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British Journal of Oral and Maxillofacial Surgery xxx (2014) xxxxxx

Is the incidence of temporomandibular disorder increased in


polycystic ovary syndrome?
Sidika Sinem Soydan a, , Kagan Deniz b,1 , Sina Uckan a,2 , Asl Dogruk Unal c,3 ,
Neslihan Bascl Tutuncu d,4
a Department of Oral and Maxillofacial Surgery, 11. Sokak no:26 Bahcelievler, Ankara, Trkiye
b Department of Oral and Maxillofacial Surgery, Kskl Caddesi Oymac Sokak No:7 Altunizade, skdar Istanbul, Trkiye
c Endocrinology Department, Kskl Caddesi Oymac Sokak No:7, Altunizade, skdar Istanbul, Trkiye
d Endocrinology Department, Maresal Fevzi CakmakCaddesi, 10. Sokak no:45, Ankara, Turkey

Accepted 18 July 2014

Abstract

The prevalence of temporomandibular disorders is higher among women than men (ratio 3:1 -9:1). Polycystic ovary syndrome(PCOS) is the
most common endocrine disorder in women, which is characterised by chronic low-grade inflammation and excess of androgenic hormones
that lead to metabolic aberrations and ovarian dysfunction. Increased activities of various matrix metalloproteinases (particularly MMP-
2 and 9) in the serum of these patients has been reported, and it has been hypothesised that high activities of MMP may contribute to
loss of matrix and chronic inflammation of the fibrocartilage in temporomandibular disorders. Our aim was to evaluate the incidence of
temopormandibular dysfunction in women with PCOS compared with an age-matched, disease-free, control group. We studied 50 patients
with previously diagnosed PCOS and 50 volunteers who had normal menstrual cycles. We made a comprehensive clinical examination of the
temporomandibular joint (TMJ) and muscles of mastication in both groups and recorded the Visual Analogue Scores (VAS) for pain. There
were significant differences (p < 0.001) in the incidence of temporomandibular disorders (n = 43 (86%) in the PCOS group compared with
n = 12 24% in the control group), muscle tenderness(n = 32 (64%) in the PCOS group compared with n = 14 (28%) in the control group) and
pain in the TMJ (mean (SD) VAS 2.9 (2.61) compared with 0.3 (1.56). We confirm the higher incidence and severity of disorders of the TMJ
in patients with PCOS and suspect that chronic low-grade inflammation may play a part in the aetiology of the disease.
2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Keywords: Polycystic ovary syndrome; Temporomandibular joint disorder; Temporomandibular pain; Internal derangement; Matrix metalloproteinase

Introduction
Corresponding author. Baskent University, Faculty of Dentistry, Depart-
The high female:male predominance of degenerative joint
ment of Oral and Maxillofacial Surgery, 11. Sokak no:26 Bahcelievler,
diseases is well-known and well- documented,1 and the
Ankara, Turkiye. Tel.: +903122151336; fax: +903122152962.
E-mail addresses: sdksoydan@yahoo.com (S.S. Soydan), potential effect of female sex hormones (oestrogen, proges-
kgndeniz@yahoo.com (K. Deniz), suckan@yahoo.com (S. Uckan), terone, and relaxin) on the development of degenerative joint
aslidogruk@yahoo.com (A.D. Unal), neslibascil@yahoo.com disorders (together with the presence of the receptors of these
(N.B. Tutuncu). hormones in the cartilage of the temporomandibular joint
1 Tel.: +903122151336 Fax:+903122152962.
2 Tel.: +903122151336 Fax:+903122152962. (TMJ)) have been described.25
3 Tel: +903122122912 Fax: +903122154216. The modulation of the remodelling activities of the extra-
4 Tel. +903122122912 Fax: +903122154216. cellular matrix by oestrogen, progesterone, and relaxin may

