(222) Menopausal hormone therapy and colorectal cancer recurrence and mortality: a Danish population-based cohort study

Background: Several observational studies have linked menopausal hormone therapy (MHT) to a reduced risk of colorectal cancer (CRC). However, the association of MHT with CRC recurrence and mortality among women with CRC is less clear, even though estrogen is hypothesized to have some preventive actions. Furthermore, the importance of type of MHT and timing of use in CRC prognosis is not elucidated.

Objectives: To investigate the association of prescription use of systemic MHT and risk of CRC recurrence, CRC-specific, and all-cause mortality, overall and by type and timing of MHT use.

Methods: We conducted a nationwide, population-based cohort study using Danish health care registry data. We included women aged 50+ years who underwent curative surgery for incident stage I–III CRC during 2001–2019 and registered in the Danish Cancer Registry. Use of MHT was defined as two or more filled prescriptions for systemic MHT before the date of surgery for primary CRC (i.e., pre-diagnostic use). We ascertained CRC recurrences using a validated algorithm and deaths from the national registries. Follow-up started six months after the surgery and ended on the date of CRC recurrence, death, emigration, or December 31, 2021, whichever came first. We used Cox proportional hazards regression analysis to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for each study outcome, adjusting for age, year of diagnosis, and tumor stage. In analyses of CRC recurrence, we considered death as a competing risk. We stratified by type and timing—i.e., age at first use, duration of use, and time since last use—of MHT.

Results: Among 15,921 women with CRC, 3,108 (20%) had used systemic MHT pre-diagnostically. During a median follow-up of six years, 3,519 (22%) women developed CRC recurrence and 7,546 (47%) died. While use of MHT was not associated with risk of CRC recurrence (HR=1.02, 95% CI: 0.94, 1.11), MHT use was associated with a lower risk of CRC-specific (HR=0.89, 95% CI: 0.82, 0.98) and all-cause (HR=0.90, 95% CI: 0.84, 0.96) mortality, compared with non-use. Estrogen-only formulations showed the strongest associations—with a suggestive inverse association for recurrence (HR=0.81, 95% CI: 0.50, 1.30), but estimates were imprecise. We observed no clear trend by age at first use or duration of MHT use. For time since last use, the results may suggest a lower risk of CRC recurrence (HR=0.89, 95% CI: 0.68, 1.18) and CRC-specific mortality (HR=0.84, 95% CI: 0.63, 1.13) in women who had discontinued any MHT use ≥10 years before CRC diagnosis.

Conclusions: Women who used systemic MHT pre-diagnostically had better survival after CRC diagnosis than non-users. The association with CRC recurrence was, however, unclear. The use of estrogen-only formulations might offer the strongest associations.