Cortizol Saliva

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Original article

Differences of salivary cortisol levels between long-

term and short-term wearers of dento-maxillary

prosthesis due to head and neck cancer resection

Moe Kosaka DDS*, Yuka I. Sumita DDS, PhD,Takafumi Otomaru DDS, PhD, Hisashi Taniguchi DDS, PhD

Department of Maxillofacial Prosthetics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental

University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan

1. Introduction

Following surgical treatment for head and neck cancer (HNC),

patients can experience facial disfigurement and severe

functional impairment of mastication, deglutition, and

speech. Moreover, evidence to date suggests that patients

with HNC often struggle with postsurgical stressors and

psychosocial issues, including fear of cancer recurrence,

depression, and anxiety [1]. Thus, questionnaires have been

j o u rna l o f p r o s thodont i c r e s e a r ch 5 8 ( 2 0 1 4 ) 4 1 4 7

a r t i c l e i n f o

Article history:

Received 14 November 2012

Received in revised form

2 October 2013

Accepted 15 October 2013

Available online 14 December 2013

Keywords:

Saliva

Cortisol levels

Dento-maxillary prosthesis wearers

a b s t r a c t

Purpose: The purpose of this study was to use cortisol awakening response (CAR) to

investigate the differences in daily life stress experienced by individuals wearing either a

long-term (LT) or a short-term (ST) dento-maxillary prosthesis following head and neck

cancer(HNC) resection.Alsoweused theUniversity ofWashingtonQuality of Life (UW-QOL)

version 4 questionnaireto evaluate thedifferences in quality of life (QOL) scoresbetween ST

and LT wearers of a dento-maxillary prosthesis.

Methods: Salivary samples were collected from 11 LT and 10 ST prosthesis wearers on twoconsecutive days at two time points, immediately after waking up (T0) and 30min later

(T30), by passive drool collection. Cortisol levels were measured using a high sensitivity

salivary cortisol enzymeimmunoassaykit(Salimetrics, LLC,StateCollege,PA,USA) andCAR

(the differences between thecortisol levelsat T0 andT30)was compared betweenLT andST

prosthesis wearers. In addition, both the groups completed theUW-QOLquestionnaireand

the scores were compared.

Results: A significant differencewasobserved inCARbetween thetwogroups. CARof theST

prosthesis wearers wassignificantly lower compared with that of theLT prosthesis wearers;

moreover, the ST prosthesis wearers revealed significantly lower total UW-QOL scores and

there were significant differences in appearance, activity, recreation, speech, and anxiety.

Conclusion: Within the limitations of this study, the findings suggest that individuals

wearing ST dento-maxillary prostheses following HNC resection experience some sort of

daily life stress and complicated socio-demographic factors may influence their QOL.# 2013 Japan Prosthodontic Society. Published by Elsevier Ireland. All rights reserved.

* Corresponding author. Tel.: +81 3 5803 5556; fax: +81 3 5803 5556.E-mail address: [email protected] (M. Kosaka).

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: www.elsevier.com/locate/jpor

1883-1958/$ see front matter# 2013 Japan Prosthodontic Society. Published by Elsevier Ireland. All rights reserved.

http://dx.doi.org/10.1016/j.jpor.2013.10.001
http://dx.doi.org/10.1016/j.jpor.2013.10.001mailto:[email protected]://www.sciencedirect.com/science/journal/18831958http://dx.doi.org/www.elsevier.com/locate/jporhttp://dx.doi.org/10.1016/j.jpor.2013.10.001http://dx.doi.org/10.1016/j.jpor.2013.10.001http://dx.doi.org/www.elsevier.com/locate/jporhttp://www.sciencedirect.com/science/journal/18831958mailto:[email protected]://dx.doi.org/10.1016/j.jpor.2013.10.001http://crossmark.crossref.org/dialog/?doi=10.1016/j.jpor.2013.10.001&domain=pdfhttp://crossmark.crossref.org/dialog/?doi=10.1016/j.jpor.2013.10.001&domain=pdf


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used to investigate subjective assessments of stress, including

psychosocial factors, in patients with HNC [25]. However, to

the best of our knowledge, objective stress assessments of

such patients have not been sufficiently investigated.

