Cognition, mood, and physiological concentrations of sex hormones in the early and late postmenopause Victor W. Hendersona,b,1, Jan A. St. Johnc,d, Howard N. Hodisc,d,e,f, Carol A. McClearyg, Frank Z. Stanczykd,h, Roksana Karimd,i, Donna Shoupeh, Naoko Konoc,d, Laurie Dustinc,d, Hooman Allayeec,d, and Wendy J. Mackc,d Departments of aHealth Research and Policy (Epidemiology) and bNeurology and Neurological Sciences, Stanford University, Stanford, CA 94305; c Atherosclerosis Research Unit and Departments of dPreventive Medicine, eMedicine, gNeurology, hObstetrics and Gynecology, and iPediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033; and fDepartment of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, CA 90033 Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved October 23, 2013 (received for review June 30, 2013)

Variations in the hormonal milieu after menopause may influence neural processes concerned with cognition, cognitive aging, and mood, but findings are inconsistent. In particular, cognitive effects of estradiol may vary with time since menopause, but this prediction has not been assessed directly using serum hormone concentrations. We studied 643 healthy postmenopausal women not using hormone therapy who were recruited into early (1–2 units/d >2 units/d Body mass index, kg/m2 Systolic blood pressure, mmHg Diastolic blood pressure, mmHg Hemoglobin A1c, % (269, 369) Intelligence quotient estimate‡ Mood (CES-D), median, IQR Possible depression§ ApoE e4 carrier status{ (257, 354) Serum concentrations, median, IQR Total E2, pg/mL Free E2, pg/mL (268, 370) E1, pg/mL (269, 372) P4, ng/mL (271, 370) Total T, ng/dL (269, 372) Free T, pg/dL (268, 370) SHBG, nmol/L (268, 370)

Early postmenopause (n = 271)

Late postmenopause (n = 372)

55.4 (4.1)

65.4 (6.0)

174 (64.2%) 24 (8.9%) 41 (15.1%) 32 (11.8%) 0

266 35 49 21 1

(71.5%) (9.4%) (13.2%) (5.7%) (0.3%)

1 75 195 51.9 3.5

2 137 233 47.9 14.3

(0.5%) (36.8%) (62.6%) (5.8) (11.5, 18.7)

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Cognition, mood, and physiological concentrations of sex hormones in the early and late postmenopause.

Variations in the hormonal milieu after menopause may influence neural processes concerned with cognition, cognitive aging, and mood, but findings are...
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