Sleep, Quality of Life and Depression in Endometrial Cancer Survivors with Obesity Seeking Weight Loss

Abstract

Purpose:

Incidence and mortality rates of uterine cancer are increasing and, obesity, which is also rising, has been associated with uterine cancer development and mortality. A recent study found that poor sleep quality is common among endometrial cancer survivors and those with obesity had more sleep disturbances than those having normal weight. However, it is unclear if higher levels of obesity (Class III: BMI ≥ 40 kg/m²), which are rising rapidly, are differentially associated with sleep as well as depression and quality of life in endometrial cancer survivors.

Methods:

We evaluated sleep, depression and quality of life in 100 Stage I endometrial cancer survivors with obesity seeking weight loss enrolled in a lifestyle intervention ( NCT01870947) at baseline.

Results:

The average age was 60 years and mean BMI was 42.1 kg/m² with 58% having a BMI ≥ 40 kg/m². Most survivors (72.3%) had poor sleep quality and most (71.2%) reported sleeping <7 hours/night. Survivors with Class III compared to Class I obesity had significantly more sleep disturbances and daytime dysfunction; and, those with poor sleep had higher depression and lower quality of life. Survivors with a BMI ≥ 50 kg/m² (~25%) had the highest levels of depression and lowest physical and emotional well-being.

Conclusions:

Our results reveal that endometrial cancer survivors with Class III compared to Class I obesity have poorer sleep quality, higher depression and lower quality of life. Given the rising rates of obesity and uterine cancer mortality, interventions to combat both obesity and poor sleep are needed.

Introduction

Although the incidence and mortality rates of most cancers appear to be stable or decreasing, the incidence and mortality rates of uterine cancer have been rising at a rate of approximately 1.5 and 2 percent per year, respectively [1]. Uterine cancer is the fourth leading cancer in women in the U.S., with approximately 61,880 new cases annually and, the sixth leading cause of cancer death with 12,160 deaths estimated to occur in 2019 [1]. Currently, there are over 757,190 uterine cancer survivors in the U.S. and an estimated 942,670 are expected to be living in the U.S. in 2026 [2]. In particular, the incidence rates of Type I (estrogen dependent) endometrial cancer are increasing [3] and, this cancer type appears to be driving the overall rise in uterine cancer incidence rates observed, as over 95% of all uterine cancers occur in the endometrium [4].

Higher body mass index (BMI) has been associated with an increased risk of development and mortality of several cancers including endometrial cancer [4–6]. Women with obesity (BMI ≥ 30.0 kg/m²) have a 1.7 to 4.5 fold greater risk of developing endometrial cancer compared to those who are normal weight (BMI: 18.5–<25.0 kg/m²) [7–9]. Furthermore, endometrial cancer patients have the highest risk of death among all of the obesity associated cancers, with a 6-fold increased risk of all-cause mortality in women with Class III (BMI: ≥ 40.0 kg/m²) obesity and a 2.5 fold increased risk of death for women with Class I (BMI: ≥ 30.0– < 35.0 kg/m²) [10]. Cardiovascular disease (CVD) appears to be the leading cause of death in endometrial cancer patients and their risk of CVD mortality is about 50% higher than age-matched females in the general U.S. population [11;12]. Interestingly, obesity, particularly Class III (“severe” or “morbid”) obesity, continues to rise among adults in the U.S. with a 4- and 10-fold increase in BMI ≥ 40.0 kg/m² and BMI ≥ 50.0 kg/m², respectively, [13], with women having substantially higher rates of Class III obesity than men [14].

Sleep disorders have been associated with obesity and are substantially more prevalent in those with Class III obesity [15;16]. In addition, obesity has been associated with depression and morbidly obese have a higher odds of depression than normal weight individuals [17;18]. Furthermore, sleep disorders are common among cancer survivors and have been shown to adversely affect quality of life in breast, lung, and head and neck cancer patients [19;20]; however, very little is known about sleep dysfunction in endometrial cancer survivors. One recent study reported that poor sleep quality was common among early stage endometrial cancer survivors and those with obesity had more sleep disturbances than those of normal weight survivors [21]. They did not find a statistically significantly association between sleep quality and BMI categories but their study included a comparison of obese and overweight survivors to normal weight survivors and their average BMI was only 34.3 kg/m² [21]. Thus, it is unclear if higher levels of obesity (Class III: BMI ≥ 40 kg/m²), which are rising rapidly in the U.S. [13], are differentially associated with sleep quality as well as depression and quality of life in endometrial cancer survivors. Therefore, we evaluated sleep, depression and quality of life in 100 Stage I endometrial cancer survivors with obesity seeking weight loss enrolled in a lifestyle intervention ( NCT01870947) at baseline (before the trial began). We hypothesized that survivors with Class III obesity would report having poorer quality sleep, depression and quality of life.

