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Evaluation and Treatment of Galactorrhea KRISTIN S. PEÑA, M.D., and JO ANN ROSENFELD, M.D., Franklin Square Hospital, Baltimore, Maryland

Galactorrhea, or inappropriate , is a relatively common problem that occurs in approximately 20 to 25 percent of women. Lactation requires the presence of estro- O A patient infor- gen, progesterone and, most importantly, . Stress, suckling, sleep, sexual mation handout on intercourse and medications may increase prolactin levels, whereas dopamine inhibits galactorrhea, written by the authors of this its release. The differential diagnosis of galactorrhea includes pituitary adenomas, article, is provided on neurologic disorders, , numerous medications, stimulation, page 1775. chest wall irritation and physiologic causes. The evaluation includes a thorough history and physical examination, as well as selected laboratory and imaging studies to rule out secondary causes such as an intracranial mass or a tumor. Diagnostic studies include a test, a prolactin level, renal and function tests and, if indi- cated, magnetic resonance imaging of the brain. Treatment options for include observation, dopamine agonists, surgery and radiation therapy, depending on tumor size and associated symptoms. Fortunately, the prognosis for patients with pro- lactinomas is good: most prolactinomas remain stable or regress. In pregnant women, prolactinomas must be observed closely because the lesions may greatly increase in size. (Am Fam Physician 2001;63:1763-70,1775.)

atients with breast problems such inhibiting factor. Prolactin acts at the breast to as galactorrhea are often first seen promote secretion and at the ovaries to by family physicians. The true regulate the release of luteinizing incidence of galactorrhea is un- and follicle-stimulating hormone. known, but it is estimated that 20 Prolactin levels cycle and are highest during Pto 25 percent of women experience this prob- sleep. Levels in normal nonpregnant women lem at some time in their life.1,2 Although rare, range from 1 to 20 ng per mL (1 to 20 µg per galactorrhea can also occur in males. L), depending on the laboratory, and may increase to as high as 300 ng per mL (300 µg Normal Lactation and Prolactin per L) during pregnancy.3 Suckling, stress, Before lactation, the female breast is primed dehydration, exercise, sexual intercourse and by , progesterone, growth hormone, sleep increase the basal secretion rate from the insulin, thyroid hormone and glucocorticoids. , as do estrogen, thyrotropin- These aid in the growth of the duc- releasing hormone and possibly serotonin. tal system and lobules, and in the develop- ment of secretory characteristics of the alveoli. Differential Diagnosis Ironically, high levels of estrogen and proges- The differential diagnosis of galactorrhea terone also inhibit lactation at receptor sites in includes conditions affecting many different the breast tissue. The precipitous drop in the organ systems, with causes ranging from levels of these hormones after delivery, in the physiologic to malignant (Table 1).2,5-10 presence of an elevated prolactin level, facili- tates lactation. PHYSIOLOGIC CONDITIONS Prolactin is normally secreted by the ante- Galactorrhea may be considered physio- rior pituitary gland at a low basal rate, with logic. Pregnant women may lactate as early as secretion continuously suppressed by prolac- the second trimester and may continue to pro- tin inhibiting factor (Figure 1).2-4 Dopamine, duce milk for up to two years after cessation of released from the hypothalamus and delivered breast-feeding. Fluctuating hormone levels, via the hypothalamic-hypophysial portal sys- particularly during puberty or menopause, tem, is the main constituent of prolactin may also cause lactation. stimulation,

MAY 1, 2001 / VOLUME 63, NUMBER 9 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1763 commonly associated with repeated breast Lactation self-examinations or sexual activity, causes an increase in prolactin secretion. Hypothalamus Up to 5 percent of neonates produce “witch’s milk” for the first month of life.11 This milk production results from the precip- itous drop in maternal estrogen and proges- Thyrotropin-releasing hormone Dopamine terone levels after delivery.

