Stress & Premenstrual Symptoms Study

NCT02777372 | Completed Phase 4 Results

• 2 other identifiers: IRB002207941K23MH107831-01A1
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

PMDD; Stress; Mood

Keywords

Zoloft; premenstrual syndrome (PMS); Menses

Outcome Measures

Primary Outcomes (2)

• Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase

  Acoustic startle response (ASR) is measured during the follicular and luteal phase of the menstrual cycle in controls and those with PMDD. Magnitude of ASR is measured using the eyeblink reflex, by recording activity from the orbicularis oculi muscle. Recording is performed via two surface disk electrodes (Ag-AgCl) applied underneath the left eye; one in line with the pupil and one 1-2 cm lateral to the first one. For the primary outcome of baseline ASR magnitude over the menstrual cycle, peak amplitude of the blink reflex was determined in the 20-120-ms time frame following stimulus onset relative to baseline (baseline is the average baseline electromyography (EMG) level for the 50 ms immediately preceding auditory stimulus onset). ASR is measured in microvolts, and raw ASR results are standardized to t-scores. Higher ASR t-score indicates greater contraction of the the orbicularis oculi muscle. A t-score of 50 indicates the population mean with a standard deviation of 10.

  Month 1 (Follicular), Month 2 (Luteal)

• Impact of Sertraline on ASR Magnitude

  This outcome examines the impact of luteal phase treatment with a selective serotonin reuptake inhibitor (SSRI) (PMDD group only) on acoustic startle response (ASR). ASR is measured using the eyeblink reflex, measured by recording activity from the orbicularis oculi muscle. Recording is performed via two surface disk electrodes (Ag-AgCl) applied underneath the left eye; one in line with the pupil and one 1-2 cm lateral to the first one. Peak amplitude of the blink reflex is determined in the 20-120-ms time frame following stimulus onset. PMDD participants complete test day 3 (Luteal Month 3) while on sertraline and their ASR magnitude will be compared to their previous luteal test day (Luteal Month 2). ASR is measured in microvolts, and raw ASR results are standardized to t-scores. Higher ASR t-score indicates greater contraction of the the orbicularis oculi muscle. A t-score of 50 indicates the population mean with a standard deviation of 10.

  Month 2 (Luteal), Month 3 (Luteal)

Secondary Outcomes (2)

• Interleukin 6 (IL-6) Level

  Month 1 (Follicular ), Month 2 (Luteal )

• Tumor Necrosis Factor Alpha (TNF-alpha) Level

  Month 1 (Follicular ), Month 2 (Luteal )

Study Arms (2)

Sertraline

EXPERIMENTAL

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.

Drug: Sertraline

Control

NO INTERVENTION

No intervention.

Interventions

Sertraline 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.

Also known as: Zoloft

Sertraline

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must be:
• Aged 18 - 50 years, per self-report
• Able to give written informed consent, per self-report
• Fluent in written and spoken English
• Have normal or corrected to normal hearing and vision, per self-report
• Female participants must be experiencing regular menstrual cycles (24-39 days), per self-report
• Have a negative urine drug screen.

You may not qualify if:

• Participants cannot have:
• Use of an psychotropic medication anytime in the past 2 months, per self-report
• Drug or alcohol abuse history within previous 2 years
• Lifetime history of psychotic disorder including, schizophrenia, schizoaffective disorder, major depression with psychotic features and bipolar disorder, per self-report
• Currently homeless, per self-report
• 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
• Active suicidal ideation (suicide plan or suicide attempt) within the previous 6 months, per self-report
• Steroid hormone or hormonal contraceptive use in the past 6 months, per self-report, except emergency contraceptive use
• Sensitive hearing, per self-report.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

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

Baltimore, Maryland, 21205, United States

Location

Related Publications (9)

• 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.

  PMID: 17314917 BACKGROUND

• 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.

  PMID: 26377947 BACKGROUND

• 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.

  PMID: 28041003 BACKGROUND

• 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.

  PMID: 29777410 BACKGROUND

• 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.

  PMID: 32435664 BACKGROUND

• 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.

  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.

  PMID: 38091917 RESULT

• 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.

  PMID: 39096755 RESULT

• 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.

  PMID: 34292344 RESULT

MeSH Terms

Conditions

Premenstrual Syndrome

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Liisa Hantsoo, Ph.D.
• Organization: The Johns Hopkins University School of Medicine

LHantso1@jh.edu

410-502-2334

Study Officials

• Liisa Hantsoo, PhD

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2016
• First Posted: May 19, 2016
• Study Start: April 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: June 12, 2025
• Results First Posted: November 17, 2022

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)