Lipedema-like Phenotype and Cancer Prevalence in US Women: A Cross-Sectional Analysis of NHANES 2011–2014

ABSTRACT Objective To examine the association between lipedema-like peripheral fat distribution and cancer prevalence in a nationally representative sample of US women. Methods We analyzed cross-sectional data from 2,818 women aged 20 to 59 years in NHANES 2011–2014. The exposure was leg-to-trunk fat ratio (LTR) measured by DXA. Multivariable logistic regression estimated odds ratios (OR) for cancer history, adjusting for BMI, race/ethnicity, smoking, and education. Primary models excluded age to estimate the phenotype’s total effect (viewing age as a mediator). Results Cancer prevalence was 4.6%. Women with cancer exhibited lower LTR compared to controls ( P =.0048). Each 1-SD increase in LTR was associated with 20% lower cancer odds (OR 0.80; 95% CI 0.67–0.95; P =.011). This inverse association was robust among women without obesity (OR 0.67; 95% CI 0.53–0.85; P =.0007) and showed a consistent trend among women with obesity (OR 0.74; P =.07). Descriptive analyses confirmed that women with cancer presented lower LTR within all pre-menopausal age decades. Conclusions A peripheral fat distribution consistent with the lipedema-like phenotype is inversely associated with cancer prevalence. This protection appears robust in women without obesity and follows a similar directional trend in women with obesity, suggesting that gluteofemoral adipose tissue may serve as a protective immunometabolic buffer. Clinical Trial Registration: Not applicable (Analysis of publicly available NHANES data).