http://informahealthcare.com/gye ISSN: 0951-3590 (print), 1473-0766 (electronic) Gynecol Endocrinol, 2015; 31(2): 109–112 ! 2014 Informa UK Ltd. DOI: 10.3109/09513590.2014.959918
HRT AND SALIVARY BLOOD FLOW
The influence of hormone replacement therapy on the salivary flow of post-menopausal women Marı´lia Leal Ferreira Lago1, Ana Emilia Figueiredo de Oliveira1, Fernanda Ferreira Lopes1, Elza Bernardes Ferreira1, Vandilson Pinheiro Rodrigues2, and Luciane Maria Oliveira Brito2 1
Department of Dentistry, Federal University of Maranha˜o, Bacanga, Brazil and 2Department of Medicine, Federal University of Maranha˜o, Pinheiro, Brazil Abstract
Keywords
The aim of this study is to investigate the influence of hormone therapy on salivary flow in menopausal women. It is a case–control study involving 86 post-menopausal women. The case group consisted of 47 women undergoing estroprogestative or estrogen hormone replacement therapy (HRT), and the control group consisted of 39 women who did not receive any HRT. All patients were submitted to a standard questionnaire, followed by total stimulated sialometry and determination of body mass index (BMI). The salivary flow was classified as follows: normal (1.0–3.0 mL/min), low (0.7–1.0 mL/min), and hyposalivation (50.7 mL/min). The results were analyzed statistically by the chi-square test, logistic regression model, and linear regression (p50.05). The HRT group presented an association of protection, even after adjusting the analysis, for low salivary flow (Adjusted OR ¼ 0.22; 95% CI ¼ 0.05–0.88; p ¼ 0.034), and hyposalivation (Adjusted OR ¼ 0.30; 95% CI ¼ 0.10–0.92; p ¼ 0.036). The results suggest that estroprogestative therapy ( ¼ + 0.53; p ¼ 0.022) has greater influence on the increase of salivary flow than estrogen therapy ( ¼ +0.35; p ¼ 0.137). The study concludes stating salivary flow was influenced by HRT on the post-menopausal women studied.
Hormone replacement therapy, menopause, salivation
Introduction Although a physiological phenomenon, the climacteric causes symptoms that interfere with women’s well-being, such as hot flushes, dry skin, brittle nails and hair, vaginal dryness, and dyspareunia [1]. One of the treatments indicated for the relief of those symptoms is the hormone replacement therapy (HRT), which can be used in peri- or post-menopausal women. HRT consists of the administration of estrogen alone or combined with progestogens [2]. Studies have shown that the physiological changes associated with menopause can cause oral alterations, such as a reduced salivary flow and an increased sensitivity, stinging and burning sensation and pain in the oral mucosa [3]. Xerostomia is the subjective feeling of dryness in the mouth as a result of the reduction or interruption of the salivary gland function accompanied by changes in quantity or quality of saliva [4,5]. The diagnosis of xerostomia and/or reduced salivary flow is basically made in a clinical way and should take into account the various medications that can cause or exacerbate the condition [6]. The current functional status should be evaluated in detail by using quantitative methods for determination of salivary secretion at rest or after stimulation [4]. Studies have investigated possible alterations to salivary flow in pre- and post-menopausal women. In a case–control
Address for correspondence: Dr. Fernanda Ferreira Lopes, Department of Dentistry, Federal University of Maranha˜o, Portugueses Av, 1966, Bacanga, Sa˜o Luı´s, 65080850, Brazil. E-mail: fernanda.f.lopes@ gmail.com
History Received 19 May 2014 Revised 19 August 2014 Accepted 27 August 2014 Published online 15 September 2014
study analyzing salivary flow and xerostomia in pre- and post-menopausal women no association was found between menopause and xerostomia [7]. It was also reported on the specific literature that xerostomia and quantitative changes in salivary flow are common findings in post-menopausal women [8]. Although recent studies on xerostomia and/or reduced salivary flow are available, few reports have investigated the influence of HRT on these conditions in climacteric women. In addition, there is a lack of studies comparing the effects of different types of HRT on xerostomia or reduced salivary flow. Therefore, the objective of this study was to compare the salivary flow between postmenopausal women who were submitted or not to estroprogestative and estrogen HRT.
