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Oral symptoms at menopause—the role of hormone replacement therapy
Oral symptoms at menopause—the role of hormone replacement therapy Laura Tarkkila, DDS, MSc,a Miika Linna, PhD,b Aila Tiitinen, MD, PhD,c Christian Lindqvist, MD, DDS, PhD,a,d and Jukka H. Meurman, MD, DDS, PhD,a,d Helsinki, Finland UNIVERSITY OF HELSINKI, NATIONAL RESEARCH AND DEVELOPMENT CENTRE FOR WELFARE AND HEALTH, AND HELSINKI UNIVERSITY CENTRAL HOSPITAL
Objective. A questionnaire was used to investigate the prevalence of self-assessed sensations of painful mouth (PM) and dry mouth (DM) in menopause-aged women. Special attention was paid to the association of the use of hormone replacement therapy (HRT) with oral symptoms. Our hypothesis was that women using HRT have fewer oral symptoms than those who do not use HRT. Study design. Patients were selected from among 50- to 58-year-old women attending a communal mammography screening program in Helsinki, Finland. Every fifth woman was offered a structured questionnaire. Results. Completed questionnaires were received from 3173 women (response rate, 65%). Of the total sample, 46.8% (n = 1486) used HRT. The occurrence of PM was 8.2% (n = 259) and DM, 19.9% (n = 631). Climacteric symptoms were reported by 24% (n = 761) of the total sample and by 19.2% (n = 285) of the HRT users. According to logistic regression analyses, climacteric symptoms were found to be predictive of PM (P = .000) and DM (P = .000). The use of HRT also increased the occurrence of PM (P = .03). However, as a single covariate in our statistical model, the use of HRT was not a predictor of PM. The use of HRT also did not correlate with the occurrence of DM. Conclusions. The occurrence of PM and of DM seemed to be associated with climacteric symptoms in general, and the use of HRT did not prevent the oral symptoms studied.
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:276-80)
Pain and discomfort in the oral cavity are often due to local etiologic factors. Oral symptoms may also be the consequences of systemic diseases or alterations in physiological conditions, or they may be the side effects of medication. Burning or painful mouth (PM) is a condition that elicits a burning sensation in the oral cavity. When no obvious somatic pathology can be found, the condition is called burning mouth syndrome (BMS).1 BMS is a troublesome oral condition in which the patient’s complaints often seem exaggerated.2 Another disturbing oral discomfort is the sensation of dry mouth (DM). Decrease in salivary flow rate is a side effect of many drugs, but DM does not always correlate with a measured low salivary flow rate.3
Supported by grants from the Research Foundation (EVO) of the Helsinki University Central Hospital, The Finnish Dental Association, and Orion Pharmaceuticals, Espoo, Finland. aInstitute of Dentistry, University of Helsinki, Finland. bNational Research and Development Centre for Welfare and Health, Helsinki, Finland. cDepartment of Obstetrics and Gynaecology, Helsinki University Central Hospital. dDepartment of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland. Received for publication Feb 28, 2001; returned for revision Apr 18, 2001; accepted for publication May 16, 2001. Copyright © 2001 by Mosby, Inc. 1079-2104/2001/$35.00 + 0 7/13/117452 doi:10.1067/moe.2001.117452
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BMS is more likely to occur in women than in men4,5 and is common in middle-aged women.1,6,7 The prevalence of BMS has been estimated to be 0.7% to 4.5% in the general population,4,8,9 but higher figures have also been presented.10 Studies on the prevalence of BMS and the determinants of symptoms have shown that disturbances in salivary secretion and the use of hormone replacement therapy (HRT) have increased the occurrence of BMS.7,11 However, suggestions that women may actually benefit from the use of HRT for their oral symptoms have been reported.6,12 Conversely, it has been claimed that menopause and the use of HRT do not correlate with oral symptoms.13 Despite previous research, the role of HRT in the occurrence of unpleasant oral symptoms has not been clarified. Because the psychological effects of estrogen and progesterone are numerous and complex,14 it is logical to assume that the use of HRT may also affect oral symptoms and sensations. Subsequently, the aim of the present study was to investigate the prevalence of PM and DM in menopause-aged women who attended a community-based mammography screening program. Special attention was paid to several explanatory variables—including patient characteristics and the use of HRT and other medications—with respect to the symptoms. Our hypothesis was that the use of HRT is associated with a lower prevalence of oral symptoms, and women using HRT less frequently exhibit these symptoms than those women who do not use HRT.
