Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort

Objective To estimate the rate of breast cancer associated with use of vaginal oestradiol tablets according to duration and intensity of their use.Design Registry based, case-control study, nested in a nationwide cohort.Setting Based in Denmark using the civil registration system, the national regis...

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Main Authors: Christian Torp-Pedersen, Lina Steinrud Mørch, Nelsan Pourhadi, Amani Meaidi, Ellen Christine Løkkegaard
Format: Article
Language:English
Published: BMJ Publishing Group 2024-02-01
Series:BMJ Medicine
Online Access:https://bmjmedicine.bmj.com/content/3/1/e000753.full
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author Christian Torp-Pedersen
Lina Steinrud Mørch
Nelsan Pourhadi
Amani Meaidi
Ellen Christine Løkkegaard
author_facet Christian Torp-Pedersen
Lina Steinrud Mørch
Nelsan Pourhadi
Amani Meaidi
Ellen Christine Løkkegaard
author_sort Christian Torp-Pedersen
collection DOAJ
description Objective To estimate the rate of breast cancer associated with use of vaginal oestradiol tablets according to duration and intensity of their use.Design Registry based, case-control study, nested in a nationwide cohort.Setting Based in Denmark using the civil registration system, the national registry of medicinal product statistics, the Danish cancer registry, the Danish birth registry, and statistics Denmark.Participants Women aged 50-60 years in year 2000 or turning 50 years during the study period of 1 January 2000 to 31 December 2018 were included. Exclusions were a history of cancer, mastectomy, use of systemic hormone treatment, use of the levonorgestrel releasing intrauterine system, or use of vaginal oestrogen treatments other than oestradiol tablets. To each woman who developed breast cancer during follow-up (18 997), five women in the control group (94 985) were incidence density matched by birth year.Main outcome measure The main outcome was pathology confirmed breast cancer diagnosis.Results 2782 (14.6%) women with breast cancer (cases) and 14 999 (15.8%) women with no breast cancer diagnosis (controls) had been exposed to vaginal oestradiol tablets with 234 cases and 1232 controls having been in treatment for at least four years at a high intensity (>50 micrograms per week). Increasing durations and intensities of use (cumulative dose/cumulative duration) of vaginal oestradiol tablets was not associated with increasing rates of breast cancer. Compared with never-use, cumulative use of vaginal oestradiol for more than nine years was associated with an adjusted hazard ratio of 0.87 (95% confidence interval 0.69 to 1.11). Results were similar in women who had long term use (≥four years) and with high intensity of use (>50-70 micrograms per week) with an adjusted hazard ratio 0.93 (95% confidence interval 0.81 to 1.08).Conclusions Use of vaginal oestradiol tablets was not associated with increased breast cancer rate compared with never-use. Increasing duration and intensity of use was not associated with increased rates of breast cancer.
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spelling doaj-art-372a661ae07f4a2a9edf96ec959949c82025-02-03T10:05:13ZengBMJ Publishing GroupBMJ Medicine2754-04132024-02-013110.1136/bmjmed-2023-000753Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohortChristian Torp-Pedersen0Lina Steinrud Mørch1Nelsan Pourhadi2Amani Meaidi3Ellen Christine Løkkegaard4Cardiology, North Zealand Hospital, Hilleroed, DenmarkCancer Surveillance and Pharmacoepidemiology, Danish Cancer Institute, Copenhagen, DenmarkCancer Surveillance and Pharmacoepidemiology, Danish Cancer Institute, Copenhagen, DenmarkCancer Surveillance and Pharmacoepidemiology, Danish Cancer Institute, Copenhagen, DenmarkDepartment of Gynecology and Obstetrics, Nordsjællands Hospital, Hillerod, DenmarkObjective To estimate the rate of breast cancer associated with use of vaginal oestradiol tablets according to duration and intensity of their use.Design Registry based, case-control study, nested in a nationwide cohort.Setting Based in Denmark using the civil registration system, the national registry of medicinal product statistics, the Danish cancer registry, the Danish birth registry, and statistics Denmark.Participants Women aged 50-60 years in year 2000 or turning 50 years during the study period of 1 January 2000 to 31 December 2018 were included. Exclusions were a history of cancer, mastectomy, use of systemic hormone treatment, use of the levonorgestrel releasing intrauterine system, or use of vaginal oestrogen treatments other than oestradiol tablets. To each woman who developed breast cancer during follow-up (18 997), five women in the control group (94 985) were incidence density matched by birth year.Main outcome measure The main outcome was pathology confirmed breast cancer diagnosis.Results 2782 (14.6%) women with breast cancer (cases) and 14 999 (15.8%) women with no breast cancer diagnosis (controls) had been exposed to vaginal oestradiol tablets with 234 cases and 1232 controls having been in treatment for at least four years at a high intensity (>50 micrograms per week). Increasing durations and intensities of use (cumulative dose/cumulative duration) of vaginal oestradiol tablets was not associated with increasing rates of breast cancer. Compared with never-use, cumulative use of vaginal oestradiol for more than nine years was associated with an adjusted hazard ratio of 0.87 (95% confidence interval 0.69 to 1.11). Results were similar in women who had long term use (≥four years) and with high intensity of use (>50-70 micrograms per week) with an adjusted hazard ratio 0.93 (95% confidence interval 0.81 to 1.08).Conclusions Use of vaginal oestradiol tablets was not associated with increased breast cancer rate compared with never-use. Increasing duration and intensity of use was not associated with increased rates of breast cancer.https://bmjmedicine.bmj.com/content/3/1/e000753.full
spellingShingle Christian Torp-Pedersen
Lina Steinrud Mørch
Nelsan Pourhadi
Amani Meaidi
Ellen Christine Løkkegaard
Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort
BMJ Medicine
title Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort
title_full Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort
title_fullStr Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort
title_full_unstemmed Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort
title_short Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort
title_sort association of vaginal oestradiol and the rate of breast cancer in denmark registry based case control study nested in a nationwide cohort
url https://bmjmedicine.bmj.com/content/3/1/e000753.full
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