OBJECTIVES: To determine whether small decrements in global cognitive function that conjugated equine estrogen (CEE) therapies have been shown to produce in older women persist after cessation and extend to specific cognitive domains. DESIGN: Randomized controlled clinical trial. SETTING:Fourteen clinical centers of the Women's Health Initiative. PARTICIPANTS: Two thousand three hundred four women aged 65 to 80 free of probable dementia at enrollment. INTERVENTION: CEE 0.625 mg/d with or without medroxyprogesterone acetate (MPA, 10 mg/d) and matching placebos. MEASUREMENTS: Annual administrations of a battery of cognitive tests during and after the trial. RESULTS: Assignment to CEE-based therapies was associated with small mean relative decrements in global cognitive function and several domain-specific cognitive functions during the trial, which largely persisted through up to 4 years after the trial. The strongest statistical evidence was for global cognitive function (0.07-standard deviation decrements during (P=.007) and after (P=.01) the trial. For domain-specific scores, the mean decrements were slightly smaller, were less significant, and tended to be larger for CEE-alone therapy. CONCLUSION: CEE-based therapies, when initiated after the age of 65, produce a small broad-based decrement in cognitive function that persists after their use is stopped, but the differences in cognitive function are small and would not be detectable or have clinical significance for an individual woman. Differences in effects between cognitive domains suggest that more than one mechanism may be involved.
RCT Entities:
OBJECTIVES: To determine whether small decrements in global cognitive function that conjugated equine estrogen (CEE) therapies have been shown to produce in older women persist after cessation and extend to specific cognitive domains. DESIGN: Randomized controlled clinical trial. SETTING: Fourteen clinical centers of the Women's Health Initiative. PARTICIPANTS: Two thousand three hundred four women aged 65 to 80 free of probable dementia at enrollment. INTERVENTION: CEE 0.625 mg/d with or without medroxyprogesterone acetate (MPA, 10 mg/d) and matching placebos. MEASUREMENTS: Annual administrations of a battery of cognitive tests during and after the trial. RESULTS: Assignment to CEE-based therapies was associated with small mean relative decrements in global cognitive function and several domain-specific cognitive functions during the trial, which largely persisted through up to 4 years after the trial. The strongest statistical evidence was for global cognitive function (0.07-standard deviation decrements during (P=.007) and after (P=.01) the trial. For domain-specific scores, the mean decrements were slightly smaller, were less significant, and tended to be larger for CEE-alone therapy. CONCLUSION: CEE-based therapies, when initiated after the age of 65, produce a small broad-based decrement in cognitive function that persists after their use is stopped, but the differences in cognitive function are small and would not be detectable or have clinical significance for an individual woman. Differences in effects between cognitive domains suggest that more than one mechanism may be involved.
Authors: Judith K Ockene; David H Barad; Barbara B Cochrane; Joseph C Larson; Margery Gass; Sylvia Wassertheil-Smoller; JoAnn E Manson; Vanessa M Barnabei; Dorothy S Lane; Robert G Brzyski; Milagros C Rosal; Judy Wylie-Rosett; Jennifer Hays Journal: JAMA Date: 2005-07-13 Impact factor: 56.272
Authors: Shotaro Suzuki; Candice M Brown; Christopher D Dela Cruz; Enhua Yang; David A Bridwell; Phyllis M Wise Journal: Proc Natl Acad Sci U S A Date: 2007-03-26 Impact factor: 11.205
Authors: Sylvia Wassertheil-Smoller; Susan L Hendrix; Marian Limacher; Gerardo Heiss; Charles Kooperberg; Alison Baird; Theodore Kotchen; J David Curb; Henry Black; Jacques E Rossouw; Aaron Aragaki; Monika Safford; Evan Stein; Somchai Laowattana; W Jerry Mysiw Journal: JAMA Date: 2003-05-28 Impact factor: 56.272
Authors: Stephen R Rapp; Mark A Espeland; Sally A Shumaker; Victor W Henderson; Robert L Brunner; JoAnn E Manson; Margery L S Gass; Marcia L Stefanick; Dorothy S Lane; Jennifer Hays; Karen C Johnson; Laura H Coker; Maggie Dailey; Deborah Bowen Journal: JAMA Date: 2003-05-28 Impact factor: 56.272
Authors: Sally A Shumaker; Claudine Legault; Stephen R Rapp; Leon Thal; Robert B Wallace; Judith K Ockene; Susan L Hendrix; Beverly N Jones; Annlouise R Assaf; Rebecca D Jackson; Jane Morley Kotchen; Sylvia Wassertheil-Smoller; Jean Wactawski-Wende Journal: JAMA Date: 2003-05-28 Impact factor: 56.272
Authors: S M Resnick; M A Espeland; S A Jaramillo; C Hirsch; M L Stefanick; A M Murray; J Ockene; C Davatzikos Journal: Neurology Date: 2009-01-13 Impact factor: 9.910
Authors: Susan M Resnick; Pauline M Maki; Stephen R Rapp; Mark A Espeland; Robert Brunner; Laura H Coker; Iris A Granek; Patricia Hogan; Judith K Ockene; Sally A Shumaker Journal: J Clin Endocrinol Metab Date: 2006-03-07 Impact factor: 5.958
Authors: Sally A Shumaker; Claudine Legault; Lewis Kuller; Stephen R Rapp; Leon Thal; Dorothy S Lane; Howard Fillit; Marcia L Stefanick; Susan L Hendrix; Cora E Lewis; Kamal Masaki; Laura H Coker Journal: JAMA Date: 2004-06-23 Impact factor: 56.272
Authors: Mark A Espeland; Michael E Miller; Joseph S Goveas; Patricia E Hogan; Laura H Coker; Jeff Williamson; Michelle Naughton; Susan M Resnick Journal: J Womens Health (Larchmt) Date: 2011-08-05 Impact factor: 2.681
Authors: May A Beydoun; Salman M Tajuddin; Greg A Dore; Jose-Atilio Canas; Hind A Beydoun; Michele K Evans; Alan B Zonderman Journal: J Nutr Date: 2017-04-26 Impact factor: 4.798
Authors: Laura H Coker; Mark A Espeland; Patricia E Hogan; Susan M Resnick; R Nick Bryan; Jennifer G Robinson; Joseph S Goveas; Christos Davatzikos; Lewis H Kuller; Jeff D Williamson; Cheryl D Bushnell; Sally A Shumaker Journal: Neurology Date: 2014-01-02 Impact factor: 9.910
Authors: Nicole M Armstrong; Mark A Espeland; Jiu-Chiuan Chen; Kamal Masaki; Jean Wactawski-Wende; Wenjun Li; Margery L S Gass; Marcia L Stefanick; JoAnn E Manson; Jennifer A Deal; Stephen R Rapp; Frank R Lin; Susan M Resnick Journal: J Gerontol A Biol Sci Med Sci Date: 2020-02-14 Impact factor: 6.053
Authors: Mark A Espeland; Sally A Shumaker; Iris Leng; JoAnn E Manson; Candice M Brown; Erin S LeBlanc; Leslie Vaughan; Jennifer Robinson; Stephen R Rapp; Joseph S Goveas; Jean Wactawski-Wende; Marcia L Stefanick; Wenjun Li; Susan M Resnick Journal: JAMA Intern Med Date: 2013-08-12 Impact factor: 21.873