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| ID | Type | Description | Link |
|---|---|---|---|
| R21MH121726 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This pilot study experimentally manipulates ovarian hormones to examine the direct impact of estrogen (E2) and progesterone (P4) on binge eating symptom burden and the behavioral reward response in women with bulimia nervosa (n=15). This is completed by taking medications that change ovarian hormone levels. This line of research could lead to the development of pharmacological interventions developed to target specific areas of the brain, brain receptors, or pathways identified to be involved in the mechanism underlying ovarian hormone change and binge eating.
Eating disorders (EDs) affect 15 million women in the United States and have one of the highest mortality rates of any mental illness. Despite this, the underlying neurobiology remains poorly understood. EDs predominantly occur in women, and the frequency of certain symptoms change in a predictable pattern over the menstrual cycle; specifically, symptom changes appear to be triggered by normal fluctuations in the ovarian hormones estradiol (E2) and progesterone (P4).
The objective of this study is to examine the direct and mechanistic role of E2 and P4 on binge eating in women with bulimia nervosa (BN; n = 15). The experimental design parallels an established design developed to determine the hormonal triggers of premenstrual dysphoric disorder and depression: temporarily stopping the menstrual cycle using a Gonadotropin-releasing hormone (GnRH) agonist (Lupron) and addback E2 and P4 independently in a double-blind crossover design. The overarching hypothesis is that BN represents a hormone-sensitive phenotype, and this sensitivity is modulated by E2's effects on aspects of the reward response such that reward-motivated behaviors increase in the context of low E2. This line of research will provide direction for future research addressing neuroendocrine, neurobiological, and brain activity and function in BN. To date, there are no medications that have been developed specifically for the treatment of individuals with BN.
Our specific aims are to:
Aim 1: Quantify the direct effect of E2 and P4 on binge eating in women with BN.
Aim 2: Determine the effect of E2 on reward response in women with BN.
Aim 3: Examine the association between reward response and binge eating before and after E2 addback.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence A: estradiol followed by progesterone | Experimental | Participants are randomly assigned to treatment Sequence A: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence A will receive estradiol addback first, followed by progesterone. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. |
|
| Sequence B: progesterone followed by estradiol | Experimental | Participants are randomly assigned to treatment Sequence B: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence B will receive progesterone first followed by estradiol. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Estradiol | Drug | During estradiol administration, 2mg of estradiol is given twice daily via oral capsule. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Binge Eating Sum Score | Binge eating will be measured using the 8-item binge eating subscale of the Eating Pathology Symptoms Inventory (EPSI), which measures features of binge eating (e.g., consumption of large quantities of food, mindless eating) on a 5-point Likert scale from "never" to "very often." The EPSI scale is designed to assess behavior over the past 28 days; however, to be sensitive to the timeframe of the present study, the instructions will be modified to ask participants to consider the past week. Items are summed for a scale score ranging from 0-32. Higher scores indicate more frequent experiences with binge eating behavior. Change is defined by an average change score. | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention) |
| Change in Weekly Average Binge-eating Frequency | Binge eating frequency is based on a daily diary of self-reported binge eating frequency. Scores can range from 0 to infinity as they represent a self-reported frequency. Subjects self-report the number of binge eating episodes they had each day. Higher numbers indicate more frequent binge eating episodes. Average weekly frequency will be determined based on daily reported binge eating frequency. Change is defined by an average change score. | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention) |
| Change in Self-Reported Reward Sensitivity Subscale Score During Estradiol Manipulation | Sensitivity to Punishment/Sensitivity to Reward Questionnaire will be used to measure reward sensitivity during estradiol intervention. The reward sensitivity subscale will be used, which is rated on a true/false scale with scores ranging 0-24. Higher scores indicate more sensitivity to reward. Change is defined by an average change score. | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
| Change in Response Latency to Reward During the Monetary Incentive Delay Task During Estradiol Manipulation | Time (ms) between stimulus and response will be measured during the Monetary Incentive Delay (MID) task during the win trials during the estradiol intervention. During the MID task, participants need to select the correct response during "win" and "lose" conditions by pressing a button. Higher scores indicate a longer response time to the win trials. Change is defined by an average change score. |
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Inclusion Criteria
Participants will be women aged 18-42 with a current DSM-5 bulimia nervosa (BN) diagnosis who meet the below criteria. Only participants capable of giving informed consent and understanding the risks associated with the study will be enrolled.
