INTRODUCTION:

Alveolar bone loss (BL), periodontal pocket, gingival inflammation, and clinical attachment loss (CAL) are a few of the many significant clinical hallmarks of periodontitis¹. With a few notable exceptions, most cases of periodontitis are the result of chronic inflammations that can worsen either gradually or intermittently^2-4.

Bone loss next to the pocket epithelium, junctional epithelium apical to the cemento-enamel junction, multiple polymorphonuclear leukocytes in the junctional and pocket epithelium, and a dense inflammatory cell infiltrate including plasma cells, lymphocytes, and macrophages are among the histopathological characteristics pertaining to periodontitis^1,5-7. From a practical standpoint, a woman is deemed to be perimenopausal if, at the proper age (often ≥45), she exhibits irregular menstrual periods and signs of the approaching menopause. The experience that is specifically acceptable for membership in the perimenopause or menopausal transition is the onset of irregular and variable-length menstrual cycles [for specific menstrual criteria, refer to the Stages of Reproductive Ageing Workshop (STRAW) approach]. Menstrual cycles are notably shorter for many women in their late reproductive years (mean cycle duration of 25–26 days instead of 28–29 days)^8–10. Cycle length might vary from about 14 to 50 days in females approaching the perimenopause^11–13. In addition to the monthly cycle of menstruation and the menopausal transition, the majority of women in late reproductive age have at least mild symptoms^14–19. A little over half of women have symptoms such as headache, pains or stiffness in the joints, soreness in the back, insomnia, hot flushes, and difficulty focusing even prior to the early stages of perimenopause^20–21. Although typical, discomfort in the breasts lessens as one approaches the final menstrual period (FMP)^22–23. About 10% of women in a large British cohort reported having severe vasomotor symptoms (VMS) before the perimenopause, while up to 30% said they had deep VMS after the perimenopause began. Vasomotor symptoms typically worsen as the perimenopause advances from early to late, and they typically last for the whole one to three years following the menopause²⁰.

Stress originates when an individual's capacity to overcome adversity—that is, become accustomed to or endorse it—declines in tandem with real or imagined environmental demands, like an impending dangerous stimuli or circumstance. A continual state of stress is typically thought to have a detrimental effect on immune system responsiveness, which may ultimately contribute to a parasite-host disequilibrium and periodontal deterioration²⁴. Analysis illustrates that immunological responses triggered by psychological stress or other psychosomatic illnesses may assist or exacerbate changes in the oral cavity, particularly periodontitis^25,26.

Stress triggers the brain's evasive motivational system, which encourages behaviours meant to shield the organism against imagined threats in the future^27–28. In addition to being necessary for maintaining and facilitating the development of calcified tissues, such teeth and bones, calcium is also necessary for the best possible operation of muscles and other physiological systems²⁹. Low levels of oestrogen have been linked to insufficient calcium in perimenopausal and postmenopausal women because oestrogen encourages the intestines to absorb calcium and transfer it to the bone. Reduced oestrogen may make it more difficult for perimenopausal and postmenopausal women's gastrointestinal tracts to absorb calcium, which would lower their calcium levels³⁰.

Thus, the aim of the present study is to compare the relationship between psychological stress and salivary levels of calcium, a key biomarker, in two groups of perimenopausal women: one with chronic periodontitis and a second group without chronic periodontitis.

MATERIAL AND METHODS:

A minimum of 20 teeth and adequate systemic health were required for all analyses to include female participants between the ages of 45 and 55. Participants in Group I were assessed for psychological stress using the Perceived Stress Scale Questionnaire; those who answered affirmatively for moderate and severe stress were recruited in Group I. Participants in GroupI fulfilled the CDC criteria for gingival index scores of 1 to 2 (moderate gingivitis) and interdental clinical attachment loss of greater than 3 mm. GroupII participants' psychological stress was assessed using the Perceived Stress Scale Questionnaire, and those who scored low on the scale were likely to be included. The participants that met the CDC requirements for gingival index scores of less than 1 and interdental clinical attachment loss of less than 3 mm (For Group II) were chosen to participate.

