Journal of Clinical Endocrinology & Metabolism, Vol 71, 836-841, Copyright © 1990 by Endocrine Society

ARTICLES

17 Beta-estradiol and continuous norethisterone: a unique treatment for established osteoporosis in elderly women

C Christiansen and BJ Riis
Department of Clinical Chemistry, Glostrup Hospital, University of Copenhagen, Denmark.

Forty women aged 64.7 +/- 5.1 yr with established postmenopausal osteoporosis were blindly allocated to 1 yr's treatment with either continuous combined estrogen/progestogen therapy (2 mg estradiol + 1 mg norethisterone acetate + 500 mg calcium daily) or placebo + 500 mg calcium daily. In the group treated with hormones bone mineral density in the spine (dual photon absorptiometry) and bone mineral content in the ultradistal forearm (single photon absorptiometry) increased highly significantly by 8-10% during the 1 yr of treatment. Bone mineral content in the mid-shaft of the forearm (single photon absorptiometry) and the total body bone mineral (dual photon absorptiometry) increased by 3-5% when compared to that in the placebo group, which showed virtually unchanged values at all measurement sites. Seven of the women treated with hormones were examined after a further year of treatment. BMC increased by another 3-6%, reaching a 12% increase in bone mineral density in the spine after 2 yr of treatment. Biochemical estimates of bone resorption (fasting urinary calcium and hydroxyproline) and bone formation (serum alkaline phosphatase and plasma osteocalcin), decreased significantly (P less than 0.001) in the group treated with hormones, but remained unchanged in the placebo group. The reduction in indices of bone resorption was more pronounced than that in bone formation after one year, indicating a positive bone balance. No further changes were seen in these bone turnover parameters during the second year of treatment. In the group treated with hormones, serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol decreased by about 12% (P less than 0.05-P less than 0.01), whereas high density lipoprotein cholesterol decreased by about 8% (P less than 0.001). The high density lipoprotein cholesterol/low density lipoprotein cholesterol ratio was unchanged. The hormone treatment did not produce any major side effects, and only minor bleedings were experienced by a few women. The present study demonstrates that treatment with female sex hormones in this particular combination is a realistic approach to the treatment of women with established postmenopausal osteoporosis.

This article has been cited by other articles:

				J. Enriquez, A. E. Lemus, J. Chimal-Monroy, H. Arzate, G. A Garcia, B. Herrero, F. Larrea, and G. Perez-Palacios The effects of synthetic 19-norprogestins on osteoblastic cell function are mediated by their non-phenolic reduced metabolites J. Endocrinol., June 1, 2007; 193(3): 493 - 504. [Abstract] [Full Text] [PDF]

				P. Collins, M. Flather, B. Lees, R. Mister, A. J. Proudler, J. C. Stevenson, and on behalf of the WHISP (Women's Hormone Interventi Randomized trial of effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP Pilot Study Eur. Heart J., September 1, 2006; 27(17): 2046 - 2053. [Abstract] [Full Text] [PDF]

				S. Evio, A. Tiitinen, K. Laitinen, O. Ylikorkala, and M. J. Valimaki Effects of Alendronate and Hormone Replacement Therapy, Alone and in Combination, on Bone Mass and Markers of Bone Turnover in Elderly Women with Osteoporosis J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 626 - 631. [Abstract] [Full Text] [PDF]

				G. Wells, P. Tugwell, B. Shea, G. Guyatt, J. Peterson, N. Zytaruk, V. Robinson, D. Henry, D. O'Connell, and A. Cranney V. Meta-Analysis of the Efficacy of Hormone Replacement Therapy in Treating and Preventing Osteoporosis in Postmenopausal Women Endocr. Rev., August 1, 2002; 23(4): 529 - 539. [Full Text] [PDF]

				D. T. Villareal, E. F. Binder, D. B. Williams, K. B. Schechtman, K. E. Yarasheski, and W. M. Kohrt Bone Mineral Density Response to Estrogen Replacement in Frail Elderly Women: A Randomized Controlled Trial JAMA, August 15, 2001; 286(7): 815 - 820. [Abstract] [Full Text] [PDF]

				P. Alexandersen, B. J. Riis, J. A. Stakkestad, P. D. Delmas, and C. Christiansen Efficacy of Levormeloxifene in the Prevention of Postmenopausal Bone Loss and on the Lipid Profile Compared to Low Dose Hormone Replacement Therapy J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 755 - 760. [Abstract] [Full Text]

				R. Marcus, D. Leary, D. L. Schneider, E. Shane, M. Favus, and C. A. Quigley The Contribution of Testosterone to Skeletal Development and Maintenance: Lessons from the Androgen Insensitivity Syndrome J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1032 - 1037. [Abstract] [Full Text]

				P. Ravn, M. Bidstrup, R. D. Wasnich, J. W. Davis, M. R. McClung, A. Balske, C. Coupland, O. Sahota, A. Kaur, M. Daley, et al. Alendronate and Estrogen-Progestin in the Long-Term Prevention of Bone Loss: Four-Year Results from the Early Postmenopausal Intervention Cohort Study: A Randomized, Controlled Trial Ann Intern Med, December 21, 1999; 131(12): 935 - 942. [Abstract] [Full Text] [PDF]

				P. Alexandersen, B. J. Riis, and C. Christiansen Monofluorophosphate Combined with Hormone Replacement Therapy Induces a Synergistic Effect on Bone Mass by Dissociating Bone Formation and Resorption in Postmenopausal Women: A Randomized Study J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3013 - 3020. [Abstract] [Full Text]

				P. Vestergaard, A. P. Hermann, H. Ørskov, and L. Mosekilde Effect of Sex Hormone Replacement on the Insulin-Like Growth Factor System and Bone Mineral: A Cross-Sectional and Longitudinal Study in 595 Perimenopausal Women Participating in the Danish Osteoporosis Prevention Study J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2286 - 2290. [Abstract] [Full Text]

				S. L. Greenspan A 73-Year-Old Woman With Osteoporosis JAMA, April 28, 1999; 281(16): 1531 - 1540. [Full Text] [PDF]

				B. E. C. NORDIN, A. G. NEED, T. STEURER, H. A. MORRIS, B. E. CHATTERTON, and M. HOROWITZ Nutrition, Osteoporosis, and Aging Ann. N.Y. Acad. Sci., November 20, 1998; 854(1): 336 - 351. [Abstract] [Full Text] [PDF]

				P. Alexandersen, J. Haarbo, I. Sandholdt, M. Shalmi, H. Lawaetz, and C. Christiansen Norethindrone Acetate Enhances the Antiatherogenic Effect of 17ß-Estradiol : A Secondary Prevention Study of Aortic Atherosclerosis in Ovariectomized Cholesterol-Fed Rabbits Arterioscler. Thromb. Vasc. Biol., June 1, 1998; 18(6): 902 - 907. [Abstract] [Full Text] [PDF]

				B. Ettinger and D. Grady The Waning Effect of Postmenopausal Estrogen Therapy on Osteoporosis N. Engl. J. Med., October 14, 1993; 329(16): 1192 - 1193. [Full Text]