{"paper_id":"6a0c736c-1600-4f81-ab1e-6a3f3f672a83","body_text":"Abstract\nTreatment with gonadotropin-releasing hormone (GnRH) agonist leads to enhanced bone turnover and accelerated bone loss in premenopausal women with endometriosis, uterine leiomyomatomas and hirsutism. Sodium etidronate is a powerful inhibitor of bone resorption which has been proven efficacious in the prevention and treatment of postmenopausal osteoporosis. The objective of this study was to evaluate the skeletal effects of 6 months of therapy with the depot preparation of the GnRH agonist triptorelin (decapeptil 3.75 mg intramuscularly every 4 weeks) in 24 hirsute patients, aged 24–33 years, with hyperandrogenic chronic anovulation. Ten patients also received cyclical etidronate in an oral dose of 400 mg/day for 2 weeks, followed by an 11-week period of 500 mg/day elemental oral calcium (one cycle). The remaining 14 patients received 500 mg/day of elemental calcium continuously. After 6 months all treatments were discontinued for at least a further 6 months. Bone mineral density (BMD) at lumbar spine and hip (dual-energy X-ray absorptiometry, Sophos LXRA, France) and biochemical markers (serum alkaline phosphatase, osteocalcin, urinary N-telopeptide and hydroxyproline/creatinine ratio) were evaluated at baseline, 6 months and 12 months. In the group given GnRH agonist alone BMD fell significantly at all measured skeletal sites during the first 6 months. In the patients treated with etidronate a significant decrease in BMD was observed at lumbar spine but not in the femoral neck and trochanter, and the changes at lumbar spine and trochanter were significantly smaller than those in the control group. At 6 months bone turnover was also increased in patients treated with GnRH and calcium. Cyclical etidronate prevented the increase in biochemical markers of bone formation and resorption, with the exception of calcium/creatinine excretion, which was significantly increased in both groups. Six months after treatment withdrawal BMD did not recover in either group. Biochemical markers (N-telopeptide, serum alkaline phosphatase) remained increased in those patients previously treated with calcium alone while they remained close to baseline values in the patients treated with cyclical etidronate.\nOur study indicates that: (1) GnRH agonist therapy causes remarkable bone loss in young individuals with androgen excess who are expected to have increased bone mass; (2) this bone loss can be partially prevented by intermittent cyclical etidronate therapy.\nSimilar content being viewed by others\nReferences\nJohnston CC Jr, Hui SL, Witt RM, Appledorn R, Baker RS, Longcope C. Early menopausal changes in bone mass and sex steroids. J Clin Endocrinol Metab 1985;61:905–11.\nChristiansen C, Christensen MS, Larsen NE, Transbol I. Pathophysiological mechanism of estrogen effect on bone metabolism: dose-response relationship in early postmenopausal women. J Clin Endocrinol Metab 1982;55:1124–30.\nRichelson LS Wahner HW, Melton LJ III, Riggs BL. Relative contributions of aging and estrogen deficiency to postmenopausal bone loss. N Engl J Med 1984;311:1273–5.\nScharla Sh, Minne HW, Waibel-Treber S, Schaible A, Lempert UG, Wuster C, et al. Bone mass reduction after estrogen deprivation by long-acting gonadotropin-releasing hormone agonists and its relation to pretreatment serum concentrations of 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab 1990;70:1055–61.\nJohansen JS, Riis BJ, Hassager C, Moen M, Jacobson J, Christiansen C. The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism. J Clin Endocrinol Metab 1988;67:701–6.\nGudmundsson JA, Ljunghall S, Bergquist C, Wide L, Nillius SJ. Increased bone turnover during gonadotrophin-releasing hormone superagonist-induced ovulation inhibition. J Clin Endocrinol Metab 1987;65:159–63.