Objective: Women undergo two phases of involutional bone loss that have opposing effects on parathyroid hormone (PTH) secretion. During the early phase, the loss of the direct restraining effect of estrogen on bone resorption causes an outflow of skeletal calcium into the extracellular fluid. This causes a compensatory decrease in PTH secretion. In the late phase, loss of extraskeletal effects of estrogen (on intestinal and renal calcium handling) leads to increases in whole body losses of calcium and a compensatory increase in PTH secretion. Moreover, long-term estrogen replacement therapy (ERT) suppresses both basal and stimulated PTH secretion in these women. Whereas the effects of estrogen on PTH secretion have been assumed to be due to its extraskeletal actions, estrogen may also have direct effects on the parathyroid glands. The goal of the present study was to test for these possible direct effects of estrogen on PTH secretion.
Design: Basal and ethylenediaminetetraacetic acid (EDTA)-stimulated PTH secretion was assessed in 10 elderly postmenopausal women (mean age, 76.4 years) before and after acute (3 days) estrogen replacement with transdermal estradiol, 0.1 mg/day. In addition, similar studies were performed in 10 age-matched women (mean age, 74.5 years) who had been on long-term ERT. These women were studied before and after 3 days of estrogen withdrawal.
Results: Estrogen treatment or withdrawal had no significant effect on either basal or stimulated PTH secretion.
Conclusions: These data provide evidence that, in elderly postmenopausal women, estrogen does not have significant direct effects on PTH secretion and point to the importance of the actions of estrogen on intestinal and renal calcium handling as the major mechanisms for its effects on modulating calcium homeostasis and, indirectly, PTH secretion.
From the 1Endocrine Research Unit, Division of Endocrinology, Metabolism, and Nutrition, Department of Internal Medicine, the 2Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN.
Received May 28, 2002; revised and accepted August 27, 2002.
This work was supported by grants AG-04875 (National Institute on Aging) and RR-00585 from the National Institutes of Health.
Address correspondence to Sundeep Khosla, MD, Mayo Clinic, 200 First Street SW, 5–194 Joseph, Rochester, MN 55905. E-mail: email@example.com.