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Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases.

ABSTRACT: OBJECTIVE:To assess the risks of breast cancer associated with different types and durations of hormone replacement therapy (HRT). DESIGN:Two nested case-control studies. SETTING:UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data. PARTICIPANTS:98?611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, matched by age, general practice, and index date to 457?498 female controls. MAIN OUTCOME MEASURES:Breast cancer diagnosis from general practice, mortality, hospital, or cancer registry records. Odds ratios for HRT types, adjusted for personal characteristics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Separate results from QResearch or CPRD were combined. RESULTS:Overall, 33?703 (34%) women with a diagnosis of breast cancer and 134?391 (31%) controls had used HRT prior to one year before the index date. Compared with never use, in recent users (<5 years) with long term use (?5 years), oestrogen only therapy and combined oestrogen and progestogen therapy were both associated with increased risks of breast cancer (adjusted odds ratio 1.15 (95% confidence interval 1.09 to 1.21) and 1.79 (1.73 to 1.85), respectively). For combined progestogens, the increased risk was highest for norethisterone (1.88, 1.79 to 1.99) and lowest for dydrogesterone (1.24, 1.03 to 1.48). Past long term use of oestrogen only therapy and past short term (<5 years) use of oestrogen-progestogen were not associated with increased risk. The risk associated with past long term oestrogen-progestogen use, however, remained increased (1.16, 1.11 to 1.21). In recent oestrogen only users, between three (in younger women) and eight (in older women) extra cases per 10?000 women years would be expected, and in oestrogen-progestogen users between nine and 36 extra cases per 10?000 women years. For past oestrogen-progestogen users, the results would suggest between two and eight extra cases per 10?000 women years. CONCLUSION:This study has produced new generalisable estimates of the increased risks of breast cancer associated with use of different hormone replacement preparations in the UK. The levels of risks varied between types of HRT, with higher risks for combined treatments and for longer duration of use.

SUBMITTER: Vinogradova Y

PROVIDER: S-EPMC7592147 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases.

Vinogradova Yana Y Coupland Carol C Hippisley-Cox Julia J

BMJ (Clinical research ed.) 20201028

<h4>Objective</h4>To assess the risks of breast cancer associated with different types and durations of hormone replacement therapy (HRT).<h4>Design</h4>Two nested case-control studies.<h4>Setting</h4>UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data.<h4>Participants</h4>98 611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, ma ...[more]

PMID: 33115755

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Project description:ObjectiveTo assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy.DesignTwo nested case-control studies.SettingUK general practices contributing to the QResearch or Clinical Practice Research Datalink (CPRD) databases, and linked to hospital, mortality, and social deprivation data.Participants80?396 women aged 40-79 with a primary diagnosis of venous thromboembolism between 1998 and 2017, matched by age, general practice, and index date to 391?494 female controls.Main outcome measuresVenous thromboembolism recorded on general practice, mortality, or hospital records. Odds ratios were adjusted for demographics, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs.ResultsOverall, 5795 (7.2%) women who had venous thromboembolism and 21?670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Of these two groups, 4915 (85%)and 16?938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64), for both oestrogen only preparations (1.40, 1.32 to 1.48) and combined preparations (1.73, 1.65 to 1.81). Estradiol had a lower risk than conjugated equine oestrogen for oestrogen only preparations (0.85, 0.76 to 0.95) and combined preparations (0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate had the highest risk (2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted odds ratio 0.93, 95% confidence interval 0.87 to 1.01).ConclusionsIn the present study, transdermal treatment was the safest type of hormone replacement therapy when risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.

Project description:ObjectiveTo assess the risks of developing dementia associated with different types and durations of menopausal hormone therapy.DesignTwo nested case-control studies.SettingUK general practices contributing to QResearch or the Clinical Practice Research Datalink (CPRD), using all links to hospital, mortality, and social deprivation data.Participants118 501 women aged 55 and older with a primary diagnosis of dementia between 1998 and 2020, matched by age, general practice, and index date to 497 416 female controls.Main outcome measuresDementia diagnoses from general practice, mortality, and hospital records; odds ratios for menopausal hormone treatments adjusted for demographics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs.ResultsOverall, 16 291 (14%) women with a diagnosis of dementia and 68 726 (14%) controls had used menopausal hormone therapy more than three years before the index date. Overall, no increased risks of developing dementia associated with menopausal hormone therapy were observed. A decreased global risk of dementia was found among cases and controls younger than 80 years who had been taking oestrogen-only therapy for 10 years or more (adjusted odds ratio 0.85, 95% confidence interval 0.76 to 0.94). Increased risks of developing specifically Alzheimer's disease were found among women who had used oestrogen-progestogen therapy for between five and nine years (1.11, 1.04 to 1.20) and for 10 years or more (1.19, 1.06 to 1.33). This was equivalent to, respectively, five and seven extra cases per 10 000 woman years. Detailed risk associations for the specific progestogens studied are also provided.ConclusionThis study gives estimates for risks of developing dementia and Alzheimer's disease in women exposed to different types of menopausal hormone therapy for different durations and has shown no increased risks of developing dementia overall. It has shown a slightly increased risk of developing Alzheimer's disease among long term users of oestrogen-progestogen therapies.

Project description:ObjectiveTo investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account.DesignTwo nested case-control studies.SettingGeneral practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices).ParticipantsWomen aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year.Main outcome measuresOdds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets.Results5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10,000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17).ConclusionsIn these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs.

Project description:IntroductionMany studies have found an increased risk of venous thromboembolism (VTE) associated with the use of combined hormonal contraceptives, but various methodologies have been used in the study design relating to definition of VTE event and the selection of appropriate cases for analysis. This study will focus on common oral hormonal contraceptives, including compositions with cyproterone because of their contraceptive effect and will perform a number of sensitivity analyses to compare findings with previous studies.Methods and analysis2 nested case-control studies will be based on the general population using records from UK general practices within the QResearch and Clinical Practice Research Datalink databases. Cases will be female patients aged 15-49 with primary VTE diagnosed between 2001 and 2013. Each case will be matched by age, year of birth and practice to five female controls, who are alive and registered with the practice at the time of diagnosis of the case (index date). Exposure to different hormonal contraceptives will be defined as at least one prescription for that contraceptive in the year before the index date. The effects of duration and the length of any gap since last use will also be investigated. Conditional logistic regression will be applied to calculate ORs adjusted for smoking, ethnicity, comorbidities and use of other medications. Possible indications for prescribing hormonal contraceptives, such as menstrual disorders, acne or hirsutism will be included in the analyses as confounding factors. A number of sensitivity analyses will be carried out.Ethics and disseminationThe initial protocol has been reviewed and approved by ISAC (Independent Scientific Advisory Committee) for Medicine and Healthcare Products Regulatory Agency Database Research. The project has also been reviewed by QResearch and meets the requirements of the Trent Research Ethics Committee. The results will be published in a peer-reviewed journal.

Project description:BackgroundUse of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently.Methods and findingsNested case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first-third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur.ConclusionsUse of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk.

Dataset Information

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases.

Publications

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases.

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