Alcohol Use, UnspecifiedNCT04595682
Estradiol Effects on Alcohol Across the Menstrual Cycle
A study testing Alcohol in people with Alcohol Use, Unspecified, run by Mark Fillmore at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Alcohol Use, Unspecified
- What is being tested?
- Alcohol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Mar 2021to 6 Nov 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- female
- regular menstrual cycle
- consume alcohol at least once per week
- no history of drug or alcohol dependence
Who cannot join
- use of hormone-based medications
- irregular menstrual cycle
- current pregnancy
- primary sensorimotor handicap
- frank neurological disorder
- pervasive developmental disorder
Show all 12Show fewer
- frank psychosis
- diagnosed intellectual disability
- medical condition contraindicating alcohol use
- substance abuse history (except nicotine)
- body mass index (BMI) 30 or above
- alcohol abstainer
Trial locations and contacts
1 site in 1 country.
United States1 site
University Of Kentucky Psychology Research Lab
Lexington, Kentucky, 40504
About this study
Official title: 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.
Read the 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.
- Conditions
- Alcohol Use, Unspecified
- Being tested
- Placebo, Alcohol
- Keywords
- estradiol, reward, menstrual, hormone
- Medical subject headings
- Alcohol Drinking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
AlcoholDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| menstrual cycle | Experimental | Participants will have their alcohol sensitivity test once during their early follicular phase and once during their late follicular phase Receives: Drug: Placebo; Drug: Alcohol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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
Measured: 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
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2020
- Study start15 Mar 2021
- Primary completion6 Nov 2024
- Study completion6 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alcohol Use, UnspecifiedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mark Fillmore
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor-investigator, Mark Fillmore, University of Kentucky
- Investigators
- Mark Fillmore, PhD, Principal investigator, University of KentuckyMichelle Martel, PhD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04595682
- Sponsor's protocol ID
- 52637
- Other IDs
- 1R01AA027990-01A1
- Status last verified
- Aug 2025
- First submitted
- 14 Oct 2020
- Last updated
- 22 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Griffith AK, Martel MM, Fillmore MT. Effect of menstrual cycle on rewarding properties of alcohol cues in women. Psychol Addict Behav. 2024 Sep;38(6):676-687. doi: 10.1037/adb0000978. Epub 2023 Dec 7.
PubMed 38059946Griffith 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.
PubMed 36265052
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estradiol Effects on Behavioral and Reward Sensitivity to Alcohol Across the Menstrual Cycle
- ClinicalTrials.gov ID
- NCT04595682
- Acronym / sponsor ID
- 52637
- Conditions
- Alcohol Use, Unspecified
- Keywords
- estradiol, reward, menstrual, hormone
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Mark FillmoreUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 15 Mar 2021 (actual)
- Primary completion
- 6 Nov 2024 (actual)
- Study completion
- 6 Nov 2024 (actual)
- First posted
- 20 Oct 2020 (actual)
- Results
- Posted 22 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| menstrual cycle | Experimental | Drug: Placebo, Drug: AlcoholParticipants will have their alcohol sensitivity test once during their early follicular phase and once during their late follicular phase |
Who may qualify
- Ages
- 21 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- female
- regular menstrual cycle
- consume alcohol at least once per week
- no history of drug or alcohol dependence
Key exclusion criteria (12 listed)
- use of hormone-based medications
- irregular menstrual cycle
- current pregnancy
- primary sensorimotor handicap
- frank neurological disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboParticipants 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 | menstrual cycle |
| AlcoholParticipants 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. | Drug | menstrual cycle |
Primary outcome
Attentional Bias (Early Follicular Phase)
Time frame: 1 day
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.
Attentional Bias (Late Follicular Phase)
Time frame: 1 day
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.
Disinhibition (Early Follicular Phase)
Time frame: 1 day
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).
Disinhibition (Late Follicular Phase)
Time frame: 1 day
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).
Subjective Ratings of the Rewarding Effects of Alcohol (Early Follicular Phase)
Time frame: 1 day
a visual analog scale from 0-100, with 0 being not rewarding at all and 100 being very rewarding
Subjective Ratings of the Rewarding Effects of Alcohol (Late Follicular Phase)
Time frame: 1 day
a visual analog scale from 0-100, with 0 being not rewarding at all and 100 being very rewarding
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38059946Griffith AK, Martel MM, Fillmore MT. Effect of menstrual cycle on rewarding properties of alcohol cues in women. Psychol Addict Behav. 2024 Sep;38(6):676-687. doi: 10.1037/adb0000978. Epub 2023 Dec 7.
- Derived from this study: PubMed 36265052Griffith 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Fillmore, PhD principal investigator
University of Kentucky
Michelle Martel, PhD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Alcohol in people with Alcohol Use, Unspecified, run by Mark Fillmore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Attentional Bias (Early Follicular Phase) (time frame: 1 day). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04595682, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2025.