Cardiometabolic Health: Do Sex Steroids Matter?

[madman]

"Cardiometabolic Health: Do Sex Steroids Matter?" which looks at the role sex steroids play in cardiovascular health across the lifespan.




Susan R. Davis

My team who have contributed to the work presented

Conclusions

 

[madman]

Both estrogens and testosterone have vital roles in women and men

 

[madman]

Key aspect I will address

 

[madman]

Ovarian failure before the age of 45 years

 

[madman]

Estrogen has MAJOR CARDIOMETABOLIC EFFECTS that are not gender specific

 

[madman]

Mice unable to make estrogen (aromatase gene knock out) (total estrogen depletion)

 

[madman]

* To my knowledge there have been four men identified who have aromatase gene mutation and this is one of these men we studied a number of years ago




29 yo MAN with complete estrogen deficiency (aromatase gene mutation)

Estradiol patch reversed the manifestations of insulin resistance/dyslipidemia

 

[madman]

Estrogen directly effects vascular endothelial & smooth-muscle cells

 

[madman]

Cardiometabolic changes seen in postmenopausal women

Postmenopausal estrogen therapy has known cardiometabolic benefits

 

[madman]

So, estrogen should prevent cardiometabolic disease after menopause, but does it?

The Women's health initiative [WHI] Studies were designed in the 1990's to determine whether estrogen prevents CHD

Noteworthy, not a selected low risk study sample

WHI: Oral estrogen + progestin users had less self-reported incident T2 diabetes

* The graphs are impressive but the devils always in the detail

Factors associated with incident diabetes in WHI estrogen + progestin study

Estrogen + progestin: no reduction in CHD (MI/CHD death) despite small reduction in self-reported incident diabetes

 

[madman]

Estrogen-only: no reduction in CHD (MI/CHD death) over 7 y

 

[madman]

To summarize this


Women's Health Initiative [WHI] clinical trials

 

[madman]

Why didn't estrogen prevent CVD?

Maybe estrogen is only beneficial for women with hot flushes/night sweats?

Maybe the WHI studies used the 'wrong' estrogen?

All estrogens act via the same receptors and non-genomic pathways

 

[madman]

Maybe estrogen is only protective if started very early after menopause?

KEEPS Study: no effect of 4 years of. estrogen, oral/transdermal vs placedo started within 3 years of menopause on:

 

[madman]

BUT

* The main reference that keeps over and over again appearing for the argument that estrogen early prevents heart disease comes from this study which was the Boardman Cochrane review
BUT
* The kicker here is the subtext, the small print.
* The results were only significant because the analysis included the Danish osteoporosis prevention study. This was an open labeled study with no placebo group. It was a secondary outcome and if the meta analysis is done without dops included, it's not SIGNIFICANT, So the data is not ROBUST.




Meta-analysis of early vs later postmenopausal estrogen therapy

* Again at a population level you would not on this basis be TELLING ALL WOMEN THEY NEED ESTROGEN

 

[madman]

Postmenopausal women are not totally estrogen deplete

 

[madman]

Cardiometabolic disease risk & the stages of menopause

The menopause transition is not an estrogen deplete phase

Accumulation of visceral fat accelerates in EARLY perimenopause

Body composition changes emerge in EARLY perimenopause

Menopause-related sleep disturbance emerges EARLY perimenopause

Endothelial dysfunction emerges in EARLY perimenopause

 

[madman]

Adverse cardiometabolic changes emerge in early perimenopause when the ovaries are still making (often very substantial) estrogen

 

[madman]

Should you tell your patients at increased risk to stop estrogen therapy?

Waking with a hot flush increases BP, heart rate, and cardiac sympathetic activity

IN WOMEN WITH CVD

 

[madman]

NON-ORAL estrogen at approved doses no increase in VTE risk