Journal of

Oral Rehabilitation

Journal of Oral Rehabilitation 2013

A cross-sectional study of the relationship between serum

sexual hormone levels and internal derangement of
temporomandibular joint
A. S. MADANI*, A. A. SHAMSIAN, M. R. HEDAYATI-MOGHADDAM, F. FATHI-MOGHADAM,
M. R. SABOONI*, A. MIRMORTAZAVI* & M . G O L M O H A M A D I *Oral & Maxillofacial Diseases
Research Center, Department of Prosthodontics, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Research Center for
HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture and Research, Mashhad Branch, Mashhad and

Private Office, Mashhad, Iran

Temporomandibular disorders (TMD) are

defined as clinical conditions that involve the
masticatory muscles, temporomandibular joint
(TMJ) or both. The aim of this study was to evaluate
serum 17b-oestradiol and progesterone levels in
menstruating
women
affected
by
internal
derangement of the TMJ. A total of 142 women
(mean age 30
2  6
7) who referred to medical
diagnostic laboratory of Iranian Academic Centre
for Education, Culture and Research (ACECR),
Mashhad Branch, were enrolled during 2007 and
2008. Forty-seven individuals had disc displacement
with reduction (Group IIa) according to Research
Diagnostic Criteria (RDC)/TMD Axis I diagnosis.
Radioimmunoassay was used for the detection of
SUMMARY

Introduction
Epidemiologic studies indicate that TMDs are more
common in women, with the highest prevalence during their reproductive year (13). The prevalence of
TMD seems to be 25 times higher in women than
men in community samples, and a mean age of onset
around 3545 years, with two distinct age peaks for
internal joint derangements and inflammatory-degenerative disorders (46). The role of endogenous gonadal steroid levels in the development of TMDs is not
clearly understood. Joint structures may be affected
by sex hormones and remodel via extracellular matrix
2013 John Wiley & Sons Ltd

serum 17b-oestradiol and progesterone levels in

all 142 subjects. The mean progesterone level
was significantly higher in control group
(11
6  10
4 ng mL 1) compared to women with
TMD (8
4  6
8 ng mL 1, P = 0
03). No significant
difference was found in two groups regarding 17boestradiol level. Lower progesterone level in
women with TMD can suggest the more important
role of this hormone in the development of the
disorder.
KEYWORDS: oestradiol,
progesterone,
temporomandibular
joint,
internal
derangement
Accepted for publication 9 May 2013

and bone volume modifications. These modifications

result in internal derangement of the TMJ. Moreover,
animal studies have been shown that oestrogen modulates inflammation in the TMJ (7). Oestrogen and
progesterone receptors were detected in the human
articular disc (8). These hormones can increase type
III collagen content and lead to a decrease in the type
I/III collagen ratio (9). All of the above changes may
lead to alterations of connective tissue in the TMJ
structures.
The aim of this study was to evaluate 17b-oestradiol
and progesterone serum levels in menstruating
women affected by internal derangement of the TMJ.
doi: 10.1111/joor.12074

A . S . M A D A N I et al.

Materials and Methods

Results

One hundred and forty-two women who were referred

by physicians to medical diagnostic laboratory of
ACECR, Mashhad Branch, were enrolled during 2007
and 2008. They were referred to the laboratory for routine check-up. All participants were clinically examined
by the same dentist according to the RDC/TMD criteria
(10, 11). We included 47 subjects with RDC/TMD Axis
I diagnosis of disc displacement with reduction (Group
IIa) including joint clicking on at least one side and 95
women without any TMD as control group. Inclusion
criteria were healthy women aged 2040 years old
who reported at least three normal-length menstrual
cycles (2635 days duration) and referred to the luteal
phase of the menstrual cycle (2225 day based purely
on self-report of first day of menses)(12). Exclusion criteria were the presence of systemic diseases (i.e. rheumatic diseases, Psoriasis, ), medications and
therapeutic co-interventions during treatment such as
oral contraceptives, pregnancy and lactation.
One blood sample was taken from each member of
both groups at 08
00 a.m. after overnight fasting.
Blood was centrifuged, and then, serum samples were
stored at 20 C. Serum 17b-oestradiol and progesterone levels were measured using a commercially available radioimmunoassay (RIA) kit (*) from the same
batch. The normal values of oestradiol (27
277 pg mL 1) and progesterone (2
525 ng mL 1)
were determined according to the manufacturers
instructions. The technician who reported results of
serum hormone levels was blinded to study groups.
The intra-assay coefficient of variation (CV) for oestradiol and progesterone in low concentration was 9
5%
and 5
8%, respectively. The CV in high concentration
was 6
0% for oestradiol and 2
9% for progesterone.
The interassay CV for oestradiol and progesterone in
low concentration was 12
1% and 5
1%, and in high
concentration was 9
0% and 4
7%, respectively.
All participants were well informed about the aim
and method of study before giving their consent. All
aspects of the study were approved by the Ethics Committee of Mashhad University of Medical Sciences.
The data were analysed by SPSS 16.0 () software
using t and chi-square tests. The level of statistical significance was set at P < 0
05.

The mean age of TMD and control groups was

28
5  5
4 and 31
0  7
2, respectively (P = 0
02).
Temporomandibular joint pain was not observed in
TMD group, whereas only two subjects of control
group showed TMJ pain.
The mean serum levels of 17b-oestradiol were
164  104
6 (mean  s.d.) pg mL 1 and 162 
129
9 pg mL 1 in the TMD group and controls, respectively. No statistical significant difference was found
between the two groups. On the other hand, the mean
of progesterone level in control group was significantly
higher than that in TMD group (11
6  10
4 vs.
8
4  6
8 ng mL 1, respectively, P = 0
03).
The frequency of joint clicking in women with progesterone levels below normal values was significantly
higher than those with normal values (P = 0
036)
(Table 1). However, the frequency of joint clicking in
women with normal values of 17b-oestradiol was the
same of those with below or over normal values
(Table 2).