Participants with any systemic or metabolic diseases, those receiving corticosteroid therapy, antibiotics, anxiety medication, or who have had periodontal therapy in the preceding six months, as well as those who are still wearing orthodontic appliances or dental prostheses, were excluded from the current investigation. Subjects with unfavorable oral health practices were also excluded from the study, encompassing drinking alcohol, consuming betel nuts, smoking, or using any other type of tobacco. The Ethical Committee of the A B Shetty Memorial Institute of Dental Sciences (NITTE University) has approved this research endeavor. Every participant signed an informed consent form before being recruited.

The participants were categorised into two groups: Group I, that comprised perimenopausal women with chronic periodontitis, and group II, which included perimenopausal women without chronic periodontitis, based on the prevalence of periodontal diseases. Periodontal probing depth (PPD), plaque index (PI), and calculus index (CI) were the three components of full-mouth periodontal examinations used to assess periodontal health. PPD was performed on all teeth, a total of six sites per tooth, on a millimetre scale using a standardised UNC-15 periodontal probe.

Procedure:

The Perceived Stress Scale Questionnaire was used in order to gauge psychological stress.^31.

Perceived Stress Scale

The question in this scale ask you about your feeling and thoughts during the last month,

In each case, you will be asked to indicate by circling how often you felt or thought a certain way.

Name_______________________________ Date _____________

Age ________ Gender (Circle): M F Other___________________

1	In the last month, how often have you been upset because of something that happened unexpectedly?	1	2	3	4
2	In the last month, how often have you felt that you were unable to control the important things in your life?	1	2	3	4
3	In the last month, how often have you felt that nervous and ‘stressed’?	1	2	3	4
4	In the last month, how often have you felt that confident about your ability to handle your personal problems?	1	2	3	4
5	In the last month, how often have you felt that things were going your way?	1	2	3	4
6	In the last month, how often have you found that you could not cope with all the things that you had to do?	1	2	3	4
7	In the last month, how often have you felt that you were on top of things?	1	2	3	4
8	In the last month, how often have you felt that you were on top of things?	1	2	3	4
9	In the last month, how often have you been angered because of things that were outside of your control?	1	2	3	4
10	In the last month, how often have you felt difficulties were pilling up so high that you could not overcome them?	1	2	3	4

0= Never; 1= Almost Never; 2= Sometimes; 3= Fairly Often; 4= Very Often

Reverse the scores for the questions 4, 5 , 7 and 8.

Scores

0-13 Low stress

14-26 Moderate stress

27-40 High stress

A saliva sample will be utilized and using O-Cresolphthalein complex method (OCPC) will be utilized for analyzing it for calcium.Before saliva was acquired, subjects were instructed to abstain from food and liquids for at least 30 to 60 minutes and it was collected into a disposable tubes

To collect the saliva, patients were instructed to sit comfortably straight with their heads tilted slightly forward following which the samples were centrifuged for 10 minutes at 3000 rpm and was stored at -180⁰. The samples were sent to CRL, KSHEMA for estimation of salivary calcium levels.

Principle of the assay: The calcium OCPC method hinges on the apparition of a brilliantly violet complex, with maximum absorbance at 578 nm, via the chemical reactions of calcium ions (Ca+2) with O-Cresolphthalein complex in a solution with alkaline conditions. Up to 4 mmol/L, the 8-hydroxy quinolone inhibits Mg+2 interference.