Methods A case–control study was conducted at the Gynecology outpatient clinic of the Maternal and Infant University Hospital (Federal University of Maranha˜o — UFMA). The study was approved by the Ethics Committee of the institution (Permit No. 004395/2009-60) and it was carried out according to the Declaration of Helsinki, reviewed in 2008. The sample consisted of 86 women divided into a case group and a control group. The case group consisted of 47 postmenopausal women undergoing estroprogestative or estrogen HRT for at least 12 consecutive months. The control group consisted of 39 post-menopausal women who did not wish to take HRT or who presented some contraindication for its use. Women with a history of liver disease, endocrinopathy and thromboembolic events, smokers, women who had used any other
110
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hormonal medication in the last 12 months, and women with a family history (first-degree relatives) of breast, ovary or endometrial cancer were excluded from the study. Women who presented abnormalities in the laboratory tests or imaging exams (transvaginal or pelvic ultrasound and mammography) that contraindicated HRT were also excluded. After anamnesis, the patients were submitted to a full stimulated sialometry as described by Sreebny [9]. Saliva was collected with the patient in a comfortable sitting position and with the head slightly tilted forward. The women were asked to chew on a piece of tasteless paraffin (0.29 g; Parafilm ‘‘M’’Õ, American National CanÔ, Chicago, IL) to stimulate saliva production. The saliva samples produced over a period of 5 min were collected into a graduated container at 1-min intervals. Stimulated salivary flow is expressed as milliliter per minute (mL/min) and was classified as follows: normal flow (1.0–3.0 mL/min), low flow (0.7–1.0 mL/min), and hyposalivation (50.7 mL/min) [10]. A chart was used to record the following data: name, age, race, age at menarche, the duration of pre-menopausal period menacme, parity, age at menopause, duration of menopause, schooling level, marital status, and occupation. In addition to gynecological data and the findings of the general tests, the xerostomia and salivary flow evaluation results were also added. The results were analyzed by using the BioEstat 5.0 software (Mamiraua´ Civil Society/MCT, CNPq, Bele´m, Brazil). The classificatory variables (age group, race) were compared between the two groups (control and case) by the non-parametric chisquare ( 2) test for independence. The measure of association obtained by Odds Ratio (OR) with their respective confidence intervals at 95% (95% CI) was used to estimate the association between HRT and salivary flow. A multivariate logistic regression analysis was applied taking into account the confounding covariates (p50.10) to obtain the adjusted measure of association. Furthermore, a linear model was used to estimate the effect of HRT on the salivary flow. In this procedure, the measures calculated were the constant and regression coefficient ( ) and determination coefficient (R2). The level of significance for rejection of null hypothesis was set at 5%, i.e. a p value50.05 was considered to be statistically significant.
Results The comparative analysis by chi-square test revealed a significant difference (p50.05) for the variables race and salivary flow. The frequency of white women was higher in the case group (53.2%), whereas mulatto women were predominant in the control group (51.3%). Furthermore, the results suggest an association between salivary flow and HRT in the study sample (p ¼ 0.006). Most women undergoing hormone replacement showed normal salivary flow (72.3%), whereas in the control group, 61.5% of women were diagnosed with low salivary flow or hyposalivation. There were no statistically significant differences between groups for the variables related to reproduction included in this study (p 0.05). In both groups, the majority of women reported the occurrence of menarche after 13 years, menacme before the age of 32, and menopause after 45 years (Table 1). Table 2 shows the association measurement between salivary flow and HRT, obtained by logistic regression analysis. The results demonstrate that the chance of low salivary flow was 78% lower after adjusted analysis for age and race (OR ¼ 0.22; 95% CI ¼ 0.05–0.88; p ¼ 0.034) in the group of women undergoing HRT. After adjusted analysis, the data also showed that the chance of hyposalivation is 70% lower for the case group compared to the control one (OR ¼ 0.30; 95% CI ¼ 0.10–0.92; p ¼ 0.036).
