International Journal of Medical Sciences And Clinical Research
74
https://theusajournals.com/index.php/ijmscr
VOLUME
Vol.05 Issue05 2025
PAGE NO.
74-78
10.37547/ijmscr/Volume05Issue05-16
Comprehensive Therapy for Burning Mouth Syndrome
in Menopausal Women
Masharipov Sirojbek Madiyorovich
Urgench Branch of the Tashkent Medical Academy, Uzbekistan
Kuryazov Akbar Kuranbayevich
Urgench Branch of the Tashkent Medical Academy, Uzbekistan
Khabibova Nazira Nasulloyevna
Bukhara State Medical Institute, Uzbekistan
Received:
31 March 2025;
Accepted:
29 April 2025;
Published:
31 May 2025
Abstract:
Burning Mouth Syndrome (BMS) in menopausal women is a neuropathic pain disorder associated with
persistent oral burning sensations, xerostomia, and dysgeusia. The condition is linked to estrogen deficiency,
central sensitization, and altered pain modulation. This study evaluates the effectiveness of a structured
multimodal therapeutic approach. A cohort of 67 menopausal women (45
–
67 years) underwent clinical,
psychometric, and laboratory assessments, including the Visual Analog Scale (VAS) for pain, the Challacombe Scale
of Clinical Oral Dryness (CSCOD), and the Spielberger Anxiety Inventory, Montgomery
–
Åsberg Depression Rating
Scale (MADRS), and Hospital Anxiety and Depression Scale (HADS). Salivary and hormonal profiles were analyzed
to determine inflammatory mediators and estrogen levels. The therapeutic protocol included neuromodulators,
salivary stimulants, cognitive-behavioral therapy, and targeted hormonal interventions. The results demonstrated
a significant reduction in pain intensity, improved oral function, and stabilization of psychological status. The
findings support a multidisciplinary approach as a necessary strategy for effective management of BMS in
menopausal patients.
Keywords:
Burning Mouth Syndrome, Menopause, Neuropathic Pain, Estrogen Deficiency, Central Sensitization,
Xerostomia, Dysgeusia, Anxiety, Depression, Pain Modulation, Salivary Dysfunction, Multimodal Therapy,
Psychometric Assessment, Neuromodulators, Cognitive-Behavioral Therapy.
Introduction:
Burning Mouth Syndrome (BMS) is a
chronic neuropathic disorder that manifests as
persistent burning pain in the oral cavity, frequently
accompanied by xerostomia and dysgeusia. The
condition predominantly affects women in the
menopausal period, which suggests a correlation
between
hormonal
fluctuations
and
the
pathophysiological mechanisms underlying BMS. The
role of estrogen deficiency in modulating trigeminal
sensory processing, neuroinflammatory responses, and
salivary gland function has been established in clinical
studies, yet the exact mechanisms remain insufficiently
defined.
The
heterogeneity
of
clinical
manifestations
complicates both diagnosis and treatment selection.
Central sensitization, dysfunction of descending pain
inhibitory pathways, and neurotransmitter imbalance
contribute
to
altered
nociceptive
processing.
Psychological factors, including increased levels of
anxiety and depression, are consistently observed in
patients with BMS, indicating a bidirectional
relationship between neuropathic pain and affective
disturbances. Given the absence of structural lesions in
the oral mucosa, the syndrome is frequently diagnosed
by exclusion, which delays initiation of targeted
therapy.
International Journal of Medical Sciences And Clinical Research
75
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
Existing treatment approaches are characterized by
limited efficacy due to their focus on isolated
symptoms rather than the multifactorial nature of the
disorder. Neuromodulators, analgesics, and topical
agents demonstrate inconsistent results, while salivary
stimulants offer only partial relief. Hormone
replacement therapy remains controversial, with
studies yielding conflicting data on its impact on oral
pain modulation. Cognitive-behavioral therapy and
stress management strategies have shown potential in
addressing comorbid psychological disturbances, yet
they are not widely implemented in routine practice.
This study evaluates the effectiveness of a structured
multimodal therapeutic approach that incorporates
pharmacological,
psychological,
and
dental
interventions for menopausal women with BMS.