Stimulation Inhibition NEOPLASTIC PROCESSES Although galactorrhea is not associated with breast cancer, it can be caused by neo- plastic processes in the brain and pituitary Pituitary gland gland. Fortunately, most of these tumors are benign. Approximately 20 percent of women Prolactin Stimulation: with galactorrhea have radiologically evident Suckling pituitary tumors, and the prevalence Stress increases to 34 percent in women who also Dehydration 2 Exercise have amenorrhea. Sexual intercourse The most common tumor resulting in Sleep hyperprolactinemia is the pituitary prolacti- Estrogen Serotonin (?) noma, a benign growth of the prolactin-secret- ing cells of the anterior pituitary gland.Autopsy Stimulation: Breast tissue Inhibition: reports indicate that prolactinomas are present Estrogen High levels of estrogen in 10 to 30 percent of the population.4 Progesterone and progesterone Growth hormone Lactation Pituitary prolactinomas are associated with Insulin elevated prolactin levels. Clinical signs and Thyroid hormone symptoms include headache, galactorrhea, Glucocorticoids amenorrhea, defects in peripheral vision, hir- sutism, acne, and presenting as decreased libido, decreased fertility or FIGURE 1. Physiology of lactation. decreased bone density. The prognosis for Information from references 2 through 4. patients with these tumors is excellent. Most pituitary prolactinomas regress or remain stable for many years. Nonpituitary malignancies, such as bron- The Authors chogenic carcinoma, renal adenocarcinoma KRISTIN S. PEÑA, M.D., is a fellow in women’s health in the Department of Family Prac- and Hodgkin’s and T-cell lymphomas, may tice at Franklin Square Hospital, Baltimore, where she previously served as a chief res- ident in the family practice residency program. Dr. Peña received her medical degree also release prolactin. from Michigan State University College of Human Medicine, East Lansing. HYPOTHALAMIC-PITUITARY DISORDERS JO ANN ROSENFELD, M.D., is director of women’s health for the family practice resi- dency program at Franklin Square Hospital. Dr. Rosenfeld graduated from Johns Hop- Any disruption of the communication kins University School of Medicine, Baltimore, and completed a family practice resi- between the pituitary and hypothalamus dency at Case Western Reserve University School of Medicine, Cleveland. She is the author of Women’s Health in Primary Care. glands can result in increased prolactin secre- tion and milk production. Craniopharyn- Address correspondence to Kristin S. Peña, M.D., Franklin Square Hospital Family Prac- tice Residency, 9101 Franklin Square Dr., Room 205, Baltimore, MD 21237 (e-mail: giomas and other tumors, infiltrative diseases, [email protected]). Reprints are not available from the authors. pituitary-stalk resection and empty-sella syn-

1764 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 63, NUMBER 9 / MAY 1, 2001 Galactorrhea

drome may disrupt the delivery of dopamine to the pituitary gland. Many medications, illicit drugs and herbal supplements can cause galactorrhea. SYSTEMIC DISEASES Systemic diseases must also be considered in the differential diagnosis of galactorrhea. The most common is hypothyroidism. Low Consequently, the evaluation of this condi- levels of thyroid hormone result in increased tion must include a thorough and accurate levels of the thyrotropin-releasing hormone, review of current and recent medications, which increases prolactin secretion. Galactor- including herbal supplements. rhea and symptoms of hypothyroidism abate Many medications and with thyroid hormone replacement therapy. (Reglan) have lactogenic Chronic renal failure may cause galactorrhea activity because of their antidopaminergic as a result of decreased clearance of prolactin by effects. As many as 15 percent of patients the kidneys. Hypersecretion of cortisol (Cush- report galactorrhea within seven to 75 days ing’s disease) or growth hormone (acromegaly) after starting antipsychotic medication.17 may also have associated hyperprolactinemia. With the increasing use of selective sero- tonin reuptake inhibitors, more women are MEDICATIONS reporting galactorrhea as a side effect.12 As a Galactorrhea can be caused by numerous result, researchers now postulate that sero- medications and some herbs (Table 2).12-19 tonin may have a role in regulating prolactin

TABLE 1 Causes of Galactorrhea

Physiologic conditions Hypothalamic-pituitary Medications and herbs (14 percent) disorders (<10 percent) (20 percent)* Pregnancy and postpartum state Craniopharyngioma and other Chest wall irritation (<10 Breast stimulation tumors percent) “Witch’s milk” in neonates Infiltrative conditions Irritating clothes or ill-fitting Neoplastic processes brassieres (18 percent) Tuberculosis Herpes zoster () Schistosomiasis Atopic dermatitis Bronchogenic carcinoma Pituitary-stalk resection Burns Renal adenocarcinoma Multiple sclerosis Breast surgery Lymphoma Empty-sella syndrome Spinal cord injury or surgery Craniopharyngioma Systemic diseases (<10 percent) Spinal cord tumor Hydatidiform mole Hypothyroidism Esophagitis Hypernephroma Chronic renal failure Esophageal reflux Mixed growth hormone- Cushing’s disease Idiopathic (35 percent) secreting and prolactin- Acromegaly Hyperprolactinemia secreting tumors Euprolactinemia Null-cell adenoma

*—See Table 2. Information from references 2 and 5 through 10.

