Why Estrogen Protects Women’s Metabolism — and What Happens When It Declines

For decades, doctors have noticed something intriguing: women in their reproductive years are metabolically protected.

They gain less visceral fat, maintain healthier cholesterol patterns, and have far lower rates of heart disease compared with men — and even compared with other stages of their own life.

A major new review published in Atherosclerosis (van Oortmerssen et al., 2025) helps clarify why.

The answer centers on estrogen — and especially how estrogen shapes where the body stores fat, how lipids circulate, and how the liver and adipose tissue manage energy under everyday stress.

And the key mechanism may surprise you.

Estrogen’s metabolic superpower: keeping visceral fat low

The review highlights many benefits of estrogen:

• healthier LDL and HDL profiles

• better insulin sensitivity

• more flexible mitochondria

• less inflammation

• better vascular function

But one effect stands above the rest:

Estrogen protects women from accumulating visceral fat — the most dangerous type of fat for metabolic disease.

Why does this matter so much?

Because visceral fat (the fat packed around organs) isn’t just “extra weight.”It acts like an endocrine organ, pumping out inflammatory cytokines, releasing free fatty acids directly to the liver, raising triglycerides, and driving insulin resistance.

The review shows that when estrogen declines — particularly during perimenopause and menopause — visceral fat rises sharply. This single shift ripples through the entire metabolic system.

How Estrogen Protects Against Visceral Fat: The Lipoprotein Lipase (LPL) Story

One of estrogen’s most interesting metabolic effects is how it controls where fat is stored via LPL (lipoprotein lipase) — the enzyme that determines how incoming fatty acids are deposited into fat tissue.

Under healthy estrogen levels (menstrual years):

Estrogen regulates the expression of the LPL gene so that:

• Subcutaneous fat (hips, thighs, gluteal region)→ higher LPL activity

• Visceral fat (abdomen, around organs)→ lower LPL activity

This means:

Fat is directed into subcutaneous “safe storage” instead of dangerous visceral deposits.

This is why reproductive-age women naturally carry more fat in their thighs and hips — a metabolically protective pattern linked to:

• lower inflammation

• healthier HDL function

• lower VLDL production

• better insulin sensitivity

And it’s why women, despite often having more total body fat than men, still have lower cardiometabolic risk in these years.

What happens when estrogen falls (perimenopause and menopause)?

The review makes this clear:

When estradiol drops, LPL expression shifts.

• Subcutaneous LPL activity decreases

• Visceral LPL activity increases

The result:

✔ Fat moves inward

✔ Visceral fat rises

✔ Liver gets overwhelmed with free fatty acids

✔ Triglycerides rise

✔ HDL becomes smaller and less functional

✔ LDL increases (partly via increased PCSK9)

✔ Metabolic syndrome becomes 2–3× more common

In other words:

The lipid changes of menopause are not the cause of metabolic disease — they are the signature of a deeper adaptive shift driven by loss of estrogenic protection.

This explains the “metabolic advantage” of menstruating women

Women in their reproductive years sit at a metabolic sweet spot:

• strong estrogen signaling

• optimal LPL distribution

• low visceral fat

• flexible mitochondria

• healthier lipid turnover

Compared to infants (no estrogen) and menopausal women (declining estrogen), this period is metabolically unique.

The 2025 review shows that estrogen protects cardiovascular and metabolic health not only by tweaking cholesterol — but by governing energy allocation and protecting the body from visceral fat deposition.

Why this matters for women’s health now

Understanding estrogen’s role in fat distribution reframes many common health stories:

• rising abdominal fat after 45

• sudden changes in cholesterol despite the same diet

• higher inflammation during menopause

• “menopause belly”

• increased risk of diabetes or hypertension

• increased small dense LDL

• unexpected triglyceride spikes

These are not personal failures.

They are predictable physiological adaptations to hormonal change.

And because they are predictable, they can be addressed — early.

Final Thoughts

The 2025 lipid review highlights a powerful message:

Estrogen’s most important metabolic function is preventing visceral fat accumulation — the strongest driver of modern metabolic disease.

By understanding this mechanism, we can shift from blaming cholesterol numbers to addressing the deeper metabolic adaptations that shape women's health across the lifespan.

van Oortmerssen, J. A. E., Mulder, J. W. C. M., Kavousi, M., & Roeters van Lennep, J. E. (2025). Lipid metabolism in women: A review. Atherosclerosis, 405, 119213. https://doi.org/10.1016/j.atherosclerosis.2025.119213