Clinical, psychometric, and biochemical assessments
are utilized to determine the impact of the proposed
treatment strategy on pain intensity, salivary function,
and psychological status. The findings contribute to the
optimization of individualized management protocols
for this patient population.
Burning Mouth Syndrome (BMS) is a chronic orofacial
pain condition characterized by a persistent burning
sensation in the oral cavity without identifiable clinical
or laboratory abnormalities. The etiology of BMS
remains unclear, but it predominantly affects
postmenopausal women, suggesting a potential link to
hormonal changes during menopause. This literature
review examines current therapeutic approaches for
managing BMS in menopausal women, focusing on
both pharmacological and non-pharmacological
strategies.[1,5]
Hormonal fluctuations during menopause have been
implicated in the onset of BMS. Studies indicate that
decreased estrogen levels may alter taste perception
and salivary function, contributing to oral discomfort.
Hormone Replacement Therapy (HRT) has been
explored as a treatment option; however, evidence
regarding its efficacy remains inconclusive. Some
reports suggest that HRT may alleviate BMS symptoms
in postmenopausal women, while others find no
significant benefit. Therefore, further research is
needed to establish the role of HRT in BMS
management. [2]
Pharmacological interventions targeting neuropathic
pain have shown promise in BMS treatment.
Clonazepam, a benzodiazepine, has demonstrated
effectiveness
in
reducing
symptoms
when
administered orally or as a lozenge. Similarly, certain
antidepressants, such as tricyclics and selective
serotonin-norepinephrine reuptake inhibitors, have
been utilized to manage BMS-related pain, with varying
degrees of success. Additionally, alpha-lipoic acid, an
antioxidant, has been investigated for its potential
neuroprotective effects, though its clinical efficacy
requires further validation.[3]
Non-pharmacological approaches, including cognitive-
behavioral therapy (CBT), have been employed to
address the psychological components associated with
BMS. CBT aims to modify negative thought patterns
and behaviors, potentially reducing pain perception
and
improving
coping
mechanisms.
Stress
management techniques, such as mindfulness and
relaxation exercises, may also be beneficial, given the
association between psychological stress and BMS
symptomatology.[1]
Comprehensive management of BMS in menopausal
women often necessitates a multidisciplinary
approach. Collaboration among healthcare providers,
including dentists, gynecologists, and mental health
professionals, is essential to address the multifaceted
nature of BMS. Tailoring treatment plans to individual
patient needs, considering both medical and
psychosocial factors, may enhance therapeutic
outcomes.[4]
METHODS
The study included 67 women aged 45 to 67 years
diagnosed with Burning Mouth Syndrome (BMS)
according to the criteria of the International
Classification of Headache Disorders (ICHD-3). The
selection was based on the presence of persistent
burning pain in the oral cavity lasting at least three
months, absence of mucosal lesions upon clinical
examination, and exclusion of secondary causes.
Neurological examination ruled out organic pathology
of the central and peripheral nervous systems. Patients
with cardiovascular diseases, diabetes mellitus,
autoimmune disorders, psychiatric illnesses, or a
history of hormone replacement therapy were not
included.
Pain intensity was quantified using the Visual Analog
Scale (VAS). Xerostomia severity was assessed with the
Challacombe Scale of Clinical Oral Dryness (CSCOD),
measuring mucosal hydration, salivary viscosity, and
lingual papillary atrophy. Psychometric evaluation
included the Spielberger State-Trait Anxiety Inventory,
the Montgomery
–
Åsberg Depression Rating Scale
(MADRS), and the Hospital Anxiety and Depression
Scale (HADS). The Psychological Stress Measure (PSM-
25) was applied to determine the level of stress-related
somatic and behavioral disturbances. The Oral Health
Impact Profile-14 (OHIP-14) was used to assess the
impact of BMS on oral health-related quality of life.
Salivary analysis was conducted to determine estradiol
and follicle-stimulating hormone (FSH) concentrations
International Journal of Medical Sciences And Clinical Research
76
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
by immunochemiluminescence (Immulite 2000). The
levels of interleukin-6 (IL-6) and tumor necrosis factor-
alpha (TNF-
α) were measure
d by enzyme-linked
immunosorbent assay (ELISA).
