J Periodont Res 2014; 49: 770–776 © 2014 John Wiley & Sons A/S.

All rights reserved Published by John Wiley & Sons Ltd

JOURNAL OF PERIODONTAL RESEARCH

doi:10.1111/jre.12161

M. Khosravisamani1, G. Maliji2,
Effect of the menstrual cycle S. Seyfi3, A. Azadmehr4, B. Abd
Nikfarjam4, S. Madadi3, S. Jafari5

on inflammatory cytokines in
1
Department of Periodontology and
Implantology, Dental Materials Research
Center, Dental Faculty, Babol University of

the periodontium
Medical Sciences and Health Services, Babol,
Iran, 2Department of Microbiology and
Immunology, Cellular and Molecular Biology
Research Center, School of Medicine, Babol
University of Medical Sciences and Health
Services, Babol, Iran, 3Department of Oral and
Khosravisamani M, Maliji G, Seyfi S, Azadmehr A, Abd Nikfarjam B, Madadi S, Maxillofacial Pathology, Dental Faculty, Babol
Jafari S. Effect of the menstrual cycle on inflammatory cytokines in the University of Medical Sciences and Health
periodontium. J Periodont Res 2014; 49: 770–776. © 2014 John Wiley & Sons Services, Babol, Iran, 4Department of
A/S. Published by John Wiley & Sons Ltd Immunology, Qazvin University of Medical
Sciences, Qazvin, Iran and 5Student Research
Background and Objective: The effects of different levels of steroid hormones, as Committee, Dental Faculty, Babol University of
Medical Sciences and Health Services, Babol,
experienced during puberty, pregnancy and menopause, on the periodontium
Iran
have been demonstrated, but changes in sex hormone levels during the men-
strual cycle, and the influence of these changes on the periodontium, remain
unresolved. The aim of this study was to investigate the effect of the menstrual
cycle on the levels of interleukin-1beta (IL-1b) and tumor necrosis factor-alpha
(TNF-a) in gingival crevicular fluid and on periodontal clinical parameters,
including the gingival bleeding index (GBI) and the modified gingival index
(MGI), in periodontally healthy women.
Material and Methods: Twenty-seven periodontally healthy women with a regu-
lar menstrual cycle were included in the study. Clinical parameters, including
the GBI, the MGI and the simplified oral health index, were recorded during
menstruation, ovulation and premenstruation phases (e.g. on days 1–2, 12–14
and 22–24, respectively) of the menstrual cycle. Gingival crevicular fluid and
unstimulated saliva were collected, at each study phase, for assessment of IL-1b,
TNF-a, estrogen and progesterone. Ghorban Maliji, PhD, Department of
Microbiology and Immunology, Cellular and
Results: Both the GBI and the MGI increased significantly during the menstrual Molecular Biology Research Center, School of
Medicine, Babol University of Medical Sciences
cycle, and were significantly higher during ovulation than during menstruation and Health Services, Babol, Iran
or premenstruation (p < 0.001). No significant change in the simplified oral Tel: +98 111 2769685
health index was observed during the menstrual cycle ( p = 0.18). The levels of Fax: +98 111 2199936
e-mail: ghmaliji@yahoo.com.
IL-1b and TNF-a increased during the different phases of the menstrual cycle, aazadmehr@qums.ac.ir
but only the change in the TNF-a concentration was significant ( p < 0.05).
Key words: gingival crevicular fluid; interleukin-
1beta; menstrual cycle; periodontium; tumor
Conclusion: This study indicated that changes occurring during the menstrual
necrosis factor-alpha
cycle influence the periodontium and induce inflammatory conditions.
Accepted for publication November 22, 2013

The interaction and balance among
calculus, dental-plaque microorgan-
isms in the gingival crevicular fluid,
lifestyle, systemic diseases, the endo-
crine hormone system and the
immune system affect the creation
and maintenance of healthy periodon-
tal tissues (1–4).
The pituitary is regulated by gonad-
otrophin-releasing hormone produced
by the hypothalamus. When stimu-
lated with gonadotrophin-releasing
hormone, the anterior pituitary
secretes luteinizing hormone and
follicle-stimulating hormone into the
bloodstream, which leads to the secre-
tion of estrogen and progesterone by
the ovaries (5). It is known that
changes in the concentrations of sex
hormones during puberty are respon-
sible for development of the menstrual
cycle (6,7).
In addition, the presence of estro-
gen and progesterone receptors on the
surface of gingival cells, osteoblasts,
periodontal ligament fibroblasts and
sex hormones, indicates that the sal-
iva, oral mucosa and periodontium
are influenced by changes in the con-
centrations of sex hormones (6, 8–12).

Progesterone dilates small blood
vessels and hence increases vascular
permeability. The increase of vascular
permeability affects polymorphonu-
clear cell activity and changes the
serum levels of inflammatory cyto-
kines. Estrogen, on the other hand,
suppresses the production of leuko-
cytes from bone marrow and increases
polymorphonuclear cell phagocytosis
(13).
The normal duration of the men-
strual cycle is 28  3 d; half of which
is related to the follicular (or prolifer-
ation) phase and the other half to the
luteal phase. During these two phases,
gonadal hormone levels fluctuate and
hence sex-hormone changes can dras-
tically alter the severity of inflamma-
tion and the host responses in target
tissues (14).
The highest incidence of gingivitis
has been reported during puberty.
The severity of this inflammation is
higher than that observed in adults
with the same amount of plaque. This
is probably caused by changes in the
diversity of bacterial species in dental
plaque, in the host response and in
hormone concentrations (13,15).
It has been recognized that Capno-
cytophaga species are increased during
puberty in dental plaque. There is a
positive association between the
serum levels of estradiol and proges-
terone and the numbers of Prevotella
intermedia and Prevotella nigrescens
(1,13).
Pain and gingival bleeding stimu-
lates an increase of the gingival cre-
vicular fluid volume. Moreover,
increased tooth mobility is a clinical
symptom of gestational effects on the
periodontium (15–19).
Studies analyzing the effect of the
menstrual cycle on the periodontium
have reported different results. Some
studies showed an increase of bleeding
on probing (BOP) and of the levels of
interleukin-1beta (IL-1b) and inflam-
matory cytokines during the men-
strual cycle (20,21); however, Becerik
et al. (22) believes that sex-hormone
fluctuations during the menstrual
cycle have no effect on cytokine con-
centrations in the gingival crevicular
fluid. Machtei et al. (23,24) found
that the gingival index was higher in
the ovulation phase. In addition,
pregnancy, puberty and menopause
induce changes of the cytokine levels
in gingival crevicular fluid but their
associations with gingival health or
gingivitis have not been established.
The present study was conducted to
investigate the effects of the menstrual
cycle on the levels of IL-1b and tumor
necrosis factor-alpha (TNF-a) in the
gingival crevicular fluid and on peri-
odontal health using the gingival blee-
ding index (GBI) and the modified
gingival index (MGI).
Material and methods
Study design and eligibility criteria
This study was performed on 27 female
students of Babol University of Medi-
cal Sciences, Faculty of Dentistry.
The study inclusion criteria were:
age 18–25 years (mean  SD =
23.72  0.88 years); a regular men-
strual cycle (28–30 d; mean  SD:
29.24  0.98 d) in their last three
periods and a duration of menstrua-
tion of 5–7 d (mean  SD: 5.62 
0.94); no use of contraceptive drugs
and/or medications that affect sex
hormones; no use of antibiotics and
nonsteroidal anti-inflammatory drugs
3 mo before the start of the study;
not pregnant or breastfeeding; no his-
tory of systemic disease, periodontitis,
gingivitis, canker sores or inflamma-
tory mouth lesions; no severe dental
crowding; have not used cigarettes
and/or alcohol; the GBI of Ainamo &
Bay showing less than 10% of sites
with BOP within 10 s after probing;
no scaling and root planing and/or
periodontal tissue surgery at least
6 mo before the start of the study;
and no fixed dental prostheses and/or
orthodontic appliances.
Study protocol
Ethical approval was acquired from
the Ethics Committee of the Babol
University of Medical Sciences. Writ-
ten informed consent was collected
from each subject before participa-
tion. The subjects evaluated the study
criteria in terms of the duration of a
regular menstrual cycle (28  3 d)
Menstrual cycle and periodontium 771
and were followed up for three
menstrual cycles. Participants were
excluded from the study if their men-
strual cycles were longer or shorter
than 28  3 d during the 3-mo control
time period.
The participants’ periodontal health
status was evaluated using the GBI at
22–24 d of each cycle. If BOP was
found in less than 10% of sites probed
(BOP < 10%), the participant was con-
sidered as periodontally healthy and
eligible for entry to the study. To elimi-
nate the confounding factors, dental
plaque accumulation, on gingival
health, the simplified oral health index
(OHI-S) (the facial surface of teeth 3,
8, 14 and 24 and the lingual surface of
teeth 19 and 30) was used (25). Sub-
jects with an OHI-S score of ≥ 1.2 were
excluded from the study. Then, the
participants’ gingival health status was
evaluated using the OHI-S (25), the
MGI (26) and the GBI (24) on days
1–2 of menstruation (MD), days 12–14
of ovulation (OD) and days 22–24 of
premenstruation (PmD), of a men-
strual cycle.
Gingival crevicular fluid and saliva
collection
Salivary samples were collected before
gingival crevicular fluid samples. Sub-
jects were requested not to drink
(except water), eat, brush, or use dental
floss or chew gum, 90 min before sam-
ple collection. Unstimulated saliva
samples of 2 mL were collected using
the spitting method. Whole saliva sam-
ples were collected by expectoration
into polypropylene tubes. The saliva
samples were centrifuged (Spectrafuge
24D; Labnet International, Inc.,
Edison, NJ, USA) at 1077 g for 5 min;
then, the supernatants were collected
and immediately frozen at 80°C until
the sample collection was complete.
Then, the samples were analyzed.
Gingival crevicular fluid samples
were collected in the morning, 2–3 h
after breakfast. The samples were
obtained from the mesiobuccal gingi-
val sulcus of the first and second max-
illary molars (four maxillary molars)
using ISO 30 paper points with a
probing depth of 5 to ≤ 7 mm. The
sites to be sampled were separated
772 Khosravisamani et al.
with cotton rolls and gently air-dried.
Paper points were gently placed for
30 s into the pocket until slight resis-
tance was felt.
Paper points contaminated with
blood and saliva were not used for
cytokine measurements (27,28). The
paper points were then stored at 80°C
until required for use in ELISAs.
Analysis of gingival crevicular fluid
cytokines and salivary hormones
The samples of gingival crevicular
fluid were eluted from the paper
points at 4°C overnight into 200 lL
of phosphate-buffered saline contain-
ing 0.1% bovine serum albumin and
0.05% thimerosal. After centrifuga-
tion at 400 g for 4 min, the paper
points were removed.
Gingival crevicular fluid samples
were assessed using ELISA kits. Pro-
gesterone and estradiol free in saliva
(Demeditec, Kiel Wellsee, Schleswig-
holstein, Germany) were used to mea-
sure the salivary levels of estradiol
and progesterone. The lowest detect-
able level of estradiol that can be dis-
tinguished from the zero standard is
0.4 pg/mL. The lowest analytical
detectable level of progesterone that
can be distinguished from the zero
calibrator is 5.0 pg/mL.
Gingival crevicular fluid cytokines
were evaluated using an IL-1b ELISA
kit (Invitrogen, Carlsbad, CA, USA)
and a TNF-a ELISA kit (Demeditec).
ELISAs were performed according to
the manufacturer’s instructions. The
lowest analytically detectable levels of
TNF-a and IL-1b that can be distin-
guished from the zero calibrator are
7.0 and 1.0 pg/mL, respectively.
Statistical analysis
The clinical data were analyzed using
SPSS 18 software (IBM, Armonk, NY,
USA) and were expressed as mean
 SD. The total sample size was 27
subjects. The Friedman test was used
for comparison of MGI, GBI, OHI-S,
TNF-a and IL-1b values in the three
phases of the menstrual cycle. In addi-
tion, the Wilcoxon signed-rank test was
used to compare the variables between
the different phases of the cycle.
Results 1.41  1.90 pg/mL, respectively. A
statistically significant difference was
Effect of the menstrual cycle on found for TNF-a among all three
clinical parameters, including GBI, phases of the menstrual cycle in
MGI and OHI-S (p < 0.001) (Table 1).
Comparisons were performed of GBI
and MGI values in the three phases of Salivary estradiol and progesterone
the menstrual cycle (OD, PmD and levels during the three phases of
MD). The mean GBI was 2.98  2.93 the menstrual cycle
and the mean MGI was 0.12  0.08.
A significant, positive relationship was
Both GBI and MGI increased signifi-
detected between the GBI and the sali-
cantly during the menstrual cycle
vary progesterone level at the OD
and were significantly higher during
study time point ( p = 0.034). More-
the OD than during the other phases
over, a weak, positive correlation was
( p < 0.001). The mean OHI-S was
observed between MGI and salivary
0.11  0.12, with a range of 0–0.5. The
progesterone concentrations at the
OHI-S did not change significantly
OD, although the difference was not
during the menstrual cycle ( p = 0.18).
significant ( p = 0.062) (Table 2).
OHI-S was not statistically different
Changes in salivary progesterone levels
between the three phases of the cycle
among the different phases of the men-
( p > 0.05) (Table 1).
strual cycle were found to be statisti-
cally significant ( p = 0.002). The
highest and the lowest concentrations
TNF-a and IL-1b concentrations in
of salivary progesterone were observed
gingival crevicular fluid during the
at the PmD and the MD, respectively.
three phases of the menstrual cycle
There was a statistically significant dif-
The mean concentrations of IL-1b ference between PmD and OD
and TNF-a in the gingival crevicular ( p = 0.029) and between PmD and
fluid were 123.67  70.19 pg/mL and MD ( p = 0.001). The salivary proges-
Table 1. Levels of the periodontal health indicators, tumor necrosis factor-alpha (TNF-a)
and interleukin-1beta (IL-1b), in gingival crevicular fluid during the menstrual cycle in
periodontally healthy women
Variable
Study TNF-a
phase OHI-Sa MGI GBIb (pg/mL)c IL-1b(pg/mL)d
OD 0.099  0.016 0.206  0.015e 5.528  0.588 1.062  0.229 123.317  12.318
PmD 0.106  0.023 0.085  0.008 1.215  0.319 2.722  0.468 138.375  11.863
MD 0.129  0.027 0.095  0.010 2.206  0.315 0.544  0.212 109.341  14.639
p* 0.955 <0.001 <0.001 <0.001 0.453
Values are given as mean  SD.
GBI, gingival bleeding index; MD, menstruation day; MGI, modified gingival index; OD,
ovulation day; OHI-S, oral hygiene index-simplified; PmD, premenstruation day.Compari-
son between the different phases of the menstrual cycle was performed using the Wilcoxon
test.
a
No significant difference between the different phases of the menstrual cycle ( p > 0.05).
b
Significant difference in GBI between OD and MD, OD and PmD, and MD and PmD
(p = 0.001, p = 0.001 and p = 0.005, respectively).
c
Significant difference in TNF-a levels between PmD and OD, and PmD and MD
(p = 0.005 and p = 0.001 respectively) and no statistically significant difference between
OD and MD (p = 0.066).
d
No statistically significant difference in IL-1b levels between PmD and OD, PmD and
MD, and OD and MD (p = 0.275, p = 0.119 and p = 0.404, respectively).
e
Significant difference in MGI between OD and MD, and OD and PmD (p = 0.001 for
both) and no statistically significant difference between MD and PmD (p = 0.097).
*Friedman test.
 Menstrual cycle and periodontium 773

Table 2. The relationship and correlation between clinical parameters and gingival crevicu- PmD and lowest at the MD. The
lar fluid inflammatory cytokines and salivary estradiol and progesterone levels during the increasing trend in TNF-a level in
three phases of the menstrual cycle gingival crevicular fluid was also sig-
Estradiol (pg/mL) Progesterone (pg/mL) nificant during the menstrual cycle
Study phase/clinicalparameter (p = 0.001). There was no significant
and cytokines r p r p difference in the TNF-a level between
the MD and the OD (p > 0.05). How-
OD
GBI 0.175 0.364 0.396 0.034* ever, the difference in the TNF-a level
MGI 0.025 0.900 0.351 0.062 between the PmD and the OD was
IL-1b (pg/mL) 0.066 0.734 0.272 0.154 significant (p = 0.005) (Fig. 3).
TNF-a (pg/mL) 0.072 0.710 0.378 0.043* The mean rate of change in the gin-
PmD gival crevicular fluid IL-1b level was
GBI 0.051 0.801 0.180 0.370
not statistically significant among the
MGI 0.130 0.517 0.030 0.882
IL-1b (pg/mL) 0.124 0.548 0.099 0.622
different phases of the menstrual cycle
TNF-a (pg/mL) 0.249 0.230 0.030 0.886 (p = 0.207), with the highest and low-
MD est levels being observed in the PmD
GBI 0.279 0.125 0.170 0.386 and the MD, respectively (Fig. 4).
MGI 0.153 0.438 0.444 0.018*
IL-1b (pg/mL) 0.104 0.598 0.162 0.411
TNF-a (pg/mL) 0.169 0.391 0.222 0.257 Discussion
GBI, gingival bleeding index; IL-1b, interleukin-1beta; MD, menstruation day; MGI, mod- In the present study, the effect of the
ified gingival index; OD, ovulation day; p, probability value; PmD, premenstruation day; menstrual cycle on gingival crevicular
r, correlation coefficient; TNF-a, tumor necrosis factor-alpha. fluid IL-1b and TNF-a levels and on
*Statistically significant correlation at p < 0.05. the periodontal clinical parameters
MGI and GBI was investigated dur-
terone levels at the OD were signifi- est levels of this hormone were ing the three phases of this cycle in
cantly higher than those observed at observed at the OD and the MD, periodontally healthy women.
the MD (p = 0.013) (Fig. 1). respectively (p = 0.043). Salivary Unstimulated saliva was used to
Changes in salivary estradiol levels estradiol levels were not significantly measure the levels of progesterone
showed a trend to increase at the dif- different between the PmD and the and estradiol throughout the men-
ferent stages of the study and such an OD (p = 0.202) (Fig. 2). strual cycle in an attempt to identify
increase was statistically significant The mean TNF-a level in gingival the different menstrual cycle stages.
(p = 0.048). The highest and the low- crevicular fluid was highest at the The results of the present investiga-
tion showed significant changes of the
MGI and the GBI in the menstrual
cycle, with both being highest at the
OD. The highest GBI was observed
after OD at the MD; the difference in
GBI between MD and PmD phases
was statistically significant, which is
in agreement with the results of Baser
et al. This research also showed an
increased MGI in different phases,
but no significant differences were
observed (20).
Shourie et al. (31) showed that in
women with gingivitis, the MGI and
the GBI changed significantly during
the menstrual cycle. The highest
change was reported in the ovulation
phase; however, no such changes were
observed in women with healthy gums
Fig. 1. Salivary progesterone concentrations (pg/mL) during the following three phases of (31). The increase in MGI observed at
the menstrual cycle: menstruation day (MD), ovulation day (OD) and premenstruation the OD and the PmD has been attrib-
day (PmD). Values are given as mean (95% CI). Significant differences were observed uted to fluctuations in sex hormones,
between the PmD and both the OD and the MD ( p < 0.05 for both). Significant differ- as shown by Machtei et al. (23).
ences were also observed between the OD and the MD ( p < 0.05). The data in the Kawamoto et al. (32, 33) demon-
graphs are presented in the sequential order: MD, OD and PmD. strated a significant increase in BOP
774 Khosravisamani et al.

between MD and OD phases. In addi-

tion, in this research, the salivary
estrogen levels were higher in OD and
PmD phases, which was inconsistent
with the studies in which unstimulated
saliva and serum were used to mea-
sure sex hormone levels (21,34–37).
Our results are consistent with the
investigation of Becerik et al. (22) and
the physiology of the menstrual cycle.
Becerik et al. reported a slow increase
in the serum levels of estradiol during
menstruation, a peak during ovula-
tion and then a sudden decrease. A
second peak of the serum level of
estradiol was seen on days 22–24 (22).
Becerik et al. (22) showed that in a
gingivitis group, BOP was signifi-
Fig. 2. Salivary estradiol levels (pg/mL) during the following three phases of the menstrual
cantly higher during the MD, OD
cycle: menstruation day (MD), ovulation day (OD) and premenstruation day (PmD). Val-
ues are given as mean (95% CI). Significant differences were observed between the differ-
phases of the menstrual cycle than on
ent phases of the menstrual cycle (p < 0.05). A significant difference was observed between the PmD; however, there were no sig-
OD and MD (p < 0.05); no significant difference were observed between the PmD and nificant changes in BOP in the healthy
either the MD or the OD (p > 0.05 for both). The data in the graphs are presented in the group (22).
sequential order: MD, OD and PmD. A previous study showed that pro-
gesterone increases the permeability
of blood vessels (38). On this basis,
GBI and MGI values should be high-
est when progesterone peaks (i.e. at
the PmD phase). However, in our
study, a negative relationship was
observed between GBI and MGI and
the progesterone level during the MD,
and the relationship between MGI
and salivary progesterone levels dur-
ing the MD was significant. More-
over, a weak, positive correlation was
found between the MGI and the sali-
vary progesterone level at the OD
phase, although the difference was not
significant. Our data showed a signif-
icant, positive relationship between
the GBI and the salivary progester-
one level in the OD phase. Baser
et al. (20) also reported similar dif-
ferences. These differences have been
Fig. 3. Tumor necrosis factor-alpha concentrations (pg/mL) in gingival crevicular fluid
during the following three phases of the menstrual cycle: menstruation day (MD), ovula-
attributed to the sensitivity of
tion day (OD) and premenstruation day (PmD). Values are given as mean (95% CI). Sig- parameters used for assessing the
nificant differences were observed between the different phases of the menstrual cycle health of the periodontium (20). It
( p < 0.01); significant differences were observed between the PmD and both the OD and should be noted that Baser et al.
the MD ( p < 0.01 for both); no statistically significant difference was observed between used the MGI for evaluating gingivi-
the OD and the MD ( p > 0.05). The data in the graphs are presented in the sequential tis (20), whereas in the present study,
order: MD, OD and PmD. the MGI was applied to assess
inflammation. Furthermore, the MGI
in patients with periodontitis, from phase to the PmD phase; however, has a higher sensitivity compared
the follicular phase to ovulation. our results showed the highest level of with the GBI (27).
Becerik et al. (22) indicated that salivary estradiol in the OD phase; Koreeda et al. (30) showed that gin-
salivary progesterone and estradiol the lowest levels in the MD and PmD givitis and exacerbated inflammation
levels are increased from the MD phases; and a significant difference are related to a higher GBI in the OD