Methods:

Study Population:

The study population consisted of 100 obese (BMI ≥ 30.0 kg/m²) Stage I endometrial cancer patients who were seeking weight loss and who enrolled in the ‘REWARD’ lifestyle intervention at University Hospitals Case Medical Center (UHCMC) and the Cleveland Clinic (CCF) (ClinicalTrials.gov Identifier: NCT01870947). The study population consists of patients who completed assessments at baseline (before the trial began). The details of the study protocol have been described elsewhere [22]. Briefly, the trial was open to women of all races who had histologically confirmed Stage I endometrial cancer who were obese (confirmed by measured height and weight) and who were being treated at UHCMC or the CCF. We did not pre-screen patients for psychiatric illness, the use of psychotropics or having a substance use disorder. Informed written consent was obtained from all individual participants included in the study. The study was approved by the Institutional Review Boards of University Hospitals Case Medical Center and the Cleveland Clinic.

Sleep, Depression and Quality of Life Measures:

Sleep was measured using the Pittsburgh Sleep Quality Index (PSQI) [23]. The PSQI has seven components: subjective sleep quality, sleep latency (onset), sleep duration, habitual sleep efficiency, sleep disturbances, sleep medication use and daytime dysfunction [23]. Higher total (summary) scores (ranging from 0–21) and subdomain scores (ranging from 0–3 each) represent poorer sleep dysfunction with total summary scores greater than 5 indicating “poor” sleep quality [23]. The PSQI has been shown to have good reliability and validity in cancer patients [24].

Depression was assessed using the Beck Depression Inventory-II, which has 21 items, each on a scale of 0 to 3 [25]. Higher total scores (ranging from 0–63) indicate higher depressive symptoms with 0 to 13 classified as minimal, 14 to 19 classified as mild, 20 to 28 classified as moderate, and 29 to 63 classified as severe [25]. The BDI has been shown to have good psychometric properties in cancer patients [26].

Quality of life was assessed using the Functional Assessment of Cancer Therapy - General (FACT-G) to measure physical, functional, family-social, and emotional well-being domains of quality of life (QoL), the FACT-En, which is a subscale specific for endometrial cancer symptoms, and the FACIT to assess fatigue [27;28]. The total score is the sum of the subdomain scores where the subdomain scores are based on a sum of items (scores ranging 0 to 4) that are adjusted for the number of items in the scale and the number of items answered. The trial outcome index (TOI) score is a summary score of physical, functional and endometrial cancer symptom domains. Higher scores reflect higher quality of life. The FACT-G/FACIT has been shown to have good reliability and validity in cancer patients [29].

Statistical Analysis:

We used descriptive statistics to describe the study population. We used Fisher’s exact test to evaluate potential differences between sleep (PSQI) component scores and obesity categories (World Health Organization Obesity Classifications [30]: Class I (BMI: ≥ 30.0– < 35.0 kg/m²); Class II (BMI: ≥ 35.0– < 40.0 kg/m²); Class III (BMI: ≥ 40.0 kg/m²)). In addition, we evaluated potential differences in depression and quality of life (total and component) scores by sleep quality status (“poor” vs. “good” quality [23]) using a two-sample t-test (one-way ANOVA) and regression models. We adjusted models for age, time since treatment and included BMI where applicable. No other potential confounders (e.g., treatment type) substantively changed effect estimates. Given the high prevalence of BMI ≥ 50.0 kg/m² in our study population and the dearth of data on this obesity subgroup, we explored potential differences between BMI ≥ 50.0 kg/m² compared to BMI ≥ 40.0– < 50.0 kg/m², BMI ≥ 35.0– < 40.0 kg/m² and BMI: ≥ 30.0– < 35.0 kg/m² and, associations with sleep quality, depression and quality of life scores. Statistical significance was at set at a p-value ≤ 0.05. All statistical analyses were performed using SAS v9.4 software (SAS Institute, Cary, NC).