RESULTS:

Table 1 cites the 48 participants who formed a part of the study along with its characteristics. Perimenopausal women with chronic periodontitis comprised group I and perimenopausal women without chronic periodontitis comprised Group II . In group I, the mean age of the participants was 45.70±1.23, while in group II, it was 46.63±1.37 (Table 1i). Group I, which is composed of perimenopausal women with chronic periodontitis, had substantially higher periodontal indicators (plaque index, calculus index, and periodontal probing depth) than group II, which consists of perimenopausal women without chronic periodontitis. In neither group did the salivary calcium levels represent any discernible variations. An independent t-test was used to analyze the statistical test, and a p-value of less than 0.05 was deemed statistically significant (Table 1).

Table 1: Study characteristics of the perimenopausal women

Characteristics	Peri-menopausal women with chronic periodontitis (n=24)	Peri-menopausal women without chronic periodontitis (n=24)	P-value
Age	45.70 ± 1.23	44.63 ± 1.37	0.006*
Plaque index	2.24 ± 0.37	0.77 ± 0.11	0.001*
Calculus index	2.05 ± 0.20	0.76 ± 0.29	0.001*
Periodontal Probing depth	6.17 ± 0.75	3.35 ± 0.48	0.001*
Salivary Calcium Level	4.14 ± 2.26	3.93 ± 1.97	0.728

All values are expressed as mean±standard deviation (SD). The statistical test used: Independent t Test; Level of significance: *p≤0.05 is considered statistically significant.

Table 2: Comparison of stress levels among the perimenopausal women

*Groups*	Low stress	Moderate Stress	High Stress	*P-value*
Peri-menopausal women with chronic periodontitis (n=24)	0 (0%)	21 (87.5%)	3 (12.5%)	0.001*
Peri-menopausal women without chronic periodontitis (n=24)	23 (95.8%)	1 (4.2%)	0 (0%)	0.001*

All values are expressed as frequency with percentages (in parentheses). The statistical test used: Chi-Square Test: * p ≤ 0.05 is considered statistically significant.

The comparisoni of the perimenopausal women's stress levels is illustrated in Table 2. Group I comprises 24 perimenopausal women with chronic periodontitis; of them, 21 (87.5%) claimed moderate stress, 3 (12.5%) indicated high stress, and 0 (0%) reported low stress (Table 2). Of the perimenopausal women in group II who did not have chronic periodontitis, 23 (95.8%) had low stress, 1 (4.2%) had moderate stress, and 0 (0%) had low stress (Table 2). This signifies that perimenopausal women with periodontitis and stress have a positive commonality. The Chi-Square test, characterized by a statistically significant p value of ≤0.05, originated for evaluating the stress levels of perimenopausal women.

Table 3: Relationship between stress levels and salivary calcium levels in the study groups

Stress level	Salivary Calcium Levels
Stress level	r	p
Peri-menopausal women with chronic periodontitis	-0.173	0.419
Peri-menopausal women without chronic periodontitis	-0.256	0.227

The statistical test used: Spearman's rank correlation coefficient:

The data was scrutinized using Spearman’s rank correlation coefficient to obtain insight into an association between stress levels and salivary calcium levels. Researchers have found a detrimental correlation between stress levels and salivary calcium levels. This demonstrates that salivary calcium levels drop with stress levels; however, the interaction is not statistically significant (Table 3).

Figure 1: Relationship between stress levels and salivary calcium levels in Peri-menopausal women with chronic periodontitis

Figure 2: Relationship between stress levels and salivary calcium levels in Peri-menopausal women without chronic periodontitis

Figure 2 represents the relationship between stress levels and salivary calcium levels in Peri-menopausal women without chronic periodontitis which shows a weak and negative correlation between stress and salivary calcium levels.

DISCUSSION:

In accordance to studies, periodontal disease incidence and severity can potentially be modulated by aging ^32–34. For elderly women, menopause is a physiological in nature phenomenon. Perimenopause is an instance of transition for changes in the body, mind, and emotions ³⁵. The iobservation of toothi loss in elderly adults due to periodontitisi was emphasized in a review of aging and periodontal tissues. This study determined that it may reflect biological changes attributed to aging, such as moldedosteoblastsi and osteoclasts, dysregulatedi responsesi of periodontali tissue cells to the oral microbiota, that culminated in inflammatory changes, and more general biological changes corresponding alongside aging that might influence bonei and tissuei homeostasis ^36.

