The present study was designed for exploration of hormonal disturbances underlying common forms of
amenorrhea.
Polycystic ovary syndrome (PCO) patients and obese amenorrheic subjects had significantly elevated
estrone (E1) levels, elevated
luteinizing hormone/
follicle-stimulating hormone ratios, and an exaggerated
luteinizing hormone response to
luteinizing hormone-releasing hormone. However,
androstenedione (delta 4A), the precursor of E1, was elevated only in PCO. Thus, the E1/delta 4A ratio, which provides an indirect index of
aromatase activity in extraglandular sites, was raised in obese subjects as a group but not in PCO subjects. These findings suggest that elevated E1 levels, which give rise to abnormal
gonadotropin secretion, arise from increased available
androgens in PCO but from an increased effect of
aromatase (present in adipose tissue) in obese subjects. Measurement of
androgens and the E1/delta 4A ratio provides insights into the relative contributions of hyperandrogenemia and enhanced
aromatase activity to the genesis of
amenorrhea in these groups. In patients with suppressed
estradiol levels associated with
hyperprolactinemia or
weight loss,
follicle-stimulating hormone levels were suppressed, while
luteinizing hormone was not elevated.
Prolactin excess explains these findings in
hyperprolactinemia. Plasma E1 levels and the E1/delta 4A ratio were suppressed in patients with
weight loss, possibly as a consequence of reduced adiposity. This finding suggests that hypothesis that a minimum level of E1, dependent upon adequate adiposity, is critical for the normal mature function of the hypothalamic-pituitary-ovarian axis. Abnormal E1/delta 4A ratios, high in
obesity-associated
amenorrhea and suppressed in
weight loss-associated
amenorrhea, may provide specific markers for these groups of patients.