Increased Bone Turnover During Gonadotropin-Releasing Hormone Superagonist-Induced Ovulation Inhibition*

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Abstract
Superactive stimulatory analogs of GnRH inhibit ovulation in women. This investigation was done to assess bone turnover during GnRH agonist-induced anovulation. Particular interest was directed to the effects of smoking, since smokers have an increased risk of osteoporosis. Fasting serum calcium, phosphate, PTH, and bone Gla-protein (osteocalcin) levels, as well as urinary calcium, cAMP, and hydroxyproline excretion and the renal tubular threshold for phosphate were determined before and after 6 months of GnRH superagonist contraceptive treatment in 47 women, 22 of whom smoked more than 10 cigarettes daily. Before treatment the women who smoked had significantly higher serum phosphate concentrations and lower serum PTH concentrations than the women who did not smoke. Fasting serum calcium and the urinary calcium to creatinine ratio increased after treatment in all women, especially in the nonsmokers. The nonsmokers also had more pronounced increases in serum phosphate and osteocalcin concentrations. A decrease in serum PTH during treatment was confined to the nonsmokers. These results suggest increased bone resorption and turnover during GnRH agonist-induced anovulation and indicate that smoking habits should be taken into account in the evaluation of bone disease.