Hormonal Effects on Alcohol Use
Recruiting in Palo Alto (17 mi)
Overseen byMichelle Martel, PhD
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Waitlist Available
Sponsor: Mark Fillmore
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
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.
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.12345
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.36789
Is the drug Estradiol a promising treatment for reducing alcohol use?
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
See 1 more
Exclusion Criteria
Pervasive developmental disorder
Body mass index (BMI) 30 or above
I have a health condition that prevents me from drinking alcohol.
See 9 more
Treatment Details
Interventions
- Estradiol (Hormone Therapy)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Study ParticipantsExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Of Kentucky Psychology Research LabLexington, KY
Loading ...
Who Is Running the Clinical Trial?
Mark FillmoreLead Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)Collaborator
References
[Influence of the phytoestrogen drug, SoyaVital, on climacteric symptoms]. [2013]The results of phytoestrogen drug SoyaVital on the climacteric symptoms are presented. The preparation consists of 35 mg isoflavones with high content of genistein in one capsule. A group of 26 patients having climacteric symptoms have been treated by one capsule per day for a period of 12 weeks. The evaluation of the symptoms by Kuppermann score decreased statistically significant by 30.06%. The authors recommend SoyaVital as an alternative to the hormonal replacement therapy.
Changes in psychological well-being during postmenopause as a result of estrogen therapy. [2019]A study of the effects of a conjugated estrogen (Femipren) upon various climacteric symptoms, depression and anxiety scores and psycho-social factors in 120 women around the menopause, was carried out in a Menopause Clinic. In order to participate in this study, the women had to meet very strict criteria. A climacteric symptom list, the MMPI and a psycho-social questionnaire were used for assessment, and were employed before, during and at the end of 1 yr of hormone replacement therapy. Typical vasomotor and psychic symptoms changed significantly as did such factors as self-image, optimism, perception of the future and satisfaction with personal appearance, in those patients who received hormonal replacement therapy for 1 yr. As the psychological factors changed only in those patients who received long-term estrogen therapy, a tentative hypothesis of direct psychotropic effect of estrogen was formulated.
Thin endometrium problem in IVF programs. [2021]Label="METHODS" NlmCategory="METHODS">Observational, comparative, prospective, multicenter study (n = 425). Group 1 (n = 228) received estradiol hemihydrate (Divigel, Orion Corporation, Finland), group 2 (n = 197) received oral estradiol valerate (Proginova, Delpharm Lille, France).
Clinical experience with a seven-day estradiol transdermal system for estrogen replacement therapy. [2019]To describe the efficacy, safety, and wearability of estrogen replacement therapy of a 7-day estradiol transdermal system (Climara), developed using new drug-in-adhesive technology.
The effect of site of application on the transcutaneous absorption of 17-beta estradiol from a transdermal delivery system (Climara). [2019]The effect of site of application on 17-beta estradiol bioavailability was assessed in an open-label, randomized, crossover study of a once-weekly transdermal estradiol patch (Climara).
Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast. [2018]Traditional menopausal hormone therapy containing estrogens/progestin has been associated with an increased risk of breast cancer, and estrogen exposure is known to promote growth and proliferation of a majority of breast cancers. Therefore, it is important for clinicians to consider the breast safety profile of any hormone-based therapy used in postmenopausal women. This review provides an overview of the breast safety and tolerability profiles of currently marketed selective estrogen receptor modulators, antiestrogens, and the first tissue selective estrogen complex combining conjugated estrogens with the selective estrogen receptor modulator bazedoxifene in postmenopausal women. Selective estrogen receptor modulators and antiestrogens act as estrogen receptor antagonists in the breast. Tamoxifen, toremifene, and the selective estrogen receptor degrader fulvestrant are used to treat breast cancer, and tamoxifen and raloxifene protect against breast cancer in high-risk women. Postmenopausal women using selective estrogen receptor modulators for prevention or treatment of osteoporosis (raloxifene, bazedoxifene) can be reassured that these hormonal treatments do not adversely affect their risk of breast cancer and may, in the case of raloxifene, even be protective. There are limited data on breast cancer in women who use ospemifene for dyspareunia. Conjugated estrogens/bazedoxifene use for up to two years did not increase mammographic breast density or breast pain/tenderness, and there was no evidence of an increased risk of breast cancer, suggesting that conjugated estrogens/bazedoxifene has an improved breast safety profile compared with traditional menopausal hormone therapies. Future research will continue to focus on development of selective estrogen receptor modulators and selective estrogen receptor modulator combinations capable of achieving the ideal balance of estrogen receptor agonist and antagonist effects.