Results:

Characteristics of the study population are shown in Table 1. The majority of the Stage I endometrial cancer survivors were Caucasian (91%) and, on average, were approximately 60 years old. Most survivors (58%) had Class III (BMI ≥ 40.0 kg/m²) obesity as defined by the World Health Organization [30], with 22% of these survivors having a BMI ≥ 50 kg/m². The mean BMI in the study population was 42.1 kg/m². The majority of survivors completed baseline assessments within 2 years of their diagnosis (69%) and most (86%) received only surgical treatment. Most had at least some college education (63.3%) and the majority were working at least part-time (55.1%).

Table 1.

Characteristics of the Study Population of Obese Stage I Endometrial Cancer Survivors

Characteristic	Mean (s.d.) / N (%)
Age (years)	59.9 (8.8)
Race
Caucasian	91 (91%)
African-American	9 (9%)
BMI (kg/m2 )	42.1 (8.2)
Obesity Class a
Class I: BMI ≥ 30–<35 kg/m2	21 (21%)
Class II: BMI 35–<40 kg/m2	21 (21%)
Class III: BMI ≥ 40 kg/m2	58 (58%)
Treatment
Surgery Only	84 (86%)
Radiation (plus Surgery)	14 (14%)
Time Since Diagnosis
Less than or equal to 2 Years	69 (69%)
Greater than 2 Years	31 (31%)
Marital Status
Married or Living with Partner	53 (54.1%)
Single	20 (20.4%)
Divorced	10 (10.2%)
Widowed/Separated/Other	15 (15.3%)
Education
High School	36 (36.7%)
Some College or Bachelor’s Degree	28 (28.6%)
Some Graduate School or Master’s Degree	34 (34.7%)
Employment
Working Full or Part Time	54 (55.1%)
Retired or Not Working	44 (44.9%)

^aWorld Health Organization (WHO) obesity classifications

We found that poor sleep was common among obese Stage I endometrial cancer survivors with 72.3% of survivors reporting poor sleep quality (score > 5) and 27.7% reporting “fairly bad” or “very bad” sleep (Table 2). Approximately 70% reported sleeping <7 hours/night and about 70% reported at least one episode of daytime dysfunction in the past month. The average depression score was 9.47 (s.d.=8.17) with 71.1% of survivors reporting “minimal” depression levels (score: 0–13) and 28.9% reporting “mild” or greater levels (score: ≥14), of which 15.4% reported having “moderate” (score: 20–28) depression. Total quality of life (FACT) scores were generally fairly high (mean=130.0; s.d=20.5) as were the FACT-G (mean=83.0; s.d.=13.8) and component well-being scores (physical: 23.4 ± 3.8; functional: 20.0 ± 5.1; social: 20.3 ± 5.6; emotional: 19.2 ± 3.9).

Table 2.