It became apparent in the current study that participants, that is perimenopausal women without chronic periodontitis revealed low stress, whereas individuals with this condition experienced moderate and high stress. Furthermore, there was a negative link identified between salivary calcium levels and stress score, with the latter declining as stress surges. During the perimenopausal stage, hormonal imbalances lead to diminished oestrogen levels, which could potentially have a detrimental effect on the oral environment. As a result of a greater release of proinflammatory cytokines encompassing TNF-a, IL-1b, and IL-8i, which trigger periodontaliboneiloss, there is a deterioration in physical function ³⁷. Acute physiological stress has a negative effect on salivary composition, as implied by Al-Nuaimy KM et al.'s 2012 study, which found a significant stress-mediated decrease in salivary calcium concentration when juxtaposed with non-stressful the circumstances³⁸.

Oestrogen modulates the chemical composition of saliva in women who are approaching menopause ³⁹. When hormone levels of estrogen are high, during ovulation ⁴⁰, the content of calcium in submandibular saliva is low. It also would appear to be lower throughout pregnancy than during labor⁴¹. In an extensive investigation, Sewon et al. (2000) postulated that in healthy perimenopausal women experiencing hormone replacement implementation. (higher oestrogen levels), salivary calcium concentration reduced in stimulated saliva ⁴². They also maintained that there was definitely no associations between the calcium concentrations along with the flow rate. In 2018, Kaur et al. executed another experimental investigation that verified the potency of soya powder in alleviating and avoiding discomfort associated with menopause in perimenopausal women. Individuals amid the aforementioned ages of 41 and 55 had taken part this study ⁴³. The study concluded that the use of soya powder prevented and managed the menopausal problems and concluded that soya powder had effect on menopausal problems among perimenopausal women.

In 2021, Wosser et al. conducted a study with nursing students to gauge how much stress they were experienced during the initial few weeks of their clinical posting. They found that students endure stress during this threshold phase and that, to attempt to boost their coping mechanisms, they ought to be stipulated with a sensitization program⁴⁴. Interleukin 1 has an instrumental part in the aetiology of periodontal health conditions, in accordance with a review published in 2018 by Thirumalaisamy et al., which offered persuasive proof for the integral part that cytokine networks play in periodontal diseases⁴⁵. In 2019, Kadiyala et al. been elected in an investigation to gauge oxidative stress among participants with chronic periodontitis using gamma glutamyl transferase. Reviewing oxidative stress assists in comprehending the course of of the disease.⁴⁶. In 2023, Sitompul et al. designed an additional research study which illustrated an unambiguous immediate link between female sex and smoking and the risk associated with chronic periodontitis and acute coronary syndrome in participants.⁴⁷. In accordance a 2019 study by Abraham et al., there was a substantial correlation in the parameters of periodontal disease among patients with aggressive periodontitis,chronic periodontitis, and participants who were healthy. When contrasting chronic periodontitis patients to individuals in good health, there was a notable increase in plasma ferritin levels among the haematological metrics. Additionally, the research results highlighted an associated relationship amid chronic periodontitis and persistent anaemia, which was non-existent in cases of aggressive periodontitis. ⁴⁸

With the goal emphasize the association between periodontitis and interleukin 1 concentrations within gingival tissue and metabolic therapy in diabetic patients with chronic periodontitis, Pavithra et al. executed a review in 2018^.49. In 2020, Rajora et al. ultimately reached the conclusion that sounds from nature might recuperate patients, alleviate their anxiety and agitation, and archive healthcare costs⁵⁰. In 2023, Giri et al. ultimately reached a consensus that perimenopausal women's overall comprehension was inadequate at their initial assessment and intensified after the teaching program. Given that the study emerges to be routine, the quality of life can be boosted by menopausal treatment facilities that are efficient and productive and via awareness campaigns in every zone. ⁵¹ According to a study by Christina et al. in 2021, yoga rehabilitation and systematic educational initiatives were profitable for nurturing perception among perimenopausal women and drastically reducing associated menopausal symptoms.⁵²

There are numerous benefits to using saliva in lieu of serum: it is non-invasive, inexpensive to obtain, painless, and demands no specially trained individuals to collect samples. An affordable and easily implemented substituting algorithm is salivary calcium concentration ⁵³.