Safety considerations of adjuvant therapy in early breast cancer in postmenopausal women. [2018]Because of its proven efficacy profile based on long-term data, tamoxifen has been the standard adjuvant endocrine therapy for hormone-sensitive early breast cancer for the past 30 years. However, there is well-established evidence that long-term use of tamoxifen is associated with serious side effects. As adjuvant endocrine therapy is generally administered for long periods of time, the safety and tolerability of agents used in this setting are of particular importance. Due to their superior efficacy over tamoxifen, newer agents, such as the third-generation aromatase inhibitors (AIs), are already established therapies for the treatment of advanced breast cancer. In addition, recent trials indicate that the AI anastrozole ('Arimidex') has improved efficacy compared with tamoxifen in the adjuvant setting in postmenopausal women. The other third-generation AIs have reported disease-free survival benefits but not in the absence of prior treatment with tamoxifen; letrozole ('Femara') has been compared with placebo following 5 years of tamoxifen therapy and exemestane ('Aromasin') has been compared with tamoxifen following 2-3 years of prior treatment with tamoxifen. Long-term safety data show that anastrozole also has a more favorable overall safety profile compared with tamoxifen, particularly in terms of life-threatening events such as endometrial cancer and thromboembolism. Anastrozole alone, therefore, provides a new option for adjuvant therapy in postmenopausal women with hormone-receptor-positive early breast cancer. The AIs have differing pharmacological profiles, which may translate into dissimilar adverse event profiles in the adjuvant treatment setting, but patient follow-up in most trials is relatively short to make a valid comparison. It cannot, therefore, be assumed that all AIs will be equally well tolerated in the adjuvant setting. Further data on the long-term safety of AIs other than anastrozole are therefore required to allow overall risk:benefit assessments on these agents to be made.
Beyond estrogen: advances in tissue selective estrogen complexes and selective estrogen receptor modulators. [2020]Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have variable estrogen agonist and antagonist activities in different target tissues. Tamoxifen is an anti-estrogen in the breast used for treatment and prevention of breast cancer, with estrogen agonist activity in the uterus. Raloxifene prevents and treats osteoporosis and prevents breast cancer, and can be safely combined with vaginal but not systemic estrogen. The tissue selective estrogen complex combines conjugated equine estrogens (CEE) with the SERM bazedoxifene (BZA). The five Selective Estrogen Menopause and Response to Therapy studies, with up to 2 years of data, demonstrated that CEE/BZA 0.45 mg/BZA 20 mg improved vasomotor symptoms and vulvovaginal atrophy, prevented bone loss, and was neutral on breast tenderness, breast density, with breast cancer incidence similar to placebo. Protection against estrogen-induced endometrial hyperplasia and cancer was found, with similar amenorrhea rates to placebo. Ospemifene is approved to treat dyspareunia, with potential benefits on bone and the breast, while lasofoxifene is being developed to treat resistant estrogen receptor-positive breast cancer in women. Estetrol is an estrogen synthesized exclusively during pregnancy by the human fetal liver and initially considered a weak estrogen, but it appears to have dual weak estrogenic/anti-estrogenic features.
Role of anastrozole in adjuvant therapy for postmenopausal patients. [2019]For the past 25 years tamoxifen has been the mainstay for adjuvant treatment of postmenopausal patients with hormone-sensitive breast cancer. However, tamoxifen has some safety and tolerability issues, and its partial estrogen-receptor agonist activity may have efficacy implications. Highly specific aromatase inhibitors, of which anastrozole was the first, were introduced in the 1990s and have emerged as a potentially better tolerated and more effective class of agents targeting hormonally responsive breast cancer. This article provides a review of the clinical pharmacology of anastrozole (1 mg once daily) and reviews the first results of the ongoing Arimidex, Tamoxifen, Alone or in Combination early breast cancer trial, initiated in 1996. This randomized, double-blind multicenter trial compared tamoxifen (20 mg once daily) with anastrozole (1 mg once daily) alone and the combination of anastrozole plus tamoxifen, as adjuvant endocrine treatment for postmenopausal patients with operable, invasive, early breast cancer. The results of the Arimidex, Tamoxifen, Alone or in Combination trial show anastrozole to be an effective and well tolerated endocrine option for early breast cancer and provide evidence for its potential role in chemoprevention.