*Immunotech, Marseille, France.

Discussion
Epidemiologic studies revealed that TMDs are more
common in younger women (13, 1316). In
contrast, Velly et al. (17) in a casecontrol study in
which the most of the patients were young women
did not show gender and age as risk factors for disc
displacement. The aim of the present study was to
Table 1. The prevalence of temporomandibular joint (TMJ)
clicking in relation to progesterone serum levels
Serum progesterone levels

Cases (%)

Controls (%)

Increased
Normal
Decreased
Total

0
31 (66)
16 (34)
47 (100)

10
64
21
95

(10
5)
(67
4)
(22
1)
(100)

Table 2. The prevalence of temporomandibular joint (TMJ)

clicking in relation to oestradiol serum levels
Serum oestradiol levels

Cases (%)

Controls (%)

Increased
Normal
Decreased
Total

5
32
10
47

14
58
23
95

(10
6)
(68
1)
(21
3)
(100)

(14
7)
(61
1)
(24
2)
(100)

SPSS Inc., Chicago, IL, USA.

2013 John Wiley & Sons Ltd

RELATIONSHIP BETWEEN SERUM SEXUAL HORMONE LEVELS

evaluate the sexual hormonal status in a group of
women with TMJ clicking in the luteal phase of menstrual cycle, to identify a relationship between serum
levels of sexual steroids and the clinical condition.
Temporomandibular joint clicking seems to be
related to ligament problems and condyle-disc assembly alterations during jaw movement (18, 19).
Increased systemic joint laxity in pregnant women
has been linked to elevated levels of relaxin (20).
Endogenous oestrogen may affect the bone, cartilage
and related structures of TMJ (2123), which can
result in internal derangement of the TMJ. Moreover,
this hormone can stimulate specific inflammatory
response in the joint (16). 17b-oestradiol increases
histamine and serotonin for periodontal mast cells in
rats, while tamoxifen known as an oestrogen antagonist decreases such release (24). Flake et al. (25)
reported that oestrogen may exacerbate TMJ damage
due to lower TMJ extravasation (PE) in female rats.
Min et al. (26) stated that oestrogen deficiency is a
candidate cause of TMD, whereas Haskin et al. (27)
proposed that there may be an increased relationship
between circulating oestrogen levels and joint pain.
Yu et al. (28) suggested that exogenous oestrogen or
serum oestrogen is not enough to explain the female
predilection for TMD. They hypothesised that oestrogen synthesised locally in condylar cartilage have a
profound effect on the development of TMD.
In vitro studies on human osteoblasts in culture
showed that osteoblast differentiation was dose
dependent for progesterone. Also, progesterone has
complementary bone actions with oestrogen and antiresorptive therapies (29). Magnetic resonance imaging
assessment of 42 women revealed a significant less
contrast enhancement of the posterior disc attachment in the follicular phase of menstrual cycle than
luteal phase (30). In humans, increased TMJ pain is
associated with low-progesterone and concomitant
low-oestrogen state that occurs in the late luteal and
early follicular phase (31, 32). Puri et al. (7) concluded that progesterone could impact oestrogen
receptor expression and interact with 17b-oestradiol
to alter its effects. A persistent high plasma level of
progesterone, in the absence of oestrogen, produces a
consistent antinociceptive effect in a model of persistent inflammatory hyperalgesia. The gonadal steroid
progesterone attenuates the development of persistent
pain and hyperalgesia in response to tissue inflammation (33).
2013 John Wiley & Sons Ltd

Our findings suggest that women in the luteal

phase of menstrual cycle with internal derangement
of TMJ had lower levels of progesterone than healthy
subjects. In contrast to the results of Landi et al. (34),
we found no significant difference for the 17b-oestradiol levels in women with TMJ clicking and controls.
This discrepancy could be due to the different methodology or possibly due to the larger sample size of
our study.
This study has a number of limitations. First, sexual
hormones fluctuate throughout the menstrual cycle
in women. Oestrogen and progesterone levels are
both relatively low at the beginning of the cycle. During the follicular phase, oestrogen levels gradually
increase, peaking prior to ovulation. There is a precipitous drop in oestrogen in the day following ovulation
and then moderately increases during the early to
mid-luteal phase. Oestrogen then drops again during
the late luteal phase. Progesterone levels rapidly
increase after ovulation, peaking during the middle of
the luteal phase (35). We evaluated oestrogen and
progesterone levels in women between the days 22
and 25 of menstrual cycle. As single blood taking was
performed, we could not differentiate between ovulatory and anovulatory cycles. Regular cycles with normal oestradiol levels may vary in their progesterone
characteristics. Such cycles may be normally ovulatory, anovulatory or have short luteal phase lengths
that result in decreased total progesterone production
(29). Further studies are needed in which the timing
of the sample collection to the cycle can be better
standardised.
Another limitation of the present study is the multifactorial aetiology of TMDs. Although the results of
this cross-sectional study showed a relationship
between the lower serum progesterone level and TMJ
clicking, there are a number of variables affecting
TMD signs and symptoms, which have not been documented yet.

Acknowledgment
The research results given in this article were
obtained from doctoral thesis by a grant (No. 87910)
supported from the Vice Chancellor of Mashhad University of Medical Sciences and Academic Centre for
Education, Culture and Research (ACECR), Mashhad
Branch, Iran.

A . S . M A D A N I et al.

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Correspondence: Amirtaher Mirmortazavi, Department of Prosthodontics, Mashhad Dental School, Vakilabad BLV, Mashhad 123456,
Iran. E-mail: mirmortazaviat@gmail.com