Links Between Sex Hormone Ratios and Metabolic Syndrome and Inflammation in U.S. Adult Men and Women

Metabolic syndrome (MS) is a group of conditions that occur together, raising the risk for cardiovascular disease (CVD) in men and women and is associated with a number of diseases including sleep apnea, liver disease, polycystic ovary syndrome (PCOS), and hormone-sensitive cancers. 

The prevalence of metabolic syndrome varies by region and population, but it is estimated to affect around 20-25% of the global adult population. Currently, it’s estimated that approximately 1 billion people worldwide may have metabolic syndrome. 

Additionally, sex hormones play a critical role in sex differences and cardiovascular disease risk associated with MS.  However, the relationship between sex hormone rations and metabolic and inflammatory markers are unclear according to sex and age differences.  

As part of this study, Dubey et al. evaluated the associations of sex hormone ratios with MS and inflammation among males and females. 

Currently CVD accounts for 33%-40% of all mortality in the United States and European Union. Men are more likely to be at risk for CVD than women, however the risk of women developing CVD increases drastically after menopause.   

According to the authors, this study found that the Free Estradiol Index (FEI) is a more reliable indicator of metabolic syndrome (MS) and high C-reactive protein (CRP) levels than other hormone indexes in men across all age groups. For women over the age of 50, FEI is also strongly associated with these conditions. However, in women under 50, the Free Androgen Index (FAI) is more closely linked to MS and high CRP levels. 

Based on these findings, Dubey et al. recommend that doctors regularly check these hormone ratios to identify individuals at risk for cardiovascular disease (CVD) and to manage MS and inflammation early.

In men, FEI emerged as the strongest predictor of MS and high CRP levels, regardless of age. This finding aligned with the limited existing research primarily focusing on older men.  The authors point out that this study is among the first to demonstrate this association in younger men. For women aged 50 and older, a high FEI was consistently linked to adverse metabolic and inflammatory profiles. Emerging studies continue to support these findings and suggest that managing FEI levels could help reduce the risk of MS and related inflammatory conditions in older women.

For younger women under 50, FAI was identified as the most critical factor associated with MS and high CRP. The study’s findings in this area supports other research indicating that higher androgen levels are a common feature in women with MS before menopause. 

In both men and women, low levels of Sex Hormone-Binding Globulin (SHBG) were linked to higher rates of MS and CRP, indicating that SHBG is an important marker of metabolic health across all ages and sexes.

The results of this study suggest that regular evaluation of sex hormone ratios, particularly FEI and FAI, is crucial for assessing and managing the risk of MS and inflammation. The authors point out that this approach could help doctors identify individuals at risk for CVD and develop early intervention strategies. However, it is important to note that Dubey et al’s study design does not allow for the establishment of a cause-and-effect relationship. Additionally, hormone levels were measured only once, which may not accurately reflect long-term exposure.

The authors conclude the findings of this study highlight the importance of monitoring sex hormone ratios to better understand and manage metabolic and inflammatory conditions. The authors also call for additional research, especially long-term studies, to confirm these findings and to further explore the role of these hormone ratios in different age groups and sexes.

Source: Dubey P, Singh V, Venishetty N, Trivedi M, Reddy SY, Lakshmanaswamy R, Dwivedi AK. Associations of sex hormone ratios with metabolic syndrome and inflammation in US adult men and women. Front Endocrinol (Lausanne). 2024 Apr 10;15:1384603. doi: 10.3389/fendo.2024.1384603. PMID: 38660513; PMCID: PMC11039964.