Bupropion Hydrochloride in Improving Sexual Desire in Women With Breast or Gynecologic Cancer

Inclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION
* Score of \< 9 on the PHQ-4
* Patients must have a FSFI desire subscale baseline score less than 3.3

  * NOTE-Both the PHQ-4 and FSFI must be completed by the patient and data entered in Oncology Patient Enrollment Network (OPEN) at Step 1 registration to determine eligibility
* Diagnosis of breast or gynecologic cancer \[examples are lobular carcinoma in situ (LCIS),ductal carcinoma in situ (DCIS), invasive breast, ovarian, endometrial, vulvar, cervical and vaginal\]
* Completed definitive therapy consisting of surgery, chemotherapy or radiation therapy at least 180 days ago (may continue on Herceptin or endocrine therapy)
* Post menopausal as defined by at least ONE of the following:

  * 12 months (365 days) without a period;
  * Bilateral oophorectomy;
  * Chemically induced menopause as long as there are no plans to stop during the study;
  * For women 57 and under, if at least one ovary and woman has had hysterectomy, must have follicle stimulating hormone (FSH) (\> 30 mIU/mL) and estradiol in menopausal range per institution?s laboratory (\< 10 for ultra sensitive assay: \< 25-30 otherwise);
  * At least one ovary intact and 180 days without a period with FSH (\> 30 mIU/mL) and estradiol in menopausal range per institution's laboratory (\< 10 for ultra sensitive assay: \< 25-30 otherwise); Note: Women 58 and older do not have to have hormonal tests.
* History, physical and performance status of 2 or less within 180 days prior to registration
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
* Total bilirubin =\< 1.5 x ULN
* Glomerular filtration rate \> 90ml/min
* For breast cancer patients only, endocrine therapies are allowed (such as aromatase inhibitors, but not current tamoxifen. Prior tamoxifen is permitted with a 30 day wash out period). )
* Vaginal estrogen is allowed, for all protocol disease sites, if dose equal to or less than that in estring (\< 7.5 mcg) and it has been used for at least 30 days with no plans to stop or alter use during the course of the study
* Antidepressants for mood and hot flashes, including selective serotonin reuptake inhibitors (SSRIs) will be allowed if patients have been on a stable dose for the last 60 days and the dose is not expected to change during the course of the study; only subthreshold or low dose antidepressants will be allowed (e.g. Effexor up to 75 mg or Lexapro 5-10 mg or Celexa 10- 20 mg)
* The patient must provide study-specific informed consent prior to study entry/screening
* Women who report that their motivation/desire for sexual intimacy has decreased since her cancer diagnosis
* Able to swallow whole capsules
* Proficient in English (due to number of questionnaires not validated in other languages)
* Completion of the FSFI and PHQ-4; both questionnaires will be required and data entered at the time of step 1 registration
* PRIOR TO STEP 2 RANDOMIZATION
* Completion of the following baseline quality of life forms: PHQ-4, FSFI, PROMIS sexual function and satisfaction, PROMIS fatigue short form 8a, Impact of Treatment Scale, patient reported outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) items, and revised dyadic adjustment scale; these quality of life forms will be required and data must be entered in Medidata Rave at step 2 registration; if available at the time of step 1 registration, step 2 registration can take place immediately after step 1; women who do not currently have a partner do not have to complete the revised dyadic adjustment scale; enter "no partner" for this form

Exclusion Criteria:

* Untreated depression, major depressive disorder (MDD), suicidal ideations or anxiety disorders in the past 5 years per the medical chart based on Diagnostic and Statistical Manual (DSM) IV diagnoses
* Seizure disorders
* Current or history of anorexia or bulimia in the past 5 years
* Allergy to bupropion
* Use of drugs metabolized by CYP2D6
* Stage IV cancer
* History of Parkinson's disease, multiple sclerosis or fibromyalgia
* Extensive pelvic exenteration surgery, surgeries which include partial or total vaginectomy with or without reconstruction; radical vulvectomy with or without remove of clitoris
* Women who are currently undergoing or planning to undergo reconstruction surgery during the course of the study; women who have completed reconstruction surgery must be 30 days from surgery
* Oral or transdermal estrogen therapy is not allowed
* Males are not permitted to participate
* Patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs after chronic use
* Patients who discontinue monoamine oxidase (MAO)-inhibitor (I)'s within 14 days prior to starting the investigational drug
* Poorly controlled hypertension (systolic blood pressure \[BP\] \>= 160 mmHg or diastolic BP \>= 100 mmHg) on three or more readings in the past 12 months
* Patients with active bipolar disorder
* Patients with impaired decision making as determined by the treating physician
* Concurrent use of bupropion
* Concomitant invasive malignancy requiring treatment other than non-melanomatous skin cancer.
* Previous or concurrent use of flibanserin.