OR35-05 Effects of Hormonal Contraceptives on Brown Adipose Tissue Activity and Glucose Metabolism in Women of Reproductive Age

Abstract Disclosure: A.D. De Jesus: None. A. Karagiannidis: None. P. Sridhar: None. M.A. Cowley: None. T. Mustafa: None. B.A. Henry: None. Introduction: It is estimated that Worldwide, over 200 million women use a hormonal contraceptive, yet few studies have addressed possible side-effects on energy balance and glucose metabolism. To date, the role of 17β-estradiol on energy balance has been well-documented; however, the role of progesterone or synthetic progestins is largely unknown. The aim of the study was to investigate the effects of different hormonal contraceptives on energy expenditure and glucose metabolism in healthy young women. Furthermore, we aimed to address whether the dose or pharmacological profile of progestin influenced the metabolic effects of hormonal contraceptives. Methods: Young female participants (ages 18-39y/o; n=9-12), who were eumenorrheic (luteal phase of the menstrual cycle) or taking hormonal contraceptives, including either combined oral contraceptive pill (COCP) or progestin-only implant were recruited. Women using COCP were subdivided into two groups: low dose (progestin concentration of 100-150μg/ day) or high dose (progestin concentrations of 2-3mg/ day). Resting energy expenditure (REE) was determined using the indirect calorimetry in fasted conditions. Body composition (BMI, weight, waist circumference) was assessed. Cutaneous supraclavicular (SCV) temperatures in response to a mild cold exposure (15oC) or an oral glucose tolerance test (75g) were assessed using infrared thermography. Continuous glucose monitors determined changes in transcutaneous glucose concentrations over time. A single blood sample was collected to measure 17β-estradiol, progesterone, follicle stimulating hormone (FSH), and insulin concentrations. Results: Concentrations of 17β-estradiol and progesterone were negligible in women using high dose COCPs (p<0.0001). In addition, FSH levels were lower in the high dose COCP group compared to control (p<0.05) and progestin-only groups (p<0.0001). Overall, cold-induced adaptive thermogenesis was shown to be lower with contraceptive use (p<0.0001). The inhibitory effect on BAT heat production was greatest in the high dose COCP (p<0.0001) and progestin-only groups (p<0.0001). In response to the glucose challenge, BAT activity was reduced with contraceptive use (p<0.01). Similarly, the inhibitory effect on BAT temperature was greatest in the high dose COCP group (p<0.0001). Moreover, the reduction in BAT temperature was associated with increased glucose concentrations and impaired glucose tolerance in the high dose COCP group (p<0.01). Insulin levels were similar in all groups. There was no effect of low dose COCPs on BAT activation in response to cold or glucose. Conclusion: Hormonal contraceptives that contain high dose progestin inhibited BAT activation and caused glucose intolerance in young women. These results support the use of low dose COCPs particularly in women who are at risk of developing cardiometabolic disease. Presentation: Monday, July 14, 2025