Objectives

We investigated the risk of chemotherapy-related and radiotherapy-related cognitive impairment in colorectal cancer patients.

Methods

Medical use data of colorectal cancer patients were obtained from the Korean National Health Insurance Database from 2004 to 2018. We randomly selected 40% of all colorectal cancer patients (n=148,848). Cognitive impairment was defined as having 1 or more International Classification of Diseases, 10th revision diagnostic codes for dementia or mild cognitive impairment. Patients aged 18 years or younger, patients diagnosed with cognitive impairment before colorectal cancer diagnosis (n=8,225), and patients who did not receive primary resection (n=45,320) were excluded. The effects of individual chemotherapy regimens on cognitive impairment were estimated. We additionally estimated the effect of radiotherapy in rectal cancer patients. Time-dependent competing risk Cox regression was conducted to estimate the overall and age-specific hazard ratios (HR) separately for colon and rectal cancer. Landmark analyses with different lag times were conducted as sensitivity analyses.

Results

Chemotherapy did not increase the risk of cognitive impairment in colorectal cancer patients (colon cancer: HR, 0.92; 95% confidence interval [CI], 0.83 to 1.03; rectal cancer: HR, 0.88; 95% CI, 0.75 to 1.04), while radiotherapy was negatively associated with cognitive impairment in rectal cancer patients (HR, 0.01; 95% CI, 0.84 to 0.99). Varying directions of the associations between regimens and cognitive impairment were detected. The adverse effect of certain chemotherapy regimens on cognition was more prominent in older adults.

Conclusions

Chemotherapy and radiotherapy did not increase the risk of cognitive impairment. Older patients with low cognitive reserve could be affected by the adverse cognitive effects of chemotherapy.

Background

Posttraumatic stress disorder (PTSD) has been associated with increased cardiovascular risk, however, underlying mechanisms have not been fully specified. PTSD is associated with stress-related hormones, including dysregulated glucocorticoid activity. Dysregulation of aldosterone, a mineralocorticoid activated by psychological stress and implicated in cardiovascular damage, may be a relevant pathway linking PTSD and cardiovascular risk. Few studies to date have evaluated the association between PTSD and aldosterone, none with repeated measures of aldosterone. We examined if trauma and PTSD were associated with altered aldosterone levels relative to women unexposed to trauma.

Methods

The association of trauma exposure and chronic PTSD with plasma aldosterone levels was investigated in 521 middle-aged women in the Nurses' Health Study II. Aldosterone was assessed at two time points, 10-16 years apart, and trauma exposure and PTSD were also ascertained for both time points. Regarding exposure assessment, women were characterized based on a structured diagnostic interview as: having chronic PTSD (PTSD at both time points; n = 174); being trauma-exposed (trauma exposure at first time point but no PTSD; n = 174); and being unexposed (no trauma exposure at either time point; reference group for all analyses; n = 173). Linear mixed models examined associations of trauma and PTSD status with log-transformed aldosterone levels, adjusting for covariates and health-related variables that may confound or lie on the pathway between PTSD and altered aldosterone levels.

Results

Across the sample, mean aldosterone concentration decreased over time. Adjusting for covariates, women with chronic PTSD had significantly lower aldosterone levels averaged over time, compared to women unexposed to trauma (β = - 0.08, p = 0.04). Interactions between trauma/PTSD group and time were not significant, indicating change in aldosterone over time did not differ by trauma/PTSD status. Post-hoc exploratory analyses suggested that menopausal status partially mediated the relationship between chronic PTSD status and aldosterone level, such that postmenopausal status explained 7% of the effect of PTSD on aldosterone.

Conclusions

These findings indicate that PTSD is associated with lower levels of aldosterone. Further work is needed to understand implications of this type of dysregulation in a key biological stress system for cardiovascular and other health outcomes previously linked with PTSD.

Background

Posttraumatic stress disorder (PTSD) is associated with higher risk of certain chronic diseases, including ovarian cancer, but underlying mechanisms remain unclear. Although prior work has linked menopausal hormone therapy (MHT) use with elevated ovarian cancer risk, little research considers PTSD to likelihood of MHT use. We examined whether PTSD was prospectively associated with greater likelihood of initiating MHT use over 26 years.

Methods

Using data from the Nurses' Health Study II, with trauma and PTSD (symptoms and onset date) assessed by screener in 2008 and MHT assessed via biennial survey (from 1989), we performed Cox proportional regression models with women contributing person-years from age 36 years. Relevant covariates were assessed at biennial surveys. We considered potential effect modification by race/ethnicity, age at baseline, and period (1989-2002 vs. 2003-2015).

Results

Over follow-up, 22,352 of 43,025 women reported initiating MHT use. For example, compared with women with no trauma, the HR for initiating MHT was 1.18 for those with trauma/1-3 PTSD symptoms [95% confidence interval (CI), 1.13-1.22] and 1.31 for those with trauma/4-7 PTSD symptoms (95% CI, 1.25-1.36; P trend < 0.001), adjusting for sociodemographic factors. Associations were maintained when adjusting for reproductive factors and health conditions. We found evidence of effect modification by age at baseline.

Conclusions

Trauma and number of PTSD symptoms were associated with greater likelihood of initiating MHT use in a dose-response manner.

Impact

MHT may be a pathway linking PTSD to altered chronic disease risk. It is important to understand why women with PTSD initiate MHT use.