Edited 3/16/2014 to include two recent studies:
New study focusing on women at risk for AD and Estradiol:Prospective Randomized Trial to Assess Effects of Continuing Hormone Therapy on Cerebral Function in Postmenopausal Women at Risk for Dementia http://www.plosone.org/article/info%3Ad ... ne.0089095
Study focusing on estrogen associated polymorphisms and risk of AD:Estrogen associated gene polymorphisms and their interactions in the progress of Alzheimer's disease.http://www.ncbi.nlm.nih.gov/pubmed/24096044
Original Post:Accelerated Cell Aging in Female APOE-ε4 Carriers: Implications for Hormone Therapy Use
http://www.plosone.org/article/info%3Ad ... ne.0054713
"In sum, this study represents the first longitudinal demonstration of accelerated cell aging in APOE-ε4 carriers. Our finding that even high-functioning, healthy mid-life women with the ε4 allele bear markers of cellular aging suggests the need for further research to understand the potential utility of leukocyte TL as an early indicator of future dementia risk. These data provide strong evidence that the impact of the APOE risk allele on telomere attrition begins in the absence of, or prior to, clinical and behavioral evidence of dementia. Futher, the data provide initial evidence that hormone therapy, begun at the onset of the menopausal transition, might buffer against TL attrition in women at risk of cognitive decline. Importantly, terminating HT had beneficial effects for non-carriers, indicating that HT may have differential effects on cell aging across genotypic subgroups. Going forward, it will be crucial to extend these initial data to a larger epidemiological sample to systematically probe whether specific HT formulations, timing of initiation, and duration of use differentially impact cellular aging."
And for those of us who have Factor V Leiden Blood Clotting Disorder some research suggests much less risk with transdermal HRT:Factor V Leiden Thrombophiliahttp://www.ncbi.nlm.nih.gov/books/NBK1368/
"Some evidence suggests that the thrombotic risk from transdermal HRT is lower than the thrombotic risk from oral preparations, in women with and without prothrombotic mutations [Scarabin et al 2003, Straczek et al 2005, Canonico et al 2007]. In one study, women with factor V Leiden who used oral estrogen had a 16-fold higher risk for VTE than non-users without the mutation. In contrast, the thrombotic risk in women with factor V Leiden who used transdermal estrogen was similar to that in women with a mutation who did not use estrogen. Among women with factor V Leiden, the use of oral estrogen was associated with a fourfold higher risk for VTE than transdermal estrogen [Straczek et al 2005]. However, there are no prospective trials confirming the safety in women with thrombophilia and/or prior VTE. "EDIT 1/6/2014 to add new research below
(Just what we E4 women need, more ambiguity
)APOE modulates the effect of estrogen therapy on Aβ accumulation EFAD-Tg mice http://www.sciencedirect.com/science/ar ... 4013011130
The interactive effects of APOE and ERT after OVX on Aβ accumulation were determined in EFAD mice.
ERT decreased extracellular amyloid plaque and Aβ deposition with APOE2 and APOE3.
ERT increased extracellular amyloid plaque and Aβ deposition, but lowered soluble Aβ42 with APOE4.
First in vivo evidence that hAPOE differentially regulates the effects of ERT on Aβ deposition.
Aβ42 levels may be a critical read-out for APOE4 carriers enrolled in ERT trials."Postmenopausal Hormone Therapy, Timing of Initiation, APOE and Cognitive Declinehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483632/
Compared with never users, past or current HT users showed modest but statistically significant worse rates of decline in the TICS: the multivariable-adjusted difference in annual rate of decline in the TICS among current estrogen only users versus never users was −0.04 (95% CI = −0.07, −0.004); for current estrogen+progestin users, the mean difference was −0.05 (95% CI = −0.10, −0.002). These differences were equivalent to those observed in women who are 1–2 years apart in age. We observed no protective associations with early timing of hormone initiation. We found suggestive interactions with APOE e4 status (e.g., on TICS, p-interaction = 0.10), where the fastest rate of decline was observed among APOE e4 carriers who were current HT users."Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Micehttp://www.hindawi.com/journals/jnd/2013/531326/
"To our knowledge, this is the first investigation of presynaptic density in aging female apoE4 and apoE ko mice. We found a decrease in presynaptic density in the hippocampus of middle-aged female apoE4 mice compared with WT mice. This may be the result of a specific harmful interaction of estrogen with apoE4, as we did not observe any differences in male mice. In addition, we found neurogenesis to be increased in middle-aged female apoE ko mice. Previous studies have suggested a compensatory mechanism for synaptic failure by temporarily increasing the number of synaptic contacts and/or neurogenesis. The trend of increased neurogenesis found in female apoE ko mice in our study supports this hypothesis. Our results support the previously determined sex-specific differences observed between APOE genotypes, which could account for some of the sex differences in AD and CVD. Sex differences should be taken into account in any research concerning CVD, AD, or apoE. "Possible APOE Genotype and Sex Dependent Effects of 17-α- estradiol on Alzheimers Disease Pathologyhttp://www.omicsonline.org/possible-apo ... ?aid=21433
This is an editorial suggesting 17-β-estradiol (β-E2) and in particular its precursor 17-α-E2 therapy could be beneficial for both men and women.