to the pituitary gland.
SYSTEMIC DISEASES Systemic diseases must also be considered in the differential diagnosis of galactorrhea. The most common is hypothyroidism. Low levels of thyroid hormone result in increased levels of the thyrotropin-releasing hormone, which increases prolactin secretion. Galactorrhea and symptoms of hypothyroidism abate with thyroid hormone replacement therapy. Chronic renal failure may cause galactorrhea as a result of decreased clearance of prolactin by the kidneys.
MEDICATIONS Galactorrhea can be caused by numerous medications and some herbs. Consequently, the evaluation of this condition must include a thorough and accurate review of current and recent medications, including herbal supplements. Many antipsychotic medications and metoclopramide (Reglan) have lactogenic activity because of their antidopaminergic effects.At least four antihypertensive agents have been reported to cause inappropriate lactation. Methyldopa (Aldomet) inhibits the formation of dopamine, thereby raising the basal prolactin secretion rate. Galactorrhea has also been reported with the use of atenolol (Tenormin), reserpine (Serpasil) and verapamil (Calan). Estrogen and progesterone, found in oral contraceptive formulations and the medroxy-progesterone contraceptive injection (Depo-Provera), may cause lactation. Possible mechanisms include direct actions on the breast tissue or effects on gonadotropins. Galactorrhea occurs more often after discontinuation of oral contraceptive pills than during prolonged use (similar to the hormone withdrawal and lactation that can occur in the postpartum period).
CHEST WALL IRRITATION Galactorrhea can occur because of chest wall irritation from clothing or ill-fitting brassieres. It can also be caused by irritation related to skin conditions such as herpes zoster and atopic dermatitis. Burns have been associated with the development of galactorrhea. Breast surgeries, including implant placement and reduction mammoplasty, can cause postoperative galactorrhea.
IDIOPATHIC GALACTORRHEA Idiopathic galactorrhea is a diagnosis of exclusion, and patients may have normal or elevated levels of prolactin. In such situations, the mechanism of milk production may be an increased prolactin release in response to stimuli, with a normal basal prolactin rate. The differential diagnosis of galactorrhea is extensive. However, patients can be reassured that this condition is not associated with breast cancer. In fact, one study found that idiopathic galactorrhea was associated with a reduced risk of breast cancer. 20 Evaluation The evaluation of galactorrhea includes a thorough history and physical examination, selected laboratory tests and imaging studies are also important.
HISTORY The history should include the duration of galactorrhea, previous pregnancies, and other symptoms of hyperprolactinemia, such as infertility, decreased libido, acne, hirsutism and menstrual irregularity. The patient’s menstrual history is important because hyperprolactinemia, through its effect on gonadotropin-releasing hormone, may cause low estrogen levels.
PHYSICAL EXAMINATION The physical examination includes an evaluation of the patient’s visual fields, thyroid gland, breasts and skin. If the type of nipple discharge is in doubt, the physician may attempt to elicit the discharge and examine it under a microscope. In galactorrhea, microscopy reveals numerous fat globules and little cellular material. If the physician is not certain that the discharge is milk, a sample may be sent to a laboratory for special staining and evaluation, including cytology.
LABORATORY TESTS Laboratory studies may include a serum pregnancy test, a prolactin level, renal function tests and a thyroid-stimulating hormone level.
IMAGING STUDIES Imaging studies are also important in the evaluation of abnormal lactation. If the patient has symptoms suggestive of an intracranial mass, galactorrhea with amenorrhea, or an elevated prolactin level (greater than 20 ng per mL), magnetic resonance imaging (MRI) of the brain is indicated to detect a pituitary tumor or other intracranial lesion.
Treatment The goals of galactorrhea treatment include decreasing or eliminating the patient’s symptoms, curing any identified underlying cause, preventing bone loss, relieving the patient’s anxiety and fears, and, when desired, maintaining the patient’s fertility and ability to lactate.
NORMAL PROLACTIN Patients with idiopathic or physiologic galactorrhea and normal prolactin levels should be reassured. All patients with galactorrhea should be advised to avoid excessive breast stimulation, including repeated self-examinations or excessive nipple manipulation during sexual activity. If galactorrhea is caused by a medication, the agent should be discontinued if possible.
HIGH PROLACTIN LEVEL WITH NORMAL MRI STUDIES The prevention of osteoporosis is a concern in any patient with hyperprolactinemia. High prolactin levels, through their effect on gonadotropins and resulting low estrogen levels, decrease bone density and thereby increase the risk of osteoporosis.This risk can be reduced with medical therapy using dopamine agonists (e.g., bromocriptine [Parlodel], cabergoline [Dostinex]), even in the absence of a tumor. Medical therapy can also be effective in restoring fertility in the patient with galactorrhea, regardless of the prolactin levels. A prolactin level should be obtained every three to six months, and further studies should be performed if the level continues to rise.
PROLACTINOMA The treatment of a prolactinoma depends on its size and the presence or absence of symptoms indicative of increased intracranial pressure or destruction of nearby structures. If the patient has a macroadenoma or symptoms such as headache or changes in vision, medical or surgical treatment is indicated. If the patient has no symptoms of an intracranial mass and the tumor is less than 1 cm in size (microadenoma), treatment options include close observation or medical therapy. Radiation therapy is an option in the patient who cannot tolerate medications and is not a surgical candidate. Irradiation is sometimes used as an adjunct to surgical treatment.
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