The impact of nutrition, exercise, and pharmacotherapy on menstrual health in adolescents with overweight and obesity.

BACKGROUND: Menstrual health is a critical marker of physiological and psychological well-being in adolescents. While undernutrition and energy deficiency are well-known causes of menstrual disruption through hypothalamic hypogonadal suppression, the impact of overweight and obesity on menstrual physiology is an increasing clinical concern as adolescent obesity rates continue to rise globally. OBJECTIVES: This review synthesizes current evidence on how excess adiposity, diet quality, physical activity, insulin sensitizers, and weight-modifying medications affect menstrual health in adolescents through the complex interplay of metabolic fuel signaling and reproductive endocrine pathways. METHODS: We review the activity of the hypothalamic-pituitary-gonadal axis during pubertal development and the reproductive years, highlighting how metabolic signals, particularly leptin, insulin, and ghrelin, influence gonadotropin-releasing hormone secretion. We explore how excess adiposity may accelerate menarche, disrupt menstrual regularity, and increase the risk of polycystic ovary syndrome and hyperandrogenism, likely through hyperinsulinemia and altered gonadotropin-releasing hormone pulsatility. We also discuss the contributions of suboptimal diet quality and obesity to chronic inflammation and ovarian dysfunction. RESULTS: Structured lifestyle interventions, including dietary modifications and regular physical activity, remain the cornerstone of managing overweight-related menstrual irregularities, to restore cycle regularity, and improve features of polycystic ovary syndrome. Insulin sensitizers, such as metformin, offer additional benefits for both metabolic and reproductive dysfunction. Newer incretin-based therapies, including semaglutide and tirzepatide, show promise in achieving significant weight reduction and metabolic improvements, with potential downstream benefits for menstrual health. However, data on their safety, reproductive outcomes, and optimal use in adolescents remain limited, and this area of research is still emerging. CONCLUSIONS: While underweight status and malnutrition are important underpinnings of functional hypothalamic amenorrhea, the rising prevalence of overweight and obesity poses a growing risk to menstrual health in adolescents. Early, comprehensive, and personalized strategies that integrate nutrition, physical activity, psychological support, and, when appropriate, insulin sensitizers and other pharmacotherapies can help protect and enhance reproductive endocrine function, preserve fertility, and mitigate long-term health risks. Further research is needed to clarify the impact and long-term effects of novel weight-loss medications in order to inform clinical practice in adolescent care.