Preliminary evidence of increased alcohol use associated with ethinyl estradiol levels in women using oral contraceptives. [2023]Alcohol use is highly prevalent in young adult women and rates of alcohol use disorder are rising rapidly in this population. Further, emerging evidence suggests that circulating levels of ovarian hormones influence alcohol consumption, with increased consumption associated with higher estradiol and lower progesterone levels. However, less is known about the influence of synthetic hormones (contained in oral contraceptive (OC) pills) on alcohol use. The current study examined the influence of OC pill phase, ethinyl estradiol (EE) levels, and progestin levels on self-reported alcohol consumption in healthy female drinkers. Young adult female drinkers using OCs (N = 21) reported alcohol use across one OC pill pack using the Timeline Followback and provided blood samples during both pill phases to measure synthetic hormone levels. We compared alcohol use between OC pill phases (active vs. inactive) using linear mixed effects models for repeated measures and examined correlations between alcohol use and EE and progestin levels. Results showed that women with higher EE levels reported increased alcohol consumption (r = 0.56, p = 0.01) and binge drinking (r = 0.45, p = 0.04) in the active pill phase. Progestin levels and pill phase were not significantly associated with alcohol consumption. These findings provide preliminary data suggesting increased levels of EE from OC pills are associated with excessive alcohol consumption in women. Further research is needed to determine if EE plays a causal role in increased alcohol consumption. This line of research could inform female-specific AUD prevention and treatment strategies among the large subpopulation of women using hormonal contraceptives.
Alcohol use in adolescent females: correlates with estradiol and testosterone. [2019]This study investigated if self-reports of alcohol use correlated with estradiol and testosterone levels in adolescent females. Ninety-four female senior high school student volunteers from 2 schools completed a questionnaire regarding alcohol use. Twenty cc of blood was assayed for estradiol, testosterone, progesterone, and FSH. Total estradiol levels were higher in females who reported current alcohol use (p
One injection of estradiol valerate induces dramatic changes in rats' intake of alcoholic beverages. [2019]A series of experiments investigated the effects of a single injection of estradiol valerate (EV) on female rats' consumption of alcoholic beverages. EV provides sustained release of estradiol. Just after an injection of EV, rats' intake of a palatable alcoholic beverage, which had been taken regularly before, is reduced dramatically. Subsequently, rats' intake of alcoholic beverage returns to baseline levels. With continued opportunity to drink, rats take more ethanol than controls. When EV was given 15 and 31 days before the first opportunity to drink an alcoholic beverage, female rats markedly enhanced their intake of ethanol. Once enhanced intakes emerged, they were observed with different kinds of alcoholic beverages and endured for months.
Alcohol elimination at low blood concentrations among women taking combined oral contraceptives. [2019]Evidence implicating a role of natural and synthetic estrogens and/or progestin on ethanol pharmacokinetics can be traced back to the mid-1970s when reports of large metabolic differences were found suggesting that sex hormones interfered with the efficient clearance of alcohol at the liver microsomal level. Research teams in this area manipulate sex hormone levels by either examining natural-cycling women at different phases of their menstrual cycle or others taking oral contraceptives that synthetically regulate the hormonal fluctuations. These collective studies (over a dozen to date involving over 200 participants) have all been similar in focus and outcome. With one important exception, the published laboratory research since 1976 has failed to replicate the earliest research suggesting sex hormone effects. One well-controlled study in 1987 did generate renewed interest in the area with the paradoxical finding that progesterone actually enhanced alcohol elimination at low blood concentrations (
Estrogen receptor 1 gene variants and estradiol activities in alcohol dependence. [2021]Alcohol use disorders inflict a great individual and societal burden. Although sex hormone effects have been implicated in alcohol dependence, research has mostly neglected estrogen activities and female alcohol-dependent patients. Here, we investigated associations of estrogen receptor 1 (ESR1) genetics and serum estradiol activities with aspects of alcohol dependence.