Stress responses are widely characterized as involving

two main systems: the sympathetic-adrenal-medullary axis

and the hypothalamic-pituitary-adrenal (HPA) axis. The

former is primarily triggered by acute stressors, whereas thelatter is involved in the long-term effects of both acute and

chronic stress. Cortisol is regulated by a negative feedback

system and can serve as an index of HPA axis activity. In

fact, salivary cortisol has been reported to be a useful

objective marker and has been used for stress assessments

in the measurement of individual variations or comparisons

of groups matched for specific characteristics such as age

and physical conditions [611]. In addition, high correlations

between serum and salivary cortisol levels have been

reported [12,13]. A sharp increase has been observed in

individuals cortisol levels 3045 min after waking up and

has been termed the cortisol awakening response (CAR).

CAR has been analyzed using several different approaches,such as simple change in levels between waking and 30

45 min later, and area under the curve imputed from

repeated samples. Several studies have investigated this

response [1419], and variations in CAR could provide

valuable information about the psychosocial factors oper-

ating in daily life. Thus, morning salivary cortisol levels can

be a marker for objective daily life stress assessments in

patients with HNC.

A dento-maxillary prosthesis is often recommended for

the rehabilitation of functional impairment and improve-

ment of appearance following HNC resection. In mandibul-

ectomy patients, not only prosthetic treatment but also

proper surgical reconstruction is important for the oralrehabilitation [20]. Many functional evaluations after the

delivery of the dento-maxillary prosthesis have demonstrat-

ed enhancement of oral functions [21,22] and quality of life

(QOL) [23]. However, few studies have investigated the

relation between salivary cortisol levels and prosthetic

treatments. Kohno et al. reported that salivary cortisol levels

decreased after uncomfortable removable partial dentures

were adjusted [24], and Ugawa et al. reported that following

maxillectomy, patients with HNC experienced psychological

stress during speech, even if their prostheses afforded

functional improvement [25]. However, daily life stress and

salivary cortisol levels in the morning have not been

investigated in patientswith HNC wearing a dento-maxillaryprosthesis. The following were the purposes of this study: (1)

to use CAR to investigate the differences in daily life stress

experienced by individuals wearing either a long-term (LT) or

a short-term (ST) dento-maxillary prosthesis following HNC

resection; and (2) to usethe University ofWashingtonQuality

of Life (UW-QOL) version 4 questionnaire to evaluate the

differences inQOL scores betweenboththeprosthesiswearer

groups.

In this study, we tested the following null hypotheses: (1)

CAR do not differ between ST and LT wearers of a dento-

maxillaryprosthesis inHNCpatients and (2)QOL scores donot

differ between ST and LT wearers of a dento-maxillary

prosthesis.

2. Materials and methods

2.1. Subjects

The following were the inclusion criteria for the LT prosthesis

wearers: (1) they had undergone mandibulectomy because of

HNC; (2) they had no complaints with the prosthesis; (3) therewas noneed for adjustment of the prosthesis; and (4) they had

at least three months experience wearing the prosthesis. The

following were the inclusion criteria for the ST prosthesis

wearers: (1) they had undergone mandibulectomy because of

HNC; (2) they needed adjustment of the prosthesis; and (3)

they had less than three months experience wearing the

prosthesis. All the ST prosthesis wearers received their first

dento-maxillary prosthesis following HNC resection. Further,

the following were the exclusion criteria for both the patient

groups: (1) habitual smoking; (2) use of oral contraceptives; (3)

presence of severe periodontitis; (4) presence of infectious

diseases such as viral hepatitis; (5) age over 80 years; (6) scores

exceeding 65 on the State-Trait Anxiety Inventory-Form JYZ(STAI JYZ) questionnaire; (7) inability to speak, read, or

understand Japanese; (8) discontinuity of mandibular bone;

and (9) existence of a bulky flap on the reconstruction part.All

the patients received a dento-maxillary prosthesis following

HNC resection from the Department of Maxillofacial Prosthet-

ics, Tokyo Medical and Dental University Hospital Faculty of

Dentistry.

On the basis of these criteria, 21 subjects (11 LT

prosthesis wearers and 10 ST prosthesis wearers) were

recruited fromNovember 2011 to July 2012, who participated

in the study. Table 1 presents the characteristics of all the

participants.

This study was approved by the Ethics Committee of theFaculty of Dentistry, Tokyo Medical and Dental University

(Approval No. 645). Written informed consent was obtained

from all the patients prior to participation.

2.2. STAI JYZ questionnaire

To exclude severely depressed subjects, we selected the STAI

JYZ questionnaire [26] for psychological screening. This

questionnaire is a 40-item measure of the intensity of the

feeling of anxiety and distinguishes between state anxiety and

trait anxiety.All subjects were requested to complete the STAI

JYZquestionnaire,and scores of state anxietyand traitanxiety

were calculated.

2.3. Saliva sampling

Self-reporting sheets were prepared to monitor the saliva

sampling conditions, according to the reports from previous

studies [2730]. With regard to the self-reporting sheets, data

were collected regarding the time of saliva sampling, time of

waking up, bedtime, sleep quality (good, fairly good, could not

sleep), use/nonuse of an alarm clock, time and dose of any

medication taken, time and amount of alcohol consumption,

and oral conditions.

Each subject received a sampling kit containing instruc-

tions, four plastic Falcon tubes (w30 mm 115 mm),

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self-reporting sheets, the STAIJYZquestionnaire, the UW-QOL

version 4 questionnaire (Japanese version), straws

(w10 mm 50 mm) for saliva collection, ice packs, a kitchen

timer, and an expanded polystyrene box.

In addition, all the subjects received individual instruc-

tions on how to collect saliva samples at home twice a day

on two consecutive days; first, immediately after waking

up in the morning, when they were stil l in bed (T0), and

second, 30 min later (T30). The sampling instructions

contained a flowchart (Fig. 1) to enable the subjects to

clearly understand the sampling procedure. The subjects

were required to store the saliva samples in the freezer and

to record the sampling times on the self-reporting sheets

immediately after the samples were collected. In addition,

they were instructed not to eat or drink and to remain as

quiet as possible until the end of sampling. Because of

deglutition disorders and the risk of accidental swallowing,

passive drool was selected as the method of saliva

collection. Frozen saliva samples, the self-reporting sheets,

and the questionnaires were returned to the investigator

personally or by refrigerated delivery service within a few

days.

Table 1 Characteristics of all the subjects. (a) Long-term (LT) prosthesis wearers. (b) Short-term (ST) prosthesis wearers.

(a)

Patient 1 2 3 4 5 6 7 8 9 10 11 Mean S.D.

Age (year) 67 67 66 73 69 72 69 53 67 66 72 67.4 5.4

Sex (M/F) M M F F M M M M M M F

Diagnosis SCC SCC MCa SCC SCC SCC SCC SCC SCC SCC SCC

Range of mandibular resection Marg Seg Marg Marg Marg Marg Seg Marg Marg Seg Marg

With glossectomy (+/) + +

Neck dissection (+/) + + + + +

Radiotherapy (+/) + + + +

Reconstruction (+/) + + + + + + +

Time after resection (year) 3 3 28.9 2.7 29 17.3 2 5 1.2 4.8 4.4 9.2 10.7

Term of wearing the

prosthesis (day)

115 555 2213 470 1789 178 312 1094 220 375 111 675.6 717.4

No. of maxillary teeth 14 14 9 10 12 13 12 14 14 14 12 12.5 1.8

No. of mandibular teeth 5 9 1 7 4 10 8 4 11 10 4 6.6 3.2

(b)

Patient 1 2 3 4 5 6 7 8 9 10 Mean S.D.

Age (year) 77 70 59 55 73 74 36 70 70 53 63.7 12.8

Sex (M/F) F F F M F F M M M M

Diagnosis SCC SCC SCC SCC SCC SCC MCa SCC SCC SCC

Range of mandibular resection Marg Seg Seg Seg Marg Marg Marg Seg Marg Seg

With glossectomy (+/) +

Neck dissection (+/) + + + + + + + +

Radiotherapy (+/)

Reconstruction (+/) + + + + + + +

Time after resection (year) 4 1 1.1 1.1 0.9 0.9 0.6 1.4 0.7 0.7 1.24 1.0

Term of wearing the

prosthesis (day)

30 17 16 6 3 2 18 5 25 19 14.1 9.7

No. of maxillary teeth 13 14 12 13 14 11 14 16 14 14 13.5 1.4

No. of mandibular teeth 5 8 9 8 4 0 8 8 11 4 6.5 3.2

SCC, squamous cell carcinoma; MCa, mucoepidermoid carcinoma; Marg, marginal resection; Seg, segmental resection. Number of maxillary/

mandibular teeth containing bridge pontic, root cap, and stud attachment.

Fig. 1 Flowchart explaining saliva sampling. This flowchart was provided in the instructions to clarify the sampling

procedure.

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2.4. Cortisol assay

From the self-reporting sheets, the following subjects were

excluded: those who delayed the first collection of saliva for

more than 15 min after waking up; those who had classified

sleep quality as could not sleep; or those who providedincomplete/unclear answers on the self-reporting sheets.

Further, saliva samples were excluded when they were visibly

contaminated with blood.

Upon arrival at the laboratory, the saliva samples were

stored at 80 8C until required for assay. On the day of assay,

the samples were thawed for approximately 4 h to acquire

room temperature (20.023.3 8C) and were then centrifuged at

3000 rpm for 10 min. The free cortisol levels in saliva were

determined in duplicate using a high-sensitivity salivary

cortisol enzyme immunoassay kit (Salimetrics, LLC, State

College, PA, USA). The samples from each subject were

assayed in the same batch. The inter- and intra-assay

variations were below 6.41% and 3.65%, respectively.

2.5. UW-QOL questionnaire

The UW-QOL version 4 questionnaire (translated into Japa-

nese) is a common survey instrument used worldwide to

assess QOL of patients with HNC [31]. This questionnaire

includes 12 domains, namely pain, appearance, activity,

recreation, swallowing, chewing, speech, shoulder, taste,

saliva, mood, and anxiety, and three global questions that

compared QOL, health-related QOL (HRQOL) and overall QOL.

Each domain has three to six choices per item. The highest

level is assigned 100 points, whereas the lowest level or

greatest dysfunction scores 0 point.

2.6. Statistical analysis

For the analysis of salivary cortisol levels, the mean cortisol

value was calculated from the samples collected on the two

consecutive days. The differences between the cortisol levels

atT0 andT30 (CAR)were analyzed for the twogroupsusing theWilcoxon rank sum test. Moreover, each of the UW-QOL

domains and total UW-QOL scores were compared using the

Wilcoxon rank sum test. Statistical significance was set at

p < 0.05. Data were analyzed using SPSS 13.0J software (SPSS

Japan Inc., Tokyo, Japan).

3. Results

3.1. STAI JYZ scores

Table 2 presents the mean STAIJYZ scores for the two groups.

None of the subjects scored over 65 on state anxiety and traitanxiety; thus, all the subjects were included.

3.2. Cortisol levels and CAR

All the saliva samples were included in the analysis. Fig. 2

presents the changes in the cortisol levels fromT0 to T30 for

the two groups; a significant increase in CAR (differences

between the cortisol levels at T0 and T30) was observed in

the LT prosthesis wearer group but not in the ST prosthesis

wearer group. The mean CAR value was significantly lower

in the ST prosthesis wearer group (0.91 2.64 nmol/L) than

in the LT prosthesis wearer group (4.04 2.72 nmol/L;

p = 0.020).

Table 2 Mean State-Trait Anxiety Inventory-Form JYZ scores for the two groups.

State anxiety score S.D. Trait anxiety score S.D.

Long-term (LT) prosthesis wearers 35.4 9.9 34.1 8.6

Short-term (ST) prosthesis wearers 38.2 8.2 36.7 6.8

None of the subjects scored over 65 in state anxiety and trait anxiety.

Fig. 2 Changes in salivary cortisol levels between samples collected immediately after subjects woke up in the morning,

while they were still in bed (T0), and those collected 30 min later (T30) in the two groups. (a) Long-term (LT) prosthesis

wearers. (b) Short-term (ST) prosthesis wearers. Increased cortisol levels were observed in the LT prosthesis wearers but

not in the ST prosthesis wearers. CAR: the differences between the cortisol levels at T0 and T30. Attached vertical bars:

standard deviations.



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3.3. UW-QOL scores

A significantdifferencewas observed between the two groups.

The ST prosthesis wearers had significantly lower total UW-

QOL scores, and there were significant differences in appear-

ance, activity, recreation, speech, and anxiety (Table 3).

4. Discussion

The purposes of this study were to use CAR to investigate the

differences in daily life stress and also to use the UW-QOL

questionnaire to evaluate the differences in QOL scores in LT

and ST dento-maxillary prosthesis wearer groups following

HNC resection.

On the basis of the results, the two null hypotheses were

rejected: (1) significant differences were observed in the CAR

between the two prosthesis wearer groups and (2) significant

differences were observed in the UW-QOL between the two

prosthesis wearer groups in appearance, activity, recreation,

speech, anxiety and total score of UW-QOL.Decreased CAR has been reported in individuals with

posttraumatic stress disorder, those with Asperger syn-

drome [29], patients with metastatic breast cancer who are

depressed [9], and those with high levels of fatigue and

burnout [19]. In our study, the main differences between the

two groups of prosthesis wearers were the time period for

which they had worn the prosthesis and the time after

resection. Although it was still not clear whether the time

after resection or prosthesis wearing time affected CAR, we

considered that some sort of daily life stress had persisted

to suppress negative feedback to the HPA axis, contributing

to diminished CAR of the ST prosthesis wearers. We

considered that the ST prosthesis wearers did not have

adequate time to get used to their prosthesis, which could

have been a prolonged stressor. In addition, the experience

of cancer resection, which can have a devastating impact on

patients with HNC, may have influenced CAR of the ST

prosthesis wearers more than that of the LT prosthesis

wearers. However, there are several differences among

patients, not only with regard to post-surgical anatomical

and functional states but also with regard to general health,lifestyle, and other socio-demographic factors. The study

has a limitation that we did not clarify the correlations of

CAR variation and time after resection including release

from the fear of the recurrence or adapting duration of the

prosthesis.

The total UW-QOL scores were significantly higher for the

LT prosthesis wearers than for the ST prosthesis wearers,

with the latter groups scores similar to those previously

reported for patients with HNC [4], and there were significant

differences in appearance, activity, recreation, speech, and

anxiety. The experience of wearing a comfortable prosthesis

and improvement of oral functionmayhaveelevatedtheQOL

scores for the LT prosthesis wearers. Conversely, it wasthought that the ST prosthesis wearers were not satisfied

with the domains related to interpersonal relations. About

the results of UW-QOL, the study has a limitation that wedid

not clarify the correlations of the results of psychological

questionnaires and time after resection including release

from the fear of the recurrence or adapting duration of the

prosthesis.

In this study, we focused on mandibulectomy patients. In

mandibulectomy patients, the continuity of mandibular bone

and the variation of flap are important factors for functional

recovery, especially for masticatory function. Discontinuity

defect cause their unstable mandibular position because of

deviation and rotation of the remaining mandible. In case ofthe existence of a bulkyflap,denture space is little and the flap

is not able to support the prosthesis. Even if delivered to these

patients, the adjustmentof theprosthesiswouldbeprolonged.

Thus, the cases of discontinuity of mandibular bone and

existence of a bulky flap on the reconstruction part were

excluded. Because it was thought that the experience of the

prosthesis wearing and the progress period from the surgical

resection of the excluded groups such as discontinuity and

bulky flap were similar to those of the LT prosthesis wearers,

further studies should consider whether the stable prosthesis

or the surgical reconstruction method affect to CAR and

results of UW-QOL questionnaire by comparing these two

groups.It is true that further study using multiple regression

analysis is required to determine the impactof each factor and

its influence on CAR in patients with HNC and also further

research is needed to determine the differences in CAR

between dento-maxillary prosthesis wearers and normal

denture wearers, and to determine how these differences

may affect theHPA axisactivity. Inaddition further studies are

required with other questionnaires or psychological tests to

clarify the subjectss psychological variations and to deter-

mine the correlation between those tests like UW-QOL

questionnaire and CAR of patients with HNC.

However, the results of this study can be useful in

stimulating encouraging conversations with patients with

Table 3 Thepvalues for each domain, global questionsand total scores of the University of Washington Qualityof Life questionnaire.

Domains p value

1. Pain 0.29

2. Appearance 0.03*

3. Activity 0.01*

4. Recreation 0.003*5. Swallowing 0.11

6. Chewing 0.48

7. Speech 0.001*

8. Shoulder 0.4

9. Taste 0.11

10. Saliva 0.1

11. Mood 0.47

12. Anxiety 0.04*

Total UW-QOL scores 0.01*

Global questions p value

Compared QOL 0.32

HRQOL 0.09

Overall QOL 0.13

The p values of 12 domains, 3 global questions and total scores of

UW-QOL, which is the sum of the scores of 12 domainsare shown.

Statistically significant differences were observed in appearance,

activity, recreation, speech, anxiety and total UW-QOL scores.*



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HNC before commencing prosthetic treatment. There was a

clinical significance that ST prosthesis wearers were having

some sort of daily life stress and suffering from lower QOL

than LT prosthesis wearers, thus we clinicians and other co-

medical workers must keep in mind the result when we treat,

manage and deal with our patients.

5. Conclusion

Within the limitations of this study, it is suggested that the ST

wearers of a dento-maxillary prosthesis following HNC

resection experience some sort of daily life stress and

complicated socio-demographic factors may influence their

QOL.

Acknowledgements

The authors thank Professors Hiroyuki Kagechika and Akira

Toyofuku,Drs.OsamuShinozuka, ShuichiMori,Shuhei Izawa,and Ms. Masako Akiyama for providing technical support and

valuable advice. In addition, the authors thank the staff of the

Department of Maxillofacial Prosthetics, Tokyo Medical and

Dental University Hospital Faculty of Dentistry, and all

patients who participated in this study. This investigation

was supported in part by Challenging Exploratory Research

(24659853) (20122014) from the Japan Society for the Promo-

tion of Science.

r e f e r e n c e s

[1] Devins GM, Payne AYM, Lebel S, Mah K, Lee RNF, Irish J,et al. The burden of stress in head and neck cancer.Psychooncology 2013;22:66876.

[2] Rogers SN, Devine J, Lowe D, Shokar P, Brown JS,Vaughan ED. Longitudinal health-related quality oflife after mandibular resection for oral cancer: acomparison between rim and segment. Head Neck2004;26:5462.

[3] Hertrampf K, Wenz HJ, Lehmann KM, Lorenz W, Koller M.Quality of life of patients with maxillofacial defects aftertreatment for malignancy. Int J Prosthodont 2004;17:65765.

[4] Dwivedi RC, Rose SS, Chisholm EJ, Youssefi P, Hassan MSU,Khan AS, et al. Evaluation of factors affecting post-

treatment quality of life in oral and oropharyngeal cancerpatients primarily treated with curative surgery: anexploratory study. Eur Arch Otorhinolaryngol 2012;269:5919.

[5] Holloway RL, Hellewell JL, Marbella AM, Layde PM,Myers KB, Campbell BH. Psychosocial effects inlong-term head and neck cancer survivors. Head Neck2005;27:2818.

[6] Steptoe A, Brydon L, Kunz-Ebrecht S. Changes in financialstrain over three years, ambulatory blood pressure, andcortisol responses to awakening. Psychosom Med2005;67:2817.

[7] Kuehner C, Holzhauer S, Huffziger S. Decreased cortisolresponse to awakening is associated with cognitivevulnerability to depression in a nonclinical sample of

young adults. Psychoneuroendocrinology 2007;32:199209.

[8] Matsuda S, Yamaguchi T, Okada K, Gotouda A, Mikami S.Day-to-day variations in salivary cortisol measurements. JProsthodont Res 2012;56:3741.

[9] Giese-Davis J, Wilhelm FH, Conrad A, Abercrombie HC,Sephton S, Yutsis M, et al. Depression and stress reactivityin metastatic breast cancer. Psychosom Med 2006;68:67583.

[10] Kunz-Ebrecht SR, Kirschbaum C, Marmot M, Steptoe A.

Differences in cortisol awakening response on work daysand weekends in women and men from the Whitehall IIcohort. Psychoneuroendocrinology 2004;29:51628.

[11] Hellhammer J, Fries E, Schweisthal OW, Schlotz W, StoneAA, Hagemann D. Several daily measurements arenecessary to reliably assess the cortisol rise afterawakening: state- and trait components.Psychoneuroendocrinology 2007;32:806.

[12] Reid JD, Intrieri RC, Susman EJ, Beard JL. The relationship ofserumand salivary cortisol in a sample of healthy elderly. JGerontol 1992;47:1769.

[13] Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Salivarycortisol: a better measure of adrenal cortical function thanserum cortisol. Ann Clin Biochem 1983;20:32935.

[14] Adam EK, Hawkley LC, Kudielka BM, Cacioppo JT. Day-to-

day dynamics of experience-cortisol associations in apopulation-based sample of older adults. Proc Natl Acad SciUSA 2006;103:1705863.

[15] Grossi G, Perski A, Ekstedt M, Johansson T, Lindstrom M,Holm K. Themorning salivary cortisol response in burnout.J Psychosom Res 2005;59:10311.

[16] Badrick E, Kirschbaum C, Kumari M. The relationshipbetween smoking status and cortisol secretion. J ClinEndocrinol Metab 2007;92:81924.

[17] Pruessner JG, Hellhammer DH, Kirschbaum C. Burnout,perceived stress, and cortisol responses to awakening.Psychosom Med 1999;61:197204.

[18] Fries E, Dettenborn L, Kirschbaum C. The cortisolawakening response (CAR): facts and future directions. Int JPsychophysiol 2009;72:6773.

[19] Chida Y, Steptoe A. Cortisol awakening response andpsychosocial factors: a systematic review and meta-analysis. Biol Psychol 2009;80:26578.

[20] Taniguchi H, Ishiwata H, Ohyama T, Shinozuka O. Stabilityof themandibular position in occlusionofmandibulectomypatients with lateral discontinuity defect. J Oral Rehabil1997;24:84956.

[21] Teoh KH, Patel S, Hwang F, Huryn JM, Verbel D,Zlotolow IM. Prosthetic Intervention in the era ofmicrovascular reconstruction of the mandible-aretrospective analysis of functional outcome. Int JProsthodont 2005;18:4254.

[22] Hagino A, Inohara K, Sumita YI, Taniguchi H. Investigationof the factors influencing the outcome of prostheses onspeech rehabilitation of mandibulectomy patients. J Jpn

Prosthodont Soc 2008;52:5439.[23] Moroi HH, Okimoto K, Terada Y. The effect of an oral

prosthesis on the quality of life for head and neck cancerpatients. J Oral Rehabil 1999;26:26573.

[24] Kohno J, Maeda T, Inoue H. Influence of uncomfortableremovable partial dentures on stress hormone in saliva. JJpn Assoc Craniomandib Orthoped 2008;21:16.

[25] Ugawa Y, Nishigawa G, Maruo Y, Suwaki M, Minagi S.Salivary stress biomarker levels during speech in patientswith maxillectomy defect. Head Neck 2011;33:6206.

[26] Hidano T, Fukuhara M, Iwawaki M, Soga S,Spielberger CD. New STAI Manual State-Trait AnxietyInventory-Form JYZ, 1st ed., Tokyo: Jitsumu Kyouiku Press;2000 [in Japanese].

[27] Gonzalez A, Jenkins JM, Steiner M, Fleming AS. The relation

between early life adversity, cortisol awakening response

http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0005http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0005http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0005http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0015http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0015http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0015http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0015http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0025http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0025http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0025http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0025http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0030http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0030http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0030http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0030http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0035http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0035http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0035http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0035http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0040http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0040http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0040http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0045http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0045http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0045http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0045http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0050http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0050http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0050http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0050http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0055http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0055http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0055http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0055http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0055http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0060http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0060http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0060http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0065http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0065http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0065http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0070http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0070http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0070http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0070http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0075http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0075http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0075http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0075http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0075http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0080http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0080http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0080http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0085http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0085http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0085http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0090http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0090http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0090http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0095http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0095http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0095http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0100http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0100http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0100http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0100http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0100http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0100http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0105http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0105http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0105http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0105http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0105http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0110http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0110http://refhu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om/S1883-1958(13)00124-2/sbref0040http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0035http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0035http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0035http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0035http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0030http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0030http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0030http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0030http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0025http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0025http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0025http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0025http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0020http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0015http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0015http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0015http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0015http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0010http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0005http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0005http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0005


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and diurnal salivary cortisol levels in postpartum women.Psychoneuroendocrinology 2009;34:7686.

[28] Izawa S, Saito K, Shirotsuki K, Sugaya N, Nomura S.Effects of prolonged stress on salivary cortisol anddehydroepiandrosterone: a study of a two-weekteaching practice. Psychoneuroendocrinology 2012;37:8528.

[29] Brosnan M, Turner-Cobb J, Munro-Naan Z, Jessop D.

Absence of a normal cortisol awakening response (CAR) in

adolescent males with Asperger syndrome (AS).Psychoneuroendocrinology 2009;34:1095100.

[30] Meinlschmidt G, Heim C. Decreased cortisol awakeningresponse after early loss experience.Psychoneuroendocrinology 2005;30:56876.

[31] Morimata J, Otomaru T, Murase M, Haraguchi M, Sumita Y,Taniguchi H. Investigation of factoraffecting health-relatedquality of life in head and neck cancer patients.

Gerodontology 2013;30:194200.

http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0135http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0135http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0145http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0145http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0145http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0145http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0150http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0150http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0150http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0155http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0155http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0155http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0155http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0155http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0155http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0155http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0155http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0150http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0150http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0150http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0145http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0145http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0145http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0145http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0140http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0135http://refhub.elsevier.com/S1883-1958(13)00124-2/sbref0135

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