MAY 1, 2001 / VOLUME 63, NUMBER 9 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1765 secretion. Tricyclic antidepressants, the been reported with the use of atenolol (Tenor- monoamine oxidase inhibitor moclobemide min), reserpine (Serpasil) and verapamil (Manerix; available in Canada) and the anxi- (Calan).14,15

olytic buspirone (BuSpar) are also known to The histamine H2-receptor blockers cimeti- cause galactorrhea.13,14 dine (Tagamet), famotidine (Pepcid) and At least four antihypertensive agents have ranitidine (Zantac) have all been reported to been reported to cause inappropriate lacta- cause galactorrhea.16 tion. (Aldomet) inhibits the for- Estrogen and progesterone, found in oral mation of dopamine, thereby raising the basal contraceptive formulations and the medroxy- prolactin secretion rate. Galactorrhea has also progesterone contraceptive injection (Depo- Provera), may cause lactation. Possible mech- anisms include direct actions on the breast TABLE 2 tissue or effects on gonadotropins. Galactor- Medications and Herbs Associated with Galactorrhea rhea occurs more often after discontinuation of oral contraceptive pills than during pro- Antidepressants and Phenothiazines longed use (similar to the hormone with- anxiolytics Chlorpromazine (Thorazine) drawal and lactation that can occur in the Alprazolam (Xanax) Prochlorperazine (Compazine) ). Buspirone (BuSpar) Others The dosages of estrogen and progesterone Monoamine oxidase inhibitors Other drugs used in postmenopausal hormonal replace- Moclobemide (Manerix; Amphetamines available in Canada) ment therapy are generally not high enough Anesthetics Selective serotonin reuptake to cause galactorrhea. However, some pa- Arginine inhibitors tients with hyperprolactinemia may not have Cannabis Citalopram (Celexa) symptoms if they are estrogen deficient. Once Cisapride (Propulsid) Fluoxetine (Prozac) hormone replacement therapy is started, the Cyclobenzaprine (Flexeril) Paroxetine (Paxil) Danazol (Danocrine) breast tissue is primed, and galactorrhea may Sertraline (Zoloft) Dihydroergotamine (DHE 45) then occur. Tricyclic antidepressants (Motilium; available Nonpuerperal lactation can also be caused Antihypertensives in Canada and Mexico) by illicit drugs. Close questioning is advised Atenolol (Tenormin) Isoniazid (INH) because patients may be hesitant to report the Methyldopa (Aldomet) Metoclopramide (Reglan) use of amphetamines, cannabis, benzodiaze- Reserpine (Serpasil) Octreotide (Sandostatin) pines and opiates, all of which can cause lacta- Verapamil (Calan) Opiates tion. A number of herbs used in cooking and Rimantadine (Flumadine) as supplements must also be considered in the Histamine H -receptor blockers Sumatriptan (Imitrex) 2 differential diagnosis. In addition, adoptive (Tagamet) Valproic acid (Depakene) mothers have used metoclopramide to facili- Famotidine (Pepcid) Herbs tate breast-feeding. They have also used fenu- Ranitidine (Zantac) Anise greek seed and domperidone (Motilium; avail- Hormones Blessed thistle able in Canada and Mexico) to achieve Conjugated estrogen and Fennel medroxyprogesterone Fenugreek seed “induced lactation.” (Premphase, Prempro) Marshmallow Medroxyprogesterone contraceptive Nettle CHEST WALL IRRITATION injections (Depo-Provera) Red clover Galactorrhea can occur because of chest Oral contraceptive formulations Red raspberry wall irritation from clothing or ill-fitting brassieres. It can also be caused by irritation Information from references 12 through 19. related to skin conditions such as herpes zoster and atopic dermatitis. Burns have been

