Preventive effects of clomiphene citrate on estrogen-deficiency osteopenia elicited by LHRH agonist administration in the rat.
The estrogen agonist and antagonist clomiphene citrate has been shown to prevent bone loss induced by ovariectomy in the rat. In young women estrogen-deficiency bone loss is a clinical problem associated with the use of luteinizing hormone releasing hormone (LHRH) agonists, such as buserelin, to treat endometriosis. The aim of this study was to determine whether clomiphene citrate (10 mg/kg body weight per week orally) would prevent the osteopenic effect of buserelin (25 micrograms/kg body weight per day SC) in the rat. Four groups of animals with 45Ca-labeled skeletons were studied for 4 weeks: group A, placebo controls; group B, buserelin; group C, clomiphene; and group D, buserelin + clomiphene. Bone resorption was monitored by measuring the urinary excretion of 45Ca and hydroxyproline. Clomiphene slowed bone breakdown and inhibited the osteopenic effect of buserelin. Total-body calcium values (mean +/- SD) were (mg) 2635 +/- 181, 2267 +/- 85, 2566 +/- 126, and 2624 +/- 77 in groups A to D, respectively. Osteopenia was present only in group B (P less than 0.001). Interestingly buserelin lowered blood 17 beta-estradiol and uterine weights to a similar extent in the presence and absence of clomiphene. Because clomiphene inhibited estrogen-deficiency bone loss in buserelin-treated rats without depressing the hypoestrogenic action of this LHRH agonist, it is suggested that the use of clomiphene to protect the skeleton during LHRH agonist therapy of endometriosis warrants further study.
Goulding
A
A
Department of Medicine, University of Otago, Dunedin, New Zealand.
Fisher
L
L
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D001862:Bone Resorption / Q000150:complications / Q000188:drug therapy*; D002064:Buserelin / Q000494:pharmacology*; D002118:Calcium / Q000652:urine; D002996:Clomiphene / Q000494:pharmacology*; D004715:Endometriosis / Q000188:drug therapy; D004967:Estrogens / Q000097:blood / Q000172:deficiency*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006909:Hydroxyproline / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects
D004967:Estrogens; D002996:Clomiphene; D007987:Gonadotropin-Releasing Hormone; D002064:Buserelin; D006909:Hydroxyproline; D002118:Calcium