We often speak of weight as a matter of simple math—calories in, calories out. But the body doesn’t work like an equation when it’s grieving or under chronic stress. It behaves more like a survivor, clinging tightly to resources in the face of perceived danger. And in that physiological equation, cortisol—our primary stress hormone—plays a central role.

The cortisol connection

Cortisol is released by the adrenal glands in response to stress through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Under acute stress, this response is adaptive. But with chronic psychological stress, especially following significant life events, cortisol remains elevated—and that shift changes everything.

According to a 2021 review published in Obesity Reviews, prolonged cortisol elevation is associated with increased abdominal adiposity, altered glucose metabolism, and a disrupted appetite signaling system, particularly in the hypothalamus. A study in Psychoneuroendocrinology found that individuals with higher chronic stress and elevated cortisol levels experienced greater difficulty with weight loss, even when following a caloric deficit.

Put simply: Your body doesn’t know the difference between grief and famine. It just knows something is wrong. And in response, it holds on to fat as a biological insurance policy.

GLP-1s aren’t magic—especially when stress persists.

GLP-1 receptor agonists like semaglutide and tirzepatide have shown impressive results in many patients. But their efficacy still depends on the underlying hormonal environment.

A 2023 article in The Journal of Clinical Endocrinology & Metabolism noted that chronic elevations in cortisol may attenuate the appetite-suppressing effects of GLP-1s, and may also affect insulin sensitivity, compounding the metabolic challenges in stressed individuals. This might explain why some patients—particularly those under duress—respond less robustly to medications that seem almost miraculous for others.

Managing cortisol in a weight-obsessed world

While we can’t eliminate life stressors—especially the monumental ones like grief—we can modulate how our bodies respond to them. Research supports several non-pharmacologic strategies for regulating cortisol levels: consistent sleep, mindfulness-based practices, trauma-informed therapy, gentle movement like yoga or walking, and even structured social connection. A 2020 meta-analysis in Health Psychology Review found that individuals who engaged in regular mindfulness or stress-reduction interventions had significantly lower cortisol levels and improved metabolic markers. Importantly, these approaches aren’t about rapid weight loss—they’re about restoring balance to an endocrine system that’s been hijacked by chronic alarm. For patients like me, and maybe like yours, the real work isn’t about punishing the body for gaining weight—it’s about helping it feel safe enough to let it go.

The set point theory and life after loss

There’s also the question of set point theory—the idea that the body “defends” a particular weight range, adjusting hunger and energy expenditure to keep you there. Traumatic events, prolonged stress, and even medications like corticosteroids can shift that set point upward. Once that happens, returning to a previous weight becomes biologically harder, not just psychologically harder.

After my sister died, I gained 30 pounds in just four months. At first, I didn’t fight it. I was grieving, exhausted, and emotionally raw. Food brought brief moments of comfort in a season where comfort was otherwise hard to find. But eventually, I tried to turn it around. I cleaned up my diet. I returned to exercise. I even began a GLP-1 receptor agonist, hoping it might jump-start what felt like a stalled metabolism. That was three months ago. I haven’t lost a single pound.

It’s possible, based on emerging evidence, that grief itself may be a set point-altering event. The loss rewires your sleep, your appetite, your gut microbiome, and your endocrine system. That’s not a willpower problem. That’s a whole-body recalibration.

A different kind of compassion

Weight regulation is often framed as a simple matter of discipline or willpower, but this overlooks the complex interplay between stress physiology, neuroendocrine response, and emotional burden. When a patient says they can’t lose weight, it may reflect more than lifestyle habits—it may indicate a body responding appropriately to chronic stress or unresolved grief. Rather than defaulting to assumptions, clinicians should consider the possibility that weight gain is, at times, a physiological defense—a signal of dysregulation, not indulgence. Understanding this distinction can shift the clinical approach from correction to support.

Sarah White is a nurse practitioner, small business owner, and premedical student based in Virginia. With a background in clinical practice and caregiving, she brings a unique perspective to the intersection of medicine, family life, and community service. She volunteers with the Medical Reserve Corps and is preparing to apply to medical school in 2026.

Sarah is also the founder of two growing ventures: Wrinkle Relaxer, where she specializes in aesthetic treatments, and Bardot Boutique Aesthetics, a space for curated beauty and wellness services.