What women need to know: Polycystic ovary syndrome, Perimenopause, and MASLD/MASH ('Fatty Liver')

Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) (formerly called fatty liver disease or NAFLD/NASH) affects all genders and is now one of the most common liver conditions worldwide – yet it often goes undiagnosed. Certain groups of women have a higher risk of MASH/MASLD, particularly women with polycystic ovary syndrome (PCOS), and women in perimenopause and menopause. The common metabolic factor here is insulin resistance.

As discussed in a recent review article, women with PCOS have a 2-2.5 times higher risk of developing MASLD compared to age and BMI-matched women who don’t have PCOS. Insulin resistance is a key driver of PCOS, which promotes fat storage in the liver and increases inflammation. Many women with PCOS have mildly elevated testosterone levels, which is associated with a further tendency to deposit fat in and around the abdomen (visceral fat), which worsens insulin resistance. Women with PCOS also have higher rates of metabolic syndrome, elevated triglycerides, and type 2 diabetes, all of which are linked with increased risk of MASLD/MASH.

Premenopausal women generally have a lower risk of MASLD compared to men. At age 50, the prevalance is similar, and after age 60, MASLD is more common in women than men. Estrogen may provide a degree of metabolic protection, modulating inflammation in fat tissue and liver, reducing liver scarring, reducing fat production in the liver, promoting fat breakdown in fat tissue, and influencing where fat tissue is distributed (towards the hips and thighs, rather than the metabolically unfavorable abdominal fat). As estrogen levels decline in peri/menopause, insulin resistance increases, and body fat shifts toward the abdomen. These changes create an environment that promotes fat accumulation in the liver. This transition period is often accompanied by weight gain that feels difficult to control, even without major changes in eating or physical activity habits. This is not simply due to aging, but to hormonal shifts that influence metabolism. The metabolic impact of menopause extends beyond liver health, increasing the risk of type 2 diabetes and cardiovascular disease. MASLD is part of this same metabolic picture.

One might wonder whether hormone replacement therapy could protect against the development of MASLD in peri/menopause. The data is not clear on this, with conflicting results. These are generally observational studies, some suggesting benefit and some suggesting increased risk of MASLD with hormone replacement. We need well-designed clinical trials specifically investigating the effect of hormone replacement therapy on MASLD to know the answer. It is also important to assess for MASLD before and during hormone replacement therapy use. Note that hormone replacement therapy is not recommended for weight loss as data do not support that hormone replacement therapy reduces weight.

BOTTOM LINE: Women with polycystic ovary syndrome, and women going through perimenopause and in menopause have an increased risk of MASLD/MASH (‘fatty liver disease’). It is important to screen for MASLD/MASH in these women, as well as anyone else who is at risk.

And, hot off the presses: check out this brand new New England Journal of Medicine review article on how to screen, starting with a very easy calculation based on blood tests, called the FIB-4. (see also my prior related blog here)

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