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CLEAR Lab
The PINES Study

Why does suicide risk follow the menstrual cycle for some people and not others?

PINES is a five-year study using daily tracking, a placebo-controlled trial, and brain imaging to find out.

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What the study asks

Suicide risk is not steady over time. Among people who menstruate and who already experience suicidal thoughts, roughly six in ten see that risk rise and fall in a recurring monthly pattern, with the hardest days clustering around the start of a period. That is also when the ovarian hormones are in their greatest flux.

That figure comes from our own clinical samples. It describes people already in psychiatric care, not people who menstruate in general.

In three earlier randomized trials, our team found that supplementing estrogen across those days prevented the expected worsening of depression and suicidal thinking, compared with placebo. Progesterone, the other main ovarian hormone, did not have that effect. PINES asks the next question: how does that benefit actually work, and does it work the same way in everyone?

We expect that it does not, and that is the point of the study. Sensitivity to hormonal change appears to differ between people. Many show no relationship at all. PINES is built to find those differences rather than average across them.

Estrogen and progesterone are not abnormal in these patients. People with and without this pattern have the same levels and the same cycles. What differs is sensitivity to ordinary change.

Three people, three patterns. The average describes none of them.

Illustration · not study data

Daily symptoms across the menstrual cycle for three different people, with the group average Three schematic lines. One person's symptoms rise sharply in the days just before and during their period. A second person's symptoms rise earlier, in the second half of the cycle, and resolve when their period starts. A third person's symptoms stay level all month. A dashed line showing the average of the three has a single broad bump that matches none of the individual patterns. highest-risk days Ovulation Period starts Next cycle Daily symptoms Person A Person B Person C Group average
Person A gets worse in the days around their period. Person B gets worse earlier and recovers when the period starts. Person C has symptoms all month that do not follow the cycle at all. The dashed average looks like a real patient, but no one in this picture has that pattern. PINES looks for the individual patterns, not the average.

How it works

1Baseline

Two months of tracking

Participants record mood and thoughts twice a day, alongside simple at-home hormone testing.

2Trial

Treatment and brain imaging

Some participants continue to a placebo-controlled trial with MRI scans in each condition.

3Follow-up

Six months of check-ins

The team follows up at two, four, and six months.

Reporting on this work

This is not a claim about everyone who menstruates. The figures above describe psychiatric outpatients already experiencing suicidal thoughts. Many people show no cyclical pattern at all.

The hormones are not abnormal. What differs between people is sensitivity to ordinary hormonal change.

This is a mechanistic study. It is not testing a treatment that is ready for clinical use.

Journalists covering suicide are encouraged to follow established safe-reporting guidance.

Media inquiries: clearlab@uchicago.edu.

Team

Study team

Consultants