Gynecol Endocrinol, 2015; 31(2): 109–112
Table 1. Distribution of clinical characteristics and reproductive variables in the study groups. Case (n ¼ 47) Control (n ¼ 39) Variable Race White Mulatto Black Age (in years) 39 40–49 50–59 60 Salivary flow (mL/min) Normal Low Hyposalivation Menarche (in years) 513 13 413 Number of children 0 1–3 4 Menacme (in years)a 32 33–36 37 Menopause (in years)b 545 45–49 50
2 p Value
n
(%)
n
(%)
25 18 4
(53.2) (38.3) (8.5)
11 20 8
(28.2) (51.3) (20.5)
1 5 24 17
(2.1) (10.6) (51.1) (36.2)
0 10 19 10
(0) (25.6) (48.8) (25.6)
34 5 8
(72.3) (10.6) (17.1)
15 9 15
(38.5) (23.0) (38.5)
13 13 21
(27.7) (27.7) (44.6)
15 6 18
(38.5) (15.4) (46.1)
14 18 15
(29.8) (38.3) (31.9)
7 19 13
(18.0) (48.7) (33.3)
18 13 13
(41.0) (29.5) (29.5)
14 12 8
(41.2) (35.3) (23.5)
15 14 17
(33.3) (31.0) (37.7)
13 16 10
(33.4) (41.0) (25.6)
6.19 0.045*
5.16 0.160
9.98 0.006*
2.23 0.327
1.77 0.412
0.46 0.794
1.52 0.467
*Differences statistically significant (Chi-square test). Number of non-response: three (case group), five (control group). b Number of non-response: two (case group). a
Table 2. Multivariate logistic regression model of the association between hormone replacement therapy and salivary flow.
Variable
Unadjusted OR (95% CI)
Adjusted ORa (95% CI)
p Value
p Value
Salivary flow (mL/min) Normal 1.00 1.00 Low 0.24 (0.07–0.85) 0.027* 0.22 (0.05–0.88) 0.034* Hyposalivation 0.23 (0.08–0.67) 0.007* 0.30 (0.10–0.92) 0.036* OR, odds ratio; 95% CI, 95% confidence interval. *Differences statistically significant (p50.05). a Adjusted for race and age.
Table 3. Analysis of the effect of type of hormone replacement therapy in the amount of salivary flow (mL/min). Variable Both HRT Estrogen HRT Estroprogestative HRT
Constant
R2
p Value
1.12 1.12 1.12
+0.52 +0.35 +0.53
0.09 0.02 0.09
0.005* 0.137 0.022*
, regression coefficient. R2 ¼ determination coefficient. *Differences statistically significant (p50.05).
The effect of HRT on salivary flow was also estimated (Table 3). It was observed that HRT may have been responsible for 9% of the variation in salivary flow, because the data showed an increase of 0.52 mL per minute in salivary flow (p ¼ 0.005).
HRT and salivary flow
DOI: 10.3109/09513590.2014.959918
In the analysis by type of HRT, the results suggest that estroprogestative therapy ( ¼ 0.53; p ¼ 0.022) has greater influence on the increase of salivary flow than estrogen therapy ( ¼ 0.35; p ¼ 0.137).
Discussion Many women undergo HRT to relieve the symptoms of menopause and post-menopause, being oral discomfort the most frequently reported symptoms [11,12]. The present study found difference in salivary flow between post-menopausal women undergoing HRT and those not receiving this therapy. In addition, estroprogestative therapy has greater increase on salivary flow than estrogen therapy. Similarly, a comparison on salivary flow rates between pre-, peri- and post-menopausal women was done and no difference was found on the salivary flow of women using estrogen and those not treated [13]. As in other studies [7,14], salivary flow rates were higher in pre-menopausal women than in post-menopausal women. Xerostomia is a common problem among older people and results from the linear loss of acinar cells, responsible for the production of saliva, which are replaced with fat or connective tissue [15–17]. This fact is supported by clinical trials showing a reduction in salivary flow during menopause [8,16,18]. In addition to the quantitative change, case–control studies have shown changes in the concentrations of substances in the saliva of women in menopause and xerostomia [5,19–22]. However, the exclusive development of xerostomia in older people is still a matter of debate. With respect to that, it was shown that the prevalence of xerostomia increases with age, affecting about 30% of the population above the age of 65 [23]. Studies suggest that HRT improves salivary flow rates. In a longitudinal study [15], the effects of HRT on salivary gland functions were evaluated and it was observed a quantitative and qualitative improvement on the sample studied. However, in contrast to the present investigation, these authors measured salivary flow before and after HRT and the sample consisted of peri- and post-menopausal women [15]. There is no concrete evidence that aging alone is responsible for the development of xerostomia [23]. In respect of that, it was not found an association between menopause and xerostomia in a case–control study [7]. Other authors also observed improvement of salivary flow in menopausal women after HRT. However, patients of the experimental group received calcium supplements and alendronate and, in contrast to the present study, the control group consisted of