http://dx.doi.org/10.1016/j.bjoms.2014.07.100
0266-4356/ 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Soydan SS, et al. Is the incidence of temporomandibular disorder increased in polycystic ovary syndrome?
Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.07.100
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be one of the key mechanisms by which joints are predisposed history of head and neck trauma, isolated muscular tender-
to degenerative changes. Oestrogen induces the expression ness, or previous operation on the TMJ.
of matrix metalloproteinases (MMP) -3, -9, and -13 in vari- The TMJ and the masticatory muscles were evaluated
ous cells, including fibrocartilaginous cells.6,7 Progesterone by the same clinician. Patients described symptoms such as
produces a dose-dependent receptor-mediated decrease in preauricular pain, limited mouth opening, deviation or deflec-
MMP-9 expression in trophoblasts.8 Relaxin increases the tion during mouth opening, and joint sounds. All patients
turnover of fibrocartilage by the extracellular matrix, and were assessed using Okesons Muscle and temporomandibu-
induces MMP-1 (collagenase-1) and -3 (stromelysin-1), lar joint examination and treatment outcome form.15 This
which are paralleled by loss of collagen and proteogly- form records (for both TMJ) tenderness and pain in the
can from the fibrocartilaginous tissue of the disc of the masseter, temporalis, lateral pterygoid, medial pterygoid,
TMJ.9 sternocleidomastoid, trapezius, splenius capitis, and digastric
Polycystic ovary syndrome (PCOS) is the most com- muscles, as well as maximum interincisal distance, restric-
mon endocrinopathy in women during the premenopausal tion of laterotrusive and protrusive movements, joint sounds,
period, and is defined as clinical or biochemical (or both) deviation or deflection during mouth opening, and the visual
hyperandrogenism, hyperinsulinaemia, oligomenorrhoea or analogue score (VAS) for pain in the TMJ.
anovulation, and polycystic ovaries, according to the Rotter- In addition, any history of the following disorders was
dam criteria.10 In women, androgens are necessary to make recorded: rheumatological disease, neurological disease,
oestrogen, but women with PCOS have concentrations in the familial disease, muscular disease, history of closed lock or
high normal range. It is marked by a decrease in female sex dislocation of the TMJ, bruxism, single-sided chewing, and
hormones and hormonal imbalance,11 and is a state of chronic limited mouth opening. Objective assessment of muscular
low-grade inflammation that might be responsible for the tenderness, interincisal opening (mm), and VAS for pain in
development of ovarian dysfunction and metabolic abnor- the TMJ were also recorded. Magnetic resonance imaging
malities. The presence of certain cytokines in women with was used to support management where this was indicated,
the syndrome correlates with obesity and insulin resistance.12 but was not used for the purposes of this study.
Visceral adiposity is closely associated with insulin resistance
and may be attributed to dysfunctioning adipocytes and the Statistical analysis
low-grade inflammation.13
A number of studies have shown that activities of MMP-2 With the aid of SPSS (version 18.0, SPSS Inc, Chicago), and
and 9 are increased in the follicular fluid and serum of women the independent two samples t test we compared the demo-
with PCOS.14 It may be speculated that increased activities graphic data of the two groups. The proportional Z test was
of these MMP may be one of the most important factors that used to compare the significance of differences in the inci-
lead to the increased incidence of disorders of the TMJ among dence of disorders of the TMJ, incidence of pain in the TMJ,
women, particularly those with PCOS. To our knowledge and muscular tenderness in the two groups. The results of the
the incidence of such disorders has not yet been evaluated VAS were compared using the non-parametric Mann Whitney
in women with PCOS. Our aim therefore was to evaluate U test.
the incidence of disorders of the TMJ in these women and
compare it with that in an age-matched, disease-free, control
group. Results

The mean (SD) age of the PCOS group was 27 (6) and 26 (5)
Patients and Methods in control group. There was no significant difference between
the mean ages of two groups (t (93) = -1.06, p = 0.29). The
One hundred premenopausal women were included in this mean (SD) interincisal distance in the PCOS group was 44
prospective study. They were divided into 2 groups, PCOS (7) mm and in the control group 46 (5) mm. There was also no
and control. The PCOS group consisted of 50 women who significant difference between interincisal opening in the 2
had previously been diagnosed with PCOS at the endocrinol- groups (t (64) = 1.617, p = 0.11). The incidence of disorders
ogy department. The control group included 50 randomised of the TMJ did, however, differ significantly (p = = 0.001)
healthy women who had regular menstrual cycles and were being higher in the PCOS group (86%) than the control group
not taking any medication. The control group comprised (24%). There was also a significant difference in the incidence
students and staff of Baskent University Faculty of Den- of pain in the TMJ (p = 0.002) in the PCOS group (72%) com-
tistry. All subjects gave informed consent to participate in the pared withthe control group (28%) and also in the severity of
study. the pain as measured by VAS (p = 0.001), being 2.9 (SD:2.61)
Exclusion criteria were: age over 40 years, known cardio- in the PCOS group and 0.3 (SD:1.56)in the control group
vascular disease, thyroid disease, smoking, diabetes mellitus, (Table 1). The incidence of tenderness in one or more muscle
hypertension (blood pressure > 140/90 mm Hg), renal impair- was also significantly greater (p = 0.002) in the PCOS group
ment (serum creatinine > 150 mol/l), craniofacial syndromes, (64%) than in the control group (28%) (Fig. 1).

