Estradiol Effects on Alcohol Across the Menstrual Cycle

Estradiol Effects on Behavioral and Reward Sensitivity to Alcohol Across the Menstrual Cycle

This study will provide the first rigorous integrative test of the hypothesis that rapid rises in estradiol (a female hormone) increase the rewarding and disinhibiting effects of alcohol and that such increased sensitivity correlates with increased alcohol use. Identification of the behavioral mechanisms by which estradiol surges can increase alcohol use would provide a critical advancement of neurobiological theory of alcohol abuse in women, an understudied area, as well as provide new directions for personalization of alcohol abuse treatment in women.

In this study, naturally-cycling women will be examined daily over their menstrual cycle using an integrative combination of daily ecological assessments of hormone fluctuations and alcohol use along with strategically-timed laboratory tests of their acute sensitivity to the rewarding and disinhibiting effects of a controlled dose of alcohol.

Study Overview

• Status: Completed
• Conditions: Alcohol Use, Unspecified
• Intervention / Treatment: Drug: Placebo; Drug: Alcohol

Detailed Description

A longitudinal study design will test hormonal influences across the menstrual cycle on women's naturalistic drinking behavior, as well as their acute sensitivity to the rewarding and disinhibiting effects of alcohol in the laboratory, two key mechanisms of its abuse potential. Subjects will attend a diagnostic visit to assess baseline clinical characteristics. In addition, subjects will attend two laboratory visits to test alcohol sensitivity at two key points in the cycle: during the early follicular phase when E2 is low and the late follicular phase when E2 is rising (see Figure 6). Every day after their first laboratory visit for 35 consecutive days, women will provide saliva samples each morning to assess hormonal levels and complete a self-report on their drinking behavior and alcohol craving every evening through a secure online server. The daily saliva and self-report data will allow fine-grained investigation of the lagged correlations between E2 and daily alcohol use patterns and alcohol craving across the menstrual cycle. The two laboratory visits will test and compare the acute sensitivity to rewarding and disinhibiting effects of a controlled dose of alcohol during the early follicular phase when E2 is low and the late follicular phase when E2 is rising. Volunteers will be followed daily to assess when they start their next menstrual cycle (i.e., the day they start bleeding). Within 1-2 days of that point, volunteers are scheduled to attend their initial diagnostic visit. Participants are then counterbalanced to begin the study during either their early follicular phase (approximately day 5) or their late follicular phase (approximately day 12) which is also when they begin their 35 days of consecutive daily data collection. This serves to counterbalance the order of the two alcohol sensitivity test sessions: early follicular versus late follicular phase. Ovulation testing and daily salivary E2 will confirm the proximity of the late follicular phase to ovulation, with the goal of ovulation occurring 1-3 days after the late follicular visit, and capturing a higher, rising E2 level in the late follicular phase relative to a lower level in the early follicular phase.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • University Of Kentucky Psychology Research Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• female
• regular menstrual cycle
• consume alcohol at least once per week
• no history of drug or alcohol dependence

Exclusion Criteria:

• use of hormone-based medications
• irregular menstrual cycle
• current pregnancy
• primary sensorimotor handicap
• frank neurological disorder
• pervasive developmental disorder
• frank psychosis
• diagnosed intellectual disability
• medical condition contraindicating alcohol use
• substance abuse history (except nicotine)
• body mass index (BMI) 30 or above
• alcohol abstainer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: menstrual cycle; Participants will have their alcohol sensitivity test once during their early follicular phase and once during their late follicular phase