non-menopausal women [16]. HRT has been reported to cause changes in the oral mucosa, possibly improving epithelial integrity [24,25]. However, no differences were observed, in this study, on saliva production between women receiving HRT and those not receiving it, similarly to results found on a longitudinal cohort study that investigated salivary flow and biochemical variables in perimenopausal and early post-menopausal women submitted or not to HRT [25]. One possible explanation for that fact might be the low amount of saliva produced by the salivary glands of the oral and pharyngeal mucosa. The importance of saliva for physiological processes related to nutrition, speech and organic protection has been widely recognized [26,27]. However, most dentists have neglected the importance of xerostomia and related symptoms [28]. Alterations in salivary flow need to be adequately monitored and treated in order to improve the quality of oral health of affected patients. Therefore, knowledge about the etiology of the condition is necessary and the following steps need to be taken care of: control
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of the use of medications that cause this side effect, control of the underlying disease, oral hydration, and adequate symptomatic treatment [4]. Most studies investigating the effects of menopause on saliva comprised a small number of patients and there were no controlled clinical trials regarding the effect of HRT on salivary secretion and composition [12]. In addition, it was reported that the results are still conflicting, despite an increase in the number of studies in this area [29]. Therefore, randomized controlled studies taking into account the wide intra- and inter-individual variability in salivary flow rates are needed for a better understanding of this topic and, consequently, for a more adequate follow-up of those patients.
Conclusion The present results showed that salivary flow was influenced by HRT in the sample of post-menopausal women studied, and the results suggest that estroprogestative therapy has greater influence on the increase in salivary flow than estrogen therapy.
Declaration of interest The authors declare neither conflict of interest nor funding regarding the present study.
References 1. Dias BEG, Lima EC. Adaptac¸a˜o ao climate´rio e a ac¸a˜o da enfermeira. Revista Enfermagem Integrada 2008;1:25–38. 2. Pardini D. Menopause hormone therapy. Arq Bras Endocrinol Metabol 2007;51:938–42. 3. Turner M, Jahangiri L, Ship JA. Hyposalivation, xerostomia and the complete denture: a systematic review. J Am Dent Assoc 2008;139: 146–50. 4. Feio M, Sapeta P. Xerostomia in palliative care. Acta Med Port 2005;18:459–65. 5. Agha-Hosseini F, Mirzaii-Dizgah I, Mirjalili N. Relationship of unstimulated saliva cortisol level with severity of oral dryness feeling in menopausal women. Aust Den J 2011;56:171–4. 6. Rayman S, Dincer E, Almas K. Xerostomia. Diagnosis and management in dental pratice. NY State Dent J 2010;76:24–7. 7. Silva LFG, Lopes FF, Oliveira AEF. Estudo sobre o fluxo salivar e xerostomia em mulheres na pre´ e po´s-menopausa. Pesq Bras Odontoped Clin Integr 2007;7:125–9. 8. Lopes FF, Silva LFGE, Carvalho FL, Oliveira AEF. Estudo sobre xerostomia, fluxo salivar e enfermidades sisteˆmicas em mulheres na po´s-menopausa. RGO 2008;56:127–30. 9. Sreebny LM. Dry mouth and salivary gland hypofunction, Part I: diagnosis. Compendium 1988;9:569–78. 10. Moritsuka M, Kitasako Y, Burrow MF, et al. Quantitative assessment for stimulated saliva flow rate and buffering capacity in relation to different ages. J Dent 2006;34:716–20. 11. Meurman JH, Tarkkila L, Tiitinen A. The menopause and oral health. Maturitas 2009;63:56–62. 12. Mirzaii-Dizgah I, Agha-Hosseini F. Stimulated and unstimulated saliva progesterone in menopausal women with oral dryness feeling. Clin Oral Investig 2011;15:859–62. 13. Streckfus CF, Baur U, Brown LJ, et al. Effects of estrogen status and aging on salivary flow rates in healthy Caucasian women. Gerontology 1998;44:32–9. 14. Bhat S, Hegde S, Patil B, et al. A study on evaluation of the effect of menopause on saliva and dental health. J Adv Dental Res 2010;2: 33–6. 15. Laine M, Leimola-Virtanen R. Effect of hormone replacement therapy on salivary flow rate, buffer effect and pH in perimenopausal and postmenopausal women. Arch Oral Biol 1996;41:91–6. 16. Yalc¸in F, Gurgan S, Gurgan T. The effect of menopause, hormone replacement therapy (HRT), alendronate (ALN), and calcium supplements on saliva. J Contemp Dent Pract 2005;6:10–17. 17. Liu B, Dion MR, Jurasic MM, et al. Xerostomia and salivary hypofunction in vulnerable elders: prevalence and etiology. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:52–60.
