Cardiometabolic Health: Do Sex Steroids Matter?

madman · 2026-01-02T10:02:31-0600

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

My team who have contributed to the work presented

madman · 2026-01-02T10:04:28-0600

Both estrogens and testosterone have vital roles in women and men

madman · 2026-01-02T10:05:12-0600

Key aspect I will address

madman · 2026-01-02T10:10:05-0600

Ovarian failure before the age of 45 years

madman · 2026-01-02T10:12:12-0600

Estrogen has MAJOR CARDIOMETABOLIC EFFECTS that are not gender specific

madman · 2026-01-02T10:14:33-0600

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

madman · 2026-01-02T10:20:46-0600

* 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 · 2026-01-02T10:22:39-0600

Estrogen directly effects vascular endothelial & smooth-muscle cells

madman · 2026-01-02T10:25:34-0600

Cardiometabolic changes seen in postmenopausal women

Postmenopausal estrogen therapy has known cardiometabolic benefits

madman · 2026-01-02T11:21:40-0600

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 · 2026-01-02T11:25:01-0600

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

madman · 2026-01-02T11:27:13-0600

To summarize this

Women's Health Initiative [WHI] clinical trials

madman · 2026-01-02T11:37:59-0600

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 · 2026-01-02T11:46:41-0600

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 · 2026-01-02T12:02:07-0600

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