Ta not only settles annoying menopause, but also greatly reduces the risk of gastrointestinal cancer incidence and death in women!

The incidence of gastrointestinal (GI) cancers has been declining or stabilizing, yet remains the leading cause of cancer morbidity and mortality worldwide
.

Since the incidence of gastrointestinal cancer generally increases with age, it may become a major health concern in today's aging society

In Korea, the first and second most common cancers among women aged 65 or older are colorectal cancer and stomach cancer, respectively

Menopause hormone therapy (MHT) has been widely used for postmenopausal symptoms and menopause-related diseases such as osteoporosis
.

However, their use worldwide has declined over the past few decades with reports of an associated increased risk of breast cancer

However, for gastrointestinal cancers other than CRC, there are insufficient studies demonstrating an association with MHT
.

Furthermore, with the exception of CRC, few studies have assessed gastrointestinal cancer risk under MHT regimens

Furthermore, almost all research to date has been conducted in the West
.

Population-based studies have not been conducted in the East, where demographic characteristics, risk factors, and cancer prevalence may differ from those in the West

The study ultimately included 133,690 (831,311 person-years) women
.

The median follow-up time (Q1, Q3) was 79.
6 months (45.
8, 106.
5); MHT users were 79.
3 months (45.
5, 106.
5 months) and non-users were 79.
6 months (45.
9, 106.
6 months)
.

The mean follow-up time (standard deviation) was 74.

(P with _{equal variances} (P

1.
Cancer incidence: univariate analysis

During the study period, 4756 (0.
57 per 100,000 person-years) subjects were diagnosed with either type of cancer, which did not differ between MHT users and non-users (0.
60 vs.
0.
57, P = 0.
1699) (Table ​2 )
.

Gastrointestinal cancer was diagnosed in 1290 subjects (0.

​2 In each GI cancer type,

Kaplan-Meier survival curves compared cancer incidence between MHT users and non-users
.

Menopausal hormone therapy users were less likely to be diagnosed with gastrointestinal cancer (P  = 0.

Kaplan-Meier survival curves compared cancer incidence between MHT users and non-users

2.
Cox proportional hazards model: multivariate analysis

Table 2 presents a survival analysis using a Cox proportional hazards model to determine the relationship between MHT use and cancer incidence
.
Survival analysis for esophageal cancer was not performed because there were too few cases (n = 4)
.
Menopausal hormone therapy was associated with fewer gastrointestinal cancer diagnoses (HR 0.
809, 95% CI 0.
691–0.
946, P = 0.
0081)
.
By cancer type, MHT use was significantly associated with a reduction in CRC diagnosis (HR 0.
757, 95% CI 0.
577-0.
995, P = 0.
0457)
.
The association between MHT use and GC diagnosis showed marginal significance (HR 0.
787, 95% CI 0.
605–1.
023, P = 0.
0733)
.
There was no significant association between MHT use and diagnosis of hepatobiliary or pancreatic cancer (HR: 0.
847 and HR: 1.
163)
.

3.
Subgroup analysis by MHT regimen and baseline characteristics

Survival analyses by MHT protocol (type, combination) were performed using Cox proportional hazards models
.
There was no statistically significant difference among different MHT types
.
Meanwhile, estrogen-only MHT was significantly associated with increased incidence of any type of cancer (HR 1.
258, P = 0.
0015)
.
Furthermore, in most cancers the HR was greater than 1.
0 in the estrogen-only regimen, however, the HR in the combination regimen was less than 1.
0
.
In particular, estrogen-only MHT users had a significantly higher HR for pancreatic cancer diagnosis compared with non-users (HR 2.
536, P = 0.
0196)
.

Based on baseline characteristics, there were no significant differences or trends indicating a relationship between MHT use and cancer incidence
.

4.
Menopausal hormone therapy and mortality

MHT users had lower all-cause mortality than non-users (P < 0.
0001), while cancer-related mortality was not significantly associated with MHT
.
Gastrointestinal cancer mortality was lower in MHT users than in nonusers (P = 0.
0377)
.
Table 3 shows a survival analysis using a Cox proportional hazards model to determine the relationship between MHT use and mortality
.
MHT users had lower all-cause mortality than non-users (HR 0.
784, P < 0.
0001), while cancer-related mortality did not differ between groups
.

