Participants’ characteristics and follow-up
Figure 1 shows the participant selection procedures, and the baseline characteristics of all study participants with follow-up information are presented in Table 1. 105,199 cases started treatment at age 46 to 65 years in 1984−2017 and there were 224,643 matched controls. The mean (± SD) age of all participants at first treatment was 53 (± 5.02) years. The mean duration of HRT use was 6.0 (± 4.8) years. Among cases, 17,606 (17%) received oestrogen-only and 87,593 (83%) received combined therapy. Around 75% of cases were prescribed first HRT between 46 and 55 years of age.
Controls have more missing records than the cases. Incomplete medical records were more common in earlier birth cohorts, as expected from previous research that showed great improvement in recording after the initiation of the Quality and Outcomes Framework (QoF) in 2004.39 The prevalence of selected medical conditions was nearly the same for cases and controls at baseline. However, there were more oophorectomies and hysterectomies among cases (Table 1), and more participants with osteoporosis among first HRT starters in the older age group at baseline (Table S3). These conditions are more prevalent among HRT users as these are often the cause of HRT treatment.40 There were more obese controls, compared to more healthy weight and overweight cases. The proportions of ex-smokers and current smokers were slightly higher in cases. More than half of the participants had high socio-economic status (Townsend index 1-2). In earlier birth cohorts more women took oestrogen-only HRT, and in later birth cohorts more women took combined HRT.
The length of study follow-up was 32 years, and the mean follow-up of participants was 13.5 (SD ±7.0) years. The interquartile range of participant follow-up was 10.8 years. During follow-up 21,751 women died in total, of whom 6,329 (6%) were cases, and 15,422 (7%) were controls. 44 cases died per 10,000 participant-years follow-up compared to 63 controls. 29,604 (28%) cases and 61,023 (27%) controls were transferred out during follow-up.