Transdermal versus oral estrogen therapy in postmenopausal smokers: hemodynamic and endothelial effects.
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 beta2-adrenoceptor 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 beta-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 beta2-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.


CONCLUSIONS
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.
Girdler
Susan S
SS
Departments of Psychiatry, University of North Carolina at Chapel Hill, North Carolina 27599-7175, USA. susan_girdler@med.unc.edu
Hinderliter
Alan L
AL
Wells
Ellen C
EC
Sherwood
Andrew
A
Grewen
Karen M
KM
Light
Kathleen C
KC
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D005996:Nitroglycerin; D017698:Postmenopause; D012907:Smoking / Q000009:adverse effects; D013312:Stress, Physiological; D016896:Treatment Outcome; D014463:Ultrasonography
D004967:Estrogens; D005996:Nitroglycerin