Lifetime History of Oral Contraceptive Use and Development of Tumours of the Uterus and Ovary*

Abstract

Zusammenfassung Zielstellung: In der Literatur wurde konsistent bei Nutzung oraler Contraceptiva (OCs) ein reduziertes Risiko von Uterus-und Ovarialtumoren berichtet. Der Effekt von niedrigdosierten OCs ist weniger klar. Methodik: Die Deutsche Kohortenstudie zur Frauengesundheit erfasst von Frauen aller Bundesländer, die sich zur Teilnahme bereit erklärt haben, selbst berichtete Daten zur Hormonnutzung. Diese Daten umfassen Angaben zu Zeit, Typ, Dosis der Exposition wie auch zur Zeit des Auftritts von Erkrankungen. Die ersten Kohortendaten von 1998 bis 2000 wurden mittels logistischer Regression analysiert, um den Zusammenhang zwischen lebenslanger OC-Nutzung und dem Auftreten von Uterus-und Ovarialtumoren zu analysieren. Ergebnisse: Die Frauenkohorte enthält gegenwärtig rund 396 000 Frauenbeobachtungsjahre von rund 10 000 Teilnehmerinnen mit 167 malignen sowie 1676 benignen Tumoren. Das adjustierte relative Risiko [RR] des Auftretens von Uterus-oder Ovarialkrebs bei OC-Nutzern verglichen mit Nienutzern war 0,5 (95% Konfidenzintervall [95 % CI]: 0,3 ± 0,7). Der Vergleich von Nutzern niedrigdosierter OCs mit Nienutzern ergab ein adjustiertes RR von 0,1 [95 % CI 0,1 ± 0,3]). Vergleichbare Ergebnisse wurden bei benignen Tumoren der primären Reproduktionsor- AbstractObjective: The literature consistently showed a decreased risk of uterine and ovarian tumours in users of oral contraceptives (OCs). The effect of OCs with low estrogen content is less clear. Methods: The German Cohort Study on Womens Health collects self-reported data on hormone use from women who responded to a call for participation circulated in all German states. The data include information on the exposure and time, type and dose of exposure as well as time of occurrence of any outcome. Initial cohort data from 1998 to 2000 were analysed using logistic regression to determine the association between historic OC use and the occurrence of tumours of the ovary and corpus uteri. Results: The cohort currently covers about 396 000 womenyears of observation on 10 000 participants including 167 cases of malignant and 1676 cases of benign uterine and ovarian tumours. The adjusted relative risk [RR] for the occurrence of any uterine or ovarian cancer comparing users and non-users of OCs is 0.5 (95% confidence interval [95 %CI]: 0.3 to 0.7). The comparison of users of low estrogen-dose OCs versus never-users shows an adjusted RR of 0.1 [95 % CI 0.1 to 0.3]). Similar results are found for benign tumours of the primary reproductive organs. Time since last OC use was an important effect modifier in malignant, but not in benign tumours. Originalarbeit 566Institutsangaben

The Risk of Uterine and Ovarian Cancer for Different Formulations of Hormone Therapy (HT)

“…We have shown no increased risk for OvC or UC cancers in our own publications, and in fact even weak evidence for a reduced risk in young women using oral contraceptives [4,5].…”

Breast cancer risk associated with different HRT formulations: a register-based case-control study

“…The overall risk of breast cancer associated with HRT has shown variation, but has mainly been reported as significantly increased but well under a risk estimate of 2.0 [ 12 , 13 ]. In previous publications, we have shown no increased risk for gynecologic cancers at least – and in fact even weak evidence for preventive properties of sex steroids in young women using oral contraceptives [ 14 - 16 ]. The WHI study results [ 3 ] published in 2002 for breast cancer (BC) and HRT use that showed a significantly increased association with estrogen plus progestin treatment based on combined hormonal therapy of conjugated equine estrogens (CEE) with medroxyprogesterone acetate (MPA).…”

“…The study was planned in early 2003 (performed 2004–2005), and was justified by the working hypothesis that the results obtained with the HRT formulation CEE/MPA might be not generalizable for Europe with HRTs of other estrogens and progestins. This study on HRT was made possible by earlier collaborative research with German cancer registries and tumor centers in the field of gynecological cancer and exogenous steroid hormone use [ 14 - 16 ]. The study was designed as a case-control study with lifetime history of exposure and information about patient's characteristics as well as risk factors for BC.…”

“…The participants of the German Cohort Study on Women's Health, that were shown to be representative for German Women in many aspects [ 14 - 17 ], were used as pool for controls (if without history of malign tumors). Up to five controls were matched for each BC case for same age as case (year of birth +/- two years) and residency (Bundesland) as matching criteria.…”

The Risk of Breast Tumours and Lifetime History of Oral Contraceptive Use

“…Such an evaluation requires a lifetime history of OC use (calendar method) so that users of old formulations can be distinguished from those who have used only low-dose OCs for long enough to permit an analysis of tumour manifestation, i.e., it depends on how long low-dose formulations are on the market. In a previous publication on the risk of tumours of the uterus and ovary we have shown that the length of availability of low-dose OCs now permits such an evaluation [8].…”