Fatty Liver Isn't Sex-Neutral: What a Global Review Reveals About MASLD in Men and Women

The condition is now called MASLD — metabolic dysfunction-associated steatotic liver disease — which is a mouthful that replaced the older NAFLD label to make one thing explicit: this is a metabolic disease, not a moral one. According to the review by Kaushal and colleagues, MASLD affects somewhere between 25% and 58% of adults worldwide, depending on the population studied. That range alone tells you how widespread — and how variable — this is.

Here is where the sex-neutral framing breaks. Across studies from China, Japan, Korea, Taiwan, India, Israel, Spain, the Netherlands, the UK and the US, men consistently show higher MASLD prevalence than premenopausal women — roughly 23–41% in men versus 13–21% in premenopausal women. For decades, that gap has been the headline, and it has quietly shaped who gets screened, who gets worked up, and who gets told their fatigue is "probably stress."

If you are reading this somewhere in your 40s and feeling that familiar "wait, what now" sensation, here is the part that matters. The review reports that the sex disparity in MASLD narrows after menopause — and then keeps going. Postmenopausal women face a roughly 12-fold increased risk of metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis as estrogen declines. That is not a typo. The protective effect of premenopausal estrogen appears to do real work on liver fat handling, and when it leaves, the liver feels it.

It is worth being honest about what this number is and is not. It comes from a narrative review synthesizing population studies, not a single randomized trial — the editorial evidence rating here is moderate, not definitive. The direction of the signal is consistent across geographies, which is reassuring. The precise magnitude will keep shifting as more data come in.

The mechanisms behind the divergence are not subtle, and they help explain why one-size-fits-all advice keeps falling flat. The review highlights three big drivers of sex-based difference in MASLD biology.

The first is fat distribution. Men tend to deposit fat viscerally — around the organs, where it is metabolically loud and inflammatory. Premenopausal women tend toward gynoid and femoral fat patterns — hips, thighs — which is metabolically quieter. After menopause, that distribution shifts toward the visceral pattern, which is part of why the risk curve catches up.

The second is the gut. The microbiome shows up here too: the review notes that women carry a higher Firmicutes-to-Bacteroidetes ratio than men, and gut microbiota profiles influence how the liver handles bile acids, energy harvest and inflammation. This is an emerging area — fascinating, real, and not yet a place to make personal treatment decisions from.

The third is genetics. The PNPLA3 I148M variant, one of the best-known genetic risk factors for fatty liver disease, shows sex-biased risk associations — meaning the same variant does not necessarily mean the same thing in your husband's liver as in yours.

The clinical implication the authors push hardest is not a new drug. It is screening. If men get hit earlier and women get hit harder later, then risk-stratifying by sex and menopausal status — instead of treating MASLD as a single disease with one threshold — would catch the postmenopausal jump in advanced disease before it becomes irreversible fibrosis.

For a 45-year-old woman reading this, that does not mean panicking about your liver. It means asking your clinician a more specific question than "am I healthy?" The relevant questions are about metabolic risk: waist circumference, fasting glucose, triglycerides, blood pressure, and — if any of those are off — whether a non-invasive liver fibrosis assessment makes sense for you, particularly as you move through perimenopause and beyond. None of this is a directive. It is a conversation worth having on purpose, rather than by accident.

The honest takeaway from this review is not that women have been overlooked in fatty liver research — though that is part of the story — but that the disease itself has been described as if biology were uniform. It is not. The liver reads hormones, fat distribution, microbes and genes, and it reads them differently depending on who is holding the chart. The practical move, for those of us moving through the perimenopausal years, is to stop treating midlife metabolic shifts as background noise and start asking the questions the data now supports asking.