Food, Hormones, and the Female Brain: A Scientific Deep Dive

Why Maintaining a Healthy Weight Gets Harder During Menopause: Part One—Appetite Regulation and the Brain

From the moment I turned 40, I noticed something peculiar in my social media algorithm: a sudden onslaught of ads for fitness classes, supplements, and that one thing I need to know or do to help me shed that stubborn middle-age weight. I hadn’t yet ventured into the world of estrogen and menopause, nor did I grasp how deeply our sex hormones influence our health beyond reproduction. But it was clear—something about entering my forties had signaled to the opportunistic world of clickbait, marketing, and sham treatments that I was now a prime target.

Long before menopause science gained mainstream traction over the past year—pulling the conversation out of hushed corners and into the spotlight—the marketers already knew: women in their forties were suddenly struggling with weight gain, and the strategies that once worked were now useless.

In fact, weight gain - especially around the midsection—is one of the most common and distressing symptoms of estrogen depletion during the menopause transition, affecting nearly 70% of women. Even those who had never struggled with weight may find their bodies changing in unfamiliar and frustrating ways. It's more than just a physical shift; it can be deeply emotional and mentally exhausting, particularly at a stage in life when energy, resilience, and self-worth are already under pressure from a society that often values youth over experience.

The reasons behind this weight gain are layered and complex, involving several of the body’s core systems. As we now know, estrogen has far-reaching effects, influencing everything from fat cells to brain function. To understand these changes, we first need to explore how our bodies regulate appetite and energy balance - because it has far less to do with willpower and discipline than we’ve been led to believe.

Our experience of hunger and fullness—what drives us to eat or stop eating—is governed by two interconnected systems: homeostatic and hedonic regulation. Both operate through complex brain pathways, integrating signals from the body, environment, and even our memories. The homeostatic system is regulated by the hypothalamus, a small but vital brain region acting as the body's metabolic control center. It continuously receives hormonal and neural signals about our energy status—how much fat is stored, whether the stomach is full, and which nutrients are circulating in the blood.

When energy stores are low, neurons in the hypothalamus—particularly in the arcuate nucleus - are activated to increase appetite. These neurons release neuropeptides like NPY and AgRP, which stimulate hunger. Conversely, when the body has enough energy, hormones like leptin and insulin activate neurons that produce POMC and CART, which suppress appetite and promote energy expenditure.

This homeostatic system is remarkably precise. It evolved to maintain energy balance within a narrow range, which is why some people can maintain a stable weight for years without counting a single calorie.

But in our modern world—saturated with energy-dense, hyper-palatable foods—this ancient system is often overridden by another powerful force: the hedonic system. This pathway, centered in the brain’s reward circuitry (especially the ventral tegmental area and nucleus accumbens), responds to pleasurable stimuli like food. Hedonic eating isn’t driven by physical hunger but by the pursuit of pleasure, emotional comfort, or habit. The same dopamine system that craves novelty or social connection also lights up for a cream-filled, cookie-topped doughnut from Crosstown - regardless of whether we need the calories.

Importantly, these two systems don’t operate in isolation; they influence and amplify one another. For example, ghrelin - a hormone released when the stomach is empty - not only signals hunger via the hypothalamus but also enhances the reward value of food by acting on the brain's reward centers. Pay attention the next time you eat when you're truly hungry: even simple foods feel more pleasurable. The opposite is true when you're overly full —even that aforementioned doughnut doesn’t quite yield the same sense of satisfaction. That’s because leptin and insulin don’t just regulate physical hunger; they also dampen our reward response to food - even highly palatable ones. 

This interplay between physiological need and psychological desire helps explain why eating behaviors are so resistant to “just use willpower” solutions. Appetite is not a simple reflex—it’s a complex, adaptive behavior shaped by survival instincts, memory, emotion, environment, and, most importantly, our genetics. Most genes linked to obesity influence one or both of the brain systems that regulate hunger and reward. Understanding how these systems interact is essential if we want to address not just what we eat, but why. This becomes even more significant when we consider the powerful influence estrogen exerts on these pathways. Let's begin by looking at its relationship to the homeostatic drive.

Tucked deep within the base of your brain forming part of your hyperthalamus, is the arcuate nucleus—or ARC. What makes this little cluster of neurons so special is that it is one of the very few brain regions not fully shielded by the blood brain barrier. This means that it has direct access to molecules in your circulation such as ghrelin, leptin, insulin, amino acids, and glucose. Those molecules act like messengers, constantly updating your brain on your body’s energy needs and reserves. You can think of the ARC as a metabolic switchboard constantly assessing whether you’re hungry, full, energized, or depleted.