CONCLUSION:

Consequently, the present investigation concludes a finding that stress levels and salivary calcium have a negative association. It proves that salivary calcium decreases when stress levels rise, but the correlation is not statistically significant.An preliminary diagnostic algorithm for perimenopausal women may attempt to predict the salivary calcium levels observed in their saliva.

REFERENCES:

1. Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Laboratory Investigation; A Journal of Technical Methods and Pathology. 1976; Mar 1; 34(3): 235-49. PMID: 765622

2. Löe H, Anerud A, Boysen H, Morrison E. Natural history of periodontal disease in man: rapid, moderate and no loss of attachment in Sri Lankan laborers 14 to 46 years of age. Journal of Clinical Periodontology. 1986; May; 13(5): 431-40. https://doi.org/10.1111/j.1600-051X.1986.tb01487.x

3. Socransky SS, Haffajee AD, Goodson JM, Lindhe J. New concepts of destructive periodontal disease. Journal of Clinical Periodontology. 1984; Jan; 11(1): 21-32. https://doi.org/10.1111/j.1600-051X.1984.tb01305.x

4. Jeffcoat MK, Reddy MS. Progression of probing attachment loss in adult periodontitis. Journal of periodontology. 1991; Mar; 62(3): 185-9. https://doi.org/10.1902/jop.1991.62.3.185

5. Page RC, Simpson DM, Ammons WF. Host tissue response in chronic inflammatory periodontal disease IV. The periodontal and dental status of a group of aged great apes. Journal of Periodontology. 1975; Mar; 46(3): 144-55. https://doi.org/10.1902/jop.1975.46.3.144

6. Selvig KA. Ultrastructural changes in cementum and adjacent connective tissue in periodontal disease. Acta Odontologica Scandinavica. 1966; Jan 1; 24(4): 459-500. https://doi.org/10.3109/00016356609028233

7. Seymour GJ, Greenspan JS. The phenotypic characterization of lymphocyte subpopulations in established human periodontal disease. Journal of Periodontal Research. 1979; Feb; 14(1): 39-46. https://doi.org/10.1111/j.1600-0765.1979.tb00216.x

8. Harlow SD, Cain K, Crawford S, Dennerstein L, Little R, Mitchell ES, Nan B, Randolph Jr JF, Taffe J, Yosef M. Evaluation of four proposed bleeding criteria for the onset of late menopausal transition. The Journal of Clinical Endocrinology and Metabolism. 2006; Sep 1; 91(9): 3432-8. https://doi.org/10.1210/jc.2005-2810

9. Klein NA, Harper AJ, Houmard BS, Sluss PM, Soules MR. Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development?. The Journal of Clinical Endocrinology and Metabolism. 2002; Dec 1; 87(12): 5746-50. https://doi.org/10.1210/jc.2002-020622

10. Lenton EA, Landgren BM, Sexton L, Harper R. Normal variation in the length of the follicular phase of the menstrual cycle: effect of chronological age. BJOG: An International Journal of Obstetrics and Gynaecology. 1984; Jul; 91(7): 681-4. https://doi.org/10.1111/j.1471-0528.1984.tb04830.x

11. Dudley EC, Hopper JL, Taffe J, Guthrie JR, Burger HG, Dennerstein L. Using longitudinal data to define the perimenopause by menstrual cycle characteristics. Climacteric. 1998; Jan 1; 1(1): 18-25. https://doi.org/10.3109/13697139809080677

12. AE T. Variation of the human menstrual cycle through reproductive life. Int. J. Fertil.. 1970; 12(1): 90-124.1573105974735768192

13. Hale GE, Hughes CL, Burger HG, Robertson DM, Fraser IS. Atypical estradiol secretion and ovulation patterns caused by luteal out-of-phase (LOOP) events underlying irregular ovulatory menstrual cycles in the menopausal transition. Menopause. 2009; Jan 1; 16(1): 50-9. 10.1097/gme.0b013e31817ee0c2

14. Gorrindo T, Lu Y, Pincus S, Riley A, Simon JA, Singer BH, Weinstein M. Lifelong menstrual histories are typically erratic and trending: a taxonomy. Menopause. 2007; Jan 1; 14(1): 74-88. 10.1097/01.gme.0000227853.19979.7f

15. Seltzer VL, Benjamin F, Deutsch S. Perimenopausal bleeding patterns and pathologic findings. Journal of the American Medical Women's Association (1972). 1990; Jul 1; 45(4): 132-4. PMID: 2398224

16. Mansfield PK, Carey M, Anderson A, Barsom SH, Koch PB. Staging the menopausal transition: data from the TREMIN Research Program on Women’s Health. Women's Health Issues. 2004; Nov 1; 14(6): 220-6. https://doi.org/10.1016/j.whi.2004.08.002

17. Maartens LW, Knottnerus JA, Pop VJ. Menopausal transition and increased depressive symptomatology: a community based prospective study. Maturitas. 2002; Jul 25; 42(3): 195-200. https://doi.org/10.1016/S0378-5122(02)00038-5

18. Woods NF, Mitchell ES. Symptoms during the perimenopause: prevalence, severity, trajectory, and significance in women’s lives. The American Journal of Medicine. 2005; Dec 19; 118(12): 14-24. https://doi.org/10.1016/j.amjmed.2005.09.031

19. Mishra GD, Dobson AJ. Using longitudinal profiles to characterize women’s symptoms through midlife: results from a large prospective study. Menopause. 2012; May 1; 19(5): 549-55. 10.1097/gme.0b013e3182358d7c

20. Mishra GD, Kuh D. Health symptoms during midlife in relation to menopausal transition: British prospective cohort study. BMJ. 2012; Feb 8; 344. https://doi.org/10.1136/bmj.e402

21. Burger H, Woods NF, Dennerstein L, Alexander JL, Kotz K, Richardson G. Nomenclature and endocrinology of menopause and perimenopause. Expert Review of Neurotherapeutics. 2007; Nov. 1; 7(sup1): S35-43. https://doi.org/10.1586/14737175.7.11s.S35

22. Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstetrics and Gynecology. 2000; Aug 23; 96(3): 351-8. https://doi.org/10.1016/S0029-7844(00)00930-3

23. Hale GE, Hitchcock CL, Williams LA, Vigna YM, Prior JC. Cyclicity of breast tenderness and night-time vasomotor symptoms in mid-life women: information collected using the Daily Perimenopause Diary. Climacteric. 2003; Jan 1; 6(2): 128-39. https://doi.org/10.1080/cmt.6.2.128.139

24. Green LW, Tryon WW, Marks B, Huryn J. Periodontal disease as a function of life events stress. Journal of human stress. 1986; Mar 1; 12(1): 32-6. https://doi.org/10.1080/0097840X.1986.9936764

25. Bakri I, Douglas CW, Rawlinson A. The effects of stress on periodontal treatment: a longitudinal investigation using clinical and biological markers. Journal of Clinical Periodontology. 2013; Oct; 40(10): 955-61. https://doi.org/10.1111/jcpe.12142

