Investigating the Link between Low Testosterone and Metabolic Syndrome

Prior studies have reached contradictory conclusions about how strongly low levels of total testosterone (TT) correlate with high levels of metabolic syndrome (MetS).

Now, a meta-study explains the apparent contradictions with analysis that suggests the strength of the correlation varies among the different components of MetS and, sometimes, among fatter and leaner patients.

Overall, the study authors wrote in PLoS ONE, there are very significant connections between low TT and MetS‑‑and those connections are significant, in turn, because MetS greatly increases the risk of both cardiovascular disease and type 2 diabetes.

Men in any given quartile of the TT distribution were 69% more likely to have MetS at the outset of the component studies than men in the next quartile up (95% confidence interval [CI] 1.60 to 1.77). They were also 25% more likely to develop MetS than men in the next quartile up (95% CI, 1.16-1.36).

A man in the lowest TT quartile was, in other words, about five times as likely as a man in the highest quartile to have MetS at the beginning of a study and, if he did not start with it, nearly twice as likely to develop it.

The strength of the association between TT and the chance of developing MetS varied, however, with patient BMI. It was, unexpectedly, strongest in men with the lowest BMIs < 25 kg/m2 and weakest in men with middling BMIs. (Different BMIs were not associated with any significant differences in the relationship between TT and preexisting MetS.)

The association with testosterone levels was also stronger for some MetS components than others. Hypertriglyceridemia, abdominal obesity and hyperglycemia exhibited the strongest ties to testosterone levels. Hypertension exhibited the weakest ties.

“The major strength of our study was that by re-analyzing the individual data from 20 observational studies, we were able to study relevant subgroups and individual MetS components with sufficient statistical power,” the meta-study authors wrote.

“Furthermore, the use of raw data enabled us to apply consistent methods for MetS assessment and FT estimation, and to adjust for potential confounders in a uniform way.”

The research team, which was led by Judith S. Brand, MSc, began by identifying 33 cross-sectional or prospective published studies that looked at how total testosterone and sex hormone-binding globulin (SHBG) were associated with MetS.

The authors of 20 studies agreed to share raw data with Brand’s team, which asked for information about a wide range of patient characteristics: waist circumference, systolic and diastolic blood pressure, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, TT and SHBG concentrations, age at recruitment, use of hormonal therapy, timing of blood sample collection and details of any overnight fast, assay methods and length of follow-up for prospective data. If available, data were also collected on ethnicity, smoking status, alcohol consumption, physical activity, BMI, insulin concentration, history of CVD, type 2 diabetes and hypertension.

Eventually, the researchers got nearly complete data on nearly 10,000 patients and began crunching the numbers to spot relationships.

The meta-study authors noted several potential limitations in their work‑‑issues that ranged from methodological differences in the underlying studies to the fact that 13 original studies were not included‑‑but concluded that their results were likely quite robust.