Alcohol and Sex Hormones' Effects on Sleep

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Lauren Whitehurst

Must not be taking: Antidepressants, Anxiolytics, Beta-blockers, others

Disqualifiers: Liver disease, Diabetes, Insomnia, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Rates of heavy drinking and Alcohol Use Disorder (AUD) are increasing in women, but research on alcohol-related harms in women - including alcohol's impact on sleep - has been minimal. Numerous studies in men show that alcohol impairs sleep, and preliminary evidence suggests that women may be even more sensitive to alcohol-disrupted sleep due to their sex hormones, which fluctuate across both their menstrual cycles and their reproductive lifespans. This study will investigate the influence of sex, menstrual cycle phase, and sex hormones on alcohol-disrupted sleep in adults ages 21-45. Healthy women and men will complete two sets of placebo-controlled lab sessions, during the mid-follicular and late luteal phases of female participants' menstrual cycles. During these sessions, participants will receive a dose of alcohol or a placebo (saline) and they will then be monitored (with polysomnography) while they sleep. At-home sleep and alcohol use will also be measured through actigraphy, daily sleep and wake diaries, and alcohol wrist sensors. Investigators hypothesize that women will show greater disruption of sleep following alcohol use or administration than men, and that alcohol-disrupted sleep will be more pronounced in the late luteal phase compared to the mid-follicular phase. Investigators also expect that estradiol will be negatively associated with alcohol-disrupted sleep, whereas progesterone will be positively associated with alcohol-disrupted sleep.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that affect sleep or heart function, such as antidepressants or beta-blockers, and any medications that should not be mixed with alcohol.

What evidence supports the effectiveness of alcohol and sex hormones as a treatment for sleep issues?

Research shows that alcohol can affect hormone levels, such as increasing testosterone in women and altering other sex hormones. However, these changes are not directly linked to improving sleep, and alcohol is generally known to disrupt sleep patterns. ^{1 2 3 4 5}

Is the combination of alcohol and sex hormones safe for human use?

Research on sex hormones like estrogen, progesterone, and testosterone shows they can affect sleep patterns, but their safety in humans is generally supported when used appropriately. However, the specific combination of alcohol and sex hormones has not been directly studied for safety, so caution is advised. ^{6 7 8 9 10}

How does alcohol affect sex hormones and sleep differently from other treatments?

This treatment is unique because it explores how alcohol, rather than a traditional drug, affects sex hormones and sleep. Unlike standard treatments, alcohol can alter hormone levels by affecting liver metabolism, which may influence sleep patterns differently than other therapies. ^{1 3 5 11 12}

Research Team

Eligibility Criteria

This trial is for adults aged 21-45 who drink alcohol at least twice a week, including weekly binge episodes. Women must have regular menstrual cycles. Participants need to be fluent in English and have at least a high school education.

Inclusion Criteria

I am between 21 and 45 years old.

You have completed high school.

I drink alcohol at least twice a week and have weekly binge episodes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Mid-Follicular Phase

Participants receive alcohol or placebo intravenously during the mid-follicular phase and are monitored with polysomnography during sleep

1-2 days

2 lab sessions (in-person)

Treatment - Late Luteal Phase

Participants receive alcohol or placebo intravenously during the late luteal phase and are monitored with polysomnography during sleep

1-2 days

2 lab sessions (in-person)

At-home Monitoring

Participants complete at-home monitoring of naturalistic sleep and alcohol consumption patterns using actigraphy, sleep diaries, and alcohol wrist sensors

5 days per phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Alcohol (Other)
• Sex Hormones (Hormone Therapy)

Trial Overview The study examines how sex hormones and the menstrual cycle phase affect sleep disruption by alcohol in men and women. It involves two lab sessions with either an alcohol dose or placebo, followed by sleep monitoring, plus at-home sleep tracking.

Participant Groups

Group I: Alcohol Administration - Mid-Follicular Phase Experimental Treatment 1 Intervention

During the mid-follicular phase of a female participant's menstrual cycle, participants will complete a lab session where alcohol is administered intravenously. The infusion will include a 30-minute linear ascension from 0mg% breath alcohol content (BrAC) to 100mg%, followed by a 60-minute 'clamping' of BrAC at 100mg%. Subjects will then be monitored while they sleep, using polysomnography. Male subjects will complete this and the placebo session at intervals that are matched to the female subjects. The placebo and alcohol sessions during mid-follicular luteal phase will take place 1-2 days apart, and their order will be randomized.

Group II: Alcohol Administration - Late Luteal Phase Experimental Treatment 1 Intervention

During the late luteal phase of a female participant's menstrual cycle, participants will complete a lab session where alcohol is administered intravenously. The infusion will include a 30-minute linear ascension from 0mg% breath alcohol content (BrAC) to 100mg%, followed by a 60-minute 'clamping' of BrAC at 100mg%. Subjects will then be monitored while they sleep, using polysomnography. Male subjects will complete this and the placebo session at intervals that are matched to the female subjects. The placebo and alcohol sessions during late luteal phase will take place 1-2 days apart, and their order will be randomized.