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Table I. Prevalence (%/n) of sensation of PM or DM in selected variables Variable Use of antidepressants (n = 187) Climacteric symptoms (n = 775) Use of dentures (n = 691) Smoking (n = 823) Use of respiratory drugs (n = 123) Use of endocrinologic drugs (n = 223) Use of hormone replacement therapy (n = 1415) Use of antihypertensives (n = 647) Sensation of dry mouth (DM) (n = 631) Sensation of painful mouth (PM) (n = 259)
PM 16%/26 14%/101 12%/74 11%/81 16%/18 11%/20 10 %/136 11%/65 23%/135 —
PATIENTS AND METHODS Patients and questionnaire The ethical committee of the city of Helsinki, Finland, approved our study plan. The patients were selected from among women attending a communal mammography screening program in Helsinki. The age cohorts were 50-, 52-, 54-, 56-, and 58-year-olds. The nurse in charge of the mammography examination offered every fifth woman in the selected cohorts a structured study questionnaire with 36 total questions on medication, self-assessed oral and general health, and oral symptoms. The sensation of PM, excluding toothache, and the sensation of DM were queried, with the following responses elicited: “yes, presently suffering” and “no.” If a woman reported PM at present, detailed questions on pain and its treatment attempts followed in the questionnaire. In addition, questions on menstrual history, climacteric complaints in general (ie, hot flushes, sweating, etc), and smoking habits were included. The women filled out the questionnaires at the mammography clinic and returned the forms to the nurse. Questionnaires with inappropriate answers were excluded from the data analyses. Only 9 of the forms returned had to be discarded because of incomplete answers. Data The occurrence of DM, PM, climacteric symptoms, and the use of HRT and other medications, as well as smoking and the use of dentures, were coded as dichotomized variables. Binary variables were constructed from each so that those reporting symptoms at present and those who were current smokers or had dentures were assigned a score of 1, whereas those with no symptoms, nonsmokers, or those with no dentures were assigned a score of 0. Selfassessed general health was coded by using a scale of 1 to 5 (1, good; 2, fairly good; 3, moderate; 4, fairly bad; and 5, bad). Statistical analyses The multinomial logistic regression (LR) model was used to estimate the coefficients for proportional risk for
No PM
DM
84%/141 86%/607 88%/525 89%/666 84%/93 89%/154 90%/1245 89%/529 77%/449 —
51%/88 34%/250 25%/156 27%/208 38%/43 37%/67 22%/316 28%/174 — 54%/136
No DM 49%/86 66%/483 75%/476 73%/551 62%/70 63%/116 78%/1100 72%/439 — 46%/115
PM and DM. In this estimation, PM and DM were used as dependent variables and a set of selected correlates served as independent variables. Independent variables were included in the model by using a stepwise procedure in which likelihood ratio tests indicated the inclusion/omission of variables in the model specification. The final model estimates were used to calculate odds ratios (OR) and 95% CIs. The estimations were accomplished by using LIMDEP’s logit–subroutines.15
RESULTS Completed questionnaires were received from 3173 women, a response rate of 65%. The response rate varied in the age cohorts, with the 50-year-old women having the highest (70%) rate and the 58-year-olds having the lowest (55%). HRT was used by 46.8% (n = 1486) of the total sample. The age distribution of the use of HRT is given in Fig 1. The prevalence of reported PM among all the women was 8.2% (n = 259); 7.2% (n = 227) did not respond to this question. Of those who reported PM, 23% (n = 59) had complained about their oral pain to the dentist and 12% (n = 37) to the physician. Fourteen percent (n = 37) had complained about their symptoms both to the dentist and the physician. However, 68% (n = 177) did not undergo any treatment to relieve the painful sensation. DM was reported by 19.9% (n = 631) of the total sample; 6.3% (n = 200) who did not respond. DM was ameliorated mainly by drinking more liquids (41%, n = 257) or by drinking more liquids in general and eating pastilles and using chewing gum (20%, n = 152). Because there were a few nonresponses on the questions concerning PM or DM, the total numbers of observations used in our analyses were 2946 for PM and 2973 for DM, respectively. Climacteric symptoms were reported by 24% (n = 761) of the total sample and by 19.2% (n = 285) of the women who used HRT. The LR tests indicated that several of the covariates included in the model had a statistically significant association with the occurrence of PM or DM. The prevalence of PM or DM in the selected variables is given in Table I.
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Fig 1. Use of hormone replacement therapy (%) in studied age cohorts.
