Hormone Therapy in Preventing Endometrial Cancer in Patients With a Genetic Risk For Hereditary Nonpolyposis Colon Cancer

Inclusion Criteria:

* Women with known mutation of an HNPCC-associated gene (hMLH-1, hMSH-2, or hMSH-6) or fulfill Amsterdam Criteria and have had one or more HNPCC-associated cancers
* No prior hysterectomy; (participants may be scheduled for prophylactic hysterectomy following the study)
* Voluntary consent documented by a signed and witnessed informed consent
* Negative serum pregnancy test at baseline evaluation
* No history of pelvic irradiation for whatever cause
* No chemotherapy for two years
* Women \>= 40 must have had a screening mammogram within the last 12 months prior to participation in this study
* Women who are at 50% risk of having a mutation and willing to have genetic testing

Exclusion Criteria:

* Use of oral contraceptives or depoMPA or hormonal exposure, such as hormonal IUD, tamoxifen, raloxifene, or other selective estrogen receptor modulators (SERMs) within four months of initiating study; women will be asked to be off oral contraceptives or other hormonal exposure for 4 months prior to initiating study
* Medical contraindication to use of oral contraceptives or depoMPA including:

  * Known or suspected pregnancy
  * Undiagnosed vaginal bleeding
  * Known or suspected malignancy of breast or endometrium
  * Active thrombophlebitis, or current or past history of thromboembolic disorders, or cerebral vascular disease
  * Gall bladder disease or liver dysfunction or disease, including hepatic adenomas or carcinoma, or abnormal liver function tests
  * Known hypersensitivity to depoMPA contraceptive injection (medroxyprogesterone acetate or any of its other ingredients)
  * Depression that is currently not under control, in the judgement of the Principal Investigator
  * History of epilepsy
  * History of diabetes
  * Coronary artery disease
  * Age \>=35 and a current tobacco smoker
* Known inability to participate in the scheduled follow-up tests (i.e., alcohol dependence or illicit drug use)
* Significant medical history or psychiatric problems which would make the participant a poor protocol candidate, in the opinion of the principal investigator
* Post surgical removal of both ovaries
* Postmenopausal women with amenorrhea greater than 12 months
* Previous history of endometrial biopsy, hysteroscopy, dilatation and curettage, or IUD in place within the past 3 months
* Known participation in a concurrent protocol with a pharmacological intervention
* Recent or concurrent use of systemic steroids (i.e. prednisone) within the past four months of initiating study
* Positive serum pregnancy test at baseline evaluation
* Fasting triglycerides level \>= 400 mg/dl
* Cholesterol level \>= 240 mg/dl
* LDL level \>= 160 mg/dl
* HDL level =\< 35 mg/dl
* Hypertension that is currently not under good control, in the judgement of the principal investigator