Estrogen deficiency results in bone mass reduction of largely varying extent in postmenopausal females, indicating that additional mechanisms influence the response of bone. They are by no ways identified in either the animal experiment or under clinical conditions. In search for factors, conditioning the response of bone to estrogen deficiency, we have conducted a study in females under treatment with the GnRH agonist decapeptyl (D-Trp6-LHRH). This drug blocks ovarian function and was administered for treatment of endometriosis or uterine leiomyoma. We determined spinal (dual photon absorptiometry) and forearm (single photon absorptiometry) bone mineral density before and 3 and 6 months after the onset of therapy and measured biochemical parameters of bone metabolism. Our results showed an increase in bone turnover after initiation of estrogen deficiency, as indicated by the elevation of alkaline phosphatase and osteocalcin. This resulted in a secondary decrease in serum intact PTH and 1,25-dihydroxy-vitamin D3. Furthermore, we found a positive correlation between pretreatment values of serum 1,25-dihydroxyvitamin D3 as well as its decrease and the reduction in bone mass during GnRH agonist treatment. This demonstrates that the patients' metabolic conditions predict their response to estrogen deficiency.