Nejm 1996;335:640

Cause:

Prolonged, unopposed (by progesterone) estrogen (estradiol esp) exposure from many possible sources including:

• Estrogens given for menopausal sx, risk persists 10+ yr after cessation (Nejm 1985;313:969)
• Polycystic ovary/metabolic (Stein-Leventhal) syndrome
• Granulosa/theca cell tumors (100× incidence)
• Anovulation, esp perimenopausal
• Turner's syndrome
• Tamoxifen use

Genetic syndromes w breast and right-sided colon cancers

Pathophys: Continuous estrogen stimulation causes hyperplasia and eventually can convert to carcinoma; rarely metastasizes distantly

20% of all female genital cancers; 4th most frequent cancer in women; 34 000 cases/yr, 6000 deaths/yr in US; rare before age 40 yr unless ovarian pathology, median age at dx = 63 yr, only 25% occur in premenopausal women. Lower incidence in smokers, because of smoking's antiestrogen effect (Nejm 1986;315:1305)

Incidence in US is decreasing since the early 1980s, perhaps due to the increased use of progesterone (Am J Pub Hlth 1990;80:935) in ERT

Sx:

Postmenopausal vaginal bleeding, r/o atrophic uterine mucosa, bacterial endometritis, polyp; or premenopausal metrorrhagia; or intermenstrual bleeding

h/o infertility, irregular menses, late menopause, obesity, estrogen replacement, hypertension, diabetes

Si:

Pelvic/uterine mass

• Stage I: confined to fundus
• Stage II: in cervix and fundus
• Stage III: extension beyond uterus
• Stage IV: extension to pelvis

With rx, 70+% overall 5-yr survival; 75% stage I, 60% stage II, 30% stage III, and 10% stage IV

Metastases, usually local. Incr risk of subsequent colorectal Ca (Ann IM 1999;131:189)

Lab:

Noninv: Transvaginal ultrasound, endometrial thickness >5 mm 90% sens, 48% specif (Nejm 1997;337:1792) vs 96% sens and 92% specif if not on HRT; and 77% specif if on HRT (Jama 1998;280:1510), perhaps do before bx and skip bx if neg?

Path:Pap smear positive in only 18% (Nejm 1974;291:191); endometrial aspiration bx in office or D&C w tumor grading 1-3

Endoscopy:Hysteroscoppy (Jama 2002;288:1610)

Rx:

Prevent by always withdrawing at least q3mo with progesterone, eg, medroxyprogesterone (Provera) 10 mg qd × 10 d when using estrogen for menopause or osteoporosis, or if obese and having irregular menses, or other chronic estrogen-stimulation situation (Obgyn 1984;63:759)

Surgery, TAH-BSOO, pelvic node dissection; for stages I and II, with or without pre-postirradiation (Jama 2006;295:389); for stages III and IV, individualized rx including radiation, surgery, as well as hormonal w progesterone (as Megace), and chemotherapy w cyclophosphamide, 5-FU, adriamycin