Neuroprotective effects of female sex steroids in humans: current controversies and future directions.
Recent findings from the Women's Health Initiative (WHI) have raised considerable concern over prolonged use of opposed and unopposed oral conjugated equine estrogen (CEE), given the increased risk of serious adverse effects, including stroke and venous thromboembolic complications. Furthermore, results from the WHI Memory Study (WHIMS) indicated that over 5 years of therapy with Prempro impaired performance on global cognitive tests and nearly doubled the risk of dementia. These surprising findings were contradictory to cumulative evidence from basic science, epidemiological and some intervention studies suggesting hormone therapy was cardioprotective and could potentially reduce the risk of dementia. This review paper focuses on the neurobiology of estrogen, summarizing the clinical evidence for neuroprotective and cognition-enhancing efficacy of estrogen. Further, the paper briefly discusses variables that may account for the unexpected findings of WHIMS, and offers suggestions for future research.
Gleason
C E
CE
Wm. S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705, USA. ceg@medicine.wisc.edu
Cholerton
B
B
Carlsson
C M
CM
Johnson
S C
SC
Asthana
S
S
D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*
D004967:Estrogens; D012739:Gonadal Steroid Hormones; D018696:Neuroprotective Agents
J Thorac Cardiovasc Surg. 2011 May;141(5):1317-8
20855092
Eur Heart J Cardiovasc Imaging. 2013 Jul;14 (7):611-44
23733442
Eur Heart J Cardiovasc Imaging. 2015 Dec;16(12):1389
26420288
Eur J Cardiothorac Surg. 2012 Oct;42(4):S1-44
22922698
Interact Cardiovasc Thorac Surg. 2015 Feb;20(2):200-8
25362240
Eur J Cardiothorac Surg. 2008 Oct;34(4):760-5
18586512
Ann Cardiothorac Surg. 2013 Nov;2(6):751-7
24349977
N Engl J Med. 2014 Jan 2;370(1):23-32
24245543
J Heart Valve Dis. 2012 Jan;21(1):41-7
22474741
Circulation. 2013 May 7;127(18):1870-6
23569153
Ann Thorac Surg. 2011 Jan;91(1):165-71
21172507
Circulation. 2013 Apr 9;127(14 ):1485-92
23459614
J Thorac Cardiovasc Surg. 2014 Jan;147(1):210-9
24183333
Ann Thorac Surg. 2015 Apr;99(4):1439-42
25841832
J Thorac Cardiovasc Surg. 2015 Mar;149(3):762-8.e1
25439776
Eur Heart J. 2016 Jan 7;37(2):133-9
26152116
J Thorac Cardiovasc Surg. 2008 Apr;135(4):885-93, 893.e1-2
18374775
IEEE Trans Med Imaging. 2010 Sep;29(9):1636-51
20442044
J Thorac Cardiovasc Surg. 2010 Jan;139(1):76-83; discussion 83-4
19931098
Ann Thorac Surg. 2009 Jun;87(6):1715-20
19463584
Thorac Cardiovasc Surg. 2015 Jun;63(4):258-69
26011675
Clin Res Cardiol. 2015 Feb;104(2):112-23
25573638
Eur J Cardiothorac Surg. 2013 Jul;44(1):e8-15
23530029
Eur Heart J. 2003 Jul;24(13):1231-43
12831818
Ann Thorac Surg. 2011 Mar;91(3):677-84; discussion p 684
21352979
Multimed Man Cardiothorac Surg. 2010 Jan 1;2010(809):mmcts.2010.004523
24413680
Circulation. 2002 Sep 10;106(11):1355-61
12221052
Eur Heart J Cardiovasc Imaging. 2012 Jan;13(1):1-46
22275509
Circulation. 2005 Jan 25;111(3):295-301
15655133
Circulation. 2006 May 9;113(18):2238-44
16651470
J Thorac Cardiovasc Surg. 2012 Aug;144(2):308-12
22698565
N Engl J Med. 2005 Mar 3;352(9):875-83
15745978
Ann Cardiothorac Surg. 2013 Nov;2(6):787-95
24349983
Ann Thorac Surg. 2006 Mar;81(3):1153-61
16488757
Rev Esp Cardiol. 2011 Dec;64(12 ):1169-81
22032935
Lancet. 2006 Sep 16;368(9540):1005-11
16980116
Catheter Cardiovasc Interv. 2015 Oct;86(4):747-60
26386239
Circulation. 2013 Jul 30;128(5):483-91
23804253
Nat Rev Cardiol. 2011 Mar;8(3):162-72
21263455