The HPG Axis: Where Hormones and Psyche Meet
When we speak about hormones we often think of fertility, libido, or menopause. But the HPG axis (hypothalamic-pituitary-gonadal axis) is much more than a reproduction system. It is a core biological rhythm that shapes not just our physical capacity for reproduction but our vitality, mood, motivation, and connection to both body and self. In this article we will explore how the HPG axis works, how it interfaces with the psyche, how other systems (the gut, immune, HPA, thyroid) interact with it, how functional testing can go beyond standard labs, how imbalances present in psychiatric symptoms, and how we can think holistically about restoring balance. A case example will illustrate the principles.
Physiology of the HPG Axis
At the heart of the HPG axis is a cascade of communication between the brain and the gonads. The hypothalamus secretes gonadotropin-releasing hormone (GnRH) in a pulsatile fashion. The pituitary gland responds by releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These travel to the gonads (ovaries in females, testes in males) and prompt the production of sex steroids: estrogen (especially 17β-estradiol), progesterone, testosterone, and their metabolites (Acevedo‐Rodriguez et al., 2018). These sex steroids do not just act on peripheral tissues; they feed back on the brain (hypothalamus and pituitary), thus closing loops of regulation.
The pulsatility of GnRH is critical: too frequent or too infrequent pulses can alter LH/FSH ratios and downstream steroid production. Kisspeptin neurons in the hypothalamus have emerged as major regulators of GnRH release (Kaprara & Huhtaniemi, 2018). The reproductive system is thus tightly regulated but always responsive to context.
Hormones, Psyche, and Emotion
The sex steroids produced by the HPG axis shape more than gonadal function. They influence mood, cognition, motivation, and relationship to self and others. For example:
Estrogen supports serotonergic and dopaminergic signaling, enhances verbal fluency, strengthens social attunement, and contributes to mood stability.
Progesterone, through its metabolite allopregnanolone, binds GABA-A receptors and produces anxiolytic and calming effects.
Testosterone, present in both sexes albeit in different quantities, supports drive, focus, confidence, vitality and even aspects of identity.
When estrogen dips (for example, pre-menstrually, postpartum, or during perimenopause) many individuals experience irritability, anxiety, low mood. When progesterone is low, sleep may be disturbed, anxiety heightened, and the nervous system may default into a state of overarousal. When testosterone falls (men or women) fatigue, low libido, cognitive dulling and a flattening of emotional life may appear.
Thus the HPG axis is not just “reproduction” but vitality, emotional resilience, relationality, and even the texture of inner life. Dysregulation may show up as mood disorders, anxiety, irritability, low motivation or libido, cognitive fog.
The Interconnected Web: HPA, Gut, Immune, Thyroid
The HPG axis does not operate in isolation. It is integrated with other major systems. Some key connections:
HPA axis (hypothalamic-pituitary-adrenal system): Chronic stress and elevated cortisol suppress GnRH and thus reduce LH/FSH and sex steroid production (Mbiydzenyuy, Turner & Gordon, 2024). That is, when the body perceives threat it down-regulates reproduction and vitality in favour of survival.
Thyroid/HPT axis: Thyroid hormones affect sex steroid metabolism and receptor sensitivity; hypothyroidism may blunt ovarian/testicular responsiveness and shift the balance of sex hormones.
Gut microbiome / estrobolome: The gut microbial community plays a critical role in metabolising estrogens. For example the enzyme β-glucuronidase secreted by certain gut bacteria deconjugates estrogens, making them available for recirculation (Baker et al., 2017). Dysbiosis may reduce circulating free estrogen, with consequences for mood, cognition and endocrine health.
Immune system/inflammation: Sex steroids modulate immune responses and inflammation in turn influences receptor sensitivity and hormone feedback loops. For example, chronic inflammation alters gonadal steroid action and may blunt HPG axis function (Ma et al., 2025).
Metabolic/insulin system: Insulin resistance, adiposity and metabolic syndrome disrupt sex steroid balance, SHBG (sex hormone-binding globulin) levels, and possibly gonadal function.
