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.


METHODS
Prospective, randomized, double-blind, placebo-controlled, crossover trial.


METHODS
Clinical research center, university hospital.


METHODS
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.


METHODS
Collection of serum and urine samples and measurement of bone density. Sex hormone, calcitropic hormone, and bone density studies were performed at baseline and at 12 and 24 weeks.


RESULTS
In both protocol A and B, LH and E(2) 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.
Carr
Bruce R
BR
Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA. bruce.carr@utsouthwestern.edu
Breslau
Neil A
NA
Peng
Noel
N
Adams-Huet
Beverley
B
Bradshaw
Karen D
KD
Steinkampf
Michael P
MP
D000328:Adult; D015519:Bone Density; D002118:Calcium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006706:Homeostasis; D006801:Humans; D018231:Leiomyomatosis / Q000188:drug therapy / Q000378:metabolism*; D016729:Leuprolide / Q000627:therapeutic use*; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D010919:Placebos; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D010919:Placebos; D007987:Gonadotropin-Releasing Hormone; D017258:Medroxyprogesterone Acetate; D016729:Leuprolide; D002118:Calcium