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

100 Participants Needed

Trial Summary

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 data supports the idea that Hormonal Effects on Alcohol Use is an effective drug?

The available research does not provide direct evidence supporting the effectiveness of Hormonal Effects on Alcohol Use for its intended purpose. However, it does show that similar hormonal treatments, like estrogen therapy, have positive effects on symptoms related to menopause, such as improving psychological well-being and reducing climacteric symptoms. For example, one study found that estrogen therapy improved self-image, optimism, and satisfaction with personal appearance in women undergoing menopause. Another study showed a significant reduction in climacteric symptoms with a phytoestrogen drug, SoyaVital, which is recommended as an alternative to hormonal replacement therapy. These findings suggest that hormonal treatments can have beneficial effects, but specific data on Hormonal Effects on Alcohol Use for its intended purpose is not provided. ^{1 2 3 4 5}

What safety data exists for hormonal treatments like Estradiol?

The safety data for hormonal treatments such as Estradiol, which is marketed under various names like Divigel, includes studies on its effects in different contexts. For instance, a study involving estradiol hemihydrate (Divigel) in IVF programs provides some safety insights. Additionally, traditional menopausal hormone therapies containing estrogens have been associated with an increased risk of breast cancer, but newer combinations like conjugated estrogens with bazedoxifene show an improved breast safety profile. Long-term use of tamoxifen, a related hormone therapy, is associated with serious side effects, but newer agents like anastrozole have shown a more favorable safety profile, particularly in terms of life-threatening events. Overall, while there are safety concerns with traditional hormone therapies, newer treatments and combinations are being developed to improve safety profiles. ^{3 6 7 8 9}

Is the drug Estradiol a promising treatment for reducing alcohol use?

The research suggests that higher levels of estradiol might be linked to increased alcohol consumption, especially in women using oral contraceptives. This means Estradiol might not be a promising treatment for reducing alcohol use, as it could potentially increase it. ^{10 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

Michelle Martel, PhD

Principal Investigator

University of Kentucky

Mark Fillmore, PhD

Principal Investigator

University of Kentucky

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Study Participants Experimental Treatment 2 Interventions

Participants in this group will track their menstrual cycle, provide daily saliva samples, and undergo two rounds of alcohol sensitivity testing (with both placebo and alcohol).

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+

Findings from Research

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]

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 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]

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 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]

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]

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]

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]

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 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]

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]

References

1. Bulgaria pubmed.ncbi.nlm.nih.gov

[Influence of the phytoestrogen drug, SoyaVital, on climacteric symptoms]. [2013]

2. Ireland pubmed.ncbi.nlm.nih.gov

Changes in psychological well-being during postmenopause as a result of estrogen therapy. [2019]

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

Thin endometrium problem in IVF programs. [2021]

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

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

5. United States 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). [2019]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Beyond estrogen: advances in tissue selective estrogen complexes and selective estrogen receptor modulators. [2020]

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

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Preliminary evidence of increased alcohol use associated with ethinyl estradiol levels in women using oral contraceptives. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Alcohol use in adolescent females: correlates with estradiol and testosterone. [2019]

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

One injection of estradiol valerate induces dramatic changes in rats' intake of alcoholic beverages. [2019]

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

Alcohol elimination at low blood concentrations among women taking combined oral contraceptives. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Estrogen receptor 1 gene variants and estradiol activities in alcohol dependence. [2021]