Sex-differential testosterone response to long-term weight loss

Objectives: Obesity-associated gonadal dysfunction is common in patients seeking weight loss interventions. This study examined the incremental effect of weight loss on gonadal axes in men and women over 3 years, comparing dietary intervention (Diet) with bariatric procedures: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and laparoscopic adjustable gastric banding (LAGB). Additional analyses assessed changes in corticotropic, somatotropic, and thyroid axes. Methods: Prospective, observational study of 61 adults with BMI >30 kg/m², mean age 51 (SD 11) years. Endocrine parameters were measured at baseline and at 6 timepoints over 36 months. Results: For each 1 kg of weight lost from baseline to 36 months, total testosterone increased by 0.6% (95% CI: 0.2%, 1.0%, p=0.002) in males and decreased by 0.8% (95% CI: -1.4%, -0.3%, p=0.003) in females; changes remained significant after controlling for age and menopausal status (females). At 36 months vs Diet, RYGB women had lower total testosterone by 54% (95% CI: -90%, -17%, p=0.004), reduced free androgen index (FAI) by 65% (95% CI: -114%, -17%, p=0.009), and SG had reduced FAI by 39% (95% CI: -77%, 0%, p=0.05). No such differences between groups were noted in males. Across the cohort, per kg weight loss ACTH declined by 0.3% (95% CI: 0.0, -0.5%, p=0.05), IGF-1 increased by 0.4% (95% CI: 0.2%, 0.7%, p=0.005), with no such change in TSH. Conclusions: Testosterone changes were proportional to weight loss: androgen reduction in females was independent of age and menopausal status and more pronounced after bariatric procedures, warranting further research on functional and cognitive impacts in postmenopausal women. Observed pituitary hormone changes may contribute to metabolic benefits of bariatric surgery.

Malgorzata M. Brzozowska, Dana Bliuc, Artur Mazur, Paul A. Baldock, John A. Eisman, Jerry R. Greenfield, Jacqueline R. Center