High leptin levels independently associated with low testosterone in men

Increasing leptin levels are independently associated with decreasing testosterone and could be a cause for testosterone deficiency in men with obesity, according to data from the National Health and Nutrition Examination Survey III.

“In a large sample representative of the American population, increasing serum leptin is independently associated with both decreasing total and free testosterone levels, even when controlling for other associated factors,” Thiago Fernandes Negris Lima, MD, a research fellow in the department of urology at the University of Miami Miller School of Medicine, and colleagues wrote in a study published in Androgens: Clinical Research and Therapeutics. “Leptin is one of the several factors that can explain the underlying association between obesity and testosterone deficiency.”

Researchers conducted a cross-sectional analysis of 1,193 men aged 20 to 90 years in NHANES III from 1988 to 1991. Data on age, ethnicity, waist circumference, diabetes, hypertension, smoking status, leptin levels and testosterone levels were analyzed. Researchers examined the association between serum leptin, calculated free testosterone and testosterone levels after excluding confounding factors such as age, history of diabetes, history of hypertension and waist circumference.

Of the study population, 8.9% had a low testosterone level of less than 300 ng/dL. In multiple linear regression analysis, higher leptin levels, age and waist circumference were negatively associated with testosterone levels (P < .05). Leptin levels (P = .0004) and age (P < .001) were both negatively associated with calculated free testosterone.

For every 1 ng/mL increase in leptin levels, there was a reduction of 5.13 ng/dL of testosterone (P = .0285) and 0.11 ng/dL of calculated free testosterone (P = .0004). There was a reduction of 2.87 ng/dL of testosterone and 0.13 ng/dL decrease of calculated free testosterone for every additional year of life (P < .0001 for both). A 1 cm increase in waist circumference resulted in a reduction of 4 ng/dL in testosterone levels (P < .0001).

Waist circumference and age were the only significant predictors for leptin levels. Every 1 cm increase in waist circumference resulted in a 0.27 ng/mL increase in leptin (P < .0001) and every 1 year of age led to a 0.04 ng/mL decrease in leptin (P = .0402).

“Besides its proven relationship with body fat, leptin, in high levels, is believed to inhibit the testicular steroidogenic pathway and downregulate gonadotropin-releasing hormone production and secretion, causing low testosterone levels in men,” the researchers wrote. “This finding could justify the higher incidence of low testosterone in the obese population when compared with the nonobese. The purpose of this cross-sectional analysis was to evaluate the negative association between serum leptin, free testosterone and serum testosterone in men. Variables such as age, leptin and waist circumference negatively impacted testosterone levels, giving support to previous studies that suggested that metabolic syndrome and insulin resistance were related to hypogonadism in men.”