How many women lose bone mineral density while taking hormone replacement therapy? Results from the Postmenopausal Estrogen/Progestin Interventions Trial.

BACKGROUND The frequency of bone loss among women using postmenopausal hormone therapy is unknown. METHODS We used data from the Postmenopausal Estrogen/Progestin Interventions Trial to address the frequency of bone loss among women using postmenopausal hormone replacement therapy. Of 701 women randomized to active treatment (conjugated equine estrogens alone or in combination with 1 of 3 progestins), 538 (76.7%) were adherent and had replicate bone mineral density (BMD) measures at baseline, 12 months, and 36 months. Of 174 placebo-assigned women, 132 (75.9%) were similarly eligible. Replicate BMD measures were used to calculate within-person measurement errors, which were then used to delineate cut points that defined bone losers with 97.5%, 95.0%, 90.0%, or 75.0% confidence. RESULTS At the lumbar spine, during the first 12 months, 1.5% of hormone users lost BMD with 97.5% confidence, corresponding to a decline of -3% per year; during months 12 to 36, only 0.6% of treated women lost spinal BMD to this degree. An annual loss of -1% or more was the criterion for spinal bone loss at the 75.0% confidence level; 5.1% and 8.0% of hormone users met this criterion in the first year and in months 12 to 36, respectively. For the total hip, during the first 12 months, 2.3% of hormone-adherent women lost -3.0% per year or more, the 97.5% confidence definition of loss; 0.4% were so classified during months 12 to 36. To be 75.0% confident of hip BMD loss, a -1.0% per year decline in BMD was required; using this criterion, 14.5% and 11.8% of hormone users lost total hip BMD between 0 to 12 and 12 to 36 months, respectively. Among hormone-adherent women, at the spine and hip, there was virtually no overlap between women classified as bone losers in the first 12 months and those classified as such in the last 24 months. With 95.0% certainty, corresponding to an approximate loss of -2.5% at the spine and hip, 31.3% and 11.7% of placebo-adherent women lost spinal BMD in the first 12 and last 24 months, respectively. Parallel figures for the hip were 32.3% and 7.9%, respectively. CONCLUSION Bone loss while taking postmenopausal hormones is rare, and bone loss among untreated women is far from universal.

[1]  Susan R. Johnson,et al.  Rationale, design, and conduct of the PEPI trial , 1995 .

[2]  S. Cummings,et al.  Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of Osteoporotic Fractures Research Group. , 1998, The New England journal of medicine.

[3]  D. Anderson,et al.  A simple method for the assay of eight steroids in small volumes of plasma , 1976, Steroids.

[4]  Susan R. Johnson,et al.  Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. , 1996, JAMA.

[5]  E. Barrett-Connor,et al.  Endogenous Sex Steroids and Bone Mineral Density in Older Women and Men: The Rancho Bernardo Study , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. , 1996, JAMA.

[7]  S. Ingles,et al.  Leisure, home, and occupational physical activity and cardiovascular risk factors in postmenopausal women. The Postmenopausal Estrogens/Progestins Intervention (PEPI) Study. , 1996, Archives of internal medicine.

[8]  J. Eisman,et al.  Sources of Variability in Bone Mineral Density Measurements: Implications for Study Design and Analysis of Bone Loss , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  Susan R. Johnson,et al.  Effects of Estrogen or Estrogen/ Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial , 1995 .

[10]  H. Genant,et al.  Low‐dosage micronized 17‐estradiol prevents bone loss in postmenopausal women , 1992 .

[11]  T. Bush,et al.  Rationale, design, and conduct of the PEPI Trial. Postmenopausal Estrogen/Progestin Interventions. , 1995, Controlled clinical trials.

[12]  E. Barrett-Connor,et al.  Lifestyle Factors and Bone Mineral Density: The Postmenopausal Estrogen/Progestins Intervention Study , 1995 .

[13]  S. Cummings,et al.  Hormonal Predictors of Bone Loss in Elderly Women: A Prospective Study , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  S. Cummings,et al.  Endogenous Hormones and the Risk of Hip and Vertebral Fractures Among Older Women , 1999 .

[15]  H. Genant,et al.  Low-dosage micronized 17ß-estradiol prevents bone loss inpostmenopausal women , 1992 .

[16]  R. Recker,et al.  Effect of Oral Alendronate on Bone Mineral Density and the Incidence of Fractures in Postmenopausal Osteoporosis , 1996 .

[17]  N W Shock,et al.  Longitudinal Studies on the Rate of Decline in Renal Function with Age , 1985, Journal of the American Geriatrics Society.

[18]  R. Lobo Absorption and metabolic effects of different types of estrogens and progestogens. , 1987, Obstetrics and gynecology clinics of North America.

[19]  R. Tremblay,et al.  Plasma concentrations of free and non-TeBG bound testosterone in women on oral contraceptives. , 1974, Contraception.

[20]  R. Recker,et al.  The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial. , 1999, Annals of internal medicine.

[21]  A. Hermann,et al.  Site of Osteodensitometry in Perimenopausal Women: Correlation and Limits of Agreement Between Anatomic Regions , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  H. Genant,et al.  Low-Dosage Micronized 17β-Estradiol Prevents Bone Loss in Postmenopausal Women , 1992 .

[23]  M. Quigley,et al.  Estrogen therapy arrests bone loss in elderly women. , 1987, American journal of obstetrics and gynecology.

[24]  C. Christiansen,et al.  Pathophysiological mechanisms of estrogen effect on bone metabolism. Dose-response relationships in early postmenopausal women. , 1982, The Journal of clinical endocrinology and metabolism.

[25]  S. Ingles,et al.  Leisure, home and occupational physical activity and cardiovascular risk factors in postmenopausal women: The Post-menopausal Estrogens/Progestins Intervention (PEPI) Study , 1996 .

[26]  C. Rosen,et al.  The pathophysiology and treatment of postmenopausal osteoporosis. An evidence-based approach to estrogen replacement therapy. , 1997, Endocrinology and metabolism clinics of North America.

[27]  R. Marcus,et al.  Correlates of bone mineral density in the postmenopausal estrogen/progestin interventions trial , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  S. Cummings,et al.  Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group. , 1999, Arthritis and rheumatism.