Hormonal Effects on Alcohol Use

Overseen By Study Coordinator

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Mark Fillmore

Must not be taking: Hormone-based medications

Disqualifiers: Irregular cycle, Pregnancy, Neurological, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the female hormone estradiol (known by brand names such as Estrace, Vivelle, and Climara) might affect alcohol use by making it more rewarding and lowering inhibitions. Researchers will study women with regular menstrual cycles to determine if changes in estradiol levels during the cycle influence alcohol consumption. Women who drink alcohol at least once a week and have a regular menstrual cycle may be suitable for this study. The goal is to better understand alcohol use in women and tailor treatment approaches. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to more personalized treatment strategies for women.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not use hormone-based medications. Other medications are not specified, so check with the trial coordinators.

What prior data suggests that this protocol is safe?

Research shows that estradiol, a hormone used in women's health treatments, can interact moderately with alcohol. Some studies suggest that alcohol consumption while taking estradiol might increase hormone levels in the body. However, this increase doesn't usually lead to serious health problems.

Evidence from past research indicates that alcohol can sometimes raise estradiol levels significantly, even up to three times higher than normal. While this might seem concerning, controlled studies have not shown it to cause immediate harm. Estradiol is already used in treatments like hormone replacement therapy, indicating it is generally well-tolerated.

In summary, while an interaction between estradiol and alcohol can occur, research suggests that the treatment is generally safe when monitored. Clinical trial participants will be closely observed to manage any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using estradiol to study alcohol use because it offers a fresh perspective on understanding how hormonal changes might affect alcohol sensitivity. Unlike traditional treatment options like behavioral therapy or medications that target neurotransmitter systems, estradiol focuses on the hormonal fluctuations during the menstrual cycle. This approach could lead to personalized treatments for alcohol use based on hormonal phases, potentially offering more effective and tailored interventions for individuals, particularly women.

What evidence suggests that estradiol is effective in influencing alcohol use?

Research has shown that estradiol, a female hormone, can affect alcohol use. This trial will test participants' alcohol sensitivity during different phases of their menstrual cycle, which naturally affects estradiol levels. One study found that estradiol can lead to behaviors that increase the desire to drink alcohol. High levels of estradiol might also make alcohol feel more rewarding and lower inhibitions, potentially leading to increased drinking. Another study suggested that higher progesterone levels compared to estradiol might help protect women from excessive drinking. These findings indicate that changes in estradiol levels might influence how alcohol affects women, possibly leading to new personalized treatments for alcohol abuse. ^{6 7 8 9 10}

Who Is on the Research Team?

Michelle Martel, PhD

Principal Investigator

University of Kentucky

Mark Fillmore, PhD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for women with regular menstrual cycles who drink alcohol at least once a week. They must not be pregnant, have a BMI of 30 or above, use hormone-based medications, or have any history of substance abuse (except nicotine) or certain medical and psychological conditions.

Inclusion Criteria

I am female.

Consume alcohol at least once per week

No history of drug or alcohol dependence

Exclusion Criteria

Pervasive developmental disorder

Body mass index (BMI) 30 or above

I have a health condition that prevents me from drinking alcohol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Menstrual Cycle Monitoring

Participants track their menstrual cycle and provide daily saliva samples to assess hormone fluctuations.

4 weeks

Daily assessments

Alcohol Sensitivity Testing

Participants undergo two rounds of alcohol sensitivity testing with both placebo and alcohol.

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after testing

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol

Trial Overview The study investigates how estradiol (a female hormone) affects the rewarding and disinhibiting effects of alcohol during different phases of the menstrual cycle. It involves daily monitoring and lab tests to see if changes in estradiol levels influence alcohol consumption.

How Is the Trial Designed?

Group I: menstrual cycle Experimental Treatment 2 Interventions

Participants will have their alcohol sensitivity test once during their early follicular phase and once during their late follicular phase

Estradiol is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Approved in United States as Estradiol for:

• Moderate to severe vasomotor symptoms due to menopause
• Vulvar and vaginal atrophy due to menopause
• Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
• Prevention of postmenopausal osteoporosis
• Palliative treatment of breast cancer
• Palliative treatment of prostate cancer

Approved in Canada as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Who Is Running the Clinical Trial?

Mark Fillmore

Lead Sponsor

Trials

3

Recruited

250+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

A single injection of estradiol valerate (EV) significantly reduces alcohol consumption in female rats immediately after administration, but their intake returns to normal levels shortly after.

