Relationships among Gonadotropins, Sex Hormones, and Vascular Function in Adolescents with Normal Weight or Obesity

Objective: Childhood obesity may lead to premature cardiovascular disease in adulthood. Excess adiposity suppresses gonadotropin [luteinizing hormone (LH), follicle-stimulating hormone (FSH)] production in both adolescent males and females, which act upon the gonads, leading to the release of the sex hormones (estrogen and testosterone). Both estrogen and testosterone have been linked to vascular function. Relationships among gonadotropins, sex hormones, and vascular function are not completely understood in male and female adolescents across the weight-status spectrum. We, therefore, sought to examine associations among gonadotropins, sex hormones, and vascular health in adolescents with normal weight or obesity. We hypothesized that increased levels of gonadotropins would be associated with worsened vascular function, and higher levels of estrogen would be associated with favorable vascular function. Methods and Data: Adolescents (n=58; 12– <18-years of age) were stratified according to body mass index (BMI) percentile into normal weight (5th – <85th BMI percentile; n=25) and obesity (³95th BMI percentile; n=33) categories. Fasting blood samples were collected to measure FSH, LH, testosterone, estradiol, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), very-low-density lipoprotein cholesterol (VLDL), high-density lipoprotein cholesterol (HDL), glucose, and insulin. Insulin resistance was calculated using the homeostatic model assessment (HOMA-IR). Vascular function was measured via ultrasonography for measures of carotid artery compliance and distensibility [i.e., diameter compliance (cDC), incremental elastic modulus (cIEM)], and brachial artery flow mediated dilation (FMD). Results: Female adolescents with obesity had a significantly greater ( p=0.009) FMD compared to females with normal weight. Triglycerides, VLDL, total cholesterol-to-HDL ratio, HOMA-IR, and insulin were also significantly greater (all p<0.05) in adolescents with obesity compared to those with normal weight, while HDL was significantly lower ( p<0.0001). FSH, LH, testosterone, and estradiol did not statistically significantly differ between the normal weight and obesity groups in either sex. After adjusting for age, multiple comparisons, and stratifying by sex, higher testosterone was associated with decreased cDC (p=0.018) in females. Additionally in females, higher testosterone was associated with increased cIEM ( p=0.002). In adolescent males, higher estrogen was associated with decreased cDC ( p=0.006) and increased cIEM ( p=0.003). Conclusion: Adding to previous research showing relationships between sex hormones and vascular health in adults, the current study shows associations between sex hormones and cDC and cIEM in adolescents. That said, we found no associations between gonadotropins and measures of vascular function in adolescents with normal weight or obesity. Future studies are needed to confirm these results in a larger cohort and among those with BMI in the overweight (85th - <95th BMI percentile) category and differentiating severe obesity (>120% of the 95th percentile, or >35 kg/m2). Dr. Kelly serves as an unpaid investigator, consultant, and educator for Eli Lilly, Novo Nordisk, and Vivus; an unpaid consultant for Boehringer Ingelheim; receives donated study medication from Novo Nordisk and Vivus for NIDDK-funded clinical trials. Dr. Bomberg has served as a site principal investigator and site co-investigator for Novo Nordisk. His research program is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award number K23DK125668. The content is solely the responsibility of the authors and does not necessarily represent the offcial views of the NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.