EFFICACY OF ESTROGEN IN HYPERPROLACTINEMIC AMENORRHEA

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The medical and economic importance of estrogen replacement therapy in postmenopausal women is demonstrated by a decreased incidence of fractures and coronary heart disease. Postmenopausal women are not, however, the only individuals who may develop the consequences of estrogen deficiency. Over 1.5 million young women in the United States with secondary amenorrhea have estrogen levels comparable to those seen after the menopause and are at risk to develop premature osteoporosis and heart disease. Over one-third of these amenorrheic women have prolactin secreting pituitary tumors. Autonomous production of prolactin by the pituitary tumor leads to cessation of ovarian function, menopausal symptoms and loss of spinal bone mineral. When fertility is an issue short-term administration of a dopamine agonist is effective but the drug must be given chronically to maintain regular menses and physiologic estrogen levels. Chronic dopamine agonist therapy is expensive, poorly tolerated and the effects of long-term therapy are not known. Consequently, the majority of women with hyperprolactinemia do not receive therapy and remain amenorrheic. Unlike most amenorrheic women who are treated with estrogen, the standard of practice for patients with prolactin secreting pituitary tumors is to avoid estrogen containing compounds because of the potential for stimulating tumor growth. The concern about estrogen therapy in hyperprolactinemic women is based on estrogen induced tumor formation in animals and isolated case reports of estrogen associated tumor growth in men and women. We will use magnetic resonance imaging to ascertain whether chronic administration of estrogen to women with hyperprolactinemic amenorrhea will induce tumor formation or stimulate growth of a pre-existing microadenoma and dual energy x-ray absorptiometry to ascertain whether the osteopenia associated with hyperprolactinemic amenorrhea will improve or normalize with chronic estrogen administration. Reliable prospective information that exogenous estrogen is not associated with clinically significant tumor expansion would alter treatment recommendations for the over 500,000 women in the United States with hyperprolactinemic amenorrhea and could prevent progression of adverse effects on cardiovascular and skeletal function in young women.