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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 32  |  Issue : 3  |  Page : 241-246

Qualitative analysis of serum estrogen, parathyroid and calcium levels in postmenopausal women with oral dryness- A case-control study


1 Department of Oral Medicine, Diagnosis and Radiology, SGRD Institute of Dental Sciences and Research, Amritsar, Punjab; Maharaja Vinayak Global University, Jaipur, Rajasthan, India
2 Department of Oral Medicine, Diagnosis and Radiology, Jaipur Dental College, Jaipur, Rajasthan, India
3 Department of Oral Surgery, SGRD Institute of Dental Sciences and Research, Amritsar, Punjab, India
4 Department of Oral Pathology, SGRD Institute of Dental Sciences and Research, Amritsar, Punjab, India
5 Department of Orthodontics, SGRD Institute of Dental Sciences and Research, Amritsar, Punjab, India

Date of Submission12-Apr-2020
Date of Decision19-May-2020
Date of Acceptance27-Jun-2020
Date of Web Publication29-Sep-2020

Correspondence Address:
Dr. Balwinder Singh
Department of Oral Medicine and Radiology, SGRD Institute of Dental Sciences and Research, Amritsar - 143 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaomr.jiaomr_58_20

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   Abstract 


Background: The emergence of oral dryness unrelated to salivary flow volume has always raised many questions over the hypothesis of oral dryness in postmenopausal women. The current research article tries to focus on qualitative changes in saliva in the postmenopausal women suffering from oral dryness. Aim and Objectives: To correlate the severity of oral dryness with qualitative changes in serum estrogen, serum parathyroid (PTH), serum calcium levels in postmenopausal women. Materials and Methodology: This case-control study was carried out on 60 postmenopausal women with 30 forming the case groups as having oral dryness and 30 forming control group without oral dryness. The severity of oral dryness was assessed through the Xerostomia Inventory Score (XI Score). Serum estrogen and serum parathyroid levels were assessed by the ELISA method and serum calcium levels were assessed by Arsenazo III reaction using a semi-autoanalyzer in all participants. Statistical analysis was done by student's t- test and Pearson correlation. Results: Significant differences were observed in the mean values of serum estrogen levels, serum parathyroid levels, and XI score between the case and control groups. (P < 0.001). Serum calcium levels did not show significant variation (P= 0.385) between the groups. The correlation proved that there was an inverse correlation between estrogen levels and XI scores (r-value -0.777). Conclusion: The severity of oral dryness was associated with decreased levels of estrogen and increased levels of parathyroid hormones in postmenopausal women. Fall in estrogen levels is associated with an increase in oral dryness.

Keywords: Estrogen, oral dryness, postmenopausal, XI score


How to cite this article:
Singh B, Desai V, Sharma R, Kaur K, Narang RS, Kahlon S. Qualitative analysis of serum estrogen, parathyroid and calcium levels in postmenopausal women with oral dryness- A case-control study. J Indian Acad Oral Med Radiol 2020;32:241-6

How to cite this URL:
Singh B, Desai V, Sharma R, Kaur K, Narang RS, Kahlon S. Qualitative analysis of serum estrogen, parathyroid and calcium levels in postmenopausal women with oral dryness- A case-control study. J Indian Acad Oral Med Radiol [serial online] 2020 [cited 2020 Dec 5];32:241-6. Available from: https://www.jiaomr.in/text.asp?2020/32/3/241/296589




   Introduction Top


The oral cavity is often known as a window to the body because aging changes and many systemic diseases have their oral manifestations accompanying them.[1] These oral manifestations must be properly recognized and understood if the patient is to receive appropriate diagnosis and referral for an accurate treatment plan. Menopause is one of the aging mechanisms, which is a physiological change that causes some women to undergo some uncomfortable signs and symptoms such as hot flashes, sweating at night, and vaginal dryness.[2],[3] Also, a reduced level of estrogen as a result of menopause is associated with age-related factors which disproportionately increases the risk of developing cardiovascular disease, osteoporosis, Alzheimer's disease, and oral diseases. Estrogen is known to affect about 300 different tissues of the body and hence its reduced level will result in some physiological changes.[4]

Oral dryness or burning sensation has been observed in postmenopausal women with a history of medication for some systemic disorders, which are mostly because of the side effects of such medications. Oral dryness is also observed in patients with salivary hypo-function and some oral mucosal lesions.

Oral dryness has also been reported in those postmenopausal women who are not suffering from any systemic disease and thus are not under any medication. Oral dryness in these cases is unassociated with reduced salivary flow rate; has normal oral mucosal findings and is mostly attributed to estrogen deficiency.[1],[5] The cases pose a challenge to oral physicians and are difficult to diagnose, understand, and manage.[2],[6]

The composition of saliva in menopausal women is mostly estrogen- dependent.[7],[8],[9] According to F Agha-Hosseini et al. in 2007,[5] the mean concentration of stimulated whole salivary calcium is significantly higher in patients with oral dryness. The concentration of calcium in saliva becomes low when the estrogen level is high. Salivary calcium level is also decreased in stimulated saliva with hormonal replacement therapy in healthy menopausal women.[10]

Calcium is of great biological importance. Parathyroid hormone (PTH), Calcitonin, and Vitamin D are concerned with its regulation. Parathyroid hormone is an important hormone in calcium turnover. The parathyroid glands can also suffer alterations due to the lack of estrogen. Due to this, the glands occasionally become hyperactive, thereby contributing to the mobilization of calcium and phosphorus deposits in osteoporosis.[11]

Thus estrogen plays an important role in calcium metabolism by preventing the loss of calcium from bones in menopausal women. As excessive salivary calcium was found in postmenopausal women with oral dryness,[5],[7] the parathyroid hormone which regulates calcium turnover along with serum estrogen was evaluated in this study to correlate its level with severity of oral dryness in serum samples.


   Subjects and Materials Top


The subjects of this case-control study were postmenopausal women who reported to the Department of Oral Medicine and Radiology. The inclusion criteria for the selection of postmenopausal women for the study was that no menstrual cycle should have occurred for atleast past 24 months and subjects should not be taking any systemic medication. The written informed consent were obtained in both English and local language from all the patients before the conduct of the study. The research followed all the protocol and principles laid down under the Helsinki declaration: The well-being of human subjects should take precedence over the interests of science and society.

Most of the case group patients came with the chief complaint of oral dryness without any mucosal lesion being evident. The rest of the postmenopausal women patients comprised of patients reporting for a regular dental- check up or prosthesis who were put under the control group. Patients with a history of systemic diseases, Sjogren' s syndrome, gynecological problems, any disease affecting calcium, PTH metabolism were excluded from this study. Oral mucosal lesions like candidiasis, poor oral hygiene, and periodontitis were excluded from this study by a thorough intraoral clinical examination. Tobacco users were also excluded. All the participants were subjected to a questionnaire comprising of 10 questions with a list of symptoms related to xerostomia.[12][Table 1]. The participants who affirmatively answered at least one of the questions were included in the study. Thirty such postmenopausal women were selected. The participants who did not answer positively to any question formed the control group of patients without oral dryness. Thirty such postmenopausal women were selected. Each participant was then given another questionnaire so that the severity of xerostomia could be assessed.[13][Table 2]. The Xerostomia Inventory (XI) score was determined as the severity of dry mouth feeling. The scores of responses were added to provide a Xerostomia Inventory score for each individual. The minimum possible score was 11 and the maximum possible score was 55 for each individual.
Table 1: Questionnaire used for selection of subjects with xerostomia (oral dryness feeling)

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Table 2: The xerostomia inventory (XI) Score

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Blood collection

The blood was collected with a 10 ml sterile, disposable syringe, and a 24-gauge needle. Under proper aseptic conditions, the antecubital vein was punctured and 7.5ml blood was drawn. The collected blood was transferred to a sterile blood collecting tube. This was centrifuged at 2000 Rpm for five minutes and the serum was separated and stored at –20°C for determination of estrogen, parathyroid level. The estrogen and parathyroid hormone were estimated by Enzyme- Linked Immunosorbent Assay Method with the help of ELISA reader. The calcium levels were assessed the same day by a mechanism of the Arsenazo III reaction with the help of a semi-autoanalyzer.

Statistical analysis

The two-tailed Student's unpaired t-test was used to check if a significant difference exists between means of two sets of observations for XI Score, serum estrogen, serum calcium, serum PTH. The Pearson correlation was used to check if any linear correlation exist between XI Score and variables of study that are serum calcium, serum PTH and serum estrogen levels. Statistical analysis was conducted using SPSS for windows version 17 (SPSS Inc. Chicago, IL, USA).P < 0.05 was considered statistically significant.