When EV is administered weeks before the opportunity to drink, it leads to a long-lasting increase in alcohol consumption, suggesting that early exposure to estradiol can enhance the preference for alcohol over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One injection of estradiol valerate induces dramatic changes in rats' intake of alcoholic beverages. Reid, LD., Marinelli, PW., Bennett, SM., et al.[2019]

A study involving 17 women on combined oral contraceptives found no significant differences in alcohol metabolism during different phases of their menstrual cycle, suggesting that sex hormones have limited effects on how alcohol is processed in the body.

This research adds to over a dozen studies since the 1970s that have generally failed to replicate earlier findings of significant hormonal impacts on alcohol clearance, reinforcing the idea that sex hormones do not substantially alter ethanol pharmacokinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alcohol elimination at low blood concentrations among women taking combined oral contraceptives. King, AR., Hunter, PJ.[2019]

In a study of 300 participants (113 men and 87 women alcohol-dependent patients, and 133 men and 107 women healthy controls), it was found that bioavailable estradiol levels decreased during alcohol withdrawal treatment, which may impact recovery outcomes.

The research indicates that higher estradiol levels in male patients were associated with more alcohol-related readmissions and liver damage, while female patients had lower estradiol-to-testosterone activities compared to healthy controls, highlighting the importance of sex hormones in alcohol dependence outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen receptor 1 gene variants and estradiol activities in alcohol dependence. Mühle, C., Barry, B., Weinland, C., et al.[2021]

Tamoxifen has been the standard treatment for hormone-sensitive early breast cancer for 30 years, but its long-term use is linked to serious side effects, highlighting the need for safer alternatives.

Anastrozole, a third-generation aromatase inhibitor, shows improved efficacy and a better safety profile compared to tamoxifen, particularly in reducing risks of life-threatening events, making it a promising option for postmenopausal women with early breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations of adjuvant therapy in early breast cancer in postmenopausal women. Gradishar, WJ.[2018]

In a study of 21 young adult women using oral contraceptives, higher levels of ethinyl estradiol (EE) were linked to increased alcohol consumption and binge drinking during the active pill phase.

Progestin levels and the phase of the pill did not significantly affect alcohol use, suggesting that EE may play a key role in influencing drinking behavior, highlighting the need for further research to explore this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evidence of increased alcohol use associated with ethinyl estradiol levels in women using oral contraceptives. Strzelecki, AM., Gipson, CD., Childs, E., et al.[2023]

In a study of 94 adolescent females, those who reported current alcohol use had significantly higher levels of estradiol, suggesting a potential link between hormone levels and alcohol consumption.

Higher levels of both testosterone and estradiol were associated with a greater likelihood of current alcohol use, indicating that hormonal changes during adolescence may influence alcohol use behaviors and future health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alcohol use in adolescent females: correlates with estradiol and testosterone. Martin, CA., Mainous, AG., Curry, T., et al.[2019]

Anastrozole, a highly specific aromatase inhibitor, has emerged as a potentially better tolerated and more effective treatment for postmenopausal patients with hormone-sensitive breast cancer compared to tamoxifen, which has safety and tolerability issues.

The ongoing Arimidex, Tamoxifen, Alone or in Combination trial indicates that anastrozole is an effective and well-tolerated option for adjuvant endocrine treatment in early breast cancer, suggesting its potential role in chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anastrozole in adjuvant therapy for postmenopausal patients. Buzdar, AU.[2019]

In a study involving 26 patients with climacteric symptoms, the phytoestrogen drug SoyaVital, containing 35 mg of isoflavones, significantly reduced symptoms by 30.06% over 12 weeks.

The results suggest that SoyaVital could be a viable alternative to hormonal replacement therapy for managing climacteric symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Influence of the phytoestrogen drug, SoyaVital, on climacteric symptoms]. Rachev, E., Stamenov, G., Davidkova, N.[2013]

The 7-day estradiol transdermal patch (Climara) effectively reduces hot flushes in women, with a mean decline of 74.6% for the higher dose compared to 64.5% for the lower dose, showing comparable efficacy to traditional hormone therapies.

The Climara patch is well tolerated, with a low withdrawal rate due to adverse events (8.9%), primarily related to skin reactions, and it demonstrated better adhesion compared to other patches, making it a practical option for estrogen replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a seven-day estradiol transdermal system for estrogen replacement therapy. Gordon, SF.[2019]

In a study of 425 women undergoing in vitro fertilization, transdermal estradiol hemihydrate (Divigel) resulted in a comparable increase in endometrial thickness to oral estradiol valerate, while requiring significantly lower doses and shorter treatment duration.