Group III: Placebo - Late Luteal Phase Placebo Group 1 Intervention

During the late luteal phase of a female participant's menstrual cycle, participants will complete a lab session where saline is administered intravenously, as placebo, for 90 minutes. Subjects will then be monitored while they sleep, using polysomnography. Male subjects will complete this and the experimental session at intervals that are matched to the female subjects. The placebo and alcohol sessions during late luteal phase will take place 1-2 days apart, and their order will be randomized.

Group IV: Placebo - Mid-Follicular Phase Placebo Group 1 Intervention

During the mid-follicular phase of a female participant's menstrual cycle, participants will complete a lab session where saline is administered intravenously, as placebo, for 90 minutes. Subjects will then be monitored while they sleep, using polysomnography. Male subjects will complete this and the experimental session at intervals that are matched to the female subjects. The placebo and alcohol sessions during mid-follicular phase will take place 1-2 days apart, and their order will be randomized.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Kentucky Lexington, KY

Who Is Running the Clinical Trial?

Lauren Whitehurst

Lead Sponsor

Trials

1

Patients Recruited

130+

Ohio State University

Collaborator

Trials

891

Patients Recruited

2,659,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Patients Recruited

1,091,000+

Findings from Research

In a study involving 21 premenopausal women on oral contraceptives and 10 nonusers, alcohol consumption led to an acute increase in plasma testosterone levels and a decrease in androstenedione levels, with these effects lasting throughout the alcohol elimination period.

The study suggests that alcohol affects steroid hormone levels by inhibiting their breakdown in the liver, indicating that the liver plays a significant role in the acute hormonal effects of alcohol in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the liver in the acute effect of alcohol on androgens in women. Sarkola, T., Adlercreutz, H., Heinonen, S., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of abstinence on sex hormone profile in alcoholic patients without liver failure. Iturriaga, H., Valladares, L., Hirsch, S., et al.[2019]

Moderate to high doses of alcohol can suppress testosterone levels in men, although some studies show conflicting results; alcohol may inhibit testosterone production directly in the testes.

In women, alcohol does not decrease estradiol or affect LH levels during the late follicular phase, and it can actually increase levels of estradiol, progesterone, and testosterone during the midluteal phase, suggesting different hormonal responses to alcohol between genders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of ethanol on sex hormones in non-alcoholic men and women. Ellingboe, J.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypothalamic-pituitary-gonadal axis, prolactin, and cortisol in alcoholics during withdrawal and after three weeks of abstinence: comparison with healthy control subjects. Heinz, A., Rommelspacher, H., Gräf, KJ., et al.[2022]

In a study of 87 premenopausal women, alcohol consumption significantly increased total and free testosterone levels, particularly in women using oral contraceptives, suggesting a potential impact on hormone levels related to alcohol intake.

Alcohol also lowered androstenedione levels while increasing the testosterone to androstenedione ratio, indicating that alcohol may enhance the conversion of androstenedione to testosterone in the liver, which could have implications for conditions like hyperandrogenism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effect of alcohol on androgens in premenopausal women. Sarkola, T., Fukunaga, T., Mäkisalo, H., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in the sleep electroencephalogram (EEG) during male to female transgender therapy. Künzel, HE., Murck, H., Stalla, GK., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol treatment modulates spontaneous sleep and recovery after sleep deprivation in castrated male rats. Wibowo, E., Deurveilher, S., Wassersug, RJ., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of testosterone on sleep and sleep-disordered breathing in men: its bidirectional interaction with erectile function. Andersen, ML., Tufik, S.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variations in sleep associated with different types of hormonal contraceptives. Guida, M., Rega, A., Vivone, I., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex, steroids, and sleep: a review. Manber, R., Armitage, R.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ethanol on steroid profiles in the rat testis. Andersson, SH., Sjövall, J.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sex steroids on ethanol pharmacokinetics and autonomic reactivity. Zeiner, AR., Kegg, PS.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

The role of the liver in the acute effect of alcohol on androgens in women. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Effects of abstinence on sex hormone profile in alcoholic patients without liver failure. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Acute effects of ethanol on sex hormones in non-alcoholic men and women. [2013]

4. Ireland pubmed.ncbi.nlm.nih.gov

Hypothalamic-pituitary-gonadal axis, prolactin, and cortisol in alcoholics during withdrawal and after three weeks of abstinence: comparison with healthy control subjects. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Acute effect of alcohol on androgens in premenopausal women. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Changes in the sleep electroencephalogram (EEG) during male to female transgender therapy. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Estradiol treatment modulates spontaneous sleep and recovery after sleep deprivation in castrated male rats. [2013]

8. England pubmed.ncbi.nlm.nih.gov

The effects of testosterone on sleep and sleep-disordered breathing in men: its bidirectional interaction with erectile function. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Variations in sleep associated with different types of hormonal contraceptives. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Sex, steroids, and sleep: a review. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of ethanol on steroid profiles in the rat testis. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of sex steroids on ethanol pharmacokinetics and autonomic reactivity. [2013]