Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol
Howard N Hodis, Wendy J Mack, Victor W Henderson, Donna Shoupe, Matthew J Budoff, Juliana Hwang-Levine, Yanjie Li, Mei Feng, Laurie Dustin, Naoko Kono, Frank Z Stanczyk, Robert H Selzer, Stanley P Azen, ELITE Research Group, Howard N Hodis, Liny Zurbrugg, Esther Bhimani, Martha Charlson, Irma Flores, Martha Huerta, Thelma LaBree, Sonia Lavender, Violetta McElreath, Janie Teran, Philip Zurbrugg, Robert H Selzer, Yanjie Li, Mei Feng, Lora Whitfield-Maxwell, Ming Yan, Wendy J Mack, Stanley P Azen, Farzana Choudhury, Carlos Carballo, Laurie Dustin, Adrian Herbert, Naoko Kono, George Martinez, Olga Morales, Juliana Hwang-Levine, Gail Izumi, Arletta Ramirez, Luci Rodriguez, Donna Shoupe, Juan C Felix, Pulin Sheth, Mary Yamashita, Frank Z Stanczyk, Carole Spencer, Victor W Henderson, Carol A McCleary, Janet A St John, Malcolm G Munro, Matthew J Budoff, Lily Honoris, Chris Dailing, Sivi Carson, Hooman Allayee, Leon Speroff, Robert H Knopp, Richard H Karas, Joan Hilton, Judy Hannah, Howard N Hodis, Wendy J Mack, Victor W Henderson, Donna Shoupe, Matthew J Budoff, Juliana Hwang-Levine, Yanjie Li, Mei Feng, Laurie Dustin, Naoko Kono, Frank Z Stanczyk, Robert H Selzer, Stanley P Azen, ELITE Research Group, Howard N Hodis, Liny Zurbrugg, Esther Bhimani, Martha Charlson, Irma Flores, Martha Huerta, Thelma LaBree, Sonia Lavender, Violetta McElreath, Janie Teran, Philip Zurbrugg, Robert H Selzer, Yanjie Li, Mei Feng, Lora Whitfield-Maxwell, Ming Yan, Wendy J Mack, Stanley P Azen, Farzana Choudhury, Carlos Carballo, Laurie Dustin, Adrian Herbert, Naoko Kono, George Martinez, Olga Morales, Juliana Hwang-Levine, Gail Izumi, Arletta Ramirez, Luci Rodriguez, Donna Shoupe, Juan C Felix, Pulin Sheth, Mary Yamashita, Frank Z Stanczyk, Carole Spencer, Victor W Henderson, Carol A McCleary, Janet A St John, Malcolm G Munro, Matthew J Budoff, Lily Honoris, Chris Dailing, Sivi Carson, Hooman Allayee, Leon Speroff, Robert H Knopp, Richard H Karas, Joan Hilton, Judy Hannah
Abstract
Background: Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested.
Methods: A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen.
Results: After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum.
Conclusions: Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.).
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Source: PubMed