NORETHINDRONE ACETATE ONLY PARTIALLY PROTECTS THE SKELETON OF RATS TREATED WITH THE LHRH AGONIST BUSERELIN FROM ESTROGEN-DEFICIENCY OSTEOPENIA

In women with endometriosis there is concern that therapeutic use of LH-releasing hormone (LHRH) analogues, to lower ovarian oestrogen production and control endometrial hyperplasia, leads to unwanted oestrogen-deficiency bone loss. We have developed an animal model of this LHRH-mediated oestrogen-deficiency bone loss in the rat, using buserelin. The aim was to use this model to determine whether the progestogen, norethindrone acetate, could counter oestrogen-deficiency bone loss associate with prolonged treatment with the LHRH agonist buserelin. Four groups of animals which had their bones labelled with Ca-45 were studied for 4 weeks: group A, control; group B, buserelin treated; group C, norethindrone acetate treated; group D, norethindrone acetate + buserelin treated. Buserelin was given daily (19.2 pmol/kg body wt); norethindrone was given orally three times/week (1-47 mumol/kg body wt). Bone resorption was monitored by measuring the urinary excretion of hydroxyproline and Ca-45 and bone Ca-45 content. Buserelin-treated rats developed similarly depressed plasma oestradiol-17beta values in the presence and absence of progestogen, and both groups given buserelin had significantly smaller uteri than controls or rats given norethindrone without buserelin. However, norethindrone did not prevent buserelin-mediated increases in bone resorption. At the end of the study total body calcium values (mean +/- S.D.) in the four groups were (mg) respectively; 2594 +/- 123; 2260 +/- 92 (P<0.001 compared with controls); 2616 +/- 221; 2415 +/- 130 (P<0.02 compared with controls). Rats given norethindrone and buserelin in combination had higher values (P<0.02) than animals given buserelin alone, but significantly less total body calcium than controls (P<0.02). We conclude that progestogen confers partial, but not complete, protection of the skeleton of buserelin-treated rats from oestrogen-deficiency bone loss.