   Results Top


The student t- test showed that there was no significant difference between the mean ages of case and control group with the P- value of 0.62. The mean age was 57.73 ± 5.84 years for the case group and control group the mean age was 60.70 ± 6.23. The minimum age of the subject included in the study was 49 years and the maximum age of the participant is of 75 years.

The mean value of XI scores in the case group was 25.6 and 15.67 in the control group with a significant difference. (P < 0.001) [Table 3],[Table 4].
Table 3: Mean values of serum calcium, serum estrogen, serum parathyroid level, xerostomia inventory score in case group & control group

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Table 4: Comparison (t.Test) of Mean Values of Serum Calcium, Serum Estrogen, Serum Parathyroid Level, Xerostomia Inventory Score in case group & control group

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The mean value of serum calcium concentration was marginally lower in the case group (8.39 mg/dl) in comparison to serum calcium in the control group (8.83 mg/dl). There was no statistically significant difference in mean values. (P- value 0.385) [Table 3],[Table 4].

The mean serum PTH levels in the case group were estimated to be 55.32 pg/ml and in the control group was 31.24 pg/ml with statistically significantly differences between the groups. (P <.001) [Table 3],[Table 4].

The mean serum estrogen concentration in the case group was estimated to be 23.0 pg/ml and in the control group was 44.16 pg/ml with statistically significantly differences between the groups. (P <.001) [Table 3],[Table 4].

A Pearson correlation was performed to see if relationships existed between XI score and other parameters of the study, the correlation proved that Xi score correlated positively with serum PTH with a correlation coefficient of 0.628 and showed an inverse correlation with serum estrogen level with a correlation coefficient of -0.777 in both the groups. There was no significant correlation found between serum calcium and XI score with a correlation coefficient of -0.060(r=0.651)in both groups together [Table 5].
Table 5: Pearson Correlations to Assess Any Correlation between all variables In The Total Sample Size

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   Discussion Top


Menopause, the physiologic process in the female is due to decreased estrogen production in the body. Oral symptoms are also found in addition to the more general manifestations of menopause. An increased incidence of dry mouth (xerostomia), burning mouth syndrome, disorders such as lichen planus, benign pemphigoid, and, as well as a debated rise in the prevalence of periodontal disease are seen as manifestations of menopause.[14]

Xerostomia, also known as dry mouth is mostly associated with a reduced salivary flow but changes in the qualitative components of saliva might have a role to play in establishing the etiopathogenesis of the oral dryness. Rather oral dryness feeling due to qualitative changes in the saliva is always more difficult to diagnose and treat. Many theories have been suggested to understand the etiopathogenesis of this oral dryness in postmenopausal women, but the most accepted theory so far is due to the hormonal changes in the body seen after menopause.[15],[16]

Our study included postmenopausal women with and without oral dryness as case and control groups, respectively. The severity of oral dryness, levels of serum calcium, serum PTH, serum estrogen, and their corelations were studied. The suggested mechanism was that a low level of estrogen in menopausal women could influence the severity of oral dryness, which also may affect the general metabolism of bone due to altered PTH levels.[11] Our study also proved that the severity of xerostomia was more in the case group in which the estrogen level was less. The oral dryness not only affects the salivary flow but also leaves its impact on the composition of saliva. The previous studies have also shown that the level of estrogen status affects the saliva composition. This was reported by F Agha- Hosseini et al. in 2007 and 2009, S Ravinder et al. in 2010, I M Dizgah et al. in 2010.[5],[7],[8],[9]

Oral dryness in such cases might be due to the undetermined qualitative changes in the salivary composition, an imbalance between the various salivary glands or changes in the mucosal sensory receptors.[17] The high prevalence of oral discomfort in women at menopause was also reported by Forabosco et al. and Wardrop et al.[16],[18]

The low estrogen levels lead to low calcium in the body. This in turn increases PTH levels which further leads to the release of calcium from bones. This leads to the weakening of bones and making them more prone to diseases like osteoporosis and fractures. With estrogen deficiency causing calcium level to oscillate downwards, it also causes the Parathyroid hormone levels to go up. Parathyroid hormone is an important hormone in calcium turnover with its main function being the maintenance of the calcium level in extracellular fluid. The secretion of parathyroid hormone is stimulated by hypocalcemia and suppressed by hypercalcemia.[19]