Fig. 4. Interleukin-1 beta concentrations (pg/mL) in gingival crevicular fluid during the
following three phases of the menstrual cycle: menstruation day (MD), ovulation day
(OD) and premenstruation day (PmD). Values are given as mean (95% CI). There was no
significant difference between the different phases of the menstrual cycle (p > 0.05).The
data in the graphs are presented in the sequential order: MD, OD and PmD.
phase compared with the MD phase
(30).
In our investigation, a significant
increase was observed in the gingival
crevicular fluid TNF-a level, which
was remarkably higher in the PmD
than in the other phases. This finding
is inconsistent with the results of Baser
et al. (20), in which there were no
remarkable differences in the gingival
crevicular fluid TNF-a level among
different phases, although the mean
cytokine level in the PmD phase was
higher than that in the other phases
(20). Likewise, in the study of Markou
et al. (29), there was no significant dif-
ference in increased TNF-a level in
ovulation and progesterone peak.
In the study of Markou et al., the
highest IL-1b level was observed in
the PmD phase, but the difference
was not significant. The mean gingival
crevicular fluid IL-1b level in the pres-
ent study was increased during the
different phases of the cycle; however,
the changes were not significant (29).
Similarly, Baser et al. reported an
increase in the IL-1b level in the PmD
phase, the level being statistically sig-
nificantly higher in this phase than in
the OD and MD phases (20). In spite
of the increased IL-1b level in the
ovulation and progesterone peak
reported in the study of Markou et al.
(29), the difference was not significant.
In the current research, the levels of
TNF-a and IL-1b in the gingival cre-
vicular fluid increased from the MD
phase to the PmD phase of the men-
strual cycle. Changes in progesterone
levels may explain the increased pro-
duction of inflammatory cytokines. In
fact, the different mechanisms of
action of progesterone control the
stimulation, production and roles of
TNF-a and IL-1b in periodontal
tissue inflammation.
As a consequence of the increased
concentrations of sex hormones during
the ovulation phase, inflammatory
mediators are indirectly elevated in
response to bacterial lipopolysaccha-
ride. Increases in gingival cytokines are
probably also influenced by the above-
mentioned factors. The differences in
the results obtained in different studies,
conducted in different populations,
may be caused by the effects of genetic
diversity, environment, race and
lifestyle, as these factors influence sex
hormone fluctuations during the men-
strual cycle, the periodontal status and
the rate of secretion of inflammatory
cytokines in gingival crevicular fluid
(2,4,39–43).
Conclusions
Based on the findings of this study,
TNF-a and IL-1b levels in gingival
Menstrual cycle and periodontium 775
crevicular fluid increased during the
menstrual cycle, although the increase
was significant only for TNF-a. Also,
clinically, the periodontium is
inflamed during the menstrual cycle,
an observation based on the MGI
and GBI results. However, more
investigations are still needed to
establish the cause of inflammation in
the periodontium; for example, the
activity of mucosal immune cells and
the effects of steroids on the functions
of these cells should be investigated
during the menstrual cycle. The
results of the present study indicate
that the menstrual cycle influences the
periodontium and induces inflamma-
tory conditions during the menstrual
cycle.
Acknowledgements
The authors would like to thank the
Deputy of Research and Technology
of Babol University of Medical Sci-
ences for financially supporting the
project, and to Dr Evangeline For-
onda for the English editing of this
manuscript.
Conflict of interest
The authors declare no conflict of
interest.
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