Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for AD.
Differential cerebral metabolic effects of various hormone therapy formulations, and their associations with cognitive status, remain to be established. The principal aim of the current study was to assess relationships between regional cerebral metabolism and estrogen-based hormone therapies. Postmenopausal women (n=53) at elevated risk for Alzheimer's disease (AD) were on estrogen-containing hormone therapy for at least one year prior to enrollment in a prospective, randomized clinical trial. Subjects underwent an FDG-PET scan, along with neuropsychological, medical, and demographic assessments at time of enrollment, to be repeated one year following randomization to hormone therapy continuation versus discontinuation, and results from analyses of the baseline assessments are reported here. Across all subjects, years of endogenous estrogen exposure correlated most closely with metabolism in right superior frontal gyrus (p<0.0005). Women taking 17β-estradiol (E) performed three standard deviations higher in verbal memory than women taking conjugated equine estrogen (CEE), and their verbal memory performance positively correlated with metabolism in Wernicke's (p=0.003) and auditory association (p=0.002) areas. Women taking progesterone-plus-estrogen had lower metabolism than women taking unopposed estrogen within the mesial and inferior lateral temporal regions (p<0.0005) and the inferior frontal cortex, contralateral to Broca's area (p<0.0005). In conclusion, particular areas of relatively preserved metabolism were seen in women with more years of endogenous estrogen exposure, as well as in women taking estradiol-based formulations or estrogen therapies unopposed by progesterone, together suggesting regionally specific neuroprotective estrogenic effects.
Silverman
Daniel H S
DH
UCLA David Geffen School of Medicine, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Clinic, CHS AR-144, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095-6942, USA. dsilver@ucla.edu
Geist
Cheri L
CL
Kenna
Heather A
HA
Williams
Katherine
K
Wroolie
Tonita
T
Powers
Bevin
B
Brooks
John
J
Rasgon
Natalie L
NL
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D015914:Estrogen Replacement Therapy / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism / Q000523:psychology; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology; D012307:Risk Factors
D004966:Estrogens, Conjugated (USP); D019788:Fluorodeoxyglucose F18; D011374:Progesterone; D004958:Estradiol
J Psychiatr Res. 1975 Nov;12(3):189-98
1202204
Menopause. 1999 Spring;6(1):71-8
10100184
Hum Reprod Update. 2007 Mar-Apr;13(2):175-87
17135285
Nature. 1994 Apr 14;368(6472):633-5
8145849
Mayo Clin Proc. 2000 Nov;75(11):1174-84
11075748
Neurology. 1998 Jun;50(6):1585-93
9633698
J Neurosci. 2004 Jan 28;24(4):982-90
14749443
Breast Cancer Res Treat. 2007 Jul;103(3):303-11
17009108
Brain Res. 1994 May 2;644(2):305-12
8050041
Psychiatry Res. 2008 Oct 30;164(1):77-80
18707852
Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8660-5
8710927
Psychoneuroendocrinology. 2008 Nov;33(10):1419-25
18977091