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18. Minicucci EM, Pires RA,VieiraRa RB, et al. Assessing the impact of menopause on salivar flow and xerostomia. Aust Dent J 2013;58: 230–4. 19. Agha-Hosseini F, Mirzaii-Dizgah I, Mirjalili N. Relationship of stimulated whole saliva cortisol level with the severity of a feeling of dry mouth in menopausal women. Gerodontology 2012; 29:43–7. 20. Mirzaii-Dizgah I, Agha-Hosseini F. Stimulated and unstimulated saliva progesterone in menopausal women with oral dryness feeling. Clin Oral Investig 2011;15:859–62. 21. Agha-Hosseini F, Moosavi MS, Mirzaii-Dizgah I. Salivary flow, testosterone, and femur bone mineral density in menopausal women with oral dryness feeling. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:612–16. 22. Agha-Hosseini F, Mirzaii-Dizgah I, Moosavi MS. Relationship of serum and saliva calcium, phosphorus and alkaline phosphatase with dry mouth feeling in menopause. Gerodontology 2012;29: 1902–7.
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23. Ship JA, Pillemer SR, Baum BJ. Xerostomia and the geriatric patient. J Am Geriatric Soc 2002;50:535–43. 24. Jensen SB, Pedersen AM, Reibel J, Nauntofte B. Xerostomia and hypofunction of the salivary glands in cancer therapy. Support Care Cancer 2003;11:207–25. 25. Tarkkila L, Furuholm J, Tiitinen A, Meurman JH. Saliva in perimenopausal and early postmenopausal women. A 2-year follow-up study. Clin Oral Investig 2012;16:767–73. 26. Ettinger RL. Xerostomia: a symptom which acts like a disease. Age Ageing 1996;25:409–12. 27. Llena-Puy C. The role of saliva in maintaining oral health and as an aid to diagnosis. Med Oral Patol Oral Cir Bucal 2006;11:E449–55. 28. Sreebny LM, Valdini A, Yu A. Xerostomia. Part II: relationship to nonoral symptoms, drugs, and diseases. Oral Surg Oral Med Oral Pathol 1989;68:419–27. 29. Ferraz PCGF, Trindade MS, Brito LGO, et al. Avaliac¸a˜o da influeˆncia da terapia hormonal na sau´de oral de mulheres na menopausa. Reprod Clim 2009;24:107–12.
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HRT AND SALIVARY BLOOD FLOW
The influence of hormone replacement therapy on the salivary flow of post-menopausal women Marı´lia Leal Ferreira Lago1, Ana Emilia Figueiredo de Oliveira1, Fernanda Ferreira Lopes1, Elza Bernardes Ferreira1, Vandilson Pinheiro Rodrigues2, and Luciane Maria Oliveira Brito2 1
Department of Dentistry, Federal University of Maranha˜o, Bacanga, Brazil and 2Department of Medicine, Federal University of Maranha˜o, Pinheiro, Brazil Abstract
Keywords
The aim of this study is to investigate the influence of hormone therapy on salivary flow in menopausal women. It is a case–control study involving 86 post-menopausal women. The case group consisted of 47 women undergoing estroprogestative or estrogen hormone replacement therapy (HRT), and the control group consisted of 39 women who did not receive any HRT. All patients were submitted to a standard questionnaire, followed by total stimulated sialometry and determination of body mass index (BMI). The salivary flow was classified as follows: normal (1.0–3.0 mL/min), low (0.7–1.0 mL/min), and hyposalivation (50.7 mL/min). The results were analyzed statistically by the chi-square test, logistic regression model, and linear regression (p50.05). The HRT group presented an association of protection, even after adjusting the analysis, for low salivary flow (Adjusted OR ¼ 0.22; 95% CI ¼ 0.05–0.88; p ¼ 0.034), and hyposalivation (Adjusted OR ¼ 0.30; 95% CI ¼ 0.10–0.92; p ¼ 0.036). The results suggest that estroprogestative therapy ( ¼ + 0.53; p ¼ 0.022) has greater influence on the increase of salivary flow than estrogen therapy ( ¼ +0.35; p ¼ 0.137). The study concludes stating salivary flow was influenced by HRT on the post-menopausal women studied.