The therapeutic protocol combined pharmacological,
psychological,
and
local
interventions.
Neuromodulatory treatment included gabapentin and
serotonin-norepinephrine reuptake inhibitors (SNRIs)
with individually adjusted dosages. Patients with
xerostomia received pilocarpine. Artificial saliva
substitutes and capsaicin-based topical applications
were used for symptomatic relief. Cognitive-behavioral
therapy (CBT) targeted maladaptive pain perception
and emotional dysregulation. Hormonal therapy was
administered to patients with confirmed estrogen
deficiency.
RESULTS AND DISCUSSION
The study included 67 menopausal women aged 45 to
67 years (mean age 56.2 ± 6.4 years) diagnosed with
Burning Mouth Syndrome (BMS). The duration of
symptoms ranged from six months to five years, with
an average of 2.4 ± 1.1 years. A high prevalence of
comorbid psychological disorders was observed: 46
patients (68.7%) had clinically significant anxiety, while
39 (58.2%) exhibited mild to moderate depressive
symptoms. Pain intensity, as measured by the Visual
Analog Scale (VAS), averaged 62.7 ± 10.3 mm.
Assessment of xerostomia using the Challacombe Scale
of Clinical Oral Dryness (CSCOD) revealed varying
degrees of severity. Mild xerostomia (CSCOD score 1
–
3) was observed in 21 patients (31.3%), moderate
xerostomia (score 4
–
6) in 33 (49.3%), and severe
xerostomia (score 7
–
10) in 13 (19.4%). Unstimulated
salivary flow rate measurements demonstrated
significantly reduced secretion in patients with severe
xerostomia (0.18 ± 0.05 mL/min) compared to those
with mild symptoms (0.35 ± 0.07 mL/min; p < 0.01).
Patients were divided into two groups. The primary
group (n = 34) received a comprehensive treatment
approach, including cognitive behavioral therapy (CBT),
gabapentin (300
–
600 mg/day), capsaicin gel, and
artificial saliva substitutes. The control group (n = 33)
received only symptomatic therapy, consisting of
artificial saliva and standard analgesics.
After 12 weeks of therapy, pain intensity on the VAS
scale significantly decreased in the primary group from
63.1 ± 10.2 mm to 31.7 ± 9.5 mm (p < 0.001), while in
the control group, the reduction was less pronounced
(from 62.3 ± 10.7 mm to 47.8 ± 11.1 mm; p = 0.02). The
Spielberger Anxiety Scale scores improved significantly
in the primary group, with an average reduction of 8.3
± 2.1 points, compared to 3.4 ± 1.7 points in the control
group (p < 0.05).
At the 12-week follow-up, 85.3% of patients in the
primary group reported improved quality of life, as
measured by the Oral Health Impact Profile-14 (OHIP-
14), with a reduction in the total score from 17.6 ± 4.3
to 9.2 ± 3.1 (p < 0.001). In contrast, the control group
showed a modest improvement, with scores
decreasing from 17.1 ± 4.1 to 13.8 ± 3.7 (p = 0.07).
Salivary biochemical analysis showed an increase in
estradiol levels in the primary group following
treatment, from 4.2 ± 1.5 pg/mL to 6.8 ± 2.1 pg/mL (p
< 0.05). A reduction in inflammatory markers was also
observed, with interleukin-6 (IL-6) decreasing by 18.7%
and tumor necrosis factor-alpha (TNF-
α) by 22.1%. In
the control group, these changes were less pronounced
and did not reach statistical significance.
Microbiological examination revealed a decrease in
Porphyromonas gingivalis colonization in the primary
group, with bacterial counts reducing from 10⁵ CFU/mL
to 10⁴ CFU/mL (p = 0.01), indicating partial restoration
of the oral microbiome.
Table 1.
