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