Among 51,182 women with medical records taken from 414 general practices, 22,101 women (43%) were hormone users and 29,081 (57%) were non-users. Overall, users and non-users had clinically similar baseline demographic characteristics, although non-users of hormones were slightly less likely to use NSAIDs, and a higher proportion of oestrogen-only users had undergone hysterectomy (Table
). A total of 23,210 women (45%) had a record of hysterectomy while 21,835 women (43%) had at least one record of pregnancy ever. The mean age of commencing hormone replacement was 49.7
years and the mean exposure duration was 5.4
years. The most common hormone replacement was combined oestrogen and progestogen; 68.3% of women were exposed to more than one type of hormone and 1% of users stopped taking hormone after one prescription.
Cohort baseline at menopause diagnosis according to use or non-use of hormone
A total of 42,724 (84%), women had ever been recorded as having GORD symptoms, with a total of 18.5% of all consultations coded as ‘Dyspepsia’, and 3.3% of consultations coded as ‘Gastro-oesophageal Reflux Disease’. The majority of these occurrences were post-menopause. Prior to the study window (pre-menopause), overall 11881 women (23%) consulted their GP for GORD symptoms; GORD reporting rates were comparable between groups prior to hormone exposure (25% of oestrogen-only and tibolone users reported GORD prior to hormone exposure compared to 22% of combined hormone and 23% of progestogen users and non-hormone users).
shows the simple analysis (unadjusted for other patient characteristics) of each form of hormone and the strength of their association with GORD, comparing unmatched with matched data. All forms of hormone were statistically significantly associated with reported GORD symptoms (Table
) both in the unmatched and the matched groups.
Risk of GORD and PPI use among hormone replacement therapy users: simple regression
Adjusted analyses (shown in Table
) explored the relative strength of association between different forms of hormone and GORD, taking into account certain patient characteristics. This showed a statistically significant independent association between oestrogen-only use and GORD (OR 1.49, 95% CI 1.18–1.89, p
0.001) when taking into account the relative effect of other risk factors (NSAID, bisphosphonate and calcium use). Other unadjusted associations between hormone therapies and GORD did not persist when models were adjusted for these risk factors. Previously known independent risk factors for GORD were confirmed; the models provide evidence of the independent but varying influence of NSAID use and calcium on GORD.
Risk of GORD among hormone replacement users: multiple regression
A total of 35639 women (34.7%) were ever-users of PPIs with a mean number of 64 PPI prescriptions. Pre-menopause, the use of PPI prescriptions was comparable across hormone and non-hormone groups for approximately 6% of women.
Simple regression, unmatched and matched analyses (Table
) showed a consistent statistically significant association between PPI use and oestrogen-only use only (OR 1.46, p
0.001 and OR 1.42, p
0.007 respectively). This association remained present in adjusted analysis (OR 1.34, 95% 1.03–1.74, p
). In unadjusted models, the association between GORD or PPI use and progestogen was not statistically significant, however, the association was significant (OR 1.50, 95% CI 1.01–2.22, p
0.044) in the adjusted analysis. The previously known association between NSAID use and PPI use was confirmed but small numbers of users of calcium supplements and bisphosphonates gave non-significant findings.
Risk of PPI use among hormone replacement users: multiple regression
Preliminary unadjusted models including BMI, alcohol and smoking had large numbers of missing data. These variables poorly fitted any model of GORD or PPI use in unadjusted analyses. When adjusted models of GORD were analysed with BMI, alcohol and smoking as independent variables, similarly none fitted at a statistically significant level. In unadjusted analysis, there was a small but unimportant association between BMI and PPI use (OR 1.04, 95% CI 1.01–1.056, p
0.001). Alcohol use (OR 4.17, 95% CI 1.20–14.52, p
0.025) was an additional independent factor in a model of PPI use among combined hormone users, this may be a chance finding in a model involving small numbers.