Exclusion Criteria
Patients will not be permitted to enter this protocol if they have any of the following:
Men will not be included in this study given the stated purpose of studying the impact of ovarian hormones.
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| Name | Affiliation | Role |
|---|---|---|
| Jessica Baker, PhD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23585773 | Background | Baker JH, Girdler SS, Bulik CM. The role of reproductive hormones in the development and maintenance of eating disorders. Expert Rev Obstet Gynecol. 2012 Nov 1;7(6):573-583. doi: 10.1586/eog.12.54. | |
| 17038206 | Background | Edler C, Lipson SF, Keel PK. Ovarian hormones and binge eating in bulimia nervosa. Psychol Med. 2007 Jan;37(1):131-41. doi: 10.1017/S0033291706008956. Epub 2006 Oct 12. |
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Deidentified individual data that supports the results will be shared beginning 18 to 24 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Deidentified individual data that supports the results will be shared beginning 18 to 24 months following publication.
Approval from an IRB, IEC, or REB, as applicable and execution of a data use/sharing agreement with UNC.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence A: Estradiol Followed by Progesterone | Participants are randomly assigned to treatment Sequence A: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence A will receive estradiol addback first, followed by progesterone. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. Estradiol: During estradiol administration, 2mg of estradiol is given twice daily via oral capsule. Micronized progesterone: During progesterone administration, 200mg of progesterone is given twice daily via oral capsule. Leuprolide Acetate: Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. Placebo Oral Capsule: Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. |
| FG001 | Sequence B: Progesterone Followed by Estradiol | Participants are randomly assigned to treatment Sequence B: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence B will receive progesterone first followed by estradiol. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. Estradiol: During estradiol administration, 2mg of estradiol is given twice daily via oral capsule. Micronized progesterone: During progesterone administration, 200mg of progesterone is given twice daily via oral capsule. Leuprolide Acetate: Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. Placebo Oral Capsule: Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lupron and Placebo Baseline (6 Weeks) |
| |||||||||||||
| First Intervention (2 Weeks) |
| |||||||||||||
| Washout (2 Weeks) |
| |||||||||||||
| Second Intervention (2 Weeks) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence A: Estradiol Followed by Progesterone | Participants are randomly assigned to treatment Sequence A: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence A will receive estradiol addback first, followed by progesterone. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. Estradiol: During estradiol administration, 2mg of estradiol is given twice daily via oral capsule. Micronized progesterone: During progesterone administration, 200mg of progesterone is given twice daily via oral capsule. Leuprolide Acetate: Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. Placebo Oral Capsule: Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Binge Eating Sum Score | Binge eating will be measured using the 8-item binge eating subscale of the Eating Pathology Symptoms Inventory (EPSI), which measures features of binge eating (e.g., consumption of large quantities of food, mindless eating) on a 5-point Likert scale from "never" to "very often." The EPSI scale is designed to assess behavior over the past 28 days; however, to be sensitive to the timeframe of the present study, the instructions will be modified to ask participants to consider the past week. Items are summed for a scale score ranging from 0-32. Higher scores indicate more frequent experiences with binge eating behavior. Change is defined by an average change score. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention) |
|
Adverse event data was tracked once participants' began receiving the Lupron and Placebo during the initial hormone suppression stage and continued through study completion (approximately 12 weeks).
