Hormone Replacement Therapy and Cancer Survival: A Longitudinal Cohort Study


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Tom Ranger1, Judith Burchardt1, Ashley Clift1, Winnie Mei1, Carol Coupland2, Pui San Tan1, Sharon Dixon1, Alexander Labeit3, Christopher Cardwell3, Julia Hippisley-Cox1
1University of Oxford, 2University of Nottingham, 3Queen’s University Belfast

Abstract

Background

Hormone replacement therapy (HRT) can help women experiencing menopausal symptoms, but usage has declined from uncertainty around cancer risk. This study investigated HRT use in women diagnosed with cancer in order to inform decision making about its risks and benefits by women and their treating clinicians.

Method

This population-based longitudinal cohort study of 18–79-year-old women diagnosed with cancer between 1998 and 2020 used the QResearch database. The outcomes for this preliminary analysis were cancer-specific mortality and all-cause mortality for colorectal, lung and ovarian cancer. HRT use pre-cancer diagnosis was defined as an oestrogen script in the 18 to 6 months prior to diagnosis. Descriptive statistics and Cox proportional hazards models, stratified by cancer site, were generated with adjustment for age, body mass index (BMI), social and lifestyle factors, and comorbidities.

Results

The cohort comprised 219,875 women, with median (IQR) age of 58 years (20) and BMI 26.1 kg/m2 (7.4) and 16,072 (7.3%) pre-diagnosis HRT users. There were: 37,930 colorectal cancer diagnoses (10,265 cancer-specific deaths [27.1%] and 17,989 total deaths [47.3%]); 40,097 lung cancer diagnoses (24,904 [62.1%] and 30,450 [75.9%]); and 16,527 ovarian cancer diagnoses (5,097 [30.9%] and 8,953 [54.2%]).

In univariate analysis, pre-diagnosis HRT use was associated with reduced risk of cancer-specific and all-cause mortality in colorectal and lung cancer patients but not ovarian cancer. In maximally adjusted models, pre-diagnosis HRT use was associated with reduced risk of cancer-specific mortality in colorectal (HR 0.87, 95%CI 0.79-0.96) and lung cancer (HR 0.92, 95%CI 0.87-0.98) but not ovarian cancer (HR 0.94, 95%CI 0.86-1.03). For all-cause mortality a reduction in risk was seen for all three sites (colorectal HR 0.79, 95%CI 0.74-0.85; lung HR 0.95, 95%CI 0.90-0.99; ovarian HR 0.88 95%CI 0.82-0.96).

Conclusion

These preliminary findings suggest a reduced risk of cancer-specific mortality and all-cause mortality in women who use HRT prior to cancer diagnosis. It is likely though, that healthy user bias affects these results. Nevertheless, none of the analyses found increased risk of cancer-specific mortality. Further investigation will include cancer treatment, and HRT: compound, dosage and means of administration.

Impact statement

These findings may inform and reassure women diagnosed with cancer and experiencing menopausal symptoms.

This work was supported by Cancer Research UK [grant no: C37316/A29656]