Neurobiology of Bulimia Nervosa

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.

Eligibility Criteria:
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.

* A regular menstrual cycle for at least three months
* \< 35 BMI \> 18.5
* Free of medication or medical condition that impacts ovarian hormones or is contraindicated for use with study interventions (including birth control pills)
* Speaks English

Exclusion Criteria

Patients will not be permitted to enter this protocol if they have any of the following:

* peanut allergy
* bipolar or psychotic disorder;
* current substance use disorder or frequent binge drinking behavior;
* frequent diuretic or laxative use, ipecac use;
* currently smoking \> 10 cigarettes daily;
* history of a suicide attempt or current suicidal ideation;
* endometriosis;
* abnormal genital/vaginal bleeding;
* undiagnosed enlargement of the ovaries;
* liver disease;
* breast cancer;
* personal history of blood clots (a history of blood clots in the legs or lungs; DVT); pregnancy related blood clots
* history of seizures or epilepsy;
* porphyria;
* diabetes mellitus;
* malignant melanoma;
* gallbladder or pancreatic disease;
* heart or kidney disease;
* cerebrovascular disease (stroke);
* history of osteoporosis or osteopenia;
* recurrent migraine with aura;
* first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol;
* Refusal to use non-hormonal contraception throughout study;
* Pregnant women will be excluded from participation (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods), and women who become pregnant (although unlikely because of the hormone manipulation) will be withdrawn;
* Any condition or symptoms considered by the study team to detrimentally impact subject safety.