Published online before print March 30, 2009, doi: 10.1161/HYPERTENSIONAHA.108.126516
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(Hypertension. 2009;53:805.)
© 2009 American Heart Association, Inc.
Original Articles |
Cardiovascular Effects of Physiological and Standard Sex Steroid Replacement Regimens in Premature Ovarian Failure
From the Centre for Cardiovascular Science (J.P.L., N.L.M., D.J.W., D.E.N.), Division of Reproductive and Developmental Sciences, Child Life and Health (L.E.B., C.J.K., W.H.B.W.), Centre for Population Health Sciences (P.W.), and Centre for Reproductive Biology (H.O.D.C.), University of Edinburgh, Edinburgh, United Kingdom.
Correspondence to David E. Newby, Centre for Cardiovascular Sciences, University of Edinburgh, Chancellor’s Building, 49 Little France Crescent, Edinburgh, EH16 4SA United Kingdom. E-mail d.e.newby{at}ed.ac.uk
Current hormone replacement therapy may not optimize cardiovascular health in women with premature ovarian failure. We compared the effects of physiological and standard sex steroid replacement regimens on cardiovascular health in these women. In an open-label, randomized, controlled crossover trial, 34 women with premature ovarian failure were randomly assigned to 4-week cycles of physiological (transdermal estradiol and vaginal progesterone) and standard (oral ethinylestradiol and norethisterone) therapy for 12 months. Cardiovascular health was assessed by 24-hour ambulatory blood pressure, arterial stiffness, and renal and humoral factors. Eighteen women (19 to 39 years of age) completed the 28-month protocol. Both regimens caused similar suppression of luteinizing hormone and follicle-stimulating hormone and provided symptom relief. In comparison with the standard regimen, physiological sex steroid replacement caused lower mean 24-hour systolic and diastolic blood pressures throughout the 12-month treatment period (ANOVA; P
0.0001 for both): systolic blood pressure was 7.3 mm Hg (95% CI: 2.5 to 12.0 mm Hg) and diastolic was 7.4 mm Hg (95% CI: 3.9 to 11.0 mm Hg) lower at 12 months. Although there were no differences in arterial stiffness, physiological sex steroid replacement reduced plasma angiotensin II (ANOVA; P=0.007) and serum creatinine (ANOVA; P=0.015) concentrations without altering plasma aldosterone concentrations. In comparison with a standard regimen, physiological sex steroid replacement in women with premature ovarian failure results in lower blood pressure, better renal function, and less activation of the renin-angiotensin system. These findings have major implications for the future cardiovascular health of young women who require long-term sex steroid replacement therapy.
Key Words: ovarian failure • premature • hypertension • hormone replacement therapy • renin-angiotensin system • ambulatory blood pressure monitoring
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