Amenorrhea during the reproductive years--is it safe?

OBJECTIVE: To collate information relating specifically to amenorrhea of different etiologies in young women, the long- and short-term implications of these states, and the optimal therapeutic strategy to treat these conditions. DATA IDENTIFICATION: Studies related to these topics were identified through literature and Medline searches. STUDY SELECTION: Those studies that relate specifically to amenorrhea in women of reproductive age, including etiology, diagnosis, and the implications of replacement therapy or nontreatment of this state, were selected.
RESULTS: Amenorrhea, as defined by the absence of menses for > or = 6 months, may be found in up to 3% of women in the reproductive years. Classification of amenorrhea involves defining the exact cause for the cessation of menses, be it hypothalamic, pituitary, ovarian, or lower genital tract in origin. The majority of amenorrheic young women have very low levels of estrogens, and a minority will have subnormal noncyclic estrogen levels, unopposed by P, due to anovulation. This distinction is important in considering the long-term implications of amenorrhea. Hypoestrogenic amenorrhea is associated with a significant loss of bone mineral density and the associated risk of osteoporosis and fractures. Lipoprotein profiles are also adversely affected, and this is associated with an increased risk of cardiovascular events. Anovulatory amenorrhea due to "unopposed" estrogen is associated with an increased risk of endometrial hyperplasia and endometrial carcinoma even in young patients. Therapy should be aimed at treating the underlying cause of amenorrhea, if possible, or reconstitution of an estrogen-P biphasic monthly cycle if not.
CONCLUSIONS: Untreated amenorrhea is associated with significant long-term morbidity, especially in young women. Early recognition and institution of treatment will minimize late complications.