Effect of gonadotropin-releasing hormone agonist and medroxyprogesterone acetate on calcium metabolism: A prospective, randomized, double-blind, placebo-controlled, crossover trial

Objective: The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/d) in either the first (protocol A) or last (protocol B) 12-week period as well as a 6-month course of the GnRH agonist (GnRH-a; leuprolide acetate; 1 mg/d, SC) on calcium (Ca) metabolism. Design: Prospective, randomized, double-blind, placebo-controlled, crossover trial. Setting: Clinical research center, university hospital. Patient(s): Twenty women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, and were then crossed over at 12 weeks to placebo or MPA, for the final 12-week interval of GnRH-a therapy. Intervention(s): Collection of serum and urine samples and measurement of bone density. Main Outcome Measure(s): Sex hormone, calcitropic hormone, and bone density studies were performed at baseline and at 12 and 24 weeks. Result(s): In both protocol A and B, LH and E₂ levels declined by 79%-81% and 83%-90% of the baseline, respectively, at 12 and 24 weeks. Serum Ca, phosphorus, alkaline phosphatase, and osteocalcin; 2-h fasting and 24-h urinary Ca excretion; and urinary hydroxyproline levels all increased significantly during GnRH-a treatment alone. Estimated Ca balance decreased significantly during GnRH-a treatment alone. The addition of MPA attenuated the increases in phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion, and the decrease in estimated Ca balance. Comparison of phase order demonstrated that MPA prevented 24-h urinary Ca excretion and urinary hydroxyproline loss and decline in estimated Ca balance when it was added back during the second 12 weeks (protocol B) but not during the first 12 weeks (protocol A). Conclusion(s): We conclude that sequential MPA appears to reverse in part the negative effects of GnRH-a on calcitropic hormones and estimated Ca balance.