NAFLD Risk Higher for Women With Long or Irregular Menstrual Cycles

Abnormal periods may put young women at a higher risk for developing nonalcoholic fatty liver disease (NAFLD), a Korean study suggested.

Among 72,092 premenopausal women under the age of 40, long or irregular menstrual cycles were linked to a 22% higher risk for incident NAFLD after adjusting for age, BMI, insulin resistance, and other factors (HR 1.22, 95% CI 1.14-1.31), reported Seungho Ryu, MD, PhD, of Sungkyunkwan University School of Medicine in Seoul, and colleagues.

In a time-dependent analysis, this relationship only strengthened the more irregular a cycle was, the group noted in the Journal of Clinical Endocrinology and Metabolism.

More specifically, women with irregular cycles lasting over 31 days in between periods saw this increased risk, with 40-day or longer cycles tied to the highest risk:

• 31- to 39-day cycles: HR 1.27 (95% CI 1.15-1.39)
• ≥40-day cycles: HR 1.49 (95% CI 1.38-1.60)

“Importantly, our results indicate that menstrual irregularity, which is easier to diagnose and usually presents earlier than PCOS [polycystic ovary syndrome], highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” Ryu’s group wrote.

“This link was not explained by obesity,” Ryu added in a statement. “Previous studies have shown that long or irregular menstrual cycles are associated with type 2 diabetes and cardiovascular disease, but our study is the first to find a link between long or irregular menstrual cycles and NAFLD.”

“Young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD as well as other cardiometabolic diseases,” he suggested.

In a subgroup analysis of women with a homeostatic model assessment of insulin resistance (HOMA-IR) less than 2.5 — indicating less insulin resistance — these associations were weakened but were still significantly high: women with 31- to 39-day and ≥40-day irregular menstrual cycles saw an 18% and 27% higher risk for developing NAFLD, respectively.

“This suggests that insulin resistance, which has been posited to contribute to the association between PCOS and NAFLD, does not fully explain the association between long or irregular menstrual cycles and NAFLD demonstrated in our study,” the researchers pointed out.

The group explained that while the mechanisms underlying the association between long or irregular menstrual cycles and NAFLD aren’t fully clear just yet, some possible explanations could be estrogen exposure, androgen excess, and hypogonadotropic hypogonadism.

The study’s final cohort included Korean women under the age of 40 who underwent annual exams at a health center in Seoul and Suwon, South Korea. Exclusion criteria included a history of liver disease, hepatitis B or C, higher alcohol consumption, and abnormal thyroid functioning.

NAFLD diagnosis was based on hepatic steatosis identified on abdominal ultrasonography performed by radiologists. At baseline, 7.1% of women had prevalent NAFLD and 27.7% had long or irregular menstrual cycles. During a median 4.4-year follow-up period, 8.9% of women developed incident NAFLD.

Ryu’s group noted that diagnosing NAFLD via ultrasonography instead of histological diagnosis — the “gold standard” — was a limitation to the study, but explained that ultrasonography was a more appropriate option for routine health screening examinations.