Hormone replacement therapy, menopause, salivation
Introduction Although a physiological phenomenon, the climacteric causes symptoms that interfere with women’s well-being, such as hot flushes, dry skin, brittle nails and hair, vaginal dryness, and dyspareunia [1]. One of the treatments indicated for the relief of those symptoms is the hormone replacement therapy (HRT), which can be used in peri- or post-menopausal women. HRT consists of the administration of estrogen alone or combined with progestogens [2]. Studies have shown that the physiological changes associated with menopause can cause oral alterations, such as a reduced salivary flow and an increased sensitivity, stinging and burning sensation and pain in the oral mucosa [3]. Xerostomia is the subjective feeling of dryness in the mouth as a result of the reduction or interruption of the salivary gland function accompanied by changes in quantity or quality of saliva [4,5]. The diagnosis of xerostomia and/or reduced salivary flow is basically made in a clinical way and should take into account the various medications that can cause or exacerbate the condition [6]. The current functional status should be evaluated in detail by using quantitative methods for determination of salivary secretion at rest or after stimulation [4]. Studies have investigated possible alterations to salivary flow in pre- and post-menopausal women. In a case–control
Address for correspondence: Dr. Fernanda Ferreira Lopes, Department of Dentistry, Federal University of Maranha˜o, Portugueses Av, 1966, Bacanga, Sa˜o Luı´s, 65080850, Brazil. E-mail: fernanda.f.lopes@ gmail.com
History Received 19 May 2014 Revised 19 August 2014 Accepted 27 August 2014 Published online 15 September 2014
study analyzing salivary flow and xerostomia in pre- and post-menopausal women no association was found between menopause and xerostomia [7]. It was also reported on the specific literature that xerostomia and quantitative changes in salivary flow are common findings in post-menopausal women [8]. Although recent studies on xerostomia and/or reduced salivary flow are available, few reports have investigated the influence of HRT on these conditions in climacteric women. In addition, there is a lack of studies comparing the effects of different types of HRT on xerostomia or reduced salivary flow. Therefore, the objective of this study was to compare the salivary flow between postmenopausal women who were submitted or not to estroprogestative and estrogen HRT.
Methods A case–control study was conducted at the Gynecology outpatient clinic of the Maternal and Infant University Hospital (Federal University of Maranha˜o — UFMA). The study was approved by the Ethics Committee of the institution (Permit No. 004395/2009-60) and it was carried out according to the Declaration of Helsinki, reviewed in 2008. The sample consisted of 86 women divided into a case group and a control group. The case group consisted of 47 postmenopausal women undergoing estroprogestative or estrogen HRT for at least 12 consecutive months. The control group consisted of 39 post-menopausal women who did not wish to take HRT or who presented some contraindication for its use. Women with a history of liver disease, endocrinopathy and thromboembolic events, smokers, women who had used any other
110
M. L. F. Lago et al.
hormonal medication in the last 12 months, and women with a family history (first-degree relatives) of breast, ovary or endometrial cancer were excluded from the study. Women who presented abnormalities in the laboratory tests or imaging exams (transvaginal or pelvic ultrasound and mammography) that contraindicated HRT were also excluded. After anamnesis, the patients were submitted to a full stimulated sialometry as described by Sreebny [9]. Saliva was collected with the patient in a comfortable sitting position and with the head slightly tilted forward. The women were asked to chew on a piece of tasteless paraffin (0.29 g; Parafilm ‘‘M’’Õ, American National CanÔ, Chicago, IL) to stimulate saliva production. The saliva samples produced over a period of 5 min were collected into a graduated container at 1-min intervals. Stimulated salivary flow is expressed as milliliter per minute (mL/min) and was classified as follows: normal flow (1.0–3.0 mL/min), low flow (0.7–1.0 mL/min), and hyposalivation (50.7 mL/min) [10]. A chart was used to record the following data: name, age, race, age at menarche, the duration of pre-menopausal period menacme, parity, age at menopause, duration of menopause, schooling level, marital status, and occupation. In addition to gynecological data and the findings of the general tests, the xerostomia and salivary flow evaluation results were also added. The results were analyzed by using the BioEstat 5.0 software (Mamiraua´ Civil Society/MCT, CNPq, Bele´m, Brazil). The classificatory variables (age group, race) were compared between the two groups (control and case) by the non-parametric chisquare ( 2) test for independence. The measure of association obtained by Odds Ratio (OR) with their respective confidence intervals at 95% (95% CI) was used to estimate the association between HRT and salivary flow. A multivariate logistic regression analysis was applied taking into account the confounding covariates (p50.10) to obtain the adjusted measure of association. Furthermore, a linear model was used to estimate the effect of HRT on the salivary flow. In this procedure, the measures calculated were the constant and regression coefficient ( ) and determination coefficient (R2). The level of significance for rejection of null hypothesis was set at 5%, i.e. a p value50.05 was considered to be statistically significant.
