Stress & Premenstrual Symptoms Study

NCT ID: NCT02777372

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-01
• Study Completion Date: 2021-12-01

Brief Summary

This study that aims to evaluate the psychophysiology of premenstrual mood disorders (PMDs) at baseline and after treatment with sertraline. Participants will include women with PMDs and healthy female controls. Participation involves a baseline visit to determine eligibility and three study visits that include questionnaires and stress reactivity assessment via an acoustic startle paradigm. Female participants with PMDs will receive sertraline during the premenstrual phase.

Detailed Description

Among women with premenstrual mood dysphoric disorder (PMDD), baseline arousal is heightened during the luteal phase of the menstrual cycle compared to the follicular phase, as measured by acoustic startle response (ASR). Healthy female controls do not show cyclic changes in this measure of physiologic arousal. It has been suggested that such heightened physiologic arousal during the luteal phase may be due to differences in neurosteroid modulation of Gamma-aminobutyric acid (GABA)-A receptor function. Research indicates that women with premenstrual mood disorders (PMDs) may have sub-optimal sensitivity to the progesterone metabolite allopregnanolone (ALLO), a GABA-A receptor modulator. In animal models, intracerebroventricular injection of corticotrophin releasing factor (CRF) increases amplitude of the acoustic startle response, while ALLO administration attenuates this CRF-enhanced startle. The primary aim of this study is to examine differences in ASR by menstrual cycle phase (follicular, luteal) and group (control, PMDD). Secondary aim is to examine the impact of luteal phase treatment with a selective serotonin reuptake inhibitor (SSRI) on psychophysiology in women with PMDs. An exploratory aim is to examine immune function among these women.

Conditions

PMDD; Stress; Mood

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sertraline

To determine the impact of short term luteal phase treatment with Sertraline 50mg tablets (PMDD group only) on acoustic startle response across the menstrual cycle. Sertraline 50 mg tablets are administered daily from ovulation until menses onset.

Group Type: EXPERIMENTAL

Sertraline

Intervention Type: DRUG

Sertraline will be provided at a dose of 50 mg daily for up to 3 weeks, depending on the length of a woman's luteal phase. Medication will be taken only during the luteal phase. Women will initiate sertraline treatment upon determining that they have ovulated (using a urine luteinizing hormone (LH) Kit) and remain on sertraline until onset of their next menstrual period at which time they will stop taking the medication.

Control

No intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Sertraline

Sertraline will be provided at a dose of 50 mg daily for up to 3 weeks, depending on the length of a woman's luteal phase. Medication will be taken only during the luteal phase. Women will initiate sertraline treatment upon determining that they have ovulated (using a urine luteinizing hormone (LH) Kit) and remain on sertraline until onset of their next menstrual period at which time they will stop taking the medication.

Intervention Type: DRUG

Other Intervention Names

Zoloft

Eligibility Criteria

Inclusion Criteria

Participants must be:

1. Aged 18 - 50 years, per self-report

2. Able to give written informed consent, per self-report

3. Fluent in written and spoken English

4. Have normal or corrected to normal hearing and vision, per self-report

5. Female participants must be experiencing regular menstrual cycles (24-39 days), per self-report

6. Have a negative urine drug screen.

Exclusion Criteria

Participants cannot have:

1. Use of an psychotropic medication anytime in the past 2 months, per self-report

2. Drug or alcohol abuse history within previous 2 years

3. Lifetime history of psychotic disorder including, schizophrenia, schizoaffective disorder, major depression with psychotic features and bipolar disorder, per self-report

4. Currently homeless, per self-report

5. History of any Axis I disorder other then specific phobia within the past 12 months, per Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) interview

6. Active suicidal ideation (suicide plan or suicide attempt) within the previous 6 months, per self-report

7. Steroid hormone or hormonal contraceptive use in the past 6 months, per self-report, except emergency contraceptive use

8. Pregnancy in the past year, per self-report. Pregnancy during the study is also exclusionary. Participants must use a reliable, nonhormonal form of birth control during the study. If a participant becomes pregnant, she must inform study staff.

