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