26. Ardila CM, Guzmán IC. Association of P orphyromonas gingivalis with high levels of stress‐induced hormone cortisol in chronic periodontitis patients. Journal of Investigative and Clinical Dentistry. 2016; Nov; 7(4): 361-7. https://doi.org/10.1111/jicd.12175

27. Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, Turner RB. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proceedings of the National Academy of Sciences. 2012; Apr 17; 109(16): 5995-9. https://doi.org/10.1073/pnas.1118355109

28. Folkman S, Lazarus RS, Dunkel-Schetter C, DeLongis A, Gruen RJ. Dynamics of a stressful encounter: cognitive appraisal, coping, and encounter outcomes. Journal of Personality and Social Psychology. 1986; May; 50(5): 992. https://doi.org/10.1037/0022-3514.50.5.992

29. Hajishengallis G. Aging and its impact on innate immunity and inflammation: implications for periodontitis. Journal of Oral Biosciences. 2014; Feb 1; 56(1): 30-7. https://doi.org/10.1016/j.job.2013.09.001

30. Wulandari P, Masulili SL, Kusdhany LS, Tadjoedin FM, Puspitadewi SR, Baziad A. Differences in periodontal severity between perimenopausal and postmenopausal women with chronic periodontitis. Pesquisa Brasileira em Odontopediatria e ClínicaIntegrada. 2020; Jan 13; 19: e5091. https://doi.org/10.4034/PBOCI.2019.191.113

31. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. Journal of Health and Social Behavior. 1983; Dec 1: 385-96. https://doi.org/10.2307/2136404

32. Penoni DC, Fidalgo TK, Torres SR, Varela VM, Masterson D, Leão AT, Maia LC. Bone density and clinical periodontal attachment in postmenopausal women: a systematic review and meta-analysis. Journal of dental research. 2017; Mar; 96(3): 261-9. https://doi.org/10.1177/0022034516682017

33. Malutan AM, Dan M, Nicolae C, Carmen M. Proinflammatory and anti-inflammatory cytokine changes related to menopause. Menopause Review/ Przegląd Menopauzalny. 2014; Jun 30; 13(3): 162-8. https://doi.org/10.5114/pm.2014.43818

34. Dodd DZ, Rowe DJ. The relationship between postmenopausal osteoporosis and periodontal disease. American Dental Hygienists' Association. 2013; Dec 1; 87(6): 336-44.87 (6) 336-344

35. Sharma U, Pal D, Prasad R. Alkaline phosphatase: an overview. Indian Journal of Clinical Biochemistry. 2014; Jul; 29: 269-78. 10.1007/s12291-013-0408-y

36. Choi JK, Kim YT, Kweon HI, Park EC, Choi SH, Lee JH. Effect of periodontitis on the development of osteoporosis: results from a nationwide population-based cohort study (2003–2013). BMC Women's Health. 2017; Dec; 17: 1-8.10.1186/s12905-017-0440-9

37. Mukaiyama K, Kamimura M, Uchiyama S, Ikegami S, Nakamura Y, Kato H. Elevation of serum alkaline phosphatase (ALP) level in postmenopausal women is caused by high bone turnover. Aging Clinical and Experimental Research. 2015; Aug; 27: 413-8.10.1007/s40520-014-0296-x

38. Al-Nuaimy KM, Al-Hamdani IH, Tawfik NO. Effect of stress on the composition and flow rate of saliva. Al-Rafidain Dental Journal. 2012; Jan 1; 12(1): 66-70.10.33899/rden.2012.42633

39. Leimola-Virtanen R, Helenius H, Laine M. Hormone replacement therapy and some salivary antimicrobial factors in post-and perimenopausal women. Maturitas. 1997; Jun 1; 27(2): 145-51. https://doi.org/10.1016/S0378-5122(97)00024-8

40. Puskulian L. Salivary electrolyte changes during the normal menstrual cycle. Journal of Dental Research. 1972; Sep; 51(5): 1212-6. https://doi.org/10.1177/00220345720510050701