Within this hub are two key types of neurons with opposing effects: NPY/AgRP neurons, which stimulate hunger and reduce energy expenditure, and POMC/CART neurons, which do the opposite—they promote fullness and encourage your body to burn energy.  And estrogen has considerable influence over them. It activates POMC neurons, enhancing feelings of satiety and increasing energy expenditure. At the same time, it inhibits NPY/AgRP neurons, dampening the signals that drive hunger. You might have noticed your appetite shifting throughout your menstrual cycle— those pre-period munchies. Now you know why. When estrogen levels drop, the signaling molecules meant to inform the ARC (arcuate nucleus) aren’t "heard" as clearly, so to speak, causing your brain to perceive a nutrient deficit that isn’t really there. But the story gets even more complicated. You might be thinking, "That doesn’t seem to happen to every woman," and you’d be absolutely right. 

For estrogen—or any signaling molecule—to influence a neuron, it must first bind to specific receptors. In the case of estrogen, these are primarily estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). Genetic variations in the genes encoding these receptors can affect how sensitive a cell is to estrogen's signal. Some women may have receptor variants that are highly responsive, allowing even low levels of estrogen to exert sufficient effects. Others may have certain polymorphisms—think of them as tiny spelling differences in the genetic code—in the ESR1 gene, which encodes estrogen receptor alpha, that have been associated with higher BMI, increased waist circumference, and disruptions in key hunger hormones like leptin and ghrelin—particularly during and after menopause. 

Let’s now turn our attention to estrogen’s influence on the hedonic drive—the desire to eat not because you’re hungry, but because it feels good. This drive originates in a different neighborhood of your brain, one that’s more concerned with reward than survival: the mesolimbic dopamine system.

At the heart of this system is the ventral tegmental area (VTA), a region that sends dopamine-producing projections to the nucleus accumbens, prefrontal cortex, and other areas that process pleasure, motivation, and reward. When you bite into a warm cookie or sip your favorite wine, this pathway lights up. It’s the reason we seek out certain foods for comfort, stress relief, or celebration—regardless of how full we are.

Estrogen plays a key role here too. It modulates how sensitive this reward circuitry is to cues like the taste, smell, and even the sight of food. Under higher estrogen conditions—such as during the first half of the menstrual cycle or with hormone therapy—the dopamine response to food tends to be more regulated. You might still enjoy that cookie, but you’re less likely to feel compelled to eat the whole box. That’s because estrogen enhances dopamine signaling efficiency, improving the brain’s ability to experience satisfaction and stop once it’s been achieved.

But when estrogen levels dip—such as before your period, during perimenopause, or after menopause—the dopamine response can become sluggish or blunted. Food no longer feels quite as rewarding, which paradoxically can lead to eating more of it in an attempt to chase the same feeling. This can especially affect women with genetic variations in dopamine-related genes or estrogen receptor function, making them more prone to emotional or reward-driven eating under low-estrogen conditions.

In essence, estrogen doesn’t just help regulate hunger—it helps regulate desire. It keeps the reward system balanced, so pleasure from food feels satisfying rather than insatiable. When that regulation falters, the hedonic drive can become louder, nudging you to seek out sugary, fatty, or highly palatable foods, not for energy—but for emotional or neurochemical relief.

So, if you’ve ever wondered why cravings hit harder before your period or why your relationship with food shifted during menopause, part of the answer lies in how estrogen shapes your brain’s reward landscape.

In short, estrogen helps regulate food intake by reducing hunger, increasing feelings of fullness, and enhancing the brain's ability to feel satisfied from eating. When levels are high, you’re more likely to stop when full and less likely to crave food for comfort. When levels drop, hunger signals increase and food feels less rewarding, which can lead to overeating despite not needing the energy. How much influence estrogen has over your appetite is largely controlled by your genes.

If you’ve found yourself gliding through the hormonal shifts of menopause without struggling with weight changes, consider it a gift of biology—not a sign of superior discipline. Others may be facing a steeper climb, not because they’re doing something wrong, but simply because they were dealt a different card.

And that is just its effect on the brain. Let’s move on and take a look at how estrogen interacts with and impacts our fat cells directly. 

Sybille Hazward