Both treatment groups had similar pregnancy and 'take home baby' rates, indicating that transdermal estrogens are effective for improving endometrial conditions without increasing the total estrogen exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thin endometrium problem in IVF programs. Vartanyan, E., Tsaturova, K., Devyatova, E.[2021]

Selective estrogen receptor modulators (SERMs) and antiestrogens, such as raloxifene and bazedoxifene, are safe options for postmenopausal women as they do not increase breast cancer risk and may even offer protection against it.

The combination of conjugated estrogens with bazedoxifene has shown an improved breast safety profile compared to traditional hormone therapies, with no increase in breast density or pain over two years, indicating a safer alternative for managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast. Pickar, JH., Komm, BS.[2018]

The tissue selective estrogen complex of conjugated equine estrogens and bazedoxifene has been shown to effectively improve menopausal symptoms and prevent bone loss without increasing breast cancer risk, based on data from five studies over two years.

Ospemifene is approved for treating painful intercourse and may also benefit bone health and breast tissue, while lasofoxifene is being developed for treating resistant breast cancer, highlighting the diverse applications of SERMs in women's health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond estrogen: advances in tissue selective estrogen complexes and selective estrogen receptor modulators. Pinkerton, JV., Conner, EA.[2020]

In a study involving 120 women undergoing menopause, those who received conjugated estrogen (Femipren) for one year experienced significant improvements in climacteric symptoms, depression, and anxiety scores.

The results suggest that long-term estrogen therapy may have a direct positive effect on psychological factors such as self-image and optimism, indicating its potential as a treatment for both physical and emotional symptoms of menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in psychological well-being during postmenopause as a result of estrogen therapy. Durst, N., Maoz, B.[2019]

In a study involving a once-weekly transdermal estradiol patch applied to either the buttocks or abdomen, the buttock application resulted in significantly higher estradiol levels, with a 125.1% peak concentration compared to the abdomen.

The buttocks provided better bioavailability of estradiol, which may benefit women experiencing menopausal symptoms, as it maintained higher hormone levels throughout the week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of site of application on the transcutaneous absorption of 17-beta estradiol from a transdermal delivery system (Climara). Taggart, W., Dandekar, K., Ellman, H., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11720806/

Effect of daily alcohol intake on sex hormone levels among ... Our trial and our preliminary analysis of NHANES data both suggest that alcohol intake may not increase estradiol levels in the presence of AI ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6585852/

Sex hormones in alcohol consumption: a systematic review ... Yet the only study to examine the effects of estrogen level on alcohol use in males reported a positive association between salivary estradiol level and alcohol ...

3. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20230027

Associations of Menstrual Cycle and Progesterone-to- ... These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females ...

4. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1282230/pdf

Estradiol mediates sex differences in aversion-resistant ... Taken together with our data, these findings suggest that circulating estradiol contributes to alcohol seeking behavior and the associated ...

5. aacrjournals.org aacrjournals.org/cebp/article/30/12/2294/674929/Alcohol-Intake-and-Endogenous-Hormones-in-Pre-and

Alcohol Intake and Endogenous Hormones in Pre Alcohol intake may influence breast cancer risk in women through hormonal changes, but the evidence to date is inconclusive.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10632661/

Preliminary evidence of increased alcohol use associated with ... These findings provide preliminary data suggesting increased levels of EE from OC pills are associated with excessive alcohol consumption in women.

7. drugs.com drugs.com/food-interactions/estradiol,climara.html

Climara and Alcohol/Food Interactions There are 4 alcohol/food/lifestyle interactions with Climara (estradiol). Moderate. Nicotine Estradiol. Moderate Drug Interaction. As you stop smoking during ...

8. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-024-01940-4

Effect of daily alcohol intake on sex hormone levels among ... Our trial and our preliminary analysis of NHANES data both suggest that alcohol intake may not increase estradiol levels in the presence of AI ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/estradiol-and-levonorgestrel-transdermal-route/description/drg-20112971

Estradiol and levonorgestrel (transdermal route) Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis ...

10. jamanetwork.com jamanetwork.com/journals/jama/article-abstract/411320%5C

Effects of Alcohol Ingestion on Estrogens in ... Acute alcohol ingestion may lead to significant and sustained elevations in circulating estradiol to levels 300% higher than those targeted in clinical use of ...