All unresolved adverse events were tracked by the investigator until the events were resolved, the subject was lost to follow-up, or the adverse event was otherwise explained.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Estradiol | Participants are randomly assigned to treatment Sequence A: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence A will receive estradiol addback first, followed by progesterone. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. Estradiol: During estradiol administration, 2mg of estradiol is given twice daily via oral capsule. Micronized progesterone: During progesterone administration, 200mg of progesterone is given twice daily via oral capsule. Leuprolide Acetate: Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. Placebo Oral Capsule: Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Localized rash at injection site | Skin and subcutaneous tissue disorders | Systematic Assessment |
Due to the COVID-19 pandemic, this trial was unable to enroll the number of participants needed to complete the study leading to only a very small number of participants.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jessica Baker, PhD | University of North Carolina at Chapel Hill | 984-235-0858 | jhbaker@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 11, 2021 | Jun 14, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 13, 2021 | May 10, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D052018 | Bulimia Nervosa |
| D002032 | Bulimia |
| D001068 | Feeding and Eating Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D006963 | Hyperphagia |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D004958 | Estradiol |
| D011374 | Progesterone |
| D016729 | Leuprolide |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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|
| Micronized progesterone | Drug | During progesterone administration, 200mg of progesterone is given twice daily via oral capsule. |
|
|
| Leuprolide Acetate | Drug | Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. |
|
|
| Placebo Oral Capsule | Drug | Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. |
|
|
| Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
| Change in Delay Discounting Parameter k Using the Monetary Choice Questionnaire With Estradiol Manipulation | During the estradiol intervention, participants will be asked to make a series of hypothetical choices between small, sooner (impulsive) vs. larger, later (self controlled) hypothetical monetary outcomes. k is a hyperbolic function with larger k values indicating more valuation of a larger delayed reward and smaller values indicating preference for more immediate, smaller rewards (more impulsivity). Change is defined as the average change in k. | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
| Change in Self-Reported Behavioral Inhibition Score During Estradiol Manipulation | This measures assesses individual disposition toward avoidance of activities during the estradiol intervention. The Behavioural Inhibition subscale of the Behavioural Inhibition Scale/Behavioral Activation Scale (BIS/BAS) assesses behavioural inhibition (BI) using participant self-reports. The minimum score on the BIS subscale is 7, maximum 28. Greater scores indicate greater behavioural inhibition. Change is defined by an average change score | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
| Change in Behavioral Activation Score During Estradiol Manipulation | This measures assesses individual disposition toward engaging in activities during the estradiol intervention. Two BIS/BAS behavioural activation (BA) subscales will be used. The BA subscales used are Fun Seeking and Drive. Each subscale is summed to get the respective subscale scores. The minimum score on BA Fun Seeking and BA Drive are minimum 4 and maximum 16. Higher scores indicate greater behavioral activation. Change is defined by an average change score. | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
| Change in Behavioral Activation Reward Responsiveness With Estradiol Manipulation | This measures assesses individual disposition toward avoiding and engaging in activities during estradiol intervention. The BIS/BAS reward responsiveness subscale will be used. The minimum score on the BA Reward Responsiveness subscale is 5, maximum 20. Higher scores indicate greater reward responsiveness. Change is defined by an average change score. | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
| Change in Behavioral Inhibition During Estradiol Administration as Assessed Through a Behavioral Task | Behavioral response inhibition will be examined during a go/no-go computerized task during the estradiol intervention. Inhibitory control is defined by the response accuracy of the go no/go trials. Percent of errors is calculated as the number of "go" responses on a "no/go" trial" divided by the total number of "no/go" trials." Fewer errors ("go" response on a "no/go" trial) indicates better inhibitory control. Change is defined by an average change score. | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
| Correlation Between Change in Reward Response and Change in Binge Eating Before and During Estradiol Manipulation | Pearson correlations between change in self-reported reward response and change in binge eating between baseline and estradiol intervention will be examined. Binge eating is defined as the sum score from the Eating Pathology Symptom Inventory (EPSI). Self-reported reward response is defined as the BAS reward responsiveness subscale score and the Sensitivity to Reward/Sensitivity to Punishment Questionnaire (SPSRQ) sensitivity to reward subscale score. Change in binge eating and change in reward response between baseline and estradiol intervention was calculated and a correlation conducted between change scores. | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
| 18307829 | Background | Klump KL, Keel PK, Culbert KM, Edler C. Ovarian hormones and binge eating: exploring associations in community samples. Psychol Med. 2008 Dec;38(12):1749-57. doi: 10.1017/S0033291708002997. Epub 2008 Feb 29. |
| 12537036 | Background | Lester NA, Keel PK, Lipson SF. Symptom fluctuation in bulimia nervosa: relation to menstrual-cycle phase and cortisol levels. Psychol Med. 2003 Jan;33(1):51-60. doi: 10.1017/s0033291702006815. |