1766 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 63, NUMBER 9 / MAY 1, 2001 Galactorrhea

associated with the development of galactor- the mechanism of milk production may be an rhea. Breast surgeries, including implant increased prolactin release in response to placement and reduction mammoplasty, can stimuli, with a normal basal prolactin rate. cause postoperative galactorrhea. The differential diagnosis of galactorrhea is Case reports have discussed galactorrhea extensive. However, patients can be reassured associated with spinal cord injury or surgery, that this condition is not associated with as well as spinal cord tumors.5-7 Severe breast cancer. In fact, one study found that esophagitis and esophageal reflux may cause idiopathic galactorrhea was associated with a galactorrhea by stimulating the thoracic reduced risk of breast cancer.20 nerves via the cervical and thoracic ganglia.8 Evaluation IDIOPATHIC GALACTORRHEA The evaluation of galactorrhea includes a Idiopathic galactorrhea is a diagnosis of thorough history and physical examination exclusion, and patients may have normal or (Figure 2). Selected laboratory tests and imag- elevated levels of prolactin. In such situations, ing studies are also important.

Evaluation of Galactorrhea

Nipple discharge

Microscopy shows fat Nongalactorrhea discharge globules in discharge.

Consider breast cancer, intraductal Galactorrhea papilloma, papillomatosis, mammary duct ectasia, fibrocystic .

Laboratory tests: Human chorionic gonadotropin level Prolactin level Thyroid-stimulating hormone level urea nitrogen and creatinine levels

High thyroid-stimulating Normal thyroid-stimulating hormone Normal thyroid-stimulating hormone level, low level, prolactin level higher than hormone level, normal thyroxine level 20 ng per mL (20 µg per L) prolactin level

No Thyroid hormone Magnetic resonance Regular menses? replacement therapy imaging of the brain Yes

Reassurance, observation

FIGURE 2. Algorithm for the evaluation of galactorrhea.

MAY 1, 2001 / VOLUME 63, NUMBER 9 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1767 Because prolactin levels are influenced by Hyperprolactinemia, possibly through its effect on estrogen, stress and breast stimulation, blood should not increases the risk of developing osteoporosis. This risk can be drawn immediately after a breast examina- tion. Rather, it should be drawn at least one be reduced with medical therapy using dopamine agonists, hour after the examination and when the even in the absence of a tumor. patient is relaxed. If the initial prolactin level is borderline, the level should be repeated one or two times because of the great fluctuation in HISTORY prolactin levels throughout the day. A level The history should include the duration of greater than 200 ng per mL (200 µg per L) is galactorrhea, previous , and other almost always associated with a prolactinoma symptoms of hyperprolactinemia, such as or other prolactin-secreting tumor. , decreased libido, acne, hirsutism Serum cortisol, growth hormone and in- and menstrual irregularity. The patient’s sulin-like growth factor levels should be ob- menstrual history is important because tained if the patient has signs or symptoms of hyperprolactinemia, through its effect on Cushing’s disease (cushingoid features) or gonadotropin-releasing hormone, may cause growth hormone excess (acromegalic features). low estrogen levels. As a result, the patient may have amenorrhea or oligomenorrhea, as IMAGING STUDIES well as decreased bone density. Imaging studies are also important in the The patient should be asked about symp- evaluation of abnormal lactation. If the pa- toms of an intracranial mass, such as visual- tient has symptoms suggestive of an intra- field defects, cranial nerve palsy and head- cranial mass, galactorrhea with amenorrhea, ache. It is also important to inquire about or an elevated prolactin level (greater than symptoms of systemic diseases, including 20 ng per mL), magnetic resonance imaging hypothyroidism and Cushing’s disease. (MRI) of the brain is indicated to detect a An accurate list of all medications, includ- pituitary tumor or other intracranial lesion. If ing over-the-counter and illicit substances, the patient has normal menses and a normal herbs and other supplements, is essential. prolactin level, the risk for pituitary adenoma is low, and imaging is not necessary. However, PHYSICAL EXAMINATION if a patient has galactorrhea associated with The physical examination includes an eval- amenorrhea or oligomenorrhea, even with a uation of the patient’s visual fields, thyroid normal prolactin level, the risk of a pituitary gland, and skin. If the type of nipple adenoma is still significant, and an imaging discharge is in doubt, the physician may study of the gland is warranted.21 attempt to elicit the discharge and examine it Given the lack of association between galact- under a microscope. In galactorrhea, micros- orrhea and breast cancer, mammography is not copy reveals numerous fat globules and little necessary unless other findings on the physical cellular material. If the physician is not cer- examination are suggestive of breast pathology. tain that the discharge is milk, a sample may that is not milky should be be sent to a laboratory for special staining and evaluated because it may be caused by intra- evaluation, including cytology. ductal papilloma, papillomatosis, mammary duct ectasia, fibrocystic breasts or carcinoma. LABORATORY TESTS Laboratory studies may include a serum Treatment pregnancy test, a prolactin level, renal function The goals of galactorrhea treatment include tests and a thyroid-stimulating hormone level. decreasing or eliminating the patient’s symp-

