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Transdermal Versus Oral Estrogen Therapy in Postmenopausal Smokers: Hemodynamic and Endothelial Effects

From the Departments of Psychiatry, Cardiology, and Obstetrics and Gynecology, University of North Carolina at Chapel Hill, North Carolina; and the Department of Psychiatry, Duke University Medical Center, Durham, North Carolina.

Address reprint requests to: Susan S. Girdler, PhD, University of North Carolina at Chapel Hill, CB #7175, Medical Research Bldg A, Chapel Hill, NC 27599–7175; e-mail: susan_girdler{at}med.unc.edu.

OBJECTIVE: To test the hypothesis that, in postmenopausal smokers, transdermal estrogen would be more effective than oral estrogen in reducing blood pressure (BP) and vascular and norepinephrine responses to stress and in increasing endothelial function and vascular ß₂-adreno-ceptor responsivity.

METHODS: By using a randomized, double-blind, placebo-controlled design, 82 healthy postmenopausal smokers were tested before and after 6 months of therapy with transdermal estrogen (0.05 mg/d) plus a progestin (2.5 mg/d; n = 31), oral conjugated equine estrogen (0.625 mg/d) plus a progestin (2.5 mg/d; n = 30), or placebo (n = 21). Dependent measures included resting and stress-induced increases in BP, total peripheral resistance, and plasma norepinephrine, as well as endothelial function and ß-adrenoceptor responsivity.

RESULTS: When compared with placebo, the transdermal estrogen group showed more consistent reductions in total peripheral resistance at rest and in response to mental stress than the oral estrogen group. Only the transdermal group showed treatment-related reductions in behavioral stress norepinephrine, baseline rest, and behavioral stress BP levels, and increases in vascular ß₂-adrenoceptor responsivity and endothelium-dependent vasodilation. Posttreatment concentrations of serum estradiol and estrone were lower and the serum estradiol/estrone ratio closer to pre-menopausal values in the group receiving transdermal estrogen compared with oral estrogen.

CONCLUSION: Six months of transdermal estrogen therapy is associated with greater reductions in measures reflecting vascular sympathetic tone than oral estrogen therapy in healthy postmenopausal smokers. Thus, transdermal estrogen may be associated with a more favorable risk/ benefit ratio in postmenopausal smokers, a group at high risk of osteoporosis and cardiovascular disease.

LEVEL OF EVIDENCE: I

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