Table II. LR model estimates, OR, and 95% CIs, with sensation of PM as dependent variable 95% CI* Variable Use of antidepressants Climacteric symptoms Use of dentures Smoking Age Use of respiratory drugs Use of endocrinologic drugs Use of hormone replacement therapy Use of antihypertensives Sensation of DM Self-assessed general health *Only
Coefficient
SE
P value
OR*
–0.32 0.445 0.295 0.093 0.041 0.209 –0.236 0.324 –0.144 1.4 0.501
0.260 0.127 0.167 0.161 0.027 0.294 0.272 0.146 0.173 0.150 0.083
.218 .001 .077 .564 .132 .476 .387 .027 .405 .000 .000
0.726 1.561 1.343 1.097 — 1.233 0.79 1.383 0.866 4.054 —
Lower Upper 0.44 1.22 0.97 0.8 — 0.69 0.46 1.04 0.62 3.02 —
1.21 2 1.86 1.51 — 2.19 1.35 1.84 1.22 5.44 —
dichotomized covariates were used.
According to LR estimations, climacteric complaints significantly correlated with the occurrence of PM (P = .000). Moreover, the women who assessed their general health as bad (score 5) had a higher occurrence of PM (P = .000). As a single variable, the use of HRT did not correlate with the occurrence of PM. However, with the full set of covariates, the use of HRT was a significant predictor of PM (P = .03). The stepwise inclusion of the model covariates indicated that smoking (P = .02) and the use of antidepressants (P = .002) significantly increased the risk for PM in a reduced-model specification in which DM was not used as an explanatory variable (results not shown). The inclusion of the DM variable in the model changed the estimates for both smoking and antidepressants, making them nonsignificant predictors of PM. When a full set of covariates was used in the model, neither smoking nor antidepressants turned out to be significant predictors of the occurrence of PM (Table II). The women with climacteric complaints in general and those who considered their general health to be poor had a significantly increased risk for DM. In addition, the use of antidepressants and respiratory and endocrinologic drugs increased the occurrence of DM.
Neither age nor the use of HRT was a predictive factor for DM. However, smoking was a highly significant risk factor for DM—regardless of whether it was used as a single covariate (P = .000) or as a joint covariate with a full set of explanatory variables in the model (P = .004; Table III). The PM model was found to be slightly more sensitive to the addition or the removal of the covariates than was the DM model—probably because of some degree of multicollinearity between DM and the other explanatory variables used in the PM model. LR estimates and the ORs and 95% CIs for PM and DM are given in Tables II and III.
DISCUSSION The present study revealed an astonishingly high occurrence of oral symptoms despite the widespread use of HRT in our patients. In contrast to our study hypothesis, the use of HRT did not appear to reduce the prevalence of PM or DM. It must be emphasized, however, that this study was not a population study that would reflect the prevalence of the symptoms in all age groups. We concentrated on women of menopausal age because previous studies have suggested that such oral
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Table III. LR model estimates, OR, and 95% CIs, with sensation of DM as dependent variable 95% CI* Variable Use of antidepressants Climacteric symptoms Use of dentures Smoking Age Use of respiratory drugs Use of endocrinologic drugs Use of hormone replacement therapy Use of antihypertensives Sensation of PM Self-assessed general health *Only
Coefficient
SE
P value
OR*
1.054 0.631 –0.104 0.334 –0.017 0.499 0.66 0.201 0.217 1.378 0.449
0.185 0.109 0.130 0.115 0.020 0.233 0.186 0.106 0.124 0.151 0.061
.000 .000 .423 .004 .377 .032 .000 .058 .080 .000 .000
2.868 1.88 0.901 1.397 — 1.647 1.934 1.223 1.242 3.968 —
Lower 2 1.52 0.7 1.12 — 1.04 1.35 0.99 0.97 2.95 —
Upper 4.12 2.33 1.16 1.75 — 2.6 2.78 1.51 1.58 5.33 —
dichotomized covariates were used.