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toms, curing any identified underlying cause, preventing bone loss, relieving the patient’s Prolactinomas can increase in size during pregnancy. anxiety and fears, and, when desired, main- taining the patient’s fertility and ability to lactate. include close observation or medical therapy. NORMAL PROLACTIN The prolactin level should be measured every Patients with idiopathic or physiologic three to six months, and imaging studies galactorrhea and normal prolactin levels should be performed every two to three years should be reassured. All patients with galac- (sooner if the prolactin levels rise). torrhea should be advised to avoid excessive Medical treatments for prolactinomas breast stimulation, including repeated self- include bromocriptine and . These examinations or excessive nipple manipula- agents activate the lactotroph D2-receptor tion during sexual activity. If galactorrhea is sites and, similar to dopamine, inhibit the syn- caused by a medication, the agent should be thesis of prolactin. Bromocriptine and caber- discontinued if possible. goline normalize prolactin levels, rapidly shrink tumors and restore vision, menses and HIGH PROLACTIN LEVEL fertility.23,24 Side effects include nausea, vomit- WITH NORMAL MRI STUDIES ing, postural hypotension, headache and nasal The prevention of osteoporosis is a concern congestion, although these are experienced in any patient with hyperprolactinemia. High less often with cabergoline. The dosage of prolactin levels, through their effect on either agent is gradually increased and titrated gonadotropins and resulting low estrogen lev- to the patient’s symptoms and prolactin level. els, decrease bone density and thereby increase Cabergoline is the agent of choice in patients the risk of osteoporosis.3 This risk can be not wishing to conceive. Its long half-life, reduced with medical therapy using dopa- twice-weekly dosing and tolerability improve mine agonists (e.g., bromocriptine [Parlodel], patient compliance. Cabergoline is also effec- cabergoline [Dostinex]), even in the absence tive in reducing prolactin levels in some of a tumor.22 tumors that are resistant to bromocriptine.23 Medical therapy can also be effective in Surgery is indicated in patients who cannot restoring fertility in the patient with galactor- tolerate medications, have tumors that are rhea, regardless of the prolactin levels. A pro- resistant to medication or experience rapid lactin level should be obtained every three to visual loss that does not respond to medical six months, and further studies should be therapy.25 Unfortunately, long-term surgical performed if the level continues to rise. cure rates for prolactinomas are poor (50 to 60 percent for microadenomas and 25 per- PROLACTINOMA cent for macroadenomas).24 The treatment of a prolactinoma depends Radiation therapy is an option in the patient on its size and the presence or absence of who cannot tolerate medications and is not a symptoms indicative of increased intracranial surgical candidate. Irradiation is sometimes pressure or destruction of nearby structures. used as an adjunct to surgical treatment. If the patient has a macroadenoma or symp- toms such as headache or changes in vision, PITUITARY ADENOMAS AND PREGNANCY medical or surgical treatment is indicated. If Close observation is required for pregnant the patient has no symptoms of an intracra- women with prolactinomas. From 1 to 5 per- nial mass and the tumor is less than 1 cm in cent of microadenomas and 23 percent of size (microadenoma), treatment options macroadenomas increase in size during preg-

MAY 1, 2001 / VOLUME 63, NUMBER 9 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1769 Galactorrhea

