Brain volumes, cognitive impairment, and conjugated equine estrogens.
BACKGROUND
Postmenopausal conjugated equine estrogens (CEE) therapies increase the risk of cognitive impairment in women aged 65 years or older and are associated with smaller regional brain volumes; however, the link between these two phenomena has not been established.


METHODS
Standardized magnetic resonance imaging was performed on 1,403 women, 1-4 years after they had participated in randomized placebo-controlled clinical trials of CEE-based therapies. Women included in this report were aged 65-80 years and free of dementia and mild cognitive impairment (MCI) when originally enrolled in the trials, which lasted an average of 4-6 years and were conducted at 14 academic U.S. medical centers. The associations that regional brain volumes and ischemic lesion volumes had with the development of cognitive impairment (i.e., dementia or MCI) were contrasted between treatment groups using analyses of covariance.


RESULTS
Fifty-three women developed MCI or probable dementia during follow-up. Among women who had been prescribed CEE-based therapies, cognitive impairment was associated with relatively smaller hippocampal (p = .0002) and total brain volumes (p = .03). Qualitatively, these associations appeared to be independent of their level of pretreatment cognitive function. Among women who had been prescribed placebo, these relationships were not evident; instead, cognitive impairment was associated with greater ischemic lesion volume in the frontal lobe (p = .007) and overall (p = .02).


CONCLUSIONS
A mechanism by which CEE-based postmenopausal hormone therapy induces cognitive impairment appears to be through increased brain atrophy.
Espeland
Mark A
MA
Department of Biostatistical Sciences, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA. mespelan@wfubmc.edu
Tindle
Hilary A
HA
Bushnell
Cheryl A
CA
Jaramillo
Sarah A
SA
Kuller
Lewis H
LH
Margolis
Karen L
KL
Mysiw
W Jerry
WJ
Maldjian
Joseph A
JA
Melhem
Elias R
ER
Resnick
Susan M
SM
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D003704:Dementia / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects*; D009483:Neuropsychological Tests; D009929:Organ Size; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology; D011379:Prognosis; D018570:Risk Assessment; D018709:Statistics, Nonparametric
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate