High aromatase activity in hypogonadal men is associated with higher spine bone mineral density, increased truncal fat and reduced lean mass

Objective: Because the aromatase enzyme catalyzes the conversion of testosterone to estradiol (E2), the activity of this enzyme could be important in the musculoskeletal health of men with low testosterone. The objective of the present study is to determine the influence of aromatase activity on the bone mineral density (BMD) and body composition of patients with hypogonadism. Design: Cross-sectional study. Methods: The baseline data of 90 patients between 40 and 74 years old who participated in a genetic study of response to testosterone therapy in men with low testosterone (i.e., <300 ng/dl) were analyzed. BMD and body composition were measured by dual-energy X-ray absorptiometry. Serum testosterone was measured by automated immunoassay, E2 was measured by ultrasensitive enzyme immunoassay, and sex hormone-binding globulin was measured by enzyme immunoassay. Results: Men in the highest tertile of E2 to testosterone ratio (E2:T) had the highest spine BMD (P≤0.037), highest truncal fat (P=0.046), and lowest truncal lean body mass (P=0.045). A similar pattern was observed in the upper extremities; that is, fat mass significantly increased (P=0.047), whereas lean mass significantly decreased (P=0.034) with increasing E2 :T tertiles. Conclusion: The present findings suggest that in men with hypogonadism, aromatase activity could be an important determinant of musculoskeletal health. Men with high aromatase activity are able to maintain a higher BMD despite low circulating testosterone, but they have lower lean and higher truncal fat mass as compared to those with lower aromatase activity.