symptoms are more prevalent in these women than in women in other age groups.6,16 Nevertheless, because of the nature of this study, it is not known how many of the women actually were premenopausal or postmenopausal, but it safely can be assumed that the younger versus the older age cohorts rightly represent these phases. The sample size used in this study was large enough to provide relevant information on the prevalence of the oral symptoms within the cohorts. In our study, 47% of the women used HRT. Such a high prevalence was expected because the age cohorts selected represented the age groups with the most frequent use of HRT. According to our results, the women reporting climacteric symptoms were also likely to suffer from oral discomfort. As shown by the LR model, the use of HRT correlated with an increased risk for PM. Among the HRT users, PM was reported by 13%. Approximately 1 out of 5 women using HRT had climacteric symptoms, and as much as 18% of this group reported having PM. Climacteric symptoms were found to also be predictive of DM. The use of HRT did not significantly correlate with DM. However, 38% of the women using HRT with reported climacteric symptoms also reported having DM. As expected, the use of other medication, as well as smoking, increased the risk of DM. The occurrence of PM was also a highly significant risk factor for DM (P = .000). The correlation between DM and PM was in agreement with that reported in previous studies.5 However, as discussed, it is difficult to reveal the causal relationships of PM, DM, and systemic medication.7 In general, climacteric symptoms are experienced by approximately 75% of women during menopause transition, with variable severity and duration. HRT is the treatment of choice for these symptoms, but it is not required by all women. In previous investigations, the prevalence of the use of HRT has been shown to be approximately 20%, but there is an increasing tendency to use HRT in Finland.17 Recently, a prevalence figure of 39%
was reported.18 However, a considerable number of women discontinue the treatment, mostly because of its side effects. A number of studies have investigated the factors causing oral symptoms—especially BMS, which has been associated with many oral and systemic conditions.19 Some studies have found a correlation between oral symptoms and climacterium. However, in these surveys the sample sizes for menopausal women have been small or participants have been selected from hormone clinics or university dental clinics.4,6,10,16,20,21 Our sample was larger and more representative than those previously reported in studies on the corresponding female age cohorts. Although the present results are based on self-assessed sensations and not on clinical examinations, they provided important information on the self-assessed oral well-being and oral health of the menopausal women. The selection of the covariates used in this study may be criticized, because it did not adequately take into account all possible systemic or psychological factors. Nevertheless, the study sought to evaluate the occurrence of self-assessed symptoms and the role of HRT in these women. The number of questions had to be limited because of practical reasons. In addition, because our study was to be a questionnaire study and the patients were neither aware of nor prepared for it until they attended the mammography screening, the answers with respect to their medication had to be categorized fairly widely. Subsequently, detailed conclusions on the effect of various medications on the studied symptoms, as well as the role they played in the symptoms, are not warranted. In summary, the occurrence of PM and DM in the approximately 3000 women studied in the present questionnaire investigation appeared to be associated with climacteric symptoms in general. The use of HRT did not seem to prevent the oral symptoms. Thus, controlled clinical trials are required to evaluate the final role of HRT in the occurrence of PM and DM. As it now stands, most menopausal women beginning HRT probably do so because of their
280 Tarkkila et al
general climacteric symptoms. Whether PM and DM in these age cohorts should be considered “climacteric symptoms” is also a matter for future discussion. REFERENCES 1. Lamey PJ, Lamb AB. Prospective study of aetiological factors in burning mouth syndrome. Br Med J 1988;296:1243-6. 2. Svensson P, Kaaber S. General health factors and denture function in patients with burning mouth syndrome and matched control subjects. J Oral Rehabil 1995;22:887-95. 3. Meurman JH, Rantonen P. Salivary flow rate, buffering capacity and yeast counts in 187 consecutive adult patients from Kuopio, Finland. Scand J Dent Res 1994;102:227-34. 4. Basker RM, Sturdee DW, Davenport JC. Patients with burning mouths. A clinical investigation of causative factors, including the climacteric and diabetes. Br Dent J 1978;145:9-16 5. Bergdahl M, Bergdahl J. Burning mouth syndrome: prevalence and associated factors. J Oral Pathol Med 1999;28:350-4. 6. Wardrop RW, Hailes J, Burger H, Reade PC. Oral discomfort at menopause. Oral Surg Oral Med Oral Pathol 1989;67:535-40. 7. Hakeberg M, Berggren U, Hägglin C, Ahlqwist M. Reported burning mouth symptoms among middle-aged and elderly women. Eur J Oral Sci 1997;105:539-43. 8. Locker D, Grushka M. Prevalence of oral and facial pain and discomfort: preliminary results of a mail survey. Community Dent Oral Epidemiol 1987;15:169-72. 9. Lipton JA, Ship JA, Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Assoc 1993;124:115-21. 10. Tammiala-Salonen T, Hiidenkari T, Parvinen T. Burning mouth in a Finnish adult population. Community Dent Oral Epidemiol 1993;21:67-71. 11. Maresky LS, van der Bijl P, Gird I. Burning mouth syndrome.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY September 2001
12.
13. 14. 15. 16. 17. 18. 19. 20. 21.
Evaluation of multiple variables among 85 patients. Oral Surg Oral Med Oral Pathol 1993;75:303-7. 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;73:570-4. Ship JA, Patton LL, Tylenda CA. An assessment of salivary function in healthy premenopausal and postmenopausal females. J Gerontol 1991;46:M11-5. Brace M, McCauley E. Oestrogens and psychological wellbeing. Ann Med 1997;29:283-90. Greene W. LIMDEP 6.0. Econometric Software Inc. Belport, NY; 1992. Massler M. Oral manifestations during the female climacteric (the postmenopausal syndrome). Oral Surg Oral Med Oral Pathol 1951;4:1234-43. Topo P, Klaukka T, Hemminki E, Uutela A. Use of hormone replacement therapy in 1976-89 by 45-64-year-old Finnish women. J Epidemiol Community Health 1991;45:277-80. Vihtamäki T, Savilahti R, Tuimala R. Why do postmenopausal women discontinue hormone replacement therapy? Maturitas 1999;33:99-105. Gorsky M, Silverman S Jr, Chinn H. Burning mouth syndrome: a review of 98 cases. J Oral Med 1987;42:7-9. Ziskin DE, Moulton R. Glossodynia: A study of idiopathic orolingual pain. J Am Dent Assoc 1946;33:1422-32. Grushka M. Clinical features of burning mouth syndrome. Oral Surg Oral Med Oral Pathol 1987;63:30-6.
Reprint requests: Laura Tarkkila, DDS, MSc Institute of Dentistry PO Box 41 FIN–00014 University of Helsinki Finland [email protected]
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Objective. A questionnaire was used to investigate the prevalence of self-assessed sensations of painful mouth (PM) and dry mouth (DM) in menopause-aged women. Special attention was paid to the association of the use of hormone replacement therapy (HRT) with oral symptoms. Our hypothesis was that women using HRT have fewer oral symptoms than those who do not use HRT. Study design. Patients were selected from among 50- to 58-year-old women attending a communal mammography screening program in Helsinki, Finland. Every fifth woman was offered a structured questionnaire. Results. Completed questionnaires were received from 3173 women (response rate, 65%). Of the total sample, 46.8% (n = 1486) used HRT. The occurrence of PM was 8.2% (n = 259) and DM, 19.9% (n = 631). Climacteric symptoms were reported by 24% (n = 761) of the total sample and by 19.2% (n = 285) of the HRT users. According to logistic regression analyses, climacteric symptoms were found to be predictive of PM (P = .000) and DM (P = .000). The use of HRT also increased the occurrence of PM (P = .03). However, as a single covariate in our statistical model, the use of HRT was not a predictor of PM. The use of HRT also did not correlate with the occurrence of DM. Conclusions. The occurrence of PM and of DM seemed to be associated with climacteric symptoms in general, and the use of HRT did not prevent the oral symptoms studied.
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:276-80)
Pain and discomfort in the oral cavity are often due to local etiologic factors. Oral symptoms may also be the consequences of systemic diseases or alterations in physiological conditions, or they may be the side effects of medication. Burning or painful mouth (PM) is a condition that elicits a burning sensation in the oral cavity. When no obvious somatic pathology can be found, the condition is called burning mouth syndrome (BMS).1 BMS is a troublesome oral condition in which the patient’s complaints often seem exaggerated.2 Another disturbing oral discomfort is the sensation of dry mouth (DM). Decrease in salivary flow rate is a side effect of many drugs, but DM does not always correlate with a measured low salivary flow rate.3
Supported by grants from the Research Foundation (EVO) of the Helsinki University Central Hospital, The Finnish Dental Association, and Orion Pharmaceuticals, Espoo, Finland. aInstitute of Dentistry, University of Helsinki, Finland. bNational Research and Development Centre for Welfare and Health, Helsinki, Finland. cDepartment of Obstetrics and Gynaecology, Helsinki University Central Hospital. dDepartment of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland. Received for publication Feb 28, 2001; returned for revision Apr 18, 2001; accepted for publication May 16, 2001. Copyright © 2001 by Mosby, Inc. 1079-2104/2001/$35.00 + 0 7/13/117452 doi:10.1067/moe.2001.117452
276
BMS is more likely to occur in women than in men4,5 and is common in middle-aged women.1,6,7 The prevalence of BMS has been estimated to be 0.7% to 4.5% in the general population,4,8,9 but higher figures have also been presented.10 Studies on the prevalence of BMS and the determinants of symptoms have shown that disturbances in salivary secretion and the use of hormone replacement therapy (HRT) have increased the occurrence of BMS.7,11 However, suggestions that women may actually benefit from the use of HRT for their oral symptoms have been reported.6,12 Conversely, it has been claimed that menopause and the use of HRT do not correlate with oral symptoms.13 Despite previous research, the role of HRT in the occurrence of unpleasant oral symptoms has not been clarified. Because the psychological effects of estrogen and progesterone are numerous and complex,14 it is logical to assume that the use of HRT may also affect oral symptoms and sensations. Subsequently, the aim of the present study was to investigate the prevalence of PM and DM in menopause-aged women who attended a community-based mammography screening program. Special attention was paid to several explanatory variables—including patient characteristics and the use of HRT and other medications—with respect to the symptoms. Our hypothesis was that the use of HRT is associated with a lower prevalence of oral symptoms, and women using HRT less frequently exhibit these symptoms than those women who do not use HRT.