Clinical and Laboratory Parameter Changes in BMS Patients
Parameter
Pre-
treatment
(Primary
Group)
Post-
treatment
(Primary
Group)
Pre-
treatment
(Control
Group)
Post-
treatment
(Control
Group)
p-value
(Between
Groups)
VAS
Pain
Score (mm)
63.1 ±
10.2
31.7 ±
9.5
62.3 ±
10.7
47.8 ±
11.1
<0.001
CSCOD
Xerostomia Score
6.2 ±
1.8
3.1
±
1.2
6.1 ±
1.7
4.7
±
1.4
0.03
OHIP-14
Score
17.6 ±
4.3
9.2
±
3.1
17.1 ±
4.1
13.8 ±
3.7
<0.001
IL-6
(pg/mL)
8.3 ±
2.4
6.2
±
1.9
8.1 ±
2.3
7.5
±
2.1
0.04
TNF-α
(pg/mL)
12.1 ±
3.5
9.4
±
3.1
11.9 ±
3.2
10.8 ±
3.3
0.05
International Journal of Medical Sciences And Clinical Research
77
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
Estradiol in
Saliva (pg/mL)
4.2 ±
1.5
6.8
±
2.1
4.1 ±
1.4
5.2
±
1.7
0.02
P. gingivalis
(CFU/mL)
10
⁵
10
⁴
10
⁵
10
⁴
.9
0.01
DISCUSSION
The comprehensive therapeutic approach, which
included CBT, gabapentin, and capsaicin gel,
demonstrated significant efficacy in reducing pain
intensity, improving psychological well-being, and
normalizing key biochemical parameters. The
reduction in IL-6 and TNF-
α suggests an inflammatory
-
neuropathic component in the pathogenesis of BMS.
Differences in clinical outcomes between the two
groups emphasize the advantages of a multimodal
approach. The integration of CBT contributed to
anxiety reduction and improved pain perception,
underscoring the role of psychological interventions in
BMS management. The observed increase in salivary
estradiol levels and improvements in microbiological
markers further support the hypothesis that hormonal
and inflammatory factors are involved in disease
progression.
A limitation of this study is the relatively short follow-
up period, which does not allow for an assessment of
long-term treatment sustainability. Future research
should focus on evaluating the long-term effects of
combination therapy and investigating the role of
estrogen receptor expression in oral tissues as a
potential therapeutic target.
The findings of this study support the necessity of a
multidisciplinary approach to BMS treatment in
menopausal women, incorporating pharmacological,
psychological, and local interventions to achieve
optimal clinical outcomes.
CONCLUSION
The findings of this study confirm the effectiveness of a
comprehensive therapeutic approach in managing
Burning Mouth Syndrome (BMS) in menopausal
women.
The
integration
of
pharmacological,
psychological, and topical treatments led to significant
reductions in pain intensity, improved psychological
well-being, and normalization of inflammatory and
hormonal markers. The observed decrease in
interleukin-6 (IL-6) and tumor necrosis factor-alpha
(TNF-
α) supports the role of inflammatory and
neuropathic mechanisms in BMS pathogenesis, while
the increase in salivary estradiol levels highlights the
involvement of hormonal regulation.
The superiority of the multimodal approach over
symptomatic therapy alone underscores the necessity
of targeting multiple pathophysiological pathways in
BMS management. Cognitive behavioral therapy (CBT)
proved to be a valuable component, significantly
reducing anxiety and improving overall treatment
outcomes. Furthermore, microbiological analysis
revealed a reduction in Porphyromonas gingivalis,
suggesting a potential link between oral microbiome
dysbiosis and BMS symptoms.
Despite these promising results, limitations include the
relatively short follow-up period and the need for
further research to evaluate the long-term efficacy of
combination therapy. Future studies should explore
the role of estrogen receptor expression in oral tissues
and the impact of prolonged intervention on symptom
recurrence. A personalized, multidisciplinary treatment
strategy appears essential for optimizing therapeutic
outcomes in menopausal women with BMS.
REFERENCES
Grushka, M., Epstein, J.B., Gorsky, M. Burning mouth
syndrome. Am Fam Physician. 2002;65(4):615-620.
Kohorst, J.J., Bruce, A.J., Torgerson, R.R., Schenck, L.A.,
Davis, M.D. A population-based study of the incidence
of burning mouth syndrome. Mayo Clin Proc.
2014;89(11):1545-1552.
Sun, A., Wu, K.M., Wang, Y.P., Lin, H.P., Chen, H.M.,
Chiang, C.P. Burning mouth syndrome: a review and
update. J Oral Pathol Med. 2013;42(9):649-655.
