When I talk about female athletes, hormones, and health, I always start from a simple but critical foundation: energy availability. It’s the balance between how much energy you take in (from food) and how much you expend (through training, daily life, and basal metabolic rate). When that balance tips too far into the negative—too little energy coming in to meet your body’s demands—it can disrupt nearly every hormonal system we have.
And one of the key players in this process is a neuropeptide called kisspeptin. Kisspeptin is a brain hormone that acts as a master switch for reproduction; it helps to trigger puberty and controls the release of other hormones that regulate the menstrual cycle and fertility.
From Rodents to Real Women
Kisspeptin was first discovered in rodent models, where scientists observed its essential role in regulating reproductive hormones. Those early studies were groundbreaking—they showed that kisspeptin acted as a master switch for the hypothalamic-pituitary-gonadal (HPG) axis, helping to control the release of GnRH (gonadotropin-releasing hormone) and, in turn, the downstream cascade of reproductive hormones like LH and FSH.
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Rodent studies were necessary in those early days because they allowed researchers to explore mechanisms we simply couldn’t study in humans at the time. But here’s the key point: we’ve since moved far beyond those animal models. Over the past two decades, researchers have conducted extensive human studies to understand how kisspeptin functions in men and women: where it’s located in the brain, how it differs in density and activity, and how it interacts with energy and stress signals.
A great 2022 review pulls together this work, showing that kisspeptin isn’t just about reproduction—it’s part of a broader network linking nutrition, stress, and endocrine function. Researchers have found that kisspeptin acts differently in men and women. In women, kisspeptin-producing neurons are more numerous and more closely linked to the hormone-releasing pathways that control reproduction, highlighting how sex differences in brain signaling influence hormonal health and fertility.
What Happens in Low Energy States
One of the landmark studies in this area came from Heather Allaway and Professor Mary Jane DeSouza (2016), who examined the metabolic and hormonal alterations in young women with functional hypothalamic amenorrhea (FHA)—a condition often triggered by low energy availability and high physical stress.
They found that these women showed:
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Growth hormone resistance and reduced IGF-1,
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Elevated cortisol,
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Increased ghrelin, peptide YY (PYY), and adiponectin, and
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Decreased leptin, triiodothyronine (T3), and kisspeptin.
In short: when you’re under-fueled, your body perceives stress and begins to downregulate reproductive function as a protective mechanism. Kisspeptin, which sits upstream of reproductive hormones, becomes suppressed.
Connecting the Dots: Kisspeptin, Appetite, and Stress
The interplay between these hormones is complex but fascinating:
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Ghrelin and PYY are both gut-derived hormones that regulate hunger and fullness. Ghrelin rises when you’re hungry; PYY signals satiety.
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In a low-energy state, ghrelin is elevated (you should feel hungry), but PYY is also elevated, blunting that hunger drive.
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Leptin, which reflects energy stores, is suppressed, further signaling to the brain that resources are scarce.
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Meanwhile, neuropeptide Y (NPY)—a powerful appetite stimulator—is modulated by kisspeptin. When kisspeptin is suppressed (as it is in low energy), NPY should rise to drive eating behavior. But with high PYY, that signal can get dampened.
The result? You feel less hungry than your body actually needs to be—so the energy deficit persists.
Adding another layer: both ghrelin and cortisol rise during stress and energy deficit. This relationship can elevate blood glucose levels, reduce insulin sensitivity, and increase catabolic signaling—all of which can interfere with recovery and adaptation from exercise.
The Bigger Picture
The takeaway is this: kisspeptin is part of a finely tuned system that integrates signals from energy intake, stress, and reproductive needs. When energy availability drops too low, the entire network—from appetite regulation to menstrual function—gets disrupted.
And while rodent studies helped us uncover the initial mechanisms, we now have robust human research that allows us to translate these findings directly into women’s health and performance.
Kisspeptin has given us critical insight into how the brain senses energy and reproductive readiness. Today, our understanding comes from data on real women in real training environments—not lab mice. As I’ve said many times before, women’s health research is uniquely complex, spanning metabolism, neuroendocrine signaling, menstrual physiology, and performance outcomes. The physiology of a female athlete is not the physiology of a rodent, and my science has never treated it that way.
My mission has always been to advance rigorous, translatable science that reflects the reality of women’s physiology—to move the field forward, not backward.
We’re long past the days of inferring female responses from animal data. The work now is about refining and applying what we know from real women, in real conditions, to drive better health, performance, and longevity outcomes.
When we recognize the signs of low energy availability—fatigue, disrupted cycles, poor recovery, and stalled performance—we can trace those effects back through the hormonal cascade that includes kisspeptin. Supporting your physiology starts with fueling well, managing stress, and honoring the interconnected systems that power your performance.
Science evolves—and so must we. That’s how progress is made, and that’s exactly where I’ll keep my focus.
Related Reading:
- Kisspeptin-54 Stimulates Gonadotropin Release Most Potently during the Preovulatory Phase of the Menstrual Cycle in Women
- Serum kisspeptin and corticotropin-releasing hormone levels in patients with functional hypothalamic amenorrhea
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Kisspeptin and LH pulsatility in patients with functional hypothalamic amenorrhea
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Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential
- Kisspeptin Neurons from Mice to Men: Similarities and Differences
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Effects of low energy availability on female reproductive function
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