Sleep Quality (Pittsburgh Sleep Quality Index, PSQI) Scores by WHO Obesity Class

	Overall	Class I BMI: 30–<35 kg/m2	Class II BMI: 35–<40 kg/m2	Class III BMI: ≥ 40 kg/m2
PSQI Summary a
≤ 5.0	26 (27.7%)	10 (10.6%)	5 (5.3%)	11 (11.7%)
> 5.0	68 (72.3%)	10 (10.6%)	14 (14.9%)	44 (46.8%)
Components:
Sleep Quality
Very Good	15 (16.0%)	5 (5.3%)	4 (4.3%)	6 (6.4%)
Fairly Good	52 (55.3%)	12 (12.8%)	8 (8.5%)	32 (34.0%)
Fairly Bad	23 (24.4%)	2 (2.1%)	7 (7.4%)	14 (14.9%)
Very Bad	4 (4.3%)	1 (1.1%)	0 (0%)	3 (3.2%)
Sleep Latency
≤ 15 min	22 (23.5%)	7 (7.4%)	3 (3.2%)	12 (12.8%)
16–30 min	44 (46.8%)	10 (10.6%)	8 (8.5%)	26 (27.6%)
31–60 min	18 (19.1%)	3 (3.2%)	6 (6.4%)	9 (9.6%)
> 60 min	10 (10.6%)	0 (0%)	2 (2.1%)	8 (8.5%)
Sleep Duration
> 7 hours	28 (29.8%)	9 (9.6%)	7 (7.4%)	12 (12.8%)
6–7 hours	27 (28.7%)	5 (5.3%)	6 (6.4%)	16 (17.0%)
5–6 hours	33 (35.1%)	6 (6.4%)	6 (6.4%)	21 (22.3%)
< 5 hours	6 (6.4%)	0 (0%)	0 (0%)	6 (6.4%)
Sleep Efficiency
≥ 85%	64 (68.1%)	15 (16.0%)	12 (12.8%)	37 (39.4%)
75–84%	20 (21.3%)	4 (4.3%)	5 (5.3%)	11 (11.7%)
65–74%	6 (6.4%)	1 (1.1%)	2 (2.1%)	3 (3.2%)
<65%	4 (4.2%)	0 (0%)	0 (0%)	4 (4.3%)
Sleep Disturbances a
0 (min; best)	2 (2.1%)	0 (0%)	1 (1.1%)	1 (1.1%)
1	41 (43.6%)	14 (14.9%)	9 (9.6%)	18 (19.1%)
2	45 (47.9%)	5 (5.3%)	9 (9.6%)	31 (33.0%)
3 (max; worst)	6 (6.4%)	1 (1.1%)	0 (0%)	5 (5.3%)
Sleep Medication Use
Not in past mo.	69 (73.4%)	17 (18.1%)	14 (14.9%)	38 (40.4%)
< Once/week	9 (9.6%)	0 (0%)	2 (2.1%)	7 (7.4%)
1–2 times/week	3 (3.2%)	1 (1.1%)	0 (0%)	2 (2.1%)
≥ 3 times/week	13 (13.8%)	2 (2.1%)	3 (3.2%)	8 (8.5%)
Daytime Dysfunction a
0 (min; best)	28 (29.8%)	11 (11.7%)	6 (6.4%)	11 (11.7%)
1	46 (48.9%)	6 (6.4%)	10 (10.6%)	30 (31.9%)
2	19 (20.2%)	3 (3.2%)	2 (2.1%)	14 (14.9%)
3 (max; worst)	1 (1.1%)	0 (0%)	1 (1.1%)	0 (0%)

^ap ≤ 0.05

Stage I endometrial cancer survivors with higher levels of obesity (Class II and Class III vs. Class I) reported having more “poor” compared to “good” quality sleep (Total PSQI scores > 5 vs. ≤ 5 [23]) (Table 2). Survivors with higher classes of obesity also reported significantly more sleep disturbances and daytime dysfunction. No other sleep component scores were statistically significantly associated with the WHO obesity classes.

Survivors reporting “poor” (P) compared to “good” (G) sleep quality had significantly lower overall quality of life (P: 125.1 ± 19.1 vs. G: 142.3 ± 19.7) and well-being component scores (Table 3). Survivors also reported greater endometrial cancer symptom scores (P: 45.3 ± 9.1 vs. G: 51.4 ± 6.7) but fatigue scores were not significantly different between those with “poor” and “good” quality sleep. These associations remained statistically significant after adjustment for age, time since diagnosis and BMI (Table 3).

Table 3.

Means and Associations (Odds Ratios) Between Quality of Life, Depression and Sleep Quality (Poor vs. Good) in Obese Endometrial Cancer Survivors

	Mean ± s.d. Poor Quality (P) vs. Good Quality (G)	Odds Ratio (95% C.I.) a	p-value
Quality of Life:
FACT Total Score	125.06 ± 19.07 (P) 142.33 ± 19.71 (G) b	0.94 (0.91–0.98)	0.001
FACT-G	79.77 ± 12.63 (P) 90.95 ± 14.18 (G) b	0.93 (0.88–0.97)	0.002
Physical Well Being	22.79 ± 3.82 (P) 25.08 ± 3.40 (G) b	0.82 (0.69–0.96)	0.01
Functional Well Being	18.85 ± 4.52 (P) 23.15 ± 5.08 (G) b	0.79 (0.69–0.90)	0.001
Social Well Being	19.34 ± 5.48 (P) 22.53 ± 5.57 (G) b	0.88 (0.79–0.98)	0.02
Emotional Well Being	18.78 ± 4.12 (P) 20.19 ± 3.35 (G)	0.92 (0.80–1.05)	0.23
FACT-Endometrial Cancer (EC) Symptoms	45.29 ± 9.06 (P) 51.38 ± 6.69 (G) b	0.90 (0.84–0.97)	0.006
TOI (Physical Well Being + Functional Well Being + EC Symptoms)	86.94 ± 14.88 (P) 99.62 ± 13.21 (G) b	0.93 (0.89–0.97)	0.001
FACIT-Fatigue	36.59 ± 4.27 (P) 36.04 ± 4.19 (G)	1.03 (0.93–1.14)	0.57
Depression:
BDI-II Total Score	11.54 ± 8.18 (P) 3.96 ± 5.17 (G) b	1.19 (1.08–1.32)	0.01

