Sex Hormone Binding Globulin Changes Tied to Weight Loss Intervention in T2D

Waist circumference mediates short-term changes in sex hormones among adults with type 2 diabetes and overweight/obesity who received an intensive lifestyle intervention for weight loss, according to study findings published in the Journal of Clinical Endocrinology & Metabolism.

Individuals with type 2 diabetes face an increased risk for cardiovascular disease (CVD), with female individuals experiencing a greater relative risk compared with male individuals. However, sex differences in CVD risk among the older population remain unclear due to mediating factors such as obesity and dyslipidemia. Furthermore, previous research findings suggest that sex hormone binding globulin (SHBG) may indicate metabolic health among older adults.

To assess the association between intensive lifestyle interventions for weight loss and sex hormones, researchers sourced data from a randomized controlled trial (LookAHEAD; ClinicalTrials.gov Identifier: NCT00017953), which included US adults aged between 45 and 75 years. In LookAHEAD, the researchers evaluated the effect of an intensive lifestyle intervention, compared with an educational control, on cardiovascular morbidity in overweight/obesity and type 2 diabetes.

For this analysis, researchers randomly selected participants who had available plasma samples at baseline, year 1, and year 4. Female individuals aged younger than 55 years, premenopausal women, individuals on hormone therapy, and male individuals receiving androgen or prostate cancer treatments were excluded from the study.

The analysis included 2334 participants (1167 female, 1167 male). Participants had a mean age of 60 years. On average, female participants had a higher body mass index (BMI) than male participants (36.3 vs 34.9 kg/m²) and lower education and income levels across both study arms.

Among female participants, the lifestyle intervention vs educational control reduced estradiol (E2) and bioavailable testosterone (bioT) by 15% and 13%, respectively, but these changes were not sustained at year 4. Adjustment for waist circumference reduced the magnitude of these changes.

Among male participants, the lifestyle intervention vs educational control increased total testosterone (T) by 14% at year 1 and by 7% at year 4. Adjustment for waist circumference reduced the magnitude of these changes. No changes in bioT or E2 were observed.

Male and female participants who received lifestyle intervention vs educational control demonstrated a 19% and 21% increase, respectively, in SHBG levels at year 1. These changes were reduced after 4 years.

Lifestyle intervention vs education was also associated with mean reduction in waist circumference at year 1 for both male (-3.7 cm) and female (-6.6 cm) participants. This reduction in mean waist circumference was a significant mediator of the long-term sex hormone changes observed at both year 1 and year 4.

Limitations include the inability to directly compare hormone changes with earlier findings due to less sensitive hormone measurement methods, the lack of data on long-term implications for these sex hormone changes, and the presence of higher fracture rates in the intensive lifestyle intervention group.

The study authors concluded, “The clinical implications of assessing changes in sex hormones due to weight loss in older adults with [type 2 diabetes] should be considered in the context of an individual patient’s health risks, including cardiovascular, bone health, menopausal symptoms, cognition and quality of life.”

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.