MON-209 Perimenopause as a Vulnerable Period for Obesogenic Medications

Abstract Disclosure: S.L. Stockman: None. M.E. Manning: None. M.V. Zanni: None. Background: Perimenopause marks a period of accelerated atherosclerotic cardiovascular disease (CVD) risk, driven in part by redistribution of body fat. During perimenopause, women experience an expansion of visceral adipose tissue (VAT), even in the context of minimal-to-modest weight gain. Concomitantly, women may experience a reduction in gluteofemoral subcutaneous adipose tissue (SAT). This pattern of redistributed fat is associated with a greater prevalence of CVD risk factors and a higher incidence of CVD events. Here we present a case of disproportionate weight gain and fat redistribution in a woman newly-initiating a potentially obesogenic long-acting injectable antipsychotic medication during perimenopause. Clinical Presentation: A 46-year-old woman with primary hypothyroidism on levothyroxine presented to her endocrinologist with concerns about weight gain. She also reported oligomenorrhea and vasomotor symptoms. She had been receiving counseling from a psychiatrist for a diagnosis of schizoaffective disorder, and within the year, had been initiated on a monthly, extended-release injectable suspension of aripiprazole lauroxil. On physical exam, her weight had increased by 9.2kg, shifting her to an overweight BMI. There was notable centripetal fat distribution, without other Cushing’s stigmata. Laboratory evaluation revealed TSH within normal limits (though previously intermittently elevated in the setting of incomplete adherence), an elevated FSH level, and an undetectable AMH. HCG was negative, and neither prolactin nor 24-hour urine free cortisol levels were elevated. Ultimately, her psychiatrist discontinued her long-acting aripiprazole therapy while continuing counseling. Two years post medication discontinuation, weight loss has not been achieved, despite implementation of dietary changes and augmented physical activity. Conclusions: New initiation during perimenopause of a medication known to have mild-to-moderate obesogenic effects resulted in dramatic weight gain (10x above that described in package insert), and excess weight was not shed despite medication discontinuation. While significant weight gain is not anticipated during the menopausal transition, this case suggests that factors related to perimenopause may have contributed to medication-induced weight gain which was centrally distributed. Given that adipocytes possess metabolic memory, complicating weight loss, this case highlights perimenopause as a critical period of metabolic vulnerability to pharmacologic insult. Clinicians caring for perimenopausal patients should exercise caution in initiating medications with obesogenic side effects. If such medications are needed, diligence is warranted in frequent re-reassessment of cardiometabolic risk indices and attention to concomitant salutary lifestyle modifications. Presentation: Monday, July 14, 2025