41. Guidozzi F, Maclennan M, Graham KM, Jooste CP. Salivary calcium, magnesium, phosphate, chloride, sodium and potassium in pregnancy and labour. South African Medical Journal= Suid-afrikaanse Tydskrifvir Geneeskunde. 1992; Feb 1; 81(3): 152-4. PMID: 1734555

42. Sewón L, Laine M, Karjalainen S, Leimola-Virtanen R, Hiidenkari T, Helenius H. The effect of hormone replacement therapy on salivary calcium concentrations in menopausal women. Archives of Oral Biology. 2000; Mar 1; 45(3): 201-6. https://doi.org/10.1016/S0003-9969(99)00137-5

43. Kaur S, Sidhu GK. Quasi-Experimental Study to Evaluate the Effectiveness of Soya Powder on Selected Menopausal Problems among Perimenopausal Women in Selected Rural Areas of Ludhiana, Punjab. Asian Journal of Nursing Education and Research. 2017; 7(4): 524-8. 10.5958/2349-2996.2017.00103

44. Wosser T, Mathew B, Idiculla J. A Study to assess the Perceived stress and its contributing factors among nursing students during the initial period of their clinical posting in selected college of nursing, Bengaluru with a view to develop a Preclinical sensitization programme. International Journal of Advances in Nursing Management. 2020; 8(4): 331-4. 10.5958/2454-2652.2020.00073.6

45. Thirumalaisamy V, Gajendran P. Role of Salivary Interleukin 1 in Chronic Periodontitis: A Review. Research Journal of Pharmacy and Technology. 2018; 11(1): 390-2. 10.5958/0974-360X.2018.00071.9

46. Kadiyala V, Savitha G. Assessment of Gamma Glutamyl Transferase in Chronic Periodontitis. Research Journal of Pharmacy and Technology. 2018; 11(11): 5083-5. 10.5958/0974-360X.2018.00927.7

47. Sitompul SI, Pikir BS, Supandi SK, Sinta ME. Effect of CRP, IL-6, leukocytes, NLR on chronic periodontitis in acute coronary syndrome. Research Journal of Pharmacy and Technology. 2023; 16(1): 391-8. 10.52711/0974-360X.2023.00067

48. Abraham C, Malaiappan S, Savitha G. Association of Hematological and Periodontal Parameters in Healthy, Chronic and Aggressive Periodontitis Patients-A Cross Sectional Study. Research Journal of Pharmacy and Technology. 2019; 12(1): 74-8. 10.5958/0974-360X.2019.00014.3

49. Pavithra RS, Varghese S. Gingival tissue level of interleukin-1 in diabetic patient with chronic periodontitis. Research Journal of Pharmacy and Technology. 2017; 10(12): 4442-4. 10.5958/0974-360X.2017.00818.6

50. Rajora MA, Goyal H, Guleria R. Effectiveness of nature-based sounds on psychological stress (agitation and anxiety) in patients under mechanical ventilation support. International Journal of Advances in Nursing Management. 2019; 7(3): 169-75. 10.5958/2454-2652.2019.00041.6

51. Giri VB, Taksande V. A study to assess the effectiveness of structured teaching programme on knowledge and attitude regarding selected aspects of perimenopausal care among perimenopausal women at Aurangabad district. International Journal of Nursing Education and Research. 2023; 11(2): 105-6. 10.52711/2454-2660.2023.00024

52. Christina RC, Ramesh RS, Subitha L, Kumar GD. Does Structured teaching program and Yoga therapy improve knowledge and symptoms related to Menopause among perimenopausal women in Rural Puducherry?-A Randomized Controlled Trial. Asian Journal of Nursing Education and Research. 2020; 10(4): 391-5. 10.5958/2349-2996.2020.00083.X

Received on 01.01.2024 Modified on 09.03.2024

Research J. Pharm. and Tech 2024; 17(11):5189-5195.

DOI: 10.52711/0974-360X.2024.00794