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Low-dose estrogen therapy for prevention of osteoporosis: working our way back to monotherapy

Richman, Susan MD; Edusa, Valentine MD; Fadiel, Ahmed PhD; Naftolin, Frederick MD, DPhil

doi: 10.1097/01.gme.0000191205.20738.01
Personal Perspective

The risks of low bone mineral density, osteoporosis and fractures, are major concerns in postmenopausal women. Although postmenopausal hormone therapy is effective for reducing these risks, safety issues have been raised by the results of studies such as the Women's Health Initiative. Although there are scientifically valid reasons to be wary of the general applicability of the Women's Health Initiative findings, the study has underscored the continuing need for research into new forms of menopausal hormone therapy. Low-dose transdermal estrogen monotherapy can preserve bone density while relieving vasomotor symptoms. Transdermal administration may offer advantages, including lack of first-pass liver metabolism, which permits the use of lower doses and avoids a negative impact on the lipid profile. Moreover, a recently published 2-year study of ultra-low-dose transdermal estrogen monotherapy in an older population similar to that of the WHI reported significant increases in bone mineral density, accompanied by significant reductions in markers of bone turnover, with no increased risk of endometrial hyperplasia or other side effects. Additional studies are warranted to shed further light on the possible benefits of low-dose estrogen monotherapy for the prevention of bone loss in postmenopausal women.

The rationale for returning to progestin-free hormone treatment for menopause is becoming increasingly clear. Recent trials of low and ultra-low estrogen monotherapy regimens are promising in this regard.

From the Department of Obstetrics, Gynecology and Reproductive Sciences and Center for Research in Reproductive Biology, Yale University, New Haven, CT.

Received November 17, 2004; revised and accepted May 12, 2005.

Address correspondence to: Frederick Naftolin, MD, DPhil, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, P. O. Box 208063, New Haven, CT 06520-8063. E-mail:

©2006The North American Menopause Society