^aAdjusted for age, time since diagnosis and BMI

^bp-value ≤ 0.05

Given the high prevalence (nearly 25%) of survivors with a BMI ≥ 50.0 kg/m² in our study population, we also explored potential differences between finer cut-points in the upper BMI range (BMI ≥ 50.0 kg/m²; BMI ≥ 40.0– < 50.0 kg/m²; BMI ≥ 35.0– < 40.0 kg/m² vs. BMI: ≥ 30.0– < 35.0 kg/m²) and sleep quality, depression and quality of life scores. Survivors with a BMI ≥ 50 kg/m² had significantly poorer quality sleep (8.6 ± 3.4 vs. 5.2 ± 2.8) and depression (11.7 ± 9.3 vs. 6.0 ± 7.6) scores compared to those with Class I obesity (Table 4). Survivors with a BMI ≥ 50 kg/m² compared to those with Class I obesity had lower physical (21.7 ± 3.5 vs. 24.5 ± 3.7) and emotional (18.0 ± 5.3 vs. 20.7 ± 2.1) well-being scores. These associations remained statistically significant after adjustment for age and time since diagnosis (Table 4). We note that associations between these BMI categories and depression were not significant when comparing those with “mild” (score: ≥ 14) or greater compared to “minimal” (score: 0–13) depression levels.

Table 4.

Mean Scores Between BMI Category and Quality of Life, Depression and Sleep Quality

	Referent (n=21) BMI 30–<35 kg/m2	BMI (n=21) 35 – <40 kg/m2	BMI (n=36) 40 – <50 kg/m2	BMI (n=22) ≥ 50 kg/m2
Quality of Life:
FACT Total	136.42 ± 20.70	127.91 ± 18.39	130.51 ± 18.04	125.36 ± 25.02
FACT-G	85.87 ± 19.94	83.91 ± 11.90	82.98 ± 13.42	79.54 ± 16.12
Physical Well Being	24.50 ± 3.68	23.52 ± 3.38	23.88 ± 3.37	21.73 ± 3.46 a,b
Functional Well Being	21.05 ± 5.35	19.81 ± 4.72	20.41 ± 4.32	18.82 ± 6.15
Social Well Being	19.67 ± 6.89	21.15 ± 4.82	19.63 ± 6.04	20.95 ± 3.38
Emotional Well Being	20.65 ± 2.13	19.43 ± 3.49	19.06 ± 3.84	18.04 ± 5.3 a,b
FACT-Endometrial Cancer (EC) Symptoms	50.55 ± 8.59	44.00 ± 9.45 b	47.53 ± 6.54	45.82 ± 10.40
TOI (Physical Well Being + Functional Well Being + EC Symptoms	96.10 ± 16.00	87.33 ± 14.19 b	91.82 ± 12.12	86.36 ± 18.87 b
FACIT-Fatigue	36.00 ± 5.85	35.12 ± 3.35	37.02 ± 3.38	36.74 ± 4.63
Depression:
BDI-II Total	6.00 ± 7.62	10.19 ± 8.70	9.62 ± 6.98	11.73 ± 9.30 a,b
Sleep Quality:
PSQI Total	5.25 ± 2.77	6.84 ± 3.06	7.30 ± 3.66	8.59 ± 3.42 a,b

^ap-value ≤ 0.05

^bp-value for trend ≤ 0.05

Discussion:

In summary, we found that most obese endometrial cancer survivors had poor sleep quality and, survivors with higher levels of obesity had significantly more sleep disturbances and daytime dysfunction. Furthermore, survivors with poor sleep quality had higher depression and lower quality of life scores and, those with a BMI ≥ 50 kg/m², which represented nearly 25% of the study population, had the highest levels of depression and lowest physical and emotional well-being scores.