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| 10438404 | Background | Friedler S, Raziel A, Schachter M, Strassburger D, Bukovsky I, Ron-El R. Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration. Hum Reprod. 1999 Aug;14(8):1944-8. doi: 10.1093/humrep/14.8.1944. |
| 15760966 | Background | Humaidan P, Bredkjaer HE, Bungum L, Bungum M, Grondahl ML, Westergaard L, Andersen CY. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005 May;20(5):1213-20. doi: 10.1093/humrep/deh765. Epub 2005 Mar 10. |
| 12082359 | Background | Mitwally MF, Gotlieb L, Casper RF. Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Menopause. 2002 Jul-Aug;9(4):236-41. doi: 10.1097/00042192-200207000-00004. |
| 15198787 | Background | Wyatt KM, Dimmock PW, Ismail KM, Jones PW, O'Brien PM. The effectiveness of GnRHa with and without 'add-back' therapy in treating premenstrual syndrome: a meta analysis. BJOG. 2004 Jun;111(6):585-93. doi: 10.1111/j.1471-0528.2004.00135.x. |
| 23815116 | Background | Forbush KT, Wildes JE, Pollack LO, Dunbar D, Luo J, Patterson K, Petruzzi L, Pollpeter M, Miller H, Stone A, Bright A, Watson D. Development and validation of the Eating Pathology Symptoms Inventory (EPSI). Psychol Assess. 2013 Sep;25(3):859-78. doi: 10.1037/a0032639. Epub 2013 Jul 1. |
| 15964149 | Background | Franken IH, Muris P, Georgieva I. Gray's model of personality and addiction. Addict Behav. 2006 Mar;31(3):399-403. doi: 10.1016/j.addbeh.2005.05.022. Epub 2005 Jun 16. |
| 20381877 | Background | Harrison A, O'Brien N, Lopez C, Treasure J. Sensitivity to reward and punishment in eating disorders. Psychiatry Res. 2010 May 15;177(1-2):1-11. doi: 10.1016/j.psychres.2009.06.010. Epub 2010 Apr 9. |
| 10875899 | Background | Knutson B, Westdorp A, Kaiser E, Hommer D. FMRI visualization of brain activity during a monetary incentive delay task. Neuroimage. 2000 Jul;12(1):20-7. doi: 10.1006/nimg.2000.0593. |
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| BG001 | Sequence B: Progesterone Followed by Estradiol | Participants are randomly assigned to treatment Sequence B: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence B will receive progesterone first followed by estradiol. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. Estradiol: During estradiol administration, 2mg of estradiol is given twice daily via oral capsule. Micronized progesterone: During progesterone administration, 200mg of progesterone is given twice daily via oral capsule. Leuprolide Acetate: Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. Placebo Oral Capsule: Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. |
| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| OG001 | Progesterone | Participants are randomly assigned to treatment Sequence B: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence B will receive progesterone first followed by estradiol. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. Estradiol: During estradiol administration, 2mg of estradiol is given twice daily via oral capsule. Micronized progesterone: During progesterone administration, 200mg of progesterone is given twice daily via oral capsule. Leuprolide Acetate: Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. Placebo Oral Capsule: Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. |
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| Primary | Change in Weekly Average Binge-eating Frequency | Binge eating frequency is based on a daily diary of self-reported binge eating frequency. Scores can range from 0 to infinity as they represent a self-reported frequency. Subjects self-report the number of binge eating episodes they had each day. Higher numbers indicate more frequent binge eating episodes. Average weekly frequency will be determined based on daily reported binge eating frequency. Change is defined by an average change score. | Posted | Mean | Standard Deviation | episodes/week | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention) |
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| Primary | Change in Self-Reported Reward Sensitivity Subscale Score During Estradiol Manipulation | Sensitivity to Punishment/Sensitivity to Reward Questionnaire will be used to measure reward sensitivity during estradiol intervention. The reward sensitivity subscale will be used, which is rated on a true/false scale with scores ranging 0-24. Higher scores indicate more sensitivity to reward. Change is defined by an average change score. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
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| Primary | Change in Response Latency to Reward During the Monetary Incentive Delay Task During Estradiol Manipulation | Time (ms) between stimulus and response will be measured during the Monetary Incentive Delay (MID) task during the win trials during the estradiol intervention. During the MID task, participants need to select the correct response during "win" and "lose" conditions by pressing a button. Higher scores indicate a longer response time to the win trials. Change is defined by an average change score. | Posted | Mean | Standard Deviation | ms | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
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| Primary | Change in Delay Discounting Parameter k Using the Monetary Choice Questionnaire With Estradiol Manipulation | During the estradiol intervention, participants will be asked to make a series of hypothetical choices between small, sooner (impulsive) vs. larger, later (self controlled) hypothetical monetary outcomes. k is a hyperbolic function with larger k values indicating more valuation of a larger delayed reward and smaller values indicating preference for more immediate, smaller rewards (more impulsivity). Change is defined as the average change in k. | Posted | Mean | Standard Deviation | k value | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
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| Primary | Change in Self-Reported Behavioral Inhibition Score During Estradiol Manipulation | This measures assesses individual disposition toward avoidance of activities during the estradiol intervention. The Behavioural Inhibition subscale of the Behavioural Inhibition Scale/Behavioral Activation Scale (BIS/BAS) assesses behavioural inhibition (BI) using participant self-reports. The minimum score on the BIS subscale is 7, maximum 28. Greater scores indicate greater behavioural inhibition. Change is defined by an average change score | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