Results The comparative analysis by chi-square test revealed a significant difference (p50.05) for the variables race and salivary flow. The frequency of white women was higher in the case group (53.2%), whereas mulatto women were predominant in the control group (51.3%). Furthermore, the results suggest an association between salivary flow and HRT in the study sample (p ¼ 0.006). Most women undergoing hormone replacement showed normal salivary flow (72.3%), whereas in the control group, 61.5% of women were diagnosed with low salivary flow or hyposalivation. There were no statistically significant differences between groups for the variables related to reproduction included in this study (p 0.05). In both groups, the majority of women reported the occurrence of menarche after 13 years, menacme before the age of 32, and menopause after 45 years (Table 1). Table 2 shows the association measurement between salivary flow and HRT, obtained by logistic regression analysis. The results demonstrate that the chance of low salivary flow was 78% lower after adjusted analysis for age and race (OR ¼ 0.22; 95% CI ¼ 0.05–0.88; p ¼ 0.034) in the group of women undergoing HRT. After adjusted analysis, the data also showed that the chance of hyposalivation is 70% lower for the case group compared to the control one (OR ¼ 0.30; 95% CI ¼ 0.10–0.92; p ¼ 0.036).
Gynecol Endocrinol, 2015; 31(2): 109–112
Table 1. Distribution of clinical characteristics and reproductive variables in the study groups. Case (n ¼ 47) Control (n ¼ 39) Variable Race White Mulatto Black Age (in years) 39 40–49 50–59 60 Salivary flow (mL/min) Normal Low Hyposalivation Menarche (in years) 513 13 413 Number of children 0 1–3 4 Menacme (in years)a 32 33–36 37 Menopause (in years)b 545 45–49 50
2 p Value
n
(%)
n
(%)
25 18 4
(53.2) (38.3) (8.5)
11 20 8
(28.2) (51.3) (20.5)
1 5 24 17
(2.1) (10.6) (51.1) (36.2)
0 10 19 10
(0) (25.6) (48.8) (25.6)
34 5 8
(72.3) (10.6) (17.1)
15 9 15
(38.5) (23.0) (38.5)
13 13 21
(27.7) (27.7) (44.6)
15 6 18
(38.5) (15.4) (46.1)
14 18 15
(29.8) (38.3) (31.9)
7 19 13
(18.0) (48.7) (33.3)
18 13 13
(41.0) (29.5) (29.5)
14 12 8
(41.2) (35.3) (23.5)
15 14 17
(33.3) (31.0) (37.7)
13 16 10
(33.4) (41.0) (25.6)
6.19 0.045*
5.16 0.160
9.98 0.006*
2.23 0.327
1.77 0.412
0.46 0.794
1.52 0.467
*Differences statistically significant (Chi-square test). Number of non-response: three (case group), five (control group). b Number of non-response: two (case group). a
Table 2. Multivariate logistic regression model of the association between hormone replacement therapy and salivary flow.
Variable
Unadjusted OR (95% CI)
Adjusted ORa (95% CI)
p Value
p Value
Salivary flow (mL/min) Normal 1.00 1.00 Low 0.24 (0.07–0.85) 0.027* 0.22 (0.05–0.88) 0.034* Hyposalivation 0.23 (0.08–0.67) 0.007* 0.30 (0.10–0.92) 0.036* OR, odds ratio; 95% CI, 95% confidence interval. *Differences statistically significant (p50.05). a Adjusted for race and age.