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Table I. Prevalence (%/n) of sensation of PM or DM in selected variables Variable Use of antidepressants (n = 187) Climacteric symptoms (n = 775) Use of dentures (n = 691) Smoking (n = 823) Use of respiratory drugs (n = 123) Use of endocrinologic drugs (n = 223) Use of hormone replacement therapy (n = 1415) Use of antihypertensives (n = 647) Sensation of dry mouth (DM) (n = 631) Sensation of painful mouth (PM) (n = 259)
PM 16%/26 14%/101 12%/74 11%/81 16%/18 11%/20 10 %/136 11%/65 23%/135 —
PATIENTS AND METHODS Patients and questionnaire The ethical committee of the city of Helsinki, Finland, approved our study plan. The patients were selected from among women attending a communal mammography screening program in Helsinki. The age cohorts were 50-, 52-, 54-, 56-, and 58-year-olds. The nurse in charge of the mammography examination offered every fifth woman in the selected cohorts a structured study questionnaire with 36 total questions on medication, self-assessed oral and general health, and oral symptoms. The sensation of PM, excluding toothache, and the sensation of DM were queried, with the following responses elicited: “yes, presently suffering” and “no.” If a woman reported PM at present, detailed questions on pain and its treatment attempts followed in the questionnaire. In addition, questions on menstrual history, climacteric complaints in general (ie, hot flushes, sweating, etc), and smoking habits were included. The women filled out the questionnaires at the mammography clinic and returned the forms to the nurse. Questionnaires with inappropriate answers were excluded from the data analyses. Only 9 of the forms returned had to be discarded because of incomplete answers. Data The occurrence of DM, PM, climacteric symptoms, and the use of HRT and other medications, as well as smoking and the use of dentures, were coded as dichotomized variables. Binary variables were constructed from each so that those reporting symptoms at present and those who were current smokers or had dentures were assigned a score of 1, whereas those with no symptoms, nonsmokers, or those with no dentures were assigned a score of 0. Selfassessed general health was coded by using a scale of 1 to 5 (1, good; 2, fairly good; 3, moderate; 4, fairly bad; and 5, bad). Statistical analyses The multinomial logistic regression (LR) model was used to estimate the coefficients for proportional risk for
No PM
DM
84%/141 86%/607 88%/525 89%/666 84%/93 89%/154 90%/1245 89%/529 77%/449 —
51%/88 34%/250 25%/156 27%/208 38%/43 37%/67 22%/316 28%/174 — 54%/136
No DM 49%/86 66%/483 75%/476 73%/551 62%/70 63%/116 78%/1100 72%/439 — 46%/115
PM and DM. In this estimation, PM and DM were used as dependent variables and a set of selected correlates served as independent variables. Independent variables were included in the model by using a stepwise procedure in which likelihood ratio tests indicated the inclusion/omission of variables in the model specification. The final model estimates were used to calculate odds ratios (OR) and 95% CIs. The estimations were accomplished by using LIMDEP’s logit–subroutines.15
RESULTS Completed questionnaires were received from 3173 women, a response rate of 65%. The response rate varied in the age cohorts, with the 50-year-old women having the highest (70%) rate and the 58-year-olds having the lowest (55%). HRT was used by 46.8% (n = 1486) of the total sample. The age distribution of the use of HRT is given in Fig 1. The prevalence of reported PM among all the women was 8.2% (n = 259); 7.2% (n = 227) did not respond to this question. Of those who reported PM, 23% (n = 59) had complained about their oral pain to the dentist and 12% (n = 37) to the physician. Fourteen percent (n = 37) had complained about their symptoms both to the dentist and the physician. However, 68% (n = 177) did not undergo any treatment to relieve the painful sensation. DM was reported by 19.9% (n = 631) of the total sample; 6.3% (n = 200) who did not respond. DM was ameliorated mainly by drinking more liquids (41%, n = 257) or by drinking more liquids in general and eating pastilles and using chewing gum (20%, n = 152). Because there were a few nonresponses on the questions concerning PM or DM, the total numbers of observations used in our analyses were 2946 for PM and 2973 for DM, respectively. Climacteric symptoms were reported by 24% (n = 761) of the total sample and by 19.2% (n = 285) of the women who used HRT. The LR tests indicated that several of the covariates included in the model had a statistically significant association with the occurrence of PM or DM. The prevalence of PM or DM in the selected variables is given in Table I.