(P (P

Furthermore, MHT users had lower gastrointestinal cancer mortality compared with non-users (HR 0.
737, P = 0.
0445), which we attributed to GC and CRC mortality (HR: 0.
411 and 0.
181, respectively)
.

5.
Dose-response relationship

A Landmark analysis was performed on subgroups by MHT dose, which included 19,543 MHT users and 96,548 non-users
.
The DDD was increased from 1 to 4, with 4 indicating an MHT dose ≥600
.
The Log rank P value was 0.
0040 by dose increasing the incidence of gastrointestinal cancer (Figure 3) .
The P value showed that there was a significant difference in the incidence of CRC in the MHT dose group (P=0.
0896), while there was no significant difference in the incidence of GC (P=0.
2146) .
In the cox proportional hazards model, the incidence of gastrointestinal tumors was inversely related to MHT dose (HR, 0.
79, 0.
71, 0.
49, 0.
55, P for _trend =0.
0002; Table 4) .

MHT dose ≥ 600
.
The Log rank P value was 0.
0040 (Figure 3)
.
The P value showed that there was a significant difference in the incidence of CRC in the MHT dose group (P=0.
0896), while there was no significant difference in the incidence of GC (P=0.
2146)
.
In the cox proportional hazards model, the incidence of gastrointestinal tumors was inversely related to MHT dose (HR, 0.
79, 0.
71, 0.
49, 0.
55, P for _trend =0.
0002; Table 4)
.
P _trend

Furthermore, HRs for CRC diagnosis decreased to 0.
84, 0.
64, 0.
63, and 0.
15 in MHT users compared with non-users when the MHT dose was increased from a DDD of less than 100 to more than 600 ( P _trend =0.
0069)
.
The hazard ratios for all-cause mortality were 0.
76, 0.
88, 0.
64, and 0.
34 in MHT users compared with non-users with increasing MHT dose ( P for _trend < 0.
0001)
.
The P _trend was also significant in cancer-related mortality and GI cancer mortality
(0.
0052 and 0.
0064, respectively), independent of other cancer mortality .

_{HRs for CRC diagnosis in} MHT users decreased to 0.
84, 0.
64, 0.
63, and 0.
15 when MHT dose increased from less than 100 DDD to more than 600 (Ptrend = 0.
0069 ) Ptrend Ptrend _{Ptrend GI cancer} mortality

6.
Sensitivity analysis

Sensitivity analyses were performed on the primary outcomes using the dataset (n = 116, 091) included in the Landmark analysis
.
MHT users had significantly lower incidences of gastrointestinal cancer and CRC than non-users (HR 0.
703, 95% CI 0.
581–0.
852, P = 0.
0003 and HR 0.
693, 95% CI 0.
502–0.
958, P = 0.
0266)
.
These results are comparable to those of the original dataset (n = 133, 690)
.
Gastric cancer diagnoses were statistically significant in the original dataset, with significantly lower gastric cancer diagnoses in MHT users compared with non-users (HR 0.
684, 95% CI 0.
497-0.
943, P = 0.
0202)
.

Overall, menopausal hormone therapy was associated with fewer gastrointestinal cancer diagnoses in Korean women, especially for CRC and GC
.
Furthermore, MHT use was significantly associated with a reduction in CRC and GC mortality
.
These associations of MHT with gastrointestinal cancer showed a dose-response relationship
.
The findings of this study, based on national sample cohort data from South Korea, confirm the need for a long-term follow-up study
.

The findings of this study, based on national sample cohort data from South Korea, confirm the need for a long-term follow-up study
.

Original source:

Ji Hyung Nam , et al.
  The effect of menopausal hormone therapy on gastrointestinal cancer risk and mortality in South Korea: a population-based cohort study.
BMC Gastroenterol.
 2021; 21: 440.

Ji Hyung Nam The effect of menopausal hormone therapy on gastrointestinal cancer risk and mortality in South Korea: a population-based cohort study.
BMC Gastroenterol.
BMC Gastroenterol.
Published online 2021 Nov 23.
  doi:  10.
1186/s12876-021-02021-y 10.
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