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| Primary | Change in Behavioral Activation Score During Estradiol Manipulation | This measures assesses individual disposition toward engaging in activities during the estradiol intervention. Two BIS/BAS behavioural activation (BA) subscales will be used. The BA subscales used are Fun Seeking and Drive. Each subscale is summed to get the respective subscale scores. The minimum score on BA Fun Seeking and BA Drive are minimum 4 and maximum 16. Higher scores indicate greater behavioral activation. Change is defined by an average change score. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
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| Primary | Change in Behavioral Activation Reward Responsiveness With Estradiol Manipulation | This measures assesses individual disposition toward avoiding and engaging in activities during estradiol intervention. The BIS/BAS reward responsiveness subscale will be used. The minimum score on the BA Reward Responsiveness subscale is 5, maximum 20. Higher scores indicate greater reward responsiveness. Change is defined by an average change score. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
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| Primary | Change in Behavioral Inhibition During Estradiol Administration as Assessed Through a Behavioral Task | Behavioral response inhibition will be examined during a go/no-go computerized task during the estradiol intervention. Inhibitory control is defined by the response accuracy of the go no/go trials. Percent of errors is calculated as the number of "go" responses on a "no/go" trial" divided by the total number of "no/go" trials." Fewer errors ("go" response on a "no/go" trial) indicates better inhibitory control. Change is defined by an average change score. | Data unavailable as task was not completed by one participant. | Posted | Mean | Standard Deviation | percentage of errors | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
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| Primary | Correlation Between Change in Reward Response and Change in Binge Eating Before and During Estradiol Manipulation | Pearson correlations between change in self-reported reward response and change in binge eating between baseline and estradiol intervention will be examined. Binge eating is defined as the sum score from the Eating Pathology Symptom Inventory (EPSI). Self-reported reward response is defined as the BAS reward responsiveness subscale score and the Sensitivity to Reward/Sensitivity to Punishment Questionnaire (SPSRQ) sensitivity to reward subscale score. Change in binge eating and change in reward response between baseline and estradiol intervention was calculated and a correlation conducted between change scores. | Posted | Number | Pearson correlation coefficient | Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention) |
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| 0 |
| 10 |
| 0 |
| 10 |
| 5 |
| 10 |
| EG001 | Progesterone | Participants are randomly assigned to treatment Sequence B: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence B will receive progesterone first followed by estradiol. Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks. Estradiol: During estradiol administration, 2mg of estradiol is given twice daily via oral capsule. Micronized progesterone: During progesterone administration, 200mg of progesterone is given twice daily via oral capsule. Leuprolide Acetate: Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. Placebo Oral Capsule: Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. | 0 | 9 | 0 | 9 | 7 | 9 |
| EG002 | Lupron and Placebo | Prior to receiving hormone treatment, hormone suppression is achieved using Lupron and placebo. Leuprolide Acetate: Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. Placebo Oral Capsule: Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication. | 0 | 10 | 0 | 10 | 10 | 10 |
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Bloating | Gastrointestinal disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Appetite increase | Metabolism and nutrition disorders | Systematic Assessment |
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| Joint discomfort | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Spotting | Reproductive system and breast disorders | Systematic Assessment |
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| Abdominal Cramps | Reproductive system and breast disorders | Systematic Assessment | Menstrual-type cramps |
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| Memory Impairment | Nervous system disorders | Systematic Assessment |
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| Hot Flashes | Endocrine disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Decreased Energy Level | General disorders | Systematic Assessment |
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| Breast Tenderness | Reproductive system and breast disorders | Systematic Assessment |
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| Insomnia | General disorders | Systematic Assessment |
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| Lethargic | Psychiatric disorders | Systematic Assessment |
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| Drowsiness | General disorders | Systematic Assessment |
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| Menstrual Bleeding | Reproductive system and breast disorders | Systematic Assessment |
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| Feeling Hot | General disorders | Systematic Assessment | Felt feverish although afebrile |
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| Temperature Dysregulation | General disorders | Systematic Assessment | Alternating between feeling hot and cold |
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Not provided
Not provided
Not provided
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D011083 |
| Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D003339 | Corpus Luteum Hormones |
| D045167 | Progesterone Congeners |
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D002241 | Carbohydrates |