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Treatment of Postmenopausal Osteoporosis with Transdermal Estrogen

Edward G. Lufkin, MD; Heinz W. Wahner, MD; William M. O'Fallon, PhD; Stephen F. Hodgson, MD; Mark A. Kotowicz, MBBS; Ann W. Lane, MPH; Howard L. Judd, MD; Robert H. Caplan, MD; and B. Lawrence Riggs, MD
[+] Article and Author Information

Requests for Reprints: Edward G. Lufkin, MD, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905.

Grant Support: By a grant from the Ciba-Geigy Corporation, Summit, New Jersey.

Current Author Addresses: Drs. Lufkin, Hodgson, and Riggs: Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN 55905. Dr. Wahner: Section of Diagnostic Nuclear Medicine, Mayo Clinic, Rochester, MN 55905.

Dr. O'Fallon and Ms. Lane: Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905.

Dr. Kotowicz: University Department of Medicine, Geelong Hospital, Geelong, 3220 Victoria, Australia.

Dr. Judd: Department of Obstetrics & Gynecology, Division of Reproductive Endocrinology, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, CA 90024.

Dr. Caplan: Endocrinology Section, Department of Internal Medicine, Gundersen Clinic, Ltd., La Crosse, WI 54601.


© 1992 American College of PhysiciansAmerican College of Physicians


Ann Intern Med. 1992;117(1):1-9. doi:10.7326/0003-4819-117-1-1
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Objective: To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures.

Design: Double-blind, randomized, placebo-controlled clinical trial lasting 1 year.

Setting: Referral-based outpatient clinic.

Patients: Seventy-five postmenopausal women, 47 to 75 years of age, with one or more vertebral fractures due to osteoporosis.

Interventions: Thirty-nine women received dermal patches delivering 0.1 mg of 17β-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle. Another 39 women received placebo.

Measurements: Bone turnover assessed by biochemical markers and iliac bone histomorphometry; bone loss assessed by serial measurement of bone density; and vertebral fracture rate.

Results: Compared with the placebo group, the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine (5.3 compared with 0.2; P = 0.007), femoral trochanter (7.6 compared with 2.1; P = 0.03), and midradius (1.0 compared with - 2.6, P < 0.001) but showed no significant difference at the femoral neck (2.6 compared with 1.4; P = 0.17). Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration (median change, - 0.35 compared with 0.02 nmol/L; P < 0.001). Histomorphometric evaluation of iliac biopsy samples confirmed the effect of estrogen on bone formation rate per bone volume (median change, - 12.9 compared with - 6.2% per year; P = 0.004). Also, 8 new fractures occurred in 7 women in the estrogen group, whereas 20 occurred in 12 women in the placebo group, yielding a lower vertebral fracture rate in the estrogen group (relative risk, 0.39; 95% Cl, 0.16 to 0.95).

Conclusions: Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis.

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