At a glance
- The HPA axis is the hypothalamus-pituitary-adrenal loop that makes cortisol, your main stress hormone.
- Cortisol tends to run a little higher in the follicular phase and a little lower in the luteal phase.
- PMDD is linked to how the HPA axis and the hormone axis that controls estrogen and progesterone interact, more than to cortisol levels by themselves.
- Guidelines point to SSRIs, certain hormonal contraceptives, and CBT; a doctor decides what fits you.
- Having somewhere to put a hard moment, like Niyora's Moon feature, can help while cortisol and hormones are both shifting.
What is the HPA axis?
HPA stands for hypothalamic-pituitary-adrenal axis. It's the loop your body uses to respond to stress, whether the trigger is a deadline, an argument, or a hormone shift before your period.
The axis is always running in the background, adjusting cortisol up or down as the day's demands change. It has three parts:
- Hypothalamus: senses stress and sends a chemical signal (CRH)
- Pituitary gland: passes that signal along (ACTH)
- Adrenal glands: release cortisol, the main stress hormone
Cortisol then feeds back to the hypothalamus and pituitary, which turns the system down once the stressor passes. In a well-regulated axis, cortisol rises when you need it and falls back once it doesn't.
How does it relate to PMS and PMDD?
The HPA axis doesn't work alone. It sits next to the HPO axis, the system that controls estrogen and progesterone, and the two influence each other all cycle long.
| Phase | Typical cortisol pattern |
|---|---|
| Follicular (after your period, before ovulation) | A little higher than the luteal phase |
| Luteal (after ovulation, before your period) | A little lower than the follicular phase |
| Right before your period starts | Lower than during your period itself |
A 2022 meta-analysis of 121 studies in 2,641 cycling women found cortisol was higher in the follicular phase than the luteal phase, and higher during the period than right before it. Most other phase-to-phase comparisons weren't significant (Frontiers in Neuroendocrinology).
The current theory is that PMDD comes from how the HPA and HPO axes respond to these normal shifts, more than from extra cortisol on its own. For more on what's thought to drive this, see what causes PMDD, and for the hormone backdrop, see the luteal phase.
What does the research say?
Beyond cortisol's rise and fall, a few other findings stand out.
- A meta-analysis of 63 studies in 5,129 women found that women with PMDD tend to have lower estradiol in the luteal phase than women without it. That points to a broader hormone-axis difference (Frontiers in Neuroendocrinology, 2021).
- In a small open-label study, sertraline taken only in the luteal phase changed markers of HPA axis activity in women with PMDD (Psychoneuroendocrinology, 2024).
- Allopregnanolone, a neurosteroid made from progesterone, helps keep the HPA axis in check through the brain chemical GABA (see allopregnanolone). Researchers think uneven regulation here explains why some brains react more strongly to ordinary hormone swings (Psychopharmacology, 2014).
None of this is settled science. Researchers studying the HPA axis across reproductive life call for more rigorous, longer-term work before the picture is clear.
Why does it matter for treatment or coping?
Stress and hormone systems are tangled together, which is part of why treatment can target either one.
Guidelines point to a few options:
- SSRIs, which some people take only in the luteal phase
- Certain hormonal contraceptives
- CBT (cognitive behavioral therapy)
A doctor decides what fits based on your history and how your symptoms show up.
Coping ideas aren't treatment, but having somewhere to put a hard moment helps while you wait for an appointment. Niyora is a PMS and PMDD support app. Its Moon feature lets you write down what happened, see it from another angle, calm down, and draft a reply you can hold for 20 minutes before you send it.
To see the hormone shifts behind all this phase by phase, read menstrual cycle hormones, or browse the full research library.
From the research library
Research on stress
664 studies in the library look at stress in PMS and PMDD. They were published from 1972 to 2026, and each one has a short summary of what was tested and found.
664
studies, 1972 to 2026
How strong the studies are
- Strong study design
- 19
- Moderate study design
- 233
- Early or limited evidence
- 412
Randomised trial, 2026
Does mindfulness training reduce PMS symptoms and fear about childbirth?
Yes. Women who completed mindfulness training had significantly fewer PMS symptoms, less fear about childbirth, and better psychological wellbeing than the control group.
Strong study design
Systematic review, 2025
Is there a link between stress, trauma, and premenstrual symptoms?
Yes. This meta-analysis of 66 studies with 38,344 people found a moderate positive link between stress and premenstrual symptoms. People with PMDD or PMS have significantly higher stress than others, and those with trauma history are more than twice as likely to have PMS.
Strong study design
Randomised trial, 2025
Does caloric restriction and aerobic exercise improve PMS symptoms in obese women?
Yes, when combined with medication, caloric restriction and aerobic exercise significantly improved PMS symptoms, reduced weight, and improved stress and reproductive hormones over 12 weeks.
Strong study design
Cohort study, 2025
How common is PMS in Chinese teenage girls, and what factors are linked to it?
About 1 in 4 Chinese girls (24.6%) has PMS. Higher stress, anger, alcohol use, menstrual cycles of 24 days or less, and period pain are all linked to increased PMS likelihood.
Strong study design
Review, 2025
How do stress hormone levels change during the menstrual cycle and how does this affect health?
Cortisol levels are higher in the first two phases of the cycle and lower in the final phase. Higher cortisol is linked to PMS symptoms, miscarriage, and reduced fertility, while birth control medications may help stabilize cortisol.
Strong study design
Systematic review, 2024
Does psychological stress cause irregular periods?
Yes. A review of 41 studies found that psychological stress is associated with irregular periods and abnormal menstrual flow in otherwise healthy women. Stress is a modifiable risk factor, meaning reducing stress may help.
Strong study design
Questions people ask
Does the HPA axis cause PMDD?+
The HPA axis doesn't cause PMDD on its own. PMDD is a different reaction to normal hormone changes, and researchers think the HPA axis and the hormone axis that controls estrogen and progesterone respond differently together in people with PMDD, rather than cortisol being abnormally high or low by itself.
Does cortisol rise before your period?+
Cortisol tends to be a little lower in the luteal phase, the one to two weeks before your period, than in the follicular phase right after it. A 2022 meta-analysis of 121 studies in 2,641 women found this pattern, though the differences were small (Frontiers in Neuroendocrinology).
What's the difference between the HPA axis and the HPO axis?+
The HPA axis handles your stress response and releases cortisol. The HPO axis (hypothalamic-pituitary-ovarian) controls your menstrual cycle and releases estrogen and progesterone. The two axes sit close together in the brain and send signals back and forth, which is part of why stress and hormones can feel tangled before your period.
Can calming the HPA axis help with PMDD symptoms?+
There's no proven way to calm the HPA axis that treats PMDD by itself. Guidelines point to SSRIs (some taken only in the luteal phase), certain hormonal contraceptives, and CBT instead, and a doctor decides what combination fits your history and how your symptoms show up.
Sources
- 1.HPA axis activity across the menstrual cycle - a systematic review and meta-analysis of longitudinal studies, Frontiers in neuroendocrinology, 2022
- 2.Luteal phase sertraline treatment of premenstrual dysphoric disorder (PMDD): Effects on markers of hypothalamic pituitary adrenal (HPA) axis activation and inflammation, Psychoneuroendocrinology, 2024
- 3.Variation in genes and hormones of the hypothalamic-pituitary-ovarian axis in female mood disorders - A systematic review and meta-analysis, Frontiers in neuroendocrinology, 2021
- 4.The role of the hypothalamic-pituitary-adrenal axis in depression across the female reproductive lifecycle: current knowledge and future directions, Frontiers in endocrinology, 2023
- 5.Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?, Psychopharmacology, 2014