Because each system influences and is influenced by the others, the integrity of the HPG axis depends on system-wide coherence. It is useful to think of the HPG axis as part of a network of physiological rhythm and regulation rather than a stand-alone pathway.
Psychophysiological Feedback: Mind-Body Interface
The relationship between the psyche and the HPG axis is deeply relational. Emotional trauma, early attachment wounds, chronic stress signal the hypothalamus through the amygdala and other limbic structures, altering GnRH pulsatility and sex steroid release. These hormonal cycles then shape neurotransmission and brain function, influencing mood, cognition and relational patterns. The loop is bidirectional: mental/emotional states affect hormones; hormones affect mental/emotional states.
For example if someone is stuck in chronic overarousal (due to unresolved trauma, acute stress) the HPA axis remains elevated, suppressing the HPG axis and lowering sex steroid levels, which may reduce emotional regulation and resilience. This in turn may make the person more reactive, less able to tolerate stress, further accelerating HPA activation—a vicious cycle. On the other hand, strong social connection, meaningful relational experience and emotional regulation support hormonal rhythm and resilience.
Testing Beyond Conventional Labs
Conventional reproductive hormone testing typically includes FSH, LH, estradiol, progesterone (often mid-luteal phase for women), and morning testosterone (for men). But a functional insights-driven approach can go further:
Free vs. total hormone levels: Bioavailability matters.
SHBG (sex hormone-binding globulin): Elevated SHBG may reduce free testosterone or estrogen functionality.
DHEA-S as an adrenal/gonadal precursor.
Metabolites of sex steroids: For example via DUTCH testing one can see pathways of estrogen detoxification (2-hydroxy, 4-hydroxy, 16-hydroxy) indicating whether estrogen metabolism is favourable or producing harmful metabolites.
Cortisol rhythm testing via saliva or hair: to assess HPA influence on HPG.
Gut markers: Microbiome checks for β-glucuronidase activity, microbial diversity, dysbiosis which can influence estrogen recycling (Escorcia Mora et al., 2025).
Inflammatory markers, insulin resistance markers (HOMA-IR), SHBG, leptin, adiponectin: to see metabolic and immune context.
Using these taxa and metabolic markers we shift from “what is the hormone level right now?” to “what is the story of hormonal rhythm, tissue access, metabolism, clearance, and interaction with other systems?”
Imbalances and Psychiatric/Neurobehavioral Manifestations
Imbalance in the HPG axis can contribute to psychiatric symptoms in several ways:
Low estrogen may reduce serotonin and dopamine signalling, contributing to depression, anxiety, irritability, cognitive fog.
Low progesterone (or poor conversion to allopregnanolone) may reduce GABAergic calming signalling, leading to heightened nervous system reactivity, panic, insomnia.
Low testosterone in men (and women) may lead to low drive, lack of motivation, cognitive slowing, even existential disengagement.
High or imbalanced estrogen (especially if detoxification/metabolite pathways are poor) may contribute to mood swings, irritability, pre-menstrual dysphoric symptoms, increased inflammation and possibly increased risk for anxiety and depression.
Dysbiosis of gut → impaired estrogen metabolism → altered sex-steroid availability → adverse mood/cognition (Zhang et al., 2025).
Chronic stress (HPA overdrive) suppressing HPG → reproductive hormone deficiency → reduced resilience and mood dysregulation.
Clinically one might see a person labelled “treatment resistant depression” or “anxiety” whose root is insufficient attention to hormonal rhythm and interplay with other systems.
Holistic Treatment Considerations
Restoring the HPG axis is not about simply “adding” a hormone. It is about restoring rhythm and coherence across body, brain, and relational life. Strategies include:
Stress & nervous system regulation
Trauma-informed therapy, mind-body practices (yoga, meditation, breathwork) to down-regulate the HPA axis and support HPG recovery.
Sleep hygiene and circadian entrainment: Sleep affects GnRH pulsatility and overall axis function.
