Altered androstenedione and estrone dynamics associated with abnormal hormonal profiles in amenorrheic subjects with weight loss or obesity

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 (Δ⁴A), the precursor of E₁, was elevated only in PCO. Thus, the E₁/Δ⁴A 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/Δ⁴A 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/Δ⁴A ratio were suppressed in patients with weight loss, possibly as a consequence of reduced adiposity. This finding suggests the 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/Δ⁴A ratios, high in obesity-associated amenorrhea and suppressed in weight loss-associated amenorrhea, may provide specific markers for these groups of patients.