Jääskeläinen, S.K. Pathophysiology of primary burning
mouth syndrome. Clin Neurophysiol. 2012;123(1):71-
77.
Imamura, Y., Shinozaki, T., Okada-Ogawa, A., Noma, N.,
Shinoda, M., Iwata, K. An updated review on
pathophysiology and management of burning mouth
syndrome with endocrinological, psychological, and
neuropathic
perspectives.
J
Oral
Rehabil.
2019;46(6):574-587.
López-Jornet, P., Camacho-Alonso, F., Andujar-Mateos,
P., Sánchez-Siles, M., Gómez-Garcia, F. Burning mouth
syndrome: an update. Med Oral Patol Oral Cir Bucal.
2010;15(4):e562-e568.
Schiavone, V., Adamo, D., Ventrella, G., Morlino, M., De
Notaris, E.B., Ravel, M.G., et al. Anxiety, depression,
and pain in burning mouth syndrome: first chicken or
egg? Headache. 2012;52(6):1019-1025.
Wardrop, R.W., Hailes, J., Burger, H., Reade, P.C. Oral
discomfort at menopause. Oral Surg Oral Med Oral
Pathol. 1989;67(5):535-540.
International Journal of Medical Sciences And Clinical Research
78
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
Forabosco, A., Criscuolo, M., Coukos, G., Uccelli, E.,
Weinstein, R., Spinato, S., et al. Efficacy of hormone
replacement therapy in postmenopausal women with
oral discomfort. Oral Surg Oral Med Oral Pathol.
1992;73(5):570-574.
Minicucci, E.M., Pires, R.B., Vieira, R.A., Miot, H.A.,
Sposto, M.R. Assessing the impact of menopause on
salivary flow and xerostomia. Aust Dent J.
2013;58(2):230-234.
Pezelj-
Ribarić, S., Kqiku, L., Brumini, G., Urek, M.M.,
Antonić, R., Kuiš, D. et al. Proinflammatory cytokine
levels in saliva in patients with burning mouth
syndrome before and after treatment with low-level
laser therapy. Lasers Med Sci. 2013;28(1):297-301.
Jääskeläinen, S.K. Is burning mouth syndrome a
neuropathic pain condition? Pain. 2018;159(3):610-
613.
Thompson, I.O., van der Bijl, P., van Wyk, C.W., van Eyk,
A.D. A comparative light-microscopic, electron-
microscopic, and chemical study of human vaginal and
buccal epithelium. Arch Oral Biol. 2001;46:1091-1098.
Välimaa, H., Savolainen, S., Soukka, T., Silvoniemi, P.,
Mäkelä, S., Kujari, H. et al. Estrogen receptor-beta is the
predominant estrogen receptor subtype in human oral
epithelium and salivary glands. J Endocrinol.
2004;180(1):55-62.
Cao, M., Shu, L., Li, J., Su, J., Zhang, W., Wang, Q. et al.
The expression of estrogen receptors and the effects of
estrogen on human periodontal ligament cells.
Methods Find Exp Clin Pharmacol. 2007;29(5):329-335.
Buencamino, M.C., Palomo, L., Thacker, H.L. How
menopause affects oral health, and what we can do
about it. Cleve Clin J Med. 2009;76(8):467-475.
Grover, C.M., More, V.P., Singh, N., Grover, S. Crosstalk
between hormones and oral health in the mid-life of
women: A comprehensive review. J Int Soc Prev
Community Dent. 2014;4(Suppl.1):S5-S10.
Poon, R., Su, N., Ching, V., Darling, M., Grushka, M.
Reduction in unstimulated salivary flow rate in burning
mouth syndrome. Br Dent J. 2014;217(7):E14.
Reeves, T., Stace, J.M. Improving patient access and
choice: Assisted Bibliotherapy for mild to moderate
stress/anxiety in primary care. J Psychiatr Ment Health
Nurs. 2005;12(3):341-346.
Montgomery, S.A., Åsberg, M. A new depression scale
designed to be sensitive to change. Br J Psychiatry.
1979;134:382-389.
