Aging, that inevitable march towards senescence, has puzzled and intrigued scientists for centuries. Traditionally, our understanding of aging has centered on wear and tear, with the belief that our cells and tissues break down over time due to accumulated damage. However, a fresh perspective by Dr. João Pedro de Magalhães challenges this narrative, suggesting that the very processes responsible for our growth and development might also be driving our decline after we hit our reproductive prime.

Perimenopause, a transitional phase preceding menopause, is increasingly recognized as a distinct and hormonally dynamic stage marked by metabolic, emotional, and reproductive changes. This review explores the neuroendocrine underpinnings of perimenopause, focusing on the role of estrogen and progesterone in modulating hypothalamic circuits that govern appetite, energy expenditure, and menstrual regularity. Experimental studies in animal models reveal how declining estrogen signaling through estrogen receptor alpha (ERα) in specific hypothalamic neurons contributes to weight gain and metabolic dysregulation, while clinical research highlights progesterone’s essential role in maintaining endometrial stability. Drawing on both mechanistic insights and large-scale interventions, we examine evidence-based strategies—including tailored nutrition, structured exercise, and hormone therapy—to mitigate the most common perimenopausal symptoms and support long-term health during this pivotal life