Drug: Placebo; Participants will attend two identical laboratory sessions to test sensitivity to the rewarding and disinhibiting effects of a controlled dose of alcohol, once during the early follicular phase and once during the late follicular phase. The test battery consists of measures of rewarding effects and alcohol (or placebo) effects on disinhibition and impulsive choice. The placebo consists of 300 ml of lemon-flavored soda with a small amount (3 ml) of alcohol floated on top.; Drug: Alcohol; Participants will attend two identical laboratory sessions to test sensitivity to the rewarding and disinhibiting effects of a controlled dose of alcohol, once during the early follicular phase and once during the late follicular phase. The test battery consists of measures of rewarding effects and alcohol effects on disinhibition and impulsive choice. The alcohol dose consists of 0.60 g/kg absolute alcohol that produces a peak blood-alcohol concentration of 80 mg/dl. Doses will be mixed with a carbonated, non-caffeinated, lemon-flavored soda and consumed within 10 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attentional Bias (Early Follicular Phase)	Attentional bias is measured by the visual dot-probe task and provides an implicit assessment of the rewarding properties of alcohol as indicated by the degree to which an acute dose of alcohol increases the drinker's attention to alcohol cues is measured. Subjects look at images on a screen and their attention to various images is measured. An alcohol-related image and a neutral control image are presented briefly side-by-side, on a computer screen. An eye tracker embedded into the monitor provides an unobtrusive measure of the duration (dwell time) that volunteers look at each image.	1 day
Attentional Bias (Late Follicular Phase)	Attentional bias is measured by the visual dot-probe task and provides an implicit assessment of the rewarding properties of alcohol as indicated by the degree to which an acute dose of alcohol increases the drinker's attention to alcohol cues is measured. Subjects look at images on a screen and their attention to various images is measured. An alcohol-related image and a neutral control image are presented briefly side-by-side, on a computer screen. An eye tracker embedded into the monitor provides an unobtrusive measure of the duration (dwell time) that volunteers look at each image.	1 day
Disinhibition (Early Follicular Phase)	Disinhibition wil be measured by the cued go/no-go task, which requires participants to respond quickly to go targets and inhibit responses to no-go targets. Participants complete 250 trials in which they are presented with a cue, followed by a target. A go target is green, and participants are instructed to press a button when presented with a go target. A no-go target is blue, and participants are instructed to do nothing when this appears. A go cue predicts a go target with 80% accuracy, whereas a no-go cue predicts a no-go target with 80% accuracy. The condition of interest is when a go cue is followed by a no-go target. The proportion reported is the proportion of trials under this condition in which participants press the button (expecting a go target but presented with a no-go target).	1 day
Disinhibition (Late Follicular Phase)	Disinhibition wil be measured by the cued go/no-go task, which requires participants to respond quickly to go targets and inhibit responses to no-go targets. Participants complete 250 trials in which they are presented with a cue, followed by a target. A go target is green, and participants are instructed to press a button when presented with a go target. A no-go target is blue, and participants are instructed to do nothing when this appears. A go cue predicts a go target with 80% accuracy, whereas a no-go cue predicts a no-go target with 80% accuracy. The condition of interest is when a go cue is followed by a no-go target. The proportion reported is the proportion of trials under this condition in which participants press the button (expecting a go target but presented with a no-go target).	1 day
Subjective Ratings of the Rewarding Effects of Alcohol (Early Follicular Phase)	a visual analog scale from 0-100, with 0 being not rewarding at all and 100 being very rewarding	1 day
Subjective Ratings of the Rewarding Effects of Alcohol (Late Follicular Phase)	a visual analog scale from 0-100, with 0 being not rewarding at all and 100 being very rewarding	1 day

Collaborators and Investigators

• Sponsor: Mark Fillmore
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Michelle Martel, PhD, University Of Kentucky; Principal Investigator: Mark Fillmore, PhD, University Of Kentucky

Publications and helpful links

General Publications

• Griffith AK, Martel MM, Eisenlohr-Moul T, Fillmore MT. Heightened sensitivity to the disinhibiting effect of alcohol in women during the late follicular phase of the menstrual cycle. Exp Clin Psychopharmacol. 2023 Aug;31(4):839-848. doi: 10.1037/pha0000611. Epub 2022 Oct 20.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Actual): November 6, 2024
• Study Completion (Actual): November 6, 2024

Study Registration Dates

• First Submitted: October 14, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: estradiol; reward; hormone; menstrual
• Additional Relevant MeSH Terms: Drinking Behavior; Alcohol Drinking
• Other Study ID Numbers: 52637; 1R01AA027990-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes