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 disgurement 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 ur na l o f p r os t hod o nt i c r e s e a r c h 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. Also we used the University of Washington Quality of Life (UW-QOL)
version 4 questionnaire to evaluate the differences in quality of life (QOL) scores between ST
and LT wearers of a dento-maxillary prosthesis.
Methods: Salivary samples were collected from11 LT and 10 ST prosthesis wearers on two
consecutive days at two time points, immediately after waking up (T0) and 30 min later
(T30), by passive drool collection. Cortisol levels were measured using a high sensitivity
salivary cortisol enzyme immunoassay kit (Salimetrics, LLC, State College, PA, USA) and CAR
(the differences between the cortisol levels at T0 and T30) was compared between LT and ST
prosthesis wearers. In addition, both the groups completed the UW-QOL questionnaire and
the scores were compared.
Results: Asignicant difference was observed in CAR between the two groups. CAR of the ST
prosthesis wearers was signicantly lower compared with that of the LT prosthesis wearers;
moreover, the ST prosthesis wearers revealed signicantly lower total UW-QOL scores and
there were signicant differences in appearance, activity, recreation, speech, and anxiety.
Conclusion: Within the limitations of this study, the ndings suggest that individuals
wearing ST dento-maxillary prostheses following HNC resection experience some sort of
daily life stress and complicated socio-demographic factors may inuence 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: kosamfp@tmd.ac.jp (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
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 sufciently 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 the
latter 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 specic 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 oral
rehabilitation [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 patients with HNC wearing a dento-maxillary
prosthesis. 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 use the University of Washington Quality
of Life (UW-QOL) version 4 questionnaire to evaluate the
differences in QOL scores betweenboththe prosthesis wearer
groups.
In this study, we tested the following null hypotheses: (1)
CAR do not differ between ST and LT wearers of a dento-
maxillary prosthesis in HNC patients and (2) QOL scores do not
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) there
was no need 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 rst
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 ap 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 the
Faculty 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
JYZ questionnaire, and scores of state anxiety and trait anxiety
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),
j o ur na l o f p r o s t ho d ont i c r e s e a r c h 5 8 ( 2 0 1 4 ) 4 1 4 7 42
self-reporting sheets, the STAI JYZ questionnaire, 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; rst, immediately after waking
up in the morning, when they were still in bed (T0), and
second, 30 min later (T30). The sampling instructions
contained a owchart (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.
j our na l of p r os t ho d ont i c r e s e a r c h 5 8 ( 2 0 1 4 ) 4 1 4 7 43
2.4. Cortisol assay
From the self-reporting sheets, the following subjects were
excluded: those who delayed the rst collection of saliva for
more than 15 min after waking up; those who had classied
sleep quality as could not sleep; or those who provided
incomplete/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
at T0 and T30 (CAR) were analyzed for the two groups using the
Wilcoxon rank sum test. Moreover, each of the UW-QOL
domains and total UW-QOL scores were compared using the
Wilcoxon rank sum test. Statistical signicance 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 STAI JYZ scores for the two groups.
None of the subjects scored over 65 on state anxiety and trait
anxiety; 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 signicant 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 signicantly 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.
j o ur na l o f p r o s t ho d ont i c r e s e a r c h 5 8 ( 2 0 1 4 ) 4 1 4 7 44
3.3. UW-QOL scores
A signicant difference was observed between the two groups.
The ST prosthesis wearers had signicantly lower total UW-
QOL scores, and there were signicant 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) signicant differences were observed in the CAR
between the two prosthesis wearer groups and (2) signicant
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 inuenced 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 signicantly 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 signicant
differences in appearance, activity, recreation, speech, and
anxiety. The experience of wearing a comfortable prosthesis
and improvement of oral function may have elevatedthe QOL
scores for the LT prosthesis wearers. Conversely, it was
thought that the ST prosthesis wearers were not satised
with the domains related to interpersonal relations. About
the results of UW-QOL, the study has a limitation that we did
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 ap 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 of
the existence of a bulky ap, denture space is little and the ap
is not able to support the prosthesis. Even if delivered to these
patients, the adjustment of the prosthesis would be prolonged.
Thus, the cases of discontinuity of mandibular bone and
existence of a bulky ap 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 ap 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 impact of each factor and
its inuence 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 the HPA axis activity. In addition 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 The p values for each domain, global questions
and total scores of the University of Washington Quality
of 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 sumof the scores of 12 domains are shown.
Statistically signicant differences were observed in appearance,
activity, recreation, speech, anxiety and total UW-QOL scores.*
j our na l of p r os t ho d ont i c r e s e a r c h 5 8 ( 2 0 1 4 ) 4 1 4 7 45
HNC before commencing prosthetic treatment. There was a
clinical signicance 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 inuence their
QOL.
Acknowledgements
The authors thank Professors Hiroyuki Kagechika and Akira
Toyofuku, Drs. Osamu Shinozuka, Shuichi Mori, 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 of
life after mandibular resection for oral cancer: a
comparison between rim and segment. Head Neck
2004;26:5462.
[3] Hertrampf K, Wenz HJ, Lehmann KM, Lorenz W, Koller M.
Quality of life of patients with maxillofacial defects after
treatment for malignancy. Int J Prosthodont 2004;17:
65765.
[4] Dwivedi RC, Rose SS, ChisholmEJ, Yousse P, Hassan MSU,
Khan AS, et al. Evaluation of factors affecting post-
treatment quality of life in oral and oropharyngeal cancer
patients primarily treated with curative surgery: an
exploratory study. Eur Arch Otorhinolaryngol 2012;269:
5919.
[5] Holloway RL, Hellewell JL, Marbella AM, Layde PM,
Myers KB, Campbell BH. Psychosocial effects in
long-term head and neck cancer survivors. Head Neck
2005;27:2818.
[6] Steptoe A, Brydon L, Kunz-Ebrecht S. Changes in nancial
strain over three years, ambulatory blood pressure, and
cortisol responses to awakening. Psychosom Med
2005;67:2817.
[7] Kuehner C, Holzhauer S, Huffziger S. Decreased cortisol
response to awakening is associated with cognitive
vulnerability 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. J
Prosthodont Res 2012;56:3741.
[9] Giese-Davis J, Wilhelm FH, Conrad A, Abercrombie HC,
Sephton S, Yutsis M, et al. Depression and stress reactivity
in 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 days
and weekends in women and men from the Whitehall II
cohort. Psychoneuroendocrinology 2004;29:51628.
[11] Hellhammer J, Fries E, Schweisthal OW, Schlotz W, Stone
AA, Hagemann D. Several daily measurements are
necessary to reliably assess the cortisol rise after
awakening: state- and trait components.
Psychoneuroendocrinology 2007;32:806.
[12] Reid JD, Intrieri RC, Susman EJ, Beard JL. The relationship of
serumand salivary cortisol in a sample of healthy elderly. J
Gerontol 1992;47:1769.
[13] Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Salivary
cortisol: a better measure of adrenal cortical function than
serum 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 a
population-based sample of older adults. Proc Natl Acad Sci
USA 2006;103:1705863.
[15] Grossi G, Perski A, Ekstedt M, Johansson T, Lindstro m M,
HolmK. The morning salivary cortisol response in burnout.
J Psychosom Res 2005;59:10311.
[16] Badrick E, Kirschbaum C, Kumari M. The relationship
between smoking status and cortisol secretion. J Clin
Endocrinol 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 cortisol
awakening response (CAR): facts and future directions. Int J
Psychophysiol 2009;72:6773.
[19] Chida Y, Steptoe A. Cortisol awakening response and
psychosocial factors: a systematic review and meta-
analysis. Biol Psychol 2009;80:26578.
[20] Taniguchi H, Ishiwata H, Ohyama T, Shinozuka O. Stability
of the mandibular position in occlusion of mandibulectomy
patients with lateral discontinuity defect. J Oral Rehabil
1997;24:84956.
[21] Teoh KH, Patel S, Hwang F, Huryn JM, Verbel D,
Zlotolow IM. Prosthetic Intervention in the era of
microvascular reconstruction of the mandible-a
retrospective analysis of functional outcome. Int J
Prosthodont 2005;18:4254.
[22] Hagino A, Inohara K, Sumita YI, Taniguchi H. Investigation
of the factors inuencing the outcome of prostheses on
speech 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 cancer
patients. J Oral Rehabil 1999;26:26573.
[24] Kohno J, Maeda T, Inoue H. Inuence of uncomfortable
removable partial dentures on stress hormone in saliva. J
Jpn Assoc Craniomandib Orthoped 2008;21:16.
[25] Ugawa Y, Nishigawa G, Maruo Y, Suwaki M, Minagi S.
Salivary stress biomarker levels during speech in patients
with maxillectomy defect. Head Neck 2011;33:6206.
[26] Hidano T, Fukuhara M, Iwawaki M, Soga S,
Spielberger CD. New STAI Manual State-Trait Anxiety
Inventory-FormJYZ, 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
j o ur na l o f p r o s t ho d ont i c r e s e a r c h 5 8 ( 2 0 1 4 ) 4 1 4 7 46
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 and
dehydroepiandrosterone: a study of a two-week
teaching 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 awakening
response after early loss experience.
Psychoneuroendocrinology 2005;30:56876.
[31] Morimata J, Otomaru T, Murase M, Haraguchi M, Sumita Y,
Taniguchi H. Investigation of factor affecting health-related
quality of life in head and neck cancer patients.
Gerodontology 2013;30:194200.
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