What we are studying
Across our prior trials in cycling outpatients with past-month suicidal ideation, roughly sixty percent showed perimenstrual worsening of mood and suicidal thinking, with the hardest days clustering around the start of a period. That is also when the ovarian hormones are in their greatest flux.
In three earlier randomized trials, our team found that supplementing estradiol across those days prevented the expected worsening of depression and suicidal thinking, compared with placebo. Progesterone alone did not. PINES asks how that benefit works, and whether it works the same way in every patient. We expect that it does not.
Hormone levels are not the abnormality. We found no differences in estradiol, progesterone, or allopregnanolone levels, or in their cyclical trajectories, between patients with and without premenstrual mood worsening. The symptoms are triggered by normal hormonal change, so ordering hormone levels will not identify these patients.
Why this is a mechanistic study rather than a treatment. Repeated estradiol administration is not a feasible long-term option for naturally cycling premenopausal patients, given clotting and cancer risk. We need to know how estradiol produces its benefit before we can build something safer that does the same thing.
Your patient stays in your care
Being under the ongoing care of a licensed outpatient mental health provider is a condition of participation, not an exclusion. Participants remain with their own providers for the full duration of the study.
Risk assessment and safety planning are built into screening and into ongoing study contact.
What participation asks of your patient
Two months of brief symptom reporting twice daily with at-home urinary hormone testing, followed for some participants by a placebo-controlled crossover trial with resting-state MRI, and then follow-up contacts at two, four, and six months.
Medications must be stable for at least one month before entering a crossover condition. Participants may remain on their existing regimens, and medication use is recorded daily.
Referring a patient
Email clearlab@uchicago.edu. We expect to begin enrolling in January 2027.
Under construction Referral pathway, provider notification, and escalation procedures will be posted here.