Low-potency oestrogen and risk of endometrial cancer: a case-control study.
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.


RESULTS
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.


CONCLUSIONS
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.
Weiderpass
E
E
Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. Elisabete.Weiderpass@mep.ki.se
Baron
J A
JA
Adami
H O
HO
Magnusson
C
C
Lindgren
A
A
Bergström
R
R
Correia
N
N
Persson
I
I
D000282:Administration, Intravaginal; D000284:Administration, Oral; D000368:Aged; D016022:Case-Control Studies; D004714:Endometrial Hyperplasia / Q000139:chemically induced* / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D004964:Estriol / Q000008:administration & dosage / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
D004964:Estriol