BACKGROUND: Urogenital symptoms are common among postmenopausal women. Such symptoms may be alleviated by low-potency oestrogen formulations administered orally or vaginally. Although low-potency oestrogen formulations are assumed to have few, if any, adverse effects on the endometrium, risk of endometrial neoplasia has not been quantified. METHODS: In a nationwide population-based case-control study in Sweden of endometrial cancer among postmenopausal women, we obtained detailed information on hormone replacement from 789 cases of endometrial cancer and 3368 population controls. In a histopathological review, 80 cases were reclassified as having endometrial atypical hyperplasia. Odds ratios and 95% CI were calculated with unconditional logistic regression. FINDINGS: After multivariate adjustment, oral use of oestriol 1-2 mg daily increased the relative risk of endometrial cancer and endometrial atypical hyperplasia: the odds ratios for at least 5 years of use compared with never use were 3.0 (95% CI 2.0-4.4) and 8.3 (4.0-17.4), respectively. The association was stronger for well-differentiated cancers and those with limited invasion. The excess relative risk was lost rapidly after cessation of treatment. Only weak associations were observed between vaginal application of low-potency oestrogen formulations and relative risk of endometrial neoplasia. INTERPRETATION: Oral, but not vaginal, treatment with low-potency oestrogen formulations increases the relative risk of endometrial neoplasia. Thus close surveillance of patients is needed, and addition of a progestagen should be considered.
BACKGROUND: Urogenital symptoms are common among postmenopausal women. Such symptoms may be alleviated by low-potency oestrogen formulations administered orally or vaginally. Although low-potency oestrogen formulations are assumed to have few, if any, adverse effects on the endometrium, risk of endometrial neoplasia has not been quantified. METHODS: In a nationwide population-based case-control study in Sweden of endometrial cancer among postmenopausal women, we obtained detailed information on hormone replacement from 789 cases of endometrial cancer and 3368 population controls. In a histopathological review, 80 cases were reclassified as having endometrial atypical hyperplasia. Odds ratios and 95% CI were calculated with unconditional logistic regression. FINDINGS: After multivariate adjustment, oral use of oestriol 1-2 mg daily increased the relative risk of endometrial cancer and endometrial atypical hyperplasia: the odds ratios for at least 5 years of use compared with never use were 3.0 (95% CI 2.0-4.4) and 8.3 (4.0-17.4), respectively. The association was stronger for well-differentiated cancers and those with limited invasion. The excess relative risk was lost rapidly after cessation of treatment. Only weak associations were observed between vaginal application of low-potency oestrogen formulations and relative risk of endometrial neoplasia. INTERPRETATION: Oral, but not vaginal, treatment with low-potency oestrogen formulations increases the relative risk of endometrial neoplasia. Thus close surveillance of patients is needed, and addition of a progestagen should be considered.
Authors: Richard J Santen; D Craig Allred; Stacy P Ardoin; David F Archer; Norman Boyd; Glenn D Braunstein; Henry G Burger; Graham A Colditz; Susan R Davis; Marco Gambacciani; Barbara A Gower; Victor W Henderson; Wael N Jarjour; Richard H Karas; Michael Kleerekoper; Roger A Lobo; JoAnn E Manson; Jo Marsden; Kathryn A Martin; Lisa Martin; JoAnn V Pinkerton; David R Rubinow; Helena Teede; Diane M Thiboutot; Wulf H Utian Journal: J Clin Endocrinol Metab Date: 2010-06-21 Impact factor: 5.958
Authors: Sara Wedrén; Lovisa Lovmar; Keith Humphreys; Cecilia Magnusson; Håkan Melhus; Ann-Christine Syvänen; Andreas Kindmark; Ulf Landegren; Maria Lagerström Fermér; Fredrik Stiger; Ingemar Persson; John A Baron; Elisabete Weiderpass Journal: BMC Cancer Date: 2008-11-06 Impact factor: 4.430
Authors: Yuqing Li; Hui-Qi Low; Jia Nee Foo; Hatef Darabi; Kristjana Einarsdόttir; Keith Humphreys; Amanda Spurdle; Douglas F Easton; Deborah J Thompson; Alison M Dunning; Paul D P Pharoah; Kamila Czene; Kee Seng Chia; Per Hall; Jianjun Liu Journal: PLoS One Date: 2012-08-02 Impact factor: 3.240