9. Sensitive hearing, per self-report.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Liisa Hantsoo, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor

Locations

Center for Women's Reproductive Mental Health, Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Countries

United States

References

Epperson CN, Pittman B, Czarkowski KA, Stiklus S, Krystal JH, Grillon C. Luteal-phase accentuation of acoustic startle response in women with premenstrual dysphoric disorder. Neuropsychopharmacology. 2007 Oct;32(10):2190-8. doi: 10.1038/sj.npp.1301351. Epub 2007 Feb 21.

Reference Type: BACKGROUND

PMID: 17314917 (View on PubMed)

Hantsoo L, Epperson CN. Premenstrual Dysphoric Disorder: Epidemiology and Treatment. Curr Psychiatry Rep. 2015 Nov;17(11):87. doi: 10.1007/s11920-015-0628-3.

Reference Type: BACKGROUND

PMID: 26377947 (View on PubMed)

Epperson CN, Hantsoo LV. Making Strides to Simplify Diagnosis of Premenstrual Dysphoric Disorder. Am J Psychiatry. 2017 Jan 1;174(1):6-7. doi: 10.1176/appi.ajp.2016.16101144. No abstract available.

Reference Type: BACKGROUND

PMID: 28041003 (View on PubMed)

Hantsoo L, Golden CEM, Kornfield S, Grillon C, Epperson CN. Startling Differences: Using the Acoustic Startle Response to Study Sex Differences and Neurosteroids in Affective Disorders. Curr Psychiatry Rep. 2018 May 18;20(6):40. doi: 10.1007/s11920-018-0906-y.

Reference Type: BACKGROUND

PMID: 29777410 (View on PubMed)

Hantsoo L, Epperson CN. Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle. Neurobiol Stress. 2020 Feb 4;12:100213. doi: 10.1016/j.ynstr.2020.100213. eCollection 2020 May.

Reference Type: BACKGROUND

PMID: 32435664 (View on PubMed)

Hantsoo, L., Kaminsky, Z., Payne, J.L. Luteal Phase Epigenetic Biomarkers Identify Premenstrual Dysphoric Disorder (PMDD) and Selective Serotonin Reuptake Inhibitor (SSRI) Response in PMDD. Neuropsychopharmacology (2022) 47:220 - 370.

Reference Type: RESULT

Miller KN, Standeven L, Morrow AL, Payne JL, Epperson CN, Hantsoo L. GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder. Psychoneuroendocrinology. 2024 Feb;160:106684. doi: 10.1016/j.psyneuen.2023.106684. Epub 2023 Nov 30.

Reference Type: RESULT

PMID: 38091917 (View on PubMed)

Barone JC, Ho A, Osborne LM, Eisenlohr-Moul TA, Morrow AL, Payne JL, Epperson CN, Hantsoo L. Luteal phase sertraline treatment of premenstrual dysphoric disorder (PMDD): Effects on markers of hypothalamic pituitary adrenal (HPA) axis activation and inflammation. Psychoneuroendocrinology. 2024 Nov;169:107145. doi: 10.1016/j.psyneuen.2024.107145. Epub 2024 Jul 24.

Reference Type: RESULT

PMID: 39096755 (View on PubMed)

Hantsoo L, Grillon C, Sammel M, Johnson R, Marks J, Epperson CN. Response to sertraline is associated with reduction in anxiety-potentiated startle in premenstrual dysphoric disorder. Psychopharmacology (Berl). 2021 Oct;238(10):2985-2997. doi: 10.1007/s00213-021-05916-6. Epub 2021 Jul 22.

Reference Type: RESULT

PMID: 34292344 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1K23MH107831-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00220794

Identifier Type: -

Identifier Source: org_study_id