--- title: How does the stress response system affect depression during reproductive stages like PMDD? description: The HPA axis, which controls the stress response, changes during reproductive stages and plays an important role in depression risk at vulnerable times like P url: https://niyora.com/research/papers/the-role-of-the-hypothalamic-pituitary-adrenal-axis-in-depression-across-the-2023/ --- - [Niyora](https://niyora.com/) - [Research](https://niyora.com/research/) - [Library](https://niyora.com/research/library/) - How does the stress response system affect depression during reproductive stages like PMDD? Review, 2023 # How does the stress response system affect depression during reproductive stages like PMDD? The HPA axis, which controls the stress response, changes during reproductive stages and plays an important role in depression risk at vulnerable times like PMDD, after birth, and perimenopause. Past stress and trauma exposure increase this risk. Early or limited evidence Review of existing research across female reproductive stages. ## What they did Reviewed existing research on how the hypothalamic-pituitary-adrenal (HPA) axis functions in depression at different stages of reproductive life: during the menstrual cycle (including PMDD), after childbirth, and during perimenopause. ## What they found The HPA axis is a major target of reproductive hormone changes and plays an important role in depression at these vulnerable windows. Each reproductive stage involves vast physiological changes and major neuroendocrine reorganization that affects the HPA axis. Past stress and trauma exposure contributes to depression risk in the context of these hormonal changes. ## What it means for you Understanding the HPA axis may help explain why depression risk changes across a woman's reproductive life and could lead to better diagnosis and treatment. This is a narrative review rather than new research, so it consolidates existing knowledge but does not test new theories. ## About the study Original title The role of the hypothalamic-pituitary-adrenal axis in depression across the female reproductive lifecycle: current knowledge and future directions Authors Hantsoo L, Jagodnik KM, Novick AM et al. Journal Frontiers in endocrinology Year 2023 Study design Review What was tested N/A Open access Yes Read the paper [doi.org/10.3389/fendo.2023.1295261](https://doi.org/10.3389/fendo.2023.1295261) Original abstract The aim of this narrative review is to consolidate knowledge on the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression pathophysiology at different reproductive stages across the female lifespan. Despite growing evidence about the impact of gonadal hormones on mood disorders, no previous review has examined the interaction between such hormonal changes and the HPA axis within the context of depressive disorders in women. We will focus on HPA axis function in depressive disorders at different reproductive stages including the menstrual cycle (e.g., premenstrual dysphoric disorder [PMDD]), perinatally (e.g., postpartum depression), and in perimenopausal depression. Each of these reproductive stages is characterized by vast physiological changes and presents major neuroendocrine reorganization. The HPA axis is one of the main targets of such functional alterations, and with its key role in stress response, it is an etiological factor in vulnerable windows for depression across the female lifespan. We begin with an overview of the HPA axis and a brief summary of techniques for measuring HPA axis parameters. We then describe the hormonal milieu of each of these key reproductive stages, and integrate information about HPA axis function in depression across these reproductive stages, describing similarities and differences. The role of a history of stress and trauma exposure as a contributor to female depression in the context of HPA axis involvement across the reproductive stages is also presented. This review advances the pursuit of understanding common biological mechanisms across depressive disorders among women. Our overarching goal is to identify unmet needs in characterizing stress-related markers of depression in women in the context of hormonal changes across the lifespan, and to support future research in women's mental health as it pertains to pathophysiology, early diagnosis, and treatment targets. Reproduced under CC-BY. ## Topics [Premenstrual dysphoric disorder (PMDD)](https://niyora.com/research/topics/condition-pmdd/)[Menstrual cycle and mood](https://niyora.com/research/topics/condition-cycle-mood/)[Low mood and depression](https://niyora.com/research/topics/symptom-depression-mood/)[Stress](https://niyora.com/research/topics/symptom-stress/)[Major depressive disorder](https://niyora.com/research/topics/comorbidity-major-depression/)[PTSD and trauma](https://niyora.com/research/topics/comorbidity-ptsd-trauma/)[Perimenopause and menopause](https://niyora.com/research/topics/comorbidity-perimenopause/)[Pregnancy and postpartum](https://niyora.com/research/topics/comorbidity-postpartum/)[Work and productivity](https://niyora.com/research/topics/life-area-work/)[Stigma, attitudes and culture](https://niyora.com/research/topics/life-area-stigma-culture/) Research tells you what helps on average. Niyora helps on the day it hits. Calm down, see it another way, and decide what to say, with a PMS and PMDD app built by a doctor. ## Related studies Review, 2012 Is depression linked to hormonal changes during the menstrual cycle, pregnancy, and menopause? Study, 2004 Did SSRIs change what people thought of as depression in women? Randomised trial, 2001 Do changing reproductive hormones disrupt the body's internal clock and cause mood disorders? Systematic review, 2026 Why do some women experience mood changes linked to their menstrual cycle? Review, 2026 Do PMDD, postpartum depression and perimenopausal depression have the same genetic causes? Review, 2019 How do brain changes during reproductive transitions cause depression in women? Ask AI about this page Copy prompt ChatGPT ↗ Claude ↗ Perplexity ↗ Google AI Mode ↗ Grok ↗