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1 June 1999 | Volume 130 Issue 11 | Pages 897-904
Background: Hormone replacement therapy (HRT), the mainstay of osteoporosis prevention, is limited because of dose-related risks, side effects, and patient acceptance. The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women.
Objective: To determine the bone-sparing effect of continuous low-dose HRT in elderly women.
Design: Randomized, double-blind, placebo-controlled trial.
Setting: University osteoporosis research and clinical center.
Patients: 128 healthy white women (age > 65 years) with low bone mass recruited by word of mouth and by local advertisement. The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less.
Intervention: Continuous therapy with conjugated equine estrogen, 0.3 mg/d, and medroxyprogesterone, 2.5 mg/d, or matching placebo. Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups.
Measurements: Bone mineral density of the spine, hip, total body, and forearm; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals; and 24-hour urine creatinine and hydroxyproline excretion at baseline, 12 months, and 42 months.
Results: During 3.5 years of observation, spinal bone mineral density increased by 3.5% (P < 0.001) in an intention-to-treat analysis and by 5.2% among patients with greater than 90% adherence to therapy. Significant increases were seen in total-body and forearm bone density (P < 0.01). Symptoms related to HRT (breast tenderness, spotting, pelvic discomfort, and mood changes) were mild and short-lived.
Conclusions: Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other, higher-dose HRT regimens in elderly women. This combination is well tolerated by most patients.
Author and Article Information
From Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska.
Grant Support: By National Institutes of Health grant AR-39221.
Acknowledgments: The following medications and matching placebos were supplied at no cost: Premarin (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania), Provera (Pharmacia & Upjohn Company, Kalamazoo, Michigan), Calderol (Organon, Inc., West Orange, New Jersey), and Tums-EX (SmithKline Beecham Consumer Healthcare, L.P., Pittsburgh, Pennsylvania).
Requests for Reprints: Robert R. Recker, MD, Osteoporosis Research Center, Creighton University, 601 North 30th Street #5766, Omaha, NE 68131.
Current Author Addresses: Drs. Recker, Davies, Dowd, and Heaney: Osteoporosis Research Center, Creighton University, 601 North 30th Street #5766, Omaha, NE 68131. ARTICLE
The Effect of Low-Dose Continuous Estrogen and Progesterone Therapy with Calcium and Vitamin D on Bone in Elderly Women
A Randomized, Controlled Trial
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