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Fig 1. Use of hormone replacement therapy (%) in studied age cohorts.
Table II. LR model estimates, OR, and 95% CIs, with sensation of PM as dependent variable 95% CI* Variable Use of antidepressants Climacteric symptoms Use of dentures Smoking Age Use of respiratory drugs Use of endocrinologic drugs Use of hormone replacement therapy Use of antihypertensives Sensation of DM Self-assessed general health *Only
Coefficient
SE
P value
OR*
–0.32 0.445 0.295 0.093 0.041 0.209 –0.236 0.324 –0.144 1.4 0.501
0.260 0.127 0.167 0.161 0.027 0.294 0.272 0.146 0.173 0.150 0.083
.218 .001 .077 .564 .132 .476 .387 .027 .405 .000 .000
0.726 1.561 1.343 1.097 — 1.233 0.79 1.383 0.866 4.054 —
Lower Upper 0.44 1.22 0.97 0.8 — 0.69 0.46 1.04 0.62 3.02 —
1.21 2 1.86 1.51 — 2.19 1.35 1.84 1.22 5.44 —
dichotomized covariates were used.
According to LR estimations, climacteric complaints significantly correlated with the occurrence of PM (P = .000). Moreover, the women who assessed their general health as bad (score 5) had a higher occurrence of PM (P = .000). As a single variable, the use of HRT did not correlate with the occurrence of PM. However, with the full set of covariates, the use of HRT was a significant predictor of PM (P = .03). The stepwise inclusion of the model covariates indicated that smoking (P = .02) and the use of antidepressants (P = .002) significantly increased the risk for PM in a reduced-model specification in which DM was not used as an explanatory variable (results not shown). The inclusion of the DM variable in the model changed the estimates for both smoking and antidepressants, making them nonsignificant predictors of PM. When a full set of covariates was used in the model, neither smoking nor antidepressants turned out to be significant predictors of the occurrence of PM (Table II). The women with climacteric complaints in general and those who considered their general health to be poor had a significantly increased risk for DM. In addition, the use of antidepressants and respiratory and endocrinologic drugs increased the occurrence of DM.
Neither age nor the use of HRT was a predictive factor for DM. However, smoking was a highly significant risk factor for DM—regardless of whether it was used as a single covariate (P = .000) or as a joint covariate with a full set of explanatory variables in the model (P = .004; Table III). The PM model was found to be slightly more sensitive to the addition or the removal of the covariates than was the DM model—probably because of some degree of multicollinearity between DM and the other explanatory variables used in the PM model. LR estimates and the ORs and 95% CIs for PM and DM are given in Tables II and III.
DISCUSSION The present study revealed an astonishingly high occurrence of oral symptoms despite the widespread use of HRT in our patients. In contrast to our study hypothesis, the use of HRT did not appear to reduce the prevalence of PM or DM. It must be emphasized, however, that this study was not a population study that would reflect the prevalence of the symptoms in all age groups. We concentrated on women of menopausal age because previous studies have suggested that such oral
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ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 92, Number 3
Table III. LR model estimates, OR, and 95% CIs, with sensation of DM as dependent variable 95% CI* Variable Use of antidepressants Climacteric symptoms Use of dentures Smoking Age Use of respiratory drugs Use of endocrinologic drugs Use of hormone replacement therapy Use of antihypertensives Sensation of PM Self-assessed general health *Only
Coefficient
SE
P value
OR*
1.054 0.631 –0.104 0.334 –0.017 0.499 0.66 0.201 0.217 1.378 0.449
0.185 0.109 0.130 0.115 0.020 0.233 0.186 0.106 0.124 0.151 0.061
.000 .000 .423 .004 .377 .032 .000 .058 .080 .000 .000
2.868 1.88 0.901 1.397 — 1.647 1.934 1.223 1.242 3.968 —
Lower 2 1.52 0.7 1.12 — 1.04 1.35 0.99 0.97 2.95 —
Upper 4.12 2.33 1.16 1.75 — 2.6 2.78 1.51 1.58 5.33 —
dichotomized covariates were used.
