HPO axis: what it means

HPO stands for hypothalamic-pituitary-ovarian. It's the communication loop that drives your menstrual cycle, and it works in three steps:

• Your hypothalamus releases a hormone called GnRH, in pulses.
• Your pituitary gland responds by releasing FSH and LH.
• Your ovaries respond to those signals by maturing an egg and making estrogen and progesterone.

Each part listens to the others. When estrogen and progesterone rise or fall, your hypothalamus and pituitary adjust their signals in response, which is why doctors call this a feedback loop rather than a one-way switch.

This loop is what triggers ovulation and sets the rhythm of the menstrual cycle hormones that shift across your month:

• Before ovulation, rising estrogen prepares an egg for release.
• After ovulation, a structure called the corpus luteum takes over hormone production for about two weeks.
• Once the corpus luteum breaks down, progesterone drops, which is usually when PMS and PMDD symptoms start.

PMS and PMDD both show up in the second half of your cycle, the luteal phase, when the HPO axis sends progesterone up, then down, before your period.

That drop in estrogen and progesterone isn't unusual by itself. Everyone's hormones fall in the days before bleeding. What seems to differ is how the brain reacts to that normal drop.

Schmidt et al. (1998, NEJM) and Dubey et al. (2017, Molecular Psychiatry) describe PMDD as a different brain reaction to typical HPO axis hormone changes, not a sign that your hormone levels are abnormal. One proposed piece of the picture is lower luteal estradiol in women with PMDD. Another is allopregnanolone, a hormone byproduct some brains react to more strongly (what it means).

This doesn't shrink what you're feeling. It means a normal biological process lands differently in your body than it does in someone else's.

Scientists are also looking at how the HPO axis interacts with the body's stress system, the HPA axis (hypothalamic-pituitary-adrenal). A few findings stand out:

This doesn't settle the question. One meta-analysis found slightly lower luteal estradiol in women with PMDD compared with controls, while the leading theory, from Schmidt et al. (1998) and Dubey et al. (2017), is that PMDD mainly involves a different brain reaction to largely normal hormone changes.

Guidelines don't target the HPO axis directly. They treat the pattern it produces. For PMDD, that usually means SSRIs (sometimes taken only in the luteal phase), some hormonal contraceptives, or CBT, and a doctor decides what fits your history.

A few related terms worth knowing:

• Luteal phase: the second half of your cycle, when progesterone rises then falls.
• Corpus luteum: the structure that makes progesterone after ovulation.
• Allopregnanolone: a hormone byproduct some PMDD brains react to differently.
• PMS and PMDD research, summarised: more studies on hormones, mood and the cycle.

Niyora is a PMS and PMDD support app. Its Moon feature lets you write down what happened in a hard moment, see it from another angle, calm down and draft a reply you can hold onto before you send anything.