Gut and liver support
Diet rich in fiber, cruciferous vegetables, and phytonutrients to support liver detoxification of estrogens and promote microbial diversity.
Probiotics/prebiotics, fermented foods to support healthy estrobolome and β-glucuronidase activity (Baker et al., 2017).
Avoidance of endocrine disrupting chemicals, reduction of toxic load to improve hormone clearance.
Nutrient and lifestyle foundations
Adequate intake of zinc, selenium, magnesium, B6, omega-3 fatty acids — all essential for sex steroid synthesis and receptor sensitivity.
Resistance training and aerobic exercise: improves insulin sensitivity, testosterone levels, and metabolic health in men and women.
Maintaining healthy body composition: excess adiposity raises aromatase, alters estrogen/testosterone balance, elevates SHBG and inflammation.
Cycle and hormone phase mapping
In women: tracking menstrual cycle phases, supporting each phase with lifestyle/nutrient/adaptogen support. For example supporting the luteal phase when progesterone is needed.
In men: focusing on metabolic context, stress reduction, weight management before exogenous hormone use.
Mind-body/relational dimension
Enhancing connection, relational support, meaning and purpose: the HPG axis is intimately tied to vitality, creativity, sexuality and relational life. Supporting meaningful connection, intimacy, and purpose can itself nurture hormonal health.
Avoid reductionist “pill for hormone” mindset; integrate emotional, social, spiritual dimensions.
Hormone therapy when indicated
In selected cases hormone replacement or supplementation may be helpful (for example bio-identical progesterone, testosterone in men under supervision). But therapy must be guided by functional testing, system context, and careful monitoring of metabolites, binding globulins, and receptor function.
Summary and Reflections
The HPG axis is often misunderstood as purely reproductive. But as we have seen it is intimately involved in our emotional life, motivation, vitality, relational and creative capacities. Hormones like estrogen, progesterone and testosterone are not just passive chemicals but mediators between brain and body, psyche and soma.
Recognising the interconnectedness of the HPG axis with the gut microbiome, the immune system, the HPA axis, metabolism, thyroid and nervous system invites a shift in how we approach hormonal health: from “test the number and give the pill” to “map the rhythm, context and coherence”. Functional testing helps us to tell the story behind the hormones. Holistic treatment invites body/mind integration, nutritional and lifestyle foundations, relational and meaning oriented work, and where appropriate, hormonal support grounded in system context.
In clinical practice or self-care the question becomes: how coherent is the system? How resilient is the rhythm? How connected are your body, mind, gut, hormones, relationships? When we bring compassion to that interface between psyche and body we begin to move from managing symptoms to restoring the full spectrum of human vitality.
References
Acevedo‐Rodriguez, A., Mani, S. K., & Handa, R. J. (2018). Emerging insights into hypothalamicpituitarygonadal axis regulation. Journal of Neuroendocrinology, 30(2). https://doi.org/10.1111/jne.12590
Baker, J. M., Al-Nakkash, L., & Herbst-Kralovetz, M. M. (2017). Estrogen–gut microbiome axis: Physiological and clinical implications. Maturitas, 103, 45-53. https://doi.org/10.1016/j.maturitas.2017.06.025
Escorcia Mora, P., et al. (2025). The role of the gut microbiota in female reproductive health: A systems-level perspective. Life, 15(5), 762.
Kaprara, A., & Huhtaniemi, I. T. (2018). The hypothalamic–pituitary–gonadal axis: Tales of mice and men. Molecular and Cellular Endocrinology, 466, 4-14.
Mbiydzenyuy, N. E., Turner, G., & Gordon, J. (2024). Stress, hypothalamic-pituitary-adrenal axis and male aggression: insights and translational implications. Metabolic Brain Disease.
Ma, Y., et al. (2025). Critical illness and sex hormones: Response and impact of the hypothalamic–pituitary–gonadal axis. Endocrinology, Diabetes & Metabolism, 8(2), e154.