symptoms are more prevalent in these women than in women in other age groups.6,16 Nevertheless, because of the nature of this study, it is not known how many of the women actually were premenopausal or postmenopausal, but it safely can be assumed that the younger versus the older age cohorts rightly represent these phases. The sample size used in this study was large enough to provide relevant information on the prevalence of the oral symptoms within the cohorts. In our study, 47% of the women used HRT. Such a high prevalence was expected because the age cohorts selected represented the age groups with the most frequent use of HRT. According to our results, the women reporting climacteric symptoms were also likely to suffer from oral discomfort. As shown by the LR model, the use of HRT correlated with an increased risk for PM. Among the HRT users, PM was reported by 13%. Approximately 1 out of 5 women using HRT had climacteric symptoms, and as much as 18% of this group reported having PM. Climacteric symptoms were found to also be predictive of DM. The use of HRT did not significantly correlate with DM. However, 38% of the women using HRT with reported climacteric symptoms also reported having DM. As expected, the use of other medication, as well as smoking, increased the risk of DM. The occurrence of PM was also a highly significant risk factor for DM (P = .000). The correlation between DM and PM was in agreement with that reported in previous studies.5 However, as discussed, it is difficult to reveal the causal relationships of PM, DM, and systemic medication.7 In general, climacteric symptoms are experienced by approximately 75% of women during menopause transition, with variable severity and duration. HRT is the treatment of choice for these symptoms, but it is not required by all women. In previous investigations, the prevalence of the use of HRT has been shown to be approximately 20%, but there is an increasing tendency to use HRT in Finland.17 Recently, a prevalence figure of 39%
was reported.18 However, a considerable number of women discontinue the treatment, mostly because of its side effects. A number of studies have investigated the factors causing oral symptoms—especially BMS, which has been associated with many oral and systemic conditions.19 Some studies have found a correlation between oral symptoms and climacterium. However, in these surveys the sample sizes for menopausal women have been small or participants have been selected from hormone clinics or university dental clinics.4,6,10,16,20,21 Our sample was larger and more representative than those previously reported in studies on the corresponding female age cohorts. Although the present results are based on self-assessed sensations and not on clinical examinations, they provided important information on the self-assessed oral well-being and oral health of the menopausal women. The selection of the covariates used in this study may be criticized, because it did not adequately take into account all possible systemic or psychological factors. Nevertheless, the study sought to evaluate the occurrence of self-assessed symptoms and the role of HRT in these women. The number of questions had to be limited because of practical reasons. In addition, because our study was to be a questionnaire study and the patients were neither aware of nor prepared for it until they attended the mammography screening, the answers with respect to their medication had to be categorized fairly widely. Subsequently, detailed conclusions on the effect of various medications on the studied symptoms, as well as the role they played in the symptoms, are not warranted. In summary, the occurrence of PM and DM in the approximately 3000 women studied in the present questionnaire investigation appeared to be associated with climacteric symptoms in general. The use of HRT did not seem to prevent the oral symptoms. Thus, controlled clinical trials are required to evaluate the final role of HRT in the occurrence of PM and DM. As it now stands, most menopausal women beginning HRT probably do so because of their
280 Tarkkila et al
general climacteric symptoms. Whether PM and DM in these age cohorts should be considered “climacteric symptoms” is also a matter for future discussion. REFERENCES 1. Lamey PJ, Lamb AB. Prospective study of aetiological factors in burning mouth syndrome. Br Med J 1988;296:1243-6. 2. Svensson P, Kaaber S. General health factors and denture function in patients with burning mouth syndrome and matched control subjects. J Oral Rehabil 1995;22:887-95. 3. Meurman JH, Rantonen P. Salivary flow rate, buffering capacity and yeast counts in 187 consecutive adult patients from Kuopio, Finland. Scand J Dent Res 1994;102:227-34. 4. Basker RM, Sturdee DW, Davenport JC. Patients with burning mouths. A clinical investigation of causative factors, including the climacteric and diabetes. Br Dent J 1978;145:9-16 5. Bergdahl M, Bergdahl J. Burning mouth syndrome: prevalence and associated factors. J Oral Pathol Med 1999;28:350-4. 6. Wardrop RW, Hailes J, Burger H, Reade PC. Oral discomfort at menopause. Oral Surg Oral Med Oral Pathol 1989;67:535-40. 7. Hakeberg M, Berggren U, Hägglin C, Ahlqwist M. Reported burning mouth symptoms among middle-aged and elderly women. Eur J Oral Sci 1997;105:539-43. 8. Locker D, Grushka M. Prevalence of oral and facial pain and discomfort: preliminary results of a mail survey. Community Dent Oral Epidemiol 1987;15:169-72. 9. Lipton JA, Ship JA, Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Assoc 1993;124:115-21. 10. Tammiala-Salonen T, Hiidenkari T, Parvinen T. Burning mouth in a Finnish adult population. Community Dent Oral Epidemiol 1993;21:67-71. 11. Maresky LS, van der Bijl P, Gird I. Burning mouth syndrome.
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Reprint requests: Laura Tarkkila, DDS, MSc Institute of Dentistry PO Box 41 FIN–00014 University of Helsinki Finland [email protected]
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