Increased risk of malignancy and uterine disease following perimenarchal hospitalization: an estrogen window effect.
The estrogen window hypothesis postulates that tumor induction by environmental carcinogens is facilitated by the endocrine effects of incomplete ovarian maturation at menarche. To determine if illness and operation at or near menarche might modify ovarian maturation and thus increase cancer risk, we studied the subsequent reproductive, surgical, and malignancy history of 125 women who were aged 10 to 15 years when admitted for possible appendicitis during 1945 to 1951. Total operative experience and cholecystectomy rates were within expectation, but excess rates for dilatation and curettage (98 versus 57 expected, P less than 0.001) and hysterectomy (41 versus 23 expected, P less than 0.0006) suggest disturbed endocrine maturation. In addition, one patient developed Cushing's syndrome and five patients developed rheumatoid arthritis. Eight malignancies were observed (twice the expected rate of 3.4, P = 0.047); six occurred before age 40 years (versus 1.54 expected, P = 0.001). Tumors and age at diagnosis were: lymphoma (20), ovarian (28), breast (32), thyroid (34), lung (36), cervix (39), endometrium (48), and colon (50). Compared with standard rates, the peak incidence in those who were menarchal at hospitalization was 20 times the expected incidence; in those who were premenarchal the rate was five times the expected incidence, and in those who were postmenarchal the rate was as expected. The results of this study support the validity of the estrogen window hypothesis and indicate the serious consequences of perimenarchal illness. Enteric disease requiring hospitalization at or near menarche appears to define a group of women at risk for gynecologic disease and malignancy; further study is needed to determine if there is an appropriate prophylactic therapy to reduce that risk.
D000293:Adolescent; D000328:Adult; D002648:Child; D003625:Data Collection; D005260:Female; D006760:Hospitalization; D006801:Humans; D008572:Menarche; D009369:Neoplasms / Q000209:etiology*; D011183:Postoperative Complications / Q000209:etiology*; D012306:Risk; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013997:Time Factors; D014591:Uterine Diseases / Q000209:etiology*