Clinical trial NCT03720847: Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality
Official title: Ovarian Hormone Withdrawal and Suicide Risk: An Experimental Approach
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Suicidal Ideation
Keywords: Steroid hormones
Estradiol
Progesterone
Depression
Suicide
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2018-10-25
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Crossover 2-Condition Placebo-Controlled Trial
Primary purpose: BASIC_SCIENCE

Brief summary: This within-person, crossover, 2-condition, placebo-controlled study compares the impact of two perimenstrual conditions on severity of suicidal symptoms in females with past-month suicidality but minimal risk of imminent suicide attempt. The two conditions are (1) natural perimenstrual withdrawal from estradiol and progesterone (during placebo), (2) perimenstrual stabilization of estradiol and progesterone using transdermal estradiol and oral micronized progesterone.

Detailed description: A large number of observational studies have documented increased risk of suicide attempt, suicide death, and more lethal attempts during the perimenstrual (around menses) window of the female reproductive cycle; however, no experiments have investigated the causal role of ovarian steroid changes across the natural perimenstrual period in risk factors for acute suicidality. In response, the proposed experimental work investigates a causal role of perimenstrual withdrawal from the hormones estradiol (E2) and progesterone (P4) in previously-documented acute perimenstrual increases in suicidality.

Participants are 30 women between the ages of 18 and 45 with current suicidal ideation but minimal risk for suicide attempt. Using a placebo-controlled, crossover within-person design, the experiment tests the hypothesis that suicidality will be heightened during natural perimenstrual E2/P4 withdrawal (under placebo), but that experimental prevention of this perimenstrual E2/P4 withdrawal (with exogenous administration of E2/P4 hormones) will prevent these perimenstrual increases in suicidality and associated risk factors.

Eligibility criteria: Inclusion Criteria:

* Ability to adhere to medication regimen
* Speaks English
* Assigned female at birth with intact ovaries
* Premenopausal
* Normal menstrual cycles between 25-35 days
* Under current care of an outpatient mental health provider with visits occurring at least once every 3 months.
* At least 1 year postpartum.
* Willing to use a barrier method of birth control during the study.
* Normal weight (BMI between 18-29)
* Must report at least some recent suicidal ideation (in the past month) at the time of recruitment.
* Must be categorized as having acceptably low imminent risk for suicidal crisis/attempt by a licensed clinical psychologist utilizing evidence-based clinical and research guidelines for imminent suicide risk management.

Exclusion Criteria:

* Must not be pregnant, breastfeeding, or trying to become pregnant.
* Must not be taking any form of exogenous hormones or hormonal intrauterine device, and must have ended previous use of hormonal preparations at least one month prior to the study.
* Must not have a personal history of any chronic medical condition, including but not limited to metabolic or autoimmune disease, epilepsy, endometriosis, cancer, diabetes, cardiovascular, gastrointestinal, hepatic, renal, or pulmonary disease, and no personal or first degree family history of thromboembolic events.
* Any current cigarette smoking is exclusionary.
* Must not report a history of clinical diagnosis or treatment for postpartum depression or premenstrual dysphoric disorder (Note: Premenstrual Dysphoric Disorder diagnosis must have been made based on prospective daily ratings).
* Must not report any history of manic episode, any history of psychotic symptoms, or current substance use disorder.

Primary outcomes:
measure: Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Ideation Score
timeFrame: Midluteal Baseline and Perimenstrual
measure: Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Planning Score
timeFrame: Midluteal Baseline and Perimenstrual
Secondary outcomes:
measure: Perimenstrual Change in Beck Hopelessness Scale (BHS) Score
timeFrame: Day 7 of Each Condition (Lab 2)
measure: Perimenstrual Change in Center for Epidemiological Studies Depression Scale (CES-D) Score
timeFrame: Day 7 of Each Condition (Lab 2)
measure: Perimenstrual Change in Lack of Premeditation Subscale Score of the "Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency (UPPSP) Impulsivity Scale"
timeFrame: Day 7 of Each Condition (Lab 2)
measure: Perimenstrual Changes in Patient-Reported Outcomes Measurement Information Systems (PROMIS) Anxiety Scale Score
timeFrame: Day 7 of Each Condition (Lab 2)
measure: Perimenstrual Change in State Self-Esteem Scale Social Evaluation Subscale (SSES-SE) Score
timeFrame: Day 7 of Each Condition (Lab 2)
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Tory A Eisenlohr-Moul, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Susan Girdler, PhD
role: STUDY_CHAIR
References: