{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:55:17Z","timestamp":1772819717821,"version":"3.50.1"},"reference-count":17,"publisher":"BMJ","issue":"6667","license":[{"start":{"date-parts":[[1989,1,21]],"date-time":"1989-01-21T00:00:00Z","timestamp":601344000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.bmj.com\/company\/legal-information\/terms-conditions\/legal-information\/tdm-licencepolicy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ"],"published-print":{"date-parts":[[1989,1,21]]},"abstract":"<jats:p>OBJECTIVE: To determine the relative risk of developing endometrial neoplasia after treatment with oestrogens alone or in conjunction with progestogens. DESIGN: Prospective cohort follow up study, average observation period 5.7 years for each patient. To have a 90% chance of detecting a relative risk of 2.0 with 95% significance the study required 78,000 person years of observation. SETTING: Community based cohort. PATIENTS: Women aged over 35 who were prescribed non-contraceptive oestrogens in the Uppsala health care region during April 1977 to March 1980 were identified from pharmacy records. Of all prescriptions issued, 95% were identified. Patients from the cohort who developed endometrial neoplasia were identified from the cancer registry of the Uppsala health care region. Compliance, sociodemographic data, and lifetime exposures to oestrogen and cyclically added progestogen were assessed by questionnaire in a sample of the cohort. The final cohort consisted of 23,244 patients (133,373 person years). The prevalence of university education, oophorectomy, and hysterectomy was higher in the cohort than the general population; no other confounding factors were identified. MEASUREMENTS: The total number of person years was divided into exposure groups by inference from the data from the questionnaire. Compensation was made for the excess of hysterectomies. Specimens from all cases of endometrial neoplasia in the cohort and 90% of cases in the general population were studied blind histopathologically. Characteristics of treatment of all women who had endometrial neoplasia were assessed by questionnaire. Relative risks and 95% confidence intervals were calculated. RESULTS: Seventy four cases of carcinoma and 33 cases of premalignant lesions occurred in the cohort. The relative risk of endometrial carcinoma was 1.8 (95% confidence interval 1.1 to 3.2) after exposure to any oestrogen compound without progestogen for more than six years; 2.2 (1.2 to 4.4) after more than three years' exposure to conjugated oestrogens without progestogen; and 2.7 (1.4 to 5.1) after more than three years' exposure to oestradiol compounds without progestogen. When carcinoma and premalignant lesions were considered together the results were similar but the relative risk was higher. Risk of carcinoma did not increase when progestogens were cyclically added to oestrogens for the entire treatment period (relative risk 0.9 (0.4 to 2.0]. CONCLUSIONS: Use of oestrogens without progestogens is associated with a twofold to threefold increase in risk of endometrial neoplasia. Use of progestogens either removes this increased risk or delays its onset. A further follow up of the cohort is essential to analyse the risks with greater statistical power.<\/jats:p>","DOI":"10.1136\/bmj.298.6667.147","type":"journal-article","created":{"date-parts":[[2009,4,2]],"date-time":"2009-04-02T15:19:55Z","timestamp":1238685595000},"page":"147-151","source":"Crossref","is-referenced-by-count":332,"title":["Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study."],"prefix":"10.1136","volume":"298","author":[{"given":"I.","family":"Persson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. O.","family":"Adami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Bergkvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Lindgren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Pettersson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Hoover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Schairer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1989,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/00006254-198006000-00027","article-title":"Effect of exogenous estrogens on postmenopausal women: the epidcmiologic evidence","volume":"35","author":"Hulka, B.","year":"1980","unstructured":"Hulka B. Effect of exogenous estrogens on postmenopausal women: the epidcmiologic evidence. Obstet Gynecol Surv 1980;35:389-99.","journal-title":"Obstet Gynecol Surv"},{"key":"ref_2","first-page":"521","article-title":"Review of epidemiologic studies of endometrial cancer and exogenous estrogen","volume":"54","author":"DL), Cramer; RC, Knapp","year":"1979","unstructured":"Cramer DL), Knapp RC. Review of epidemiologic studies of endometrial cancer and exogenous estrogen. Obstet Gynecol 1979;54:521-6.","journal-title":"Obstet Gynecol"},{"key":"ref_3","first-page":"509","article-title":"Estrogen's role in endometrial cancer","volume":"4","author":"Ziel, K.","year":"1982","unstructured":"Ziel K. Estrogen's role in endometrial cancer. Obstet Gvnecol 1982;4:509-15.","journal-title":"Obstet Gvnecol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1056\/NEJM198112313052701","article-title":"Effects of estrogens and progestins on the biochemistry and morphology of the postmenopausal endometrium","volume":"305","author":"Whitehead, M.I.; Townsend, P.T.; Prvse-Davies, J.; Ryder, T.A.; King, J.B.","year":"1981","unstructured":"Whitehead MI, Townsend PT, Prvse-Davies J, Ryder TA, King JB. Effects of estrogens and progestins on the biochemistry and morphology of the postmenopausal endometrium. N EnglJ Med 1981;305:1599-605.","journal-title":"N EnglJ Med"},{"key":"ref_5","first-page":"525","article-title":"Effects of long-term estrogen replacement therapy. Am,7 Obstet Qvnecol","volume":"133","author":"Hammond, C.B.; Jelovsek, F.R.; Lee, K.L.","year":"1979","unstructured":"Hammond CB, Jelovsek FR, Lee KL, et al. Effects of long-term estrogen replacement therapy. Am,7 Obstet Qvnecol 1979;133:525-36."},{"key":"ref_6","first-page":"107","article-title":"Pharmacies. Statistical abstracts","author":"National Corporation of","year":"1975","unstructured":"National Corporation of Pharmacies. Statistical abstracts. Stockholm: NCP, 1975:107."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/oxfordjournals.aje.a121625","article-title":"Sample size requirements in cohort and case-cohort studies of disease","volume":"99","author":"Schlesselman, J.","year":"1975","unstructured":"Schlesselman J. Sample size requirements in cohort and case-cohort studies of disease. Amtj Eptidemiol 1975;99:381-4.","journal-title":"Amtj Eptidemiol"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/BF00542350","article-title":"A cohort study of oestrogen treatment and the risk of endometrial cancer: evaluation of method and its applicability","volume":"25","author":"Persson, I.; Adami, H.O.; Johansson, E.D.B.; Lindberg, B.S.; Manell, P.; Westerholm, B.","year":"1983","unstructured":"Persson I, Adami HO, Johansson EDB, Lindberg BS, Manell P, Westerholm B. A cohort study of oestrogen treatment and the risk of endometrial cancer: evaluation of method and its applicability. EurJ7 Clin Pharmnacol 1983;25: 625-32.","journal-title":"EurJ7 Clin Pharmnacol"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3109\/00016348309156224","article-title":"Practice and patterns of oestrogen treatment in climacteric women in a Swedish population: a descriptive epidemiological study","volume":"62","year":"1983","unstructured":"Persson 1, Adami HO, Lindberg BS, Johansson EDB, Manell P. Practice and patterns of oestrogen treatment in climacteric women in a Swedish population: a descriptive epidemiological study. Part I. Acta Obstet Gynecol Scand 1983;62:289-96.","journal-title":"Part I. Acta Obstet Gynecol Scand"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/00016348309156225","article-title":"Characteristics of oestrogen treated women. A descriptive epidemiological study of a Swedish population","volume":"62","author":"Persson, I.; Adami, H.O.; Lindherg, B.S.; Johansson, E.D.B.; Manell, P.","year":"1983","unstructured":"Persson I, Adami HO, Lindherg BS, Johansson EDB, Manell P. Characteristics of oestrogen treated women. A descriptive epidemiological study of a Swedish population. Part II. Acta Obstet Gynecol Scand 1983;62:297-302.","journal-title":"Part II. Acta Obstet Gynecol Scand"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/0010-4809(83)90044-7","article-title":"A generalized effective exposure modelling program for assessing dose-response in epidemiologic investigations","volume":"16","author":"Caplan, R.J.; Marsh, G.M.; Enterline, P.E.","year":"1983","unstructured":"Caplan RJ, Marsh GM, Enterline PE. A generalized effective exposure modelling program for assessing dose-response in epidemiologic investigations. Comput Biomed Res 1983;16:587-96.","journal-title":"Comput Biomed Res"},{"issue":"493-5","key":"ref_12","first-page":"10","article-title":"The endometrial hyperplasia and their relationship to endometrial neoplasia","volume":"4","author":"Fox, H.; Buckley, C.H.","year":"1982","unstructured":"Fox H, Buckley CH. The endometrial hyperplasia and their relationship to endometrial neoplasia. Histopathology 1982;4:493-5 10.","journal-title":"Histopathology"},{"key":"ref_13","first-page":"187","article-title":"Reliability of endometrial cancer diagnoses in a Swedish cancer registry-with special reference to classification bias related to exogenous estrogens","volume":"94","author":"Persson, I.; Adami, H.O.; Lindgren, A.","year":"1986","unstructured":"Persson I, Adami HO, Lindgren A, et al. Reliability of endometrial cancer diagnoses in a Swedish cancer registry-with special reference to classification bias related to exogenous estrogens. Acta Pathol Microbiol Immunol Scand [Al 1986;94:187-93.","journal-title":"Acta Pathol Microbiol Immunol Scand [Al"},{"key":"ref_14","first-page":"320","article-title":"Stratified analysis. In: Epidemiologic research. Principles and quantitative methods","author":"Kleinbaum, D.G.; Kupper, L.L.; Morgenstern, H.","year":"1982","unstructured":"Kleinbaum DG, Kupper LL, Morgenstern H. Stratified analysis. In: Epidemiologic research. Principles and quantitative methods. Belmont, California: Lifetime Learning Publications, 1982:320-76."},{"key":"ref_15","article-title":"Risk factors for breast and endometrial cancer in a cohort of women treated with menopausal oestrogens","author":"Bergkvist, L.; Adami, H.O.; Persson, I.; Schairer, C.","unstructured":"Bergkvist L, Adami HO, Persson I, Schairer C. Risk factors for breast and endometrial cancer in a cohort of women treated with menopausal oestrogens. IntJ7 Epidemiwl (in press)."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1093\/ije\/16.2.222","article-title":"Reliability of women's histories of climacteric oestrogen treatment assessed by prescription forms","volume":"16","author":"Persson, I.; Adami, H.O.; Bergkvist, L.","year":"1987","unstructured":"Persson I, Adami HO, Bergkvist L. Reliability of women's histories of climacteric oestrogen treatment assessed by prescription forms. Int J Epidemiol 1987;16:222-8.","journal-title":"Int J Epidemiol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0140-6736(81)90960-0","article-title":"Detection bias and endometrial cancer","volume":"ii:","author":"Merletti, F.; Cole, P.","year":"1981","unstructured":"Merletti F, Cole P. Detection bias and endometrial cancer. 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