nancy.26 The pregnant patient with a prolacti- 10. Kleinberg DL, Noel GL, Frantz AG. Galactorrhea: a study of 235 cases, including 48 with pituitary noma should be referred to a specialist in pitu- tumors. N Engl J Med 1977;296:589-99. itary disorders, as management is controversial. 11. Madlon-Kay DJ. ‘Witch’s milk.’ Galactorrhea in the Because of its more extensive safety record, newborn. Am J Dis Child 1986;140:252-3. 12. Egberts AC, Meyboom RH, De Koning FH, Bakker A, bromocriptine is the drug of choice in women Leufkens HG. Non-puerperal lactation associated with pituitary adenomas who wish to con- with antidepressant drug use. Br J Clin Pharmacol ceive. Although no adverse fetal effects have 1997;44:277-81. 13. Dunn NR, Freemantle SN, Pearce GL, Mann RD. been reported, the drug should be discontin- Galactorrhoea with moclobemide [Letter]. Lancet ued once pregnancy is suspected, unless there 1998;351:802. is evidence of a very large adenoma or an 14. Physicians’ desk reference: companion guide. Mont- vale, N.J.: Medical Economics, 2000:1293,1315, enlarging adenoma. Prepregnancy surgical 1337. debulking of a large macroadenoma, followed 15. Lee ST. Hyperprolactinemia, galactorrhea, and by bromocriptine therapy, is another treat- atenolol [Letter]. Ann Intern Med 1992;116:522. 16. Guven K, Kelestimur F. Hyperprolactinemia and ment option. galactorrhea with standard-dose famotidine therapy [Letter]. Ann Pharmacother 1995;29:788. REFERENCES 17. Windgassen K, Wesselmann U, Schulze Mönking H. Galactorrhea and hyperprolactinemia in schizo- 1. Buckman M, Peake G. Untitled response to: Kem- phrenic patients on neuroleptics: frequency and eti- mann E. Incidence of galactorrhea [Letter]. JAMA ology. Neuropsychobiology 1996;33:142-6. 1976;236:2747. 18. Stuart M, ed. The Encyclopedia of herbs and herbal- 2. Edge DS, Segatore M. Assessment and manage- ism. New York: Grosset & Dunlap, 1979:176,191, ment of galactorrhea. Nurse Pract 1993;18:35-6, 239,276-7. 38,43-4, passim. 19. Fetrow CW, Avila JR. Professional’s handbook of 3. Katznelson L, Klibanski A. Hyperprolactinemia: phys- complementary & alternative medicines. Spring- iology and clinical approach. In: Krisht AF, Tindall GT, house, Pa.: Springhouse, 1999:82-3,248-9. eds. Pituitary disorders: comprehensive manage- 20. Rothenberg RE, LaRaja RD, Pryce E, Mueller SC. ment. Baltimore: Lippincott Williams & Wilkins, Breast cancer and idiopathic galactorrhea. J Med 1999:189-98. Assoc Ga 1990;79:363-5. 4. Yazigi RA, Quintero CH, Salameh WA. Prolactin dis- 21. Davajan V, Kletzky O, March CM, Roy S, Mishell DR. orders. Fertil Steril 1997;67:215-25. The significance of galactorrhea in patients with 5. Yarkony GM, Novick AK, Roth EJ, Kirschner KL, normal menses, oligomenorrhea, and secondary Rayner S, Betts HB. Galactorrhea: a complication of amenorrhea. Am J Obstet Gynecol 1978;130:894- spinal cord injury. Arch Phys Med Rehabil 1992; 904. 73:878-80. 22. Sanfilippo JS. Implications of not treating hyper- 6. Faubion WA, Nader S. Spinal cord surgery and prolactinemia. J Reprod Med 1999;449(12 suppl): galactorrhea: a case report. Am J Obstet Gynecol 1111-5. 1997;177:465-6. 23. Verhelst J, Abs R, Maiter D, Van den Bruel A, Van- 7. Katsuren E, Ishikawa S, Honda K, Saito T. Galactor- deweghe M, Velkeniers B, et al. Cabergoline in the rhoea and amenorrhoea due to an intradural neuri- treatment of hyperprolactinemia: a study in 455 noma originating from a thoracic intercostal nerve patients. J Clin Endocrinol Metab 1999;84:2518-22. radicle. Clin Endocrinol [Oxf] 1997;46:631-6. 24. Molitch ME. Medical treatment of prolactinomas. 8. Turton DB, Shakir KM. Galactorrhea caused by Endocrinol Metab Clin North Am 1999;28:143-69,vii. esophagitis. Am J Obstet Gynecol 1995;173:1629-30. 25. Biller BM. Hyperprolactinemia. Int J Fertil Womens 9. Tolis G, Somma M, Van Campenhout J, Friesen H. Med 1999;44:74-7. Prolactin secretion in sixty-five patients with galac- 26. Molitch ME. Management of prolactinomas during torrhea. Am J Obstet Gynecol 1974;118:91-101. pregnancy. J Reprod Med 1999;44:1121-6.

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