nafarelin and Osteoporosis

Topics: Buserelin; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Nafarelin; Osteoporosis

To determine if there is an age-related effect on bone mineral density (BMD) loss with GnRH agonist treatment of endometriosis and, in particular, whether the impact of this therapy in terms of BMD loss is different if it is used at an age prior to attainment of peak BMD than after attaining it.. Data from a randomized, double-placebo-controlled clinical trial comparing efficacy and safety of two GnRH agonists, without add-back, for the treatment of endometriosis, were analyzed.. No significant age-related effect was detected for either GnRH agonist on absolute BMD loss with a single, six-month course. However, in women at an age prior to peak BMD, prevention of the natural increase in BMD with these drugs may prevent women from attaining their peak BMD and thus increase their risk of osteoporosis in later life.. GnRH agonists should be used with caution and perhaps only with strategies designed to minimize the impact on BMD in women prior to attainment of peak BMD.

Topics: Absorptiometry, Photon; Adolescent; Adult; Age Factors; Aged; Bone Density; Double-Blind Method; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Nafarelin; Osteoporosis; Randomized Controlled Trials as Topic

To determine the reversibility of bone mineral density after the cessation of GnRH agonist treatment for endometriosis.. Longitudinal trial with 6-month treatment period and 6-month follow-up.. 28 Japanese premenopausal women with endometriosis.. Daily dose of 400 micrograms nafarelin was administered for 6 months.. The spine bone mineral density was measured by dual energy X-ray absorptiometry, and blood and urinary bone metabolic parameters were analyzed. The decrease of lumbar bone mineral density, which took place during treatment, continued during the first 3 months after the cessation of treatment and did not return to the initial baseline level even at 6 months after the withdrawal of treatment. The biochemical parameters, which showed a state of enhanced bone turnover during nafarelin treatment, almost returned to the pretreatment level 6 months after the termination of treatment.. These results indicate that relatively long period of bone metabolic change might be required to alter the actual bone mineral density after GnRH analog administration.

Topics: Administration, Intranasal; Adult; Alkaline Phosphatase; Bone Density; Calcium; Creatinine; Dose-Response Relationship, Drug; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Longitudinal Studies; Nafarelin; Osteocalcin; Osteoporosis; Premenopause; Time Factors

Analogues of gonadotropin-releasing hormone (GnRH) are often given to induce hypogonadism in women who have estrogen-dependent disorders such as endometriosis and uterine leiomyomas. Because estrogen deficiency causes bone loss, concern about premature osteoporosis has prevented long-term therapy with GnRH analogues. We conducted a study to determine whether parathyroid hormone could prevent bone loss in women receiving therapy with GnRH analogues.. We administered human parathyroid hormone (40 micrograms subcutaneously daily) to 20 of 40 women with endometriosis who were being treated with nafarelin (200 micrograms intranasally twice daily) for six months; the remaining 20 women received only nafarelin. Cortical and trabecular bone density and biochemical markers of bone turnover were measured every three months during the six-month study period.. Serum estradiol concentrations fell to postmenopausal values in 36 of the 40 women. In the women who received nafarelin alone, the mean (+/- SE) bone density in the lumbar spine decreased by 2.8 +/- 0.5 percent (P < 0.001) when measured in the anteroposterior projection and by 3.5 +/- 0.8 percent (P < 0.001) when measured in the lateral projection. In contrast, bone density in the lumbar spine did not change when measured in the anteroposterior projection and increased by 3.4 +/- 1.2 percent when measured in the lateral projection (P = 0.01) in the women who also received parathyroid hormone. Bone density at the femoral neck decreased slightly and similarly in both groups. Radial bone density did not change in either group. Serum alkaline phosphatase and osteocalcin concentrations and urinary hydroxyproline and pyridinoline excretion increased (P < 0.001) in the women who received nafarelin plus parathyroid hormone.. Parathyroid hormone can prevent bone loss in the lumbar spine in young women with estrogen deficiency caused by treatment with GnRH analogues.

Topics: Adult; Bone and Bones; Bone Density; Endometriosis; Estrogens; Female; Humans; Injections, Subcutaneous; Nafarelin; Osteoporosis; Parathyroid Hormone

Recent studies have shown that treatment with the LHRH agonist nafarelin gives symptomatic and objective relief to women with endometriosis. Such a treatment, however, results in increased bone turnover and loss of bone mass. In the present study 17 women with endometriosis were treated with 400 mg nafarelin combined with 1.2 mg norethisterone (NET) for 6 months, followed by 6 months with only 1.2 mg NET. The data were compared to data from a previously published study of 9 women treated for 6 months with 400 mg nafarelin alone, followed by 6 months without treatment. In the group treated with nafarelin plus NET the biochemical parameter of bone resorption (fasting urinary hydroxyproline) remained virtually unchanged, compared to a highly significant increase in the nafarelin-treated group. Estimates of bone formation (serum alkaline phosphatase and plasma bone Gla protein) increased in the nafarelin plus NET group, but to only a minor extent compared to those in the nafarelin group. In addition, bone mineral in the forearm, the spine, and the total skeleton remained virtually unchanged in the group treated with nafarelin plus NET, compared to the bone loss of 2-6%/6 months in the nafarelin group. We conclude that addition of NET to nafarelin treatment of endometriosis seems to have a bone-sparing effect.

Topics: Adult; Bone and Bones; Bone Density; Calcium; Drug Therapy, Combination; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Lipid Metabolism; Lipoproteins; Nafarelin; Norethindrone; Osteoporosis