Our results confirm an earlier report that poor sleep quality is common among early stage endometrial cancer survivors [21]. In their study, they did not find a statistically significant relationship between sleep quality and BMI categories; however, they compared obese and overweight survivors to normal weight survivors and their average BMI was only 34.3 kg/m² [21]. In our study, which had a much higher average BMI (42.1 kg/m²) and nearly 60% had Class III “morbid” obesity, we found that survivors with higher levels of obesity (Class III and Class II vs. Class I) reported more poor sleep quality and increased episodes of daytime dysfunction and sleep disturbances.

In terms of quality of life, scores were fairly high in the total study population. The FACT-G scores (83.0 ± 13.8) in our survivors were slightly lower than normative values in women without cancer (85.5 ± 16.4) [31]. In addition, overall average scores for physical (P: 23.4 ± 3.8) and functional (F: 20.0 ± 5.1) well-being were slightly lower while social (S: 20.3 ± 5.6) and emotional (E: 19.2 ± 3.9) well-being were similar to normative values in women without cancer (P: 24.5 ± 4.5; F: 21.2 ± 5.7; S: 20.4 ± 5.9; E: 19.0 ± 4.9) [31]. This is consistent with prior studies reporting that early stage endometrial cancer survivors generally report high quality of life scores, particularly those who only undergo surgical treatment and do not receive adjuvant radiotherapy [32–34]. Nearly 90% of our study population only received surgical treatment. However, we did find that survivors with poor compared to good quality sleep had worse quality of life scores. In our study, total FACT, FACT-G and physical, functional and social component scores as well as endometrial cancer symptom scores were significantly lower in those with poor quality compared to good quality sleep. Armbruster et al. [21] also found that survivors with poor quality sleep had worse scores on the 36-item Short Form Survey (SF-36) subscales including general health, bodily pain, social functioning and role limitations caused by emotional problems.

Moreover, we found that endometrial cancer survivors with Class III “morbid” obesity had poorer quality of life than those with lower levels of obesity. Our results are consistent with the only other prior study that specifically evaluated quality of life in survivors who were morbidly obese [35]. In this prior study, they measured quality of life using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30) and found that morbidly obese women (n=30; 19% of their population) reported worse physical and social functioning [35]. Our results are also generally in line with a meta-analysis of four large studies that found obese compared to non-obese survivors had poorer physical functioning and social functioning [36].

In our study, most survivors reported “minimal” levels of depression with about 30% reporting “mild” or greater levels of depression. Our average BDI-II scores (9.5 ± 8.2) were higher than those reported by Dobrzycka et al. (~6.0 ± 8.0) in a recent study of early stage endometrial cancer survivors; however, their average BMI was only 32.4 kg/m2 [32]. Our analyses revealed that survivors with Class III “morbid” obesity, particularly those with BMI ≥ 50.0 kg/m², had significantly higher depression scores (11.7 ± 9.3) compared to those with Class I obesity (6.0 ± 7.6). Our average scores were lower than scores reported in a mixed population of advanced stage cancer survivors (14.7 ± 9.9) [37], which would be expected given that all of our survivors were Stage I. Interestingly, sleep disturbances (30%) and depression (23%) were among the top 8 health issues reported in a large study of endometrial cancer survivors [38]; however, these authors did not report how these health concerns might differ based on obesity status.

Our results are consistent with prior reports in other adult cancer survivors in that survivors with higher levels of BMI report poorer physical quality of life scores. For example, in a sample of 1768 cancer survivors from the American Cancer Society’s Study of Cancer Survivors II (ACS SCS-II), obese survivors reported significantly poorer physical quality of life scores using the SF-36 (43.3 ± 11.8 vs. 49.4 ± 10.2); and, these scores are on average, lower than the normative value for the general U.S. population (50 ± 10) [39]. Another study using the ACS SCS-II cancer survivor population found that obese compared to normal weight survivors of prostate (50.2 ± 10.9 vs. 52.9 ± 9.7), breast (47.7 ± 12.1 vs. 51.2 ± 10.9), and uterine (48.7 ± 13.9 vs. 54.3 ± 11.1) cancer all reported poorer physical quality of life scores using the SF-36 [40]. In general, sleep dysfunction in cancer survivors has been correlated with poorer quality of life [41;42] and breast cancer survivors with higher BMIs have reported greater levels of depression [43]. Unfortunately, prior studies in cancer survivors have not evaluated these measures by obesity class; thus, we are not able to directly compare our results in obese endometrial cancer survivors to survivors with other types of cancer.