Please cite this article in press as: Soydan SS, et al. Is the incidence of temporomandibular disorder increased in polycystic ovary syndrome?
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Table 1 of closed lock: 0.03), deviation during mouth opening, (p


Comparison of the two groups. Data are number (%) of patients except where value of deviation during mouth opening:0.002) and unilat-
otherwise stated.
eral or bilateral clicking (p value of unilateral clicking: 0.048
Variable PCOS Control p value p value of bilateral clicking: 0.036) were significantly greater
group group
(n = 50) (n = 50)
in the PCOS group. The incidence of displacement of the disc
without reduction and deflection during mouth opening was
Incidence of 43 (86) 12 (24) 0.001
temperomandibular disease
similar.
Incidence of 36 (72) 14 (28) 0.001
temporomandibular pain
Mean (SD) VAS of pain in the 2.9 (2.61) 0.3 (1.56) 0.002 Discussion
temporomandibular joint
Incidence of muscular 32 (64) 14 (24) 0.002
tenderness This study has shown that the incidence and severity of dis-
orders of the TMJ is higher in patients with PCOS than in
PCOS = polycystic ovary syndrome. VAS = 0 (no pain) to 10 (worst pain controls. Our most important and new finding was that in
imaginable).
women with PCOS the incidence is 4 times that of controls.
Table 2 This may be related to an increase in MMP or proinflamatory
Incidence of symptoms of dysfunction of the temporomandibular joint in cytokines, but this requires more detailed study. We did not
the two groups. Data are number (%) of patients. study the incidence of PCOS in patients with disorders of the
Variable PCOS Control TMJ, but this may also be a topic for further study.
group group The high predominance of these disorders in women (ratio
(n = 50) (n = 50) between 3:1 and 9:1) is well-known.3 PCOS is the most
Unilateral internal derangement of disc 34 (68) 10 (20) common endocrine disorder in women with a prevalence
Bilateral internal derangement of disc 9 (18) 2 (4) between 6% and 15%. It is typically first identified during the
Displacement of disc with reduction 40 (80) 10 (20)
Displacement of disc without reduction 3 (6) 2 (4)
early reproductive years and its aetiology remains obscure.11
History of closed lock 9 (18) 0 Increase activity of MMP might be related to cardiovascu-
Deviation during mouth opening 34 (68) 10 (20) lar abnormalities, remodelling of the ovarian extracellular
Deflection during mouth opening 3 (6) 2 (4) matrix, formation of multiple cysts, and chronic anovulation
Unilateral clicking 16 (32) 11 (22) noted in women with PCOS.14 MMP are known acute phase
Bilateral clicking 8 (16) 0
reactants the activity of which increase during inflammation,
PCOS = polycystic ovary syndrome. and factors that stimulate their production such as oxidative
stress and the presence of inflammatory cytokines are also
Clinical signs are shown in Table 2. The incidence of present in PCOS.16
unilateral and bilateral internal derangements of the disc Female sex hormones (oestrogen, progesterone, and
(p:o.oo2 and p:0.036), displacement of the disc with reduc- relaxin) induce the expression of the various types of MMP
tion (p value of the difference of displacement of disc with in the fibrocartilagenous tissue of TMJ and lead to degen-
reduction is 0.001), history of closed lock (p value of history erative disorders of the TMJ.68 The overexpression and

Figure 1. Histogram showing the muscular tenderness in the PCOS and control groups Dark columns = polycystic ovary syndrome, and pale columns = controls.

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overactivity of MMP in an inflammatory process results in Conict of Interest


the destruction of tissue in the TMJ.17 These degenerative
changes may affect the articular cartilage, articular capsule, We have no conflict of interest.
and ligaments, the synovial membrane, and the articular bone.
Degenerative changes in the TMJ alter its physical and func-
tional properties. This leads first to reversible, and finally Ethics
to irreversible, changes that make the TMJ unable to with-
stand loading stress.17 Clinically, mild internal derangement The study was approved by the institutional Ethics Review
is characterised by displacement of the disc with or without Board.
osseous remodelling. Severe derangement includes perfora-
tion of the disc or its attachments, osseous remodelling, and
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Please cite this article in press as: Soydan SS, et al. Is the incidence of temporomandibular disorder increased in polycystic ovary syndrome?
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