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