A few studies in non-cancer adults representative of the general U.S. population have evaluated relationships between obesity class and quality of life, depression and sleep. In a sample of 9,133 adults from the U.S., National Health and Nutritional Examination Survey (NHANES; 2005–2008), women with Class I obesity (BMI: ≥30–<35 kg/m²) and Class II and III combined (BMI: ≥ 35 kg/m²) had a higher odds of depressive symptoms compared to those of normal weight (OR=3.17; 95% CI: 1.53–6.58; OR=7.38; 95% C.I.: 2.11–25.76, respectively) [44]. Furthermore, in this study, adults with depressive symptoms compared to those without depressive symptoms had significantly poorer sleep quality, which remained significant after adjustment for several factors including age, sex and BMI [44]. In a large study of 54,269 adults from the Behavioral Risk Factor Surveillance System (BRFSS) survey in 2010, 32.8% of adults reported short sleep (≤ 6 hours) and those with obesity had a higher odds of short sleep compared to those with adequate sleep (7–9 hours) after adjustment for several factors including age and sex [45]. In addition, using data from the BRFSS survey in 2006, obesity was significantly associated with sleep complaints in women but not in men [46]. BRFSS data has shown that women with obesity report significantly more days of poor physical health and activity limitations (quality of life measures) than those of normal weight and, women with Class III obesity had substantively higher odds of having ≥14 poor physical health and activity limitation days per month than those with Class I or Class obesity [47]. Although we are not able to directly compare our results to those from the NHANES or BRFSS (as they use different questionnaires for depression, sleep and quality of life), the endometrial cancer survivors in our study had a substantially higher percentage of those with morbid obesity (~58% vs. 8% [48]) and short sleep (~71% vs. 33% [45]) compared to the general U.S. population. Future studies using the same sleep, depression and quality of life measures should be conducted to enable direct comparisons between obese adults with and without endometrial cancer.

With the continued rise of obesity, particularly morbid obesity (4- and 10-fold increase in BMI ≥ 40.0 kg/m² and ≥ 50.0 kg/m², respectively) among adults in our nation [13] and, given that the number of endometrial cancer survivors is expected to continue to rise [2], interventions to combat obesity and improve sleep quality are needed. Poor sleep may be a barrier to weight loss and weight loss maintenance in endometrial cancer survivors as poor sleep has been associated with lower amounts of weight loss in obese women [49;50]. Armbruster et al. [21] found that their intervention, which increased physical activity, particularly moderate and vigorous levels of physical activity, improved sleep quality scores in early stage endometrial cancer survivors; however, the association between improved sleep and increased MVPA was not statistically significant after adjustment for confounders. Others have found that increasing physical activity helps to improve depression and quality of life scores in studies involving endometrial cancer survivors [51–53]. Importantly, as highlighted by Beavis et al. [54], the impact of these interventions on long-term health including overall mortality in endometrial cancer survivors is not known.

Strengths of our study include that we evaluated sleep quality together with depression and quality of life in obese endometrial cancer survivors. Moreover, our study population had nearly 60% of its survivors with Class III obesity and about 25% of them had a BMI of 50.0 kg/m² or greater, which enabled us to evaluate, for the first time, associations with sleep and quality of life in endometrial cancer survivors with severe obesity. Our study also has several weaknesses. First, because we only enrolled obese survivors, we were not able to make any direct comparisons to normal or overweight survivors or to non-cancer “controls”. Furthermore, our results may not be generalizable to endometrial cancer survivors who are not seeking weight loss. We did not pre-screen patients for the presence of psychiatric illness or the use of psychotropics, which could have potentially affected depression scores and related associations. In addition, we did not include a specific measure for anxiety, which could affect sleep quality as well as depression and quality of life [55].

In conclusion, our results confirm poor sleep is common among early stage endometrial cancer survivors and reveal those with Class III “morbid” obesity have poorer sleep quality, higher depression and lower quality of life. Interventions to combat both obesity and poor sleep in Stage I endometrial cancer survivors are needed. Similar to the message conveyed by Ambruster et al. [21], we urge providers to recognize the high prevalence of poor quality sleep in endometrial cancer survivors, particularly those with Class III “morbid” obesity, who experience higher levels of depression and poorer quality of life.