\nAzziz R, Ochoa TM, Bradley ELJ, Potter HD, Boots LR. Leuprolide and estrogen versus oral contraceptive pills for the treatment of hirsutism: a prospective randomized study. J Clin Endocrinol Metab 1995;80:3406–11.\nHeiner JS, Greendale GA, Kawakami AK, Lapolt PS, Fisher M, Young D, Judd HL. Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive given alone or together in the treatment of hirsutism. J Clin Endocrinol Metab 1995;80:3412–8.\nRittmaster RS. Gonadotropin-releasing hormone (GnRH) agonist and estrogen-progestin replacement for the treatment of hirsutism: evaluating the results. J Clin Endocrinol Metab 1995;80:3403–5.\nDi Carlo C, Shoham Z, MacDougall J, Patel A, Hall ML, Jacobs HS. Polycystic ovaries as a relative protective factor for bone mineral loss in young women with amenorrhea. Fertil Steril 1992;57:314–9.\nDixon JE, Rodin A, Murby B, Chapman MG, Fogelman I. Bone mass in hirsute women with androgen excess. Clin Endocrinol 1989;30:271–7.\nRiis BJ, Christiansen C, Johansen JS, Jacobson J. Is it possible to prevent bone loss in young women treated with luteinizing hormone-releasing hormone agonists? J Clin Endocrinol Metab 1990;70:920–4.\nMatta WH, Shaw RW, Hesp R, Evans R. Reversible trabecular bone density loss following induced hypo-estrogenism with the GnRH analogue buserelin in premenopausal women. Clin Endocrinol 1988;29:45–51.\nCompston JE, Yamaguchi K, Croucher PI, Garrahan NJ, Lindsay PC, Shaw RW. The effects of gonadotropin-releasing hormone agonists on iliac crest cancellous bone structure in women with endometriosis. Bone 1995;16:261–7.\nRoux C, Pelissier C, Listrat V, Kolta S, Simonetta C, Guignard M, Dougados M, Amor B. Bone loss during gonadotropin releasing hormone agonist treatment and use of nasal calcitonin. Osteoporos Int 1995;5:185–90.\nWimalawansa SJ. Combined therapy with estrogen and etidronate has an additive effect on bone mineral density in the hip and vertebrae: four-year randomized study. Ann Intern Med 1995;99:36–42.\nHarris ST, Watts NB, Jackson RD, Genant HK, Wasnich RD, Ross P, et al. Four year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy. Am J Med 1993;95:552–66.\nEhrmann DA, Barnes RB, Rosenfield RL. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr Rev 1995;16:322–53.\nMazzi G, Fioravanzo S, Scapini P. Acid hydrolysis internal standard chromatography by an ion exchange column instead of the classical apolar P-18 column. Giom It Chim Clin 1990;15:397–404.\nDevogelaer JP, Nagant de Deuxchaisnes C, Donnez J. Action of the luteinizing hormone releasing hormone agonists on bone mineral density. In: Brosens I, Donnez J, editors. The current status of endometriosis: research and management. Proceedings of the 3rd world congress on endometriosis, Brussels, June 1992. New York: Parthenon Publishing, 1993:345–68.\nComite F, Delman M, Hutchinson-Williams K, DeCherney AH, Jensen P. Reducedbone mass in reproductive-aged women with endometriosis. J Clin Endocrinol Metab 1989;69:837–42.\nHeaney RP. The bone-remodeling transient: implications for the interpretation of clinical studies of bone mass change. J Bone Miner Res 1949;9:1515–23.\nLeather AT, Studd JWW, Watson NR, Holland EFN. The prevention of bone loss in young women treated with GnRH analogues with “add-back” estrogen therapy. Obstet Gynecol 1993;81:104–7.\nFinkelstein JS, Klibanski A, Schaefer EH, Hornstein MD, Schiff I, Neer R. Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency. N Engl J Med 1994;331:1618–23.\nAuthor information\nAuthors and Affiliations\nRights and permissions\nAbout this article\nCite this article\nZamberlan, N., Castello, R., Gatti, D. et al. Intermittent etidronate partially prevents bone loss in hirsute hyperandrogenic women treated with GnRH agonist. Osteoporosis Int 7, 133–137 (1997). https://doi.org/10.1007/BF01623688\nReceived:\nAccepted:\nIssue date:\nDOI: https://doi.org/10.1007/BF01623688","source_license":"CC0","license_restricted":false}