In our study, it was found that the levels of calcium remained unchanged in both case and control groups even though changes in the levels of both PTH and estrogen were seen in both case and control groups. This confirms with the result of studies by F Agha- Hosseini in 2009 and Sewon et al. in 1998.[8],[10]

The reason for this may be that serum calcium is regulated by many other factors that may prevent its fall in blood. So, it may be possible that an elevated calcium is excreted by saliva or urine. According to Gallagher JC et al., the decrease in female hormones, especially estradiol, suppresses the intestinal absorption of calcium.[20] This may lead to elevated concentration of serum parathyroid hormone and thus causing enhanced bone resorption. The resorption of bone may lead to diffusion of calcium into the blood and further into the saliva or excreted through urine.

In our study, patients with oral dryness had significantly increased levels of parathyroid hormone and decreased levels of estrogen. The results also indicate that serum parathyroid hormone level is significantly higher in oral dryness individuals, and a positive correlation exists between serum parathyroid hormone levels, serum estrogen levels, and severity of oral dryness. These results were in harmony with the results of the study conducted previously by F Agha Hosseini in 2009, Singh R et al. in 2010 and Singh B et al. in 2016.[7],[8],[21]

A study by F Agha Hosseini in 2011 came to the same conclusion. He concluded in his study that there was a significant negative correlation between xerostomia inventory score and bone mineral density in postmenopausal women indicating that oral dryness severity was associated with decreasing bone mineral density.[22] The observations are consistent with the hypothesis suggested by Khosla Sandeep et al. in 1997 that within the first 20 years after the menopause, the direct skeletal effects of estrogen deficiency are primarily responsible for the increase in bone resorption also indirectly results in secondary hyperparathyroidism.[23]

Furthermore, estrogens prevent osteoporosis by inhibiting the stimulatory effects of certain cytokines on osteoclasts. Hence menopausal women have been considered at risk for periodontitis because of osteoporosis of the alveolar bone.[19] In many studies such as those by C. Gallagher in 1980, Yalcin F. in 2005 and, Siva Reddy et al. in 2008, it was concluded that lower levels of estrogen may also induce bone resorption.[20],[24],[25]

Hence the levels of calcium and parathyroid hormone seem to be affected mostly by the levels of estrogen. So the maintenance of estrogen level may prevent oral discomfort along with other systemic problems in postmenopausal women. So it seems that hormone replacement therapy (HRT) may play a major role in alleviating oral discomfort in these women.[10],[26] As concluded by Giuca et al. in 2009, Elliason et al. in 2003, in postmenopausal women when serum estrogen levels were maintained,[27],[28] oral health improvement was seen. In the postmenopausal women with osteoporosis who did not receive HRT had a greater incidence of adverse dental outcomes and incurred higher dental care costs than those who received HRT as projected by Allen et al. in 2000.[29]

So it can be stated that hormonal replacement may have a great role to play in normal physiological processes of the body and in maintaining the well-being of the patients regarding the severity of the effects of increased levels of parathyroid hormone.

Also, the study highlights the emergence of oral dryness feeling in postmenopausal women in the present scenario as a possible indicator for levels of serum parathyroid hormone, serum estrogen, and their possible roles in maintaining bone integrity. This study also proves that there is a positive correlation between xerostomia score and serum parathyroid hormone and a negative correlation between serum estrogen and xerostomia score. As the level of serum estrogen level goes down and the parathyroid hormone level also goes up, xerostomia score increases in postmenopausal women, to our knowledge this is the first study to find this correlation involving all of the factors together.

Further studies are needed to evaluate the role of hormone replacement therapy if instituted in such patients will result in alleviation of oral dryness symptoms. Also whether menopausal women with oral dryness suffer from osteoporosis and what the role of parathyroid hormone in these relationships could be.

Furthermore, larger sample size and a long-term assessment in the form of a longitudinal study are needed to further corroborate the findings of the present study.


   Conclusion Top


The levels of serum estrogen correlated negatively with the severity of the xerostomia score indicating a fall in estrogen level results in more oral dryness in postmenopausal women. So, the presence of signs and symptoms of oral dryness in postmenopausal women could be a possible risk factor for the possible development of osteoporosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Ethical considerations

The approval for the study was obtained from the Ethical Committee of the Maharaja Vinayak Global University, Jaipur with letter number JDC/PO/2015/1922D/1.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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