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Leptin, an adipocyte-derived hormone, is known to play an important role in body fat. Gender, age, degree of obesity and sex steroids are expressed differentially in men and women.We measured serum leptin, testosterone and β-estradiol concentration by radioimmunoassay in 300 subjects (60 normal weight, 60 underweight, 60 overweight, 60 obese and 60 morbidly obese) by age group (18–40 years and 41–62 years), using full-length recombinant human leptin as a standard.The present study found that morbidly obese and obese men and women older than 50 years had 50–70% higher body mass index (BMI)-adjusted leptin levels than younger subjects. In addition, obese and underweight subjects showed a tendency towards lower BMI-adjusted leptin levels in younger than older, in both men and women subjects. Multiple regression analysis showed that age was positively correlated with leptin in both genders, even if the slope of rise was twice as high in women than in men. Together, these results indicate that in both genders, most prominently in females, aging is associated with increased leptin production that is independent from the amount of fat and/or the role of sex hormones.In conclusion, our data show that serum leptin concentrations in men and women gradually increase during aging, being higher in women than in men, but they are independent from BMI and other hormones. The inclusion of several hormones in our regression model showed that only testosterone in men, and estradiol and androstenedione in women were independent contributions to serum leptin levels, possibly accounting for part of the leptin sexual dimorphism in a south Indian population.