Effects of Prolactin and Estrogen Deficiency in Amenorrheic Bone Loss*

Abstract

To determine whether hyperprolactinemic women with menses are at risk for the development of osteopenia and to define the effects of PRL excess and estrogen deficiency on bone mass in amenorrheic women, spinal and radial bone densities were measured in 25 hyperprolactinemic women (13 with amenorrhea and 12 with regular menstrual periods) and 11 women with hypothalamic amenorrhea. The degree of hyperprolactinemia was comparable in the hyperprolactinemic women with and without menstrual periods [mean, 55 ± 18 (±sd) and 57 ± 16 μg/L, respectively]. The mean spinal bone density in the hyperprolactinemic amenorrheic women (148 ± 26 mg/ K₂HPO₄·cm³) was significantly lower (P < 0.01) than that in 19 normal women (178 ± 21 mg/K₂HPO₄·cm³), and 6 of the former group had values greater than 2 sd below normal. However, the mean spinal bone density in the eumenorrheic hyperprolactinemic women (171 ± 22 mg/K₂HPO₄ · cm³) was similar to that in the normal women and was significantly greater (P < 0.05) than that in the hyperprolactinemic amenorrheic women. The mean spinal bone density in the women with hypothalamic amenorrhea (128 ± 24 mg/K₂HPO₄ · cm³) and normal PRL levels was also significantly (P < 0.001) lower than that in normal women or hyperprolactinemic euenorrheic women. Six of the women with hypothalamic amenorrhea had bone density measurements greater than 2 sd below normal. The spinal bone density values were similar in the amenorrheic women with or without hyperprolactinemia. The mean radial bone density in the hyperprolactinemic women with amenorrhea (0.69 ± 0.03 g/cm²) was comparable to that in the women with hypothalamic amenorrhea (0.69 ± 0.05 g/cm²), and both groups had significantly (P < 0.05) lower values than normal women (0.72 ± 0.03 g/cm²). Radial bone density was normal in the hyperprolactinemic eumenorrheic women. The mean serum estradiol level in the hyperprolactinemic amenorrheic women (120 ± 90 pmol/L) was significantly (P < 0.05) lower than that in the hyperprolactinemic eumenorrheic women measured during the follicular phase of their cycles (240 ± 180 pmol/L) and was comparable to that in the women with hypothalamic amenorrhea (80 ± 40 pmol/L). Multiple comparisons of clinical variables, serum hormone concentrations, and bone mass demonstrated a significant correlation (P = 0.0125) between bone density and serum dehydroepiandrosterone sulfate levels, which suggests a role for endogenous androgens in the maintenance of premenopausal bone mass. We also documented a profound reduction in bone mass in women with hypothalamic amenorrhea who have normal nutrition and activity levels. These data are consistent with the hypothesis that gonadal steroid insufficiency, rather than excess PRL, is a major factor in hyperprolactinemic osteopenia and indicate that hyperprolactinemia in eumenorrheic women does not lead to a reduction in bone mass.