Ann N Y Acad Sci. 2005 Jun;1052:57-74
16024751
Neurology. 2000 Sep 26;55(6):872-4
10994013
Biol Res Nurs. 2007 Oct;9(2):147-60
17909167
Gynecol Obstet Invest. 1999;47(1):29-36
9852389
Neurobiol Aging. 2000 Mar-Apr;21(2):373-83
10867223
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1837-41
1542680
Neuropsychologia. 1999 Jan;37(1):103-18
9920476
Neurology. 2000 Sep 26;55(6):875-7
10994014
Brain Res. 2006 Jun 13;1094(1):163-78
16696957
Neurology. 2006 Dec 12;67(11):2039-41
17159116
Biol Psychiatry. 1998 Nov 1;44(9):839-50
9807639
Science. 1981 Mar 13;211(4487):1183-5
6258229
Brain Res. 1984 Jan 23;291(2):391-4
6320967
J Steroid Biochem Mol Biol. 1991;40(1-3):1-14
1958513
Acta Pol Pharm. 2000 Mar-Apr;57(2):135-55
10934794
Cereb Cortex. 1996 Jan-Feb;6(1):71-9
8670640
JAMA. 1999 Apr 7;281(13):1197-202
10199429
N Engl J Med. 1996 Mar 21;334(12):752-8
8592548
JAMA. 2004 Jun 23;291(24):2947-58
15213206
Fertil Steril. 2009 Jul;92(1):197-204
18692790
Arch Neurol. 1992 Nov;49(11):1142-50
1444881
Neuroscience. 2006;138(3):1027-30
16488547
Novartis Found Symp. 2000;230:56-69; discussion 69-73
10965502
Neurobiol Learn Mem. 2007 Sep;88(2):208-16
17507257
J Clin Endocrinol Metab. 2009 Nov;94(11):4152-61
19850684
Exp Neurol. 1985 Aug;89(2):484-90
2990988
Neuroscience. 2001;108(2):331-40
11734365
Brain. 1998 Jul;121 ( Pt 7):1249-56
9679777
Am J Psychiatry. 1995 Dec;152(12):1757-64
8526242
J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62
14399272
Psychiatry Res. 2001 Jul 1;107(1):11-8
11472860
J Neurosci Res. 2008 May 15;86(7):1588-98
18431813
JAMA. 2003 May 28;289(20):2651-62
12771112
Exp Neurol. 2005 Aug;194(2):506-22
15893308
Exp Brain Res. 1981;Suppl 3:61-79
7018919
J Neurosci. 1990 Dec;10(12):4035-9
2269895
Brain Res Bull. 1995;36(3):315-20
7697386
Menopause. 2006 May-Jun;13(3):411-22
16735938
J Clin Endocrinol Metab. 2006 May;91(5):1802-10
16522699
Neurology. 2007 Sep 25;69(13):1322-30
17893293
Biol Psychiatry. 1995 Apr 1;37(7):434-41
7786956
Horm Behav. 1998 Oct;34(2):171-82
9799627
J Cereb Blood Flow Metab. 1985 Sep;5(3):393-400
4040921
Biol Psychiatry. 2000 Oct 15;48(8):854-60
11063980
Neurology. 1984 Jul;34(7):939-44
6610841
J Clin Endocrinol Metab. 2001 Feb;86(2):679-84
11158031
Arch Gen Psychiatry. 1989 Jun;46(6):527-32
2730277
J Clin Endocrinol Metab. 2006 Nov;91(11):4476-81
16912129
Horm Behav. 1985 Dec;19(4):469-98
3910535
Endocrinology. 1993 Dec;133(6):2818-26
8243309
Science. 1997 Apr 11;276(5310):264-6
9092477
J Comp Neurol. 2004 Apr 26;472(2):193-207
15048687
Neurology. 2009 Jan 13;72(2):135-42
19139364
Psychoneuroendocrinology. 1992 Oct;17(5):485-95
1484915
Neurobiol Aging. 2005 Feb;26(2):229-35
15582750
JAMA. 2004 Jun 23;291(24):2959-68
15213207
Neuroimage. 2001 Oct;14(4):789-801
11554798
Brain Lang. 1983 May;19(1):124-41
6860932
Neuroimage. 2004 Jan;21(1):364-71
14741674
Nature. 1981 Feb 5;289(5797):500-2
7464918
Horm Behav. 2008 Nov;54(5):684-93
18706905
J Cardiovasc Transl Res. 2009 Sep;2(3):228-39
19668346
J Am Geriatr Soc. 1995 Sep;43(9):1007-15
7657916
Semin Reprod Med. 2009 May;27(3):275-82
19401958
JAMA. 2003 May 28;289(20):2663-72
12771113
Neurology. 2007 Sep 11;69(11):1074-83
17761551