Table 3. Analysis of the effect of type of hormone replacement therapy in the amount of salivary flow (mL/min). Variable Both HRT Estrogen HRT Estroprogestative HRT
Constant
R2
p Value
1.12 1.12 1.12
+0.52 +0.35 +0.53
0.09 0.02 0.09
0.005* 0.137 0.022*
, regression coefficient. R2 ¼ determination coefficient. *Differences statistically significant (p50.05).
The effect of HRT on salivary flow was also estimated (Table 3). It was observed that HRT may have been responsible for 9% of the variation in salivary flow, because the data showed an increase of 0.52 mL per minute in salivary flow (p ¼ 0.005).
HRT and salivary flow
DOI: 10.3109/09513590.2014.959918
In the analysis by type of HRT, the results suggest that estroprogestative therapy ( ¼ 0.53; p ¼ 0.022) has greater influence on the increase of salivary flow than estrogen therapy ( ¼ 0.35; p ¼ 0.137).
Discussion Many women undergo HRT to relieve the symptoms of menopause and post-menopause, being oral discomfort the most frequently reported symptoms [11,12]. The present study found difference in salivary flow between post-menopausal women undergoing HRT and those not receiving this therapy. In addition, estroprogestative therapy has greater increase on salivary flow than estrogen therapy. Similarly, a comparison on salivary flow rates between pre-, peri- and post-menopausal women was done and no difference was found on the salivary flow of women using estrogen and those not treated [13]. As in other studies [7,14], salivary flow rates were higher in pre-menopausal women than in post-menopausal women. Xerostomia is a common problem among older people and results from the linear loss of acinar cells, responsible for the production of saliva, which are replaced with fat or connective tissue [15–17]. This fact is supported by clinical trials showing a reduction in salivary flow during menopause [8,16,18]. In addition to the quantitative change, case–control studies have shown changes in the concentrations of substances in the saliva of women in menopause and xerostomia [5,19–22]. However, the exclusive development of xerostomia in older people is still a matter of debate. With respect to that, it was shown that the prevalence of xerostomia increases with age, affecting about 30% of the population above the age of 65 [23]. Studies suggest that HRT improves salivary flow rates. In a longitudinal study [15], the effects of HRT on salivary gland functions were evaluated and it was observed a quantitative and qualitative improvement on the sample studied. However, in contrast to the present investigation, these authors measured salivary flow before and after HRT and the sample consisted of peri- and post-menopausal women [15]. There is no concrete evidence that aging alone is responsible for the development of xerostomia [23]. In respect of that, it was not found an association between menopause and xerostomia in a case–control study [7]. Other authors also observed improvement of salivary flow in menopausal women after HRT. However, patients of the experimental group received calcium supplements and alendronate and, in contrast to the present study, the control group consisted of non-menopausal women [16]. HRT has been reported to cause changes in the oral mucosa, possibly improving epithelial integrity [24,25]. However, no differences were observed, in this study, on saliva production between women receiving HRT and those not receiving it, similarly to results found on a longitudinal cohort study that investigated salivary flow and biochemical variables in perimenopausal and early post-menopausal women submitted or not to HRT [25]. One possible explanation for that fact might be the low amount of saliva produced by the salivary glands of the oral and pharyngeal mucosa. The importance of saliva for physiological processes related to nutrition, speech and organic protection has been widely recognized [26,27]. However, most dentists have neglected the importance of xerostomia and related symptoms [28]. Alterations in salivary flow need to be adequately monitored and treated in order to improve the quality of oral health of affected patients. Therefore, knowledge about the etiology of the condition is necessary and the following steps need to be taken care of: control
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of the use of medications that cause this side effect, control of the underlying disease, oral hydration, and adequate symptomatic treatment [4]. Most studies investigating the effects of menopause on saliva comprised a small number of patients and there were no controlled clinical trials regarding the effect of HRT on salivary secretion and composition [12]. In addition, it was reported that the results are still conflicting, despite an increase in the number of studies in this area [29]. Therefore, randomized controlled studies taking into account the wide intra- and inter-individual variability in salivary flow rates are needed for a better understanding of this topic and, consequently, for a more adequate follow-up of those patients.
Conclusion The present results showed that salivary flow was influenced by HRT in the sample of post-menopausal women studied, and the results suggest that estroprogestative therapy has greater influence on the increase in salivary flow than estrogen therapy.
Declaration of interest The authors declare neither conflict of interest nor funding regarding the present study.
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