Effect of hormone replacement therapy on periodontal health in post-menopausal women in Jeddah, Saudi Arabia

Abstract

Background

Menopause marks the cessation of menstrual cycles and brings significant changes to a woman’s body, including oral health alterations. While hormone replacement therapy (HRT) is commonly used to alleviate menopause symptoms, its impact on oral health, particularly periodontal conditions, has not been well studied in Saudi Arabia. Periodontitis, a disease that destroys the bone and soft tissue of the mouth, becomes more prevalent post-menopause. This study investigates the effect of HRT on periodontal health in post-menopausal women.

Methodology

A case-control study was conducted with 372 post-menopausal Saudi women from multiple healthcare facilities in Jeddah, Kingdom of Saudi Arabia. The study included 186 women with periodontitis (cases) and 186 women with healthy periodontium (controls). Periodontal health was assessed using the American Academy of Periodontology (AAP) 2017 classification and a validated questionnaire. Secondary objectives concerning periodontal parameters like Clinical attachment loss (CAL), saliva secretion rate, and bone loss were also measured in HRT users compared to non-users. Odds ratios (OR) and logistic regression were used for categorical data analysis, while t-tests and linear regression examined the relationship between numerical variables.

Results

HRT use was significantly associated with a lower prevalence of periodontitis. The odds of having periodontitis were 3.2 times lower in HRT users compared to non-users (OR = 0.31, p < 0.05, 95% CI: 0.11–0.89). After adjusting for medical and demographic variables, HRT users had approximately six times lower odds of having periodontitis (OR = 0.17, p < 0.05, 95% CI: 0.04–0.81). However, HRT use did not significantly impact the severity of periodontitis once the disease was present. When secondary outcomes were measured, HRT usage had a significant association with decreased clinical attachment loss (Coef = -1.13, p < 0.05, 95% CI: (-2.26, -0.02)); however, this significance was lost after adjusting for medical and social variables. HRT usage did not have a significant effect on bone loss and saliva level, which were measured both as categorical and numerical variables.

Conclusion & recommendations

HRT is associated with a lower prevalence of periodontitis but does not affect its severity. While collaborative care between dental and medical professionals is recommended, further research is needed to address study limitations and explore different HRT formulations and their impact on periodontal health.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12905-025-03757-5.

Introduction

Women experience significant hormonal fluctuations throughout life, particularly during menopause, which marks the cessation of menstrual cycles due to a rapid decline in estrogen levels [1, 2]. These hormonal changes have systemic effects, including alterations in oral health. Estrogen receptors are present in the gingiva, oral mucosa, and salivary glands, suggesting a potential role of estrogen in maintaining periodontal health [3]. Postmenopausal women have an increased prevalence of periodontitis, a chronic inflammatory disease that compromises the supporting structures of teeth, leading to tooth loss and impaired oral function [4, 5]. While hormone replacement therapy (HRT) is commonly prescribed to manage menopausal symptoms, its influence on periodontal health remains underexplored, particularly in Middle Eastern populations.

Existing studies on HRT and periodontitis present mixed findings. Some research suggests that HRT reduces periodontal disease risk, while others report no significant association, likely due to differences in study design, sample sizes, and control for confounding variables [6, 7]. Additionally, prior studies often fail to evaluate key secondary outcomes such as clinical attachment loss (CAL) and salivary secretion.

This study aims to address these gaps by assessing the association between HRT use and periodontal health in postmenopausal women in Jeddah, Saudi Arabia. We hypothesize that postmenopausal women using HRT will have a lower prevalence of periodontitis compared to non-users. Additionally, we aim to evaluate secondary outcomes, including CAL, salivary secretion, and bone loss, while considering sociodemographic and medical predictors.

Methodology

Study design and setting

A case-control study targeting Saudi postmenopausal women was conducted in Jeddah, Saudi Arabia. Participants were recruited from multiple dental clinics, including seven primary healthcare facilities operated by the Ministry of Health (MOH), three private health facilities, and the Armed Forces Hospital. Data collection took place in a single private dental clinic to ensure consistency in examination tools and procedures.

Sample size calculation

The required sample size was calculated to detect a significant odds ratio using a case-control sample size formula [8–10]. The formula considered a two-sided type I error probability (α) of 5% and a power (β) of 80%, with estimated exposure probabilities of 45% in controls and 30% in cases, calculated from previous literature. A minimum of 308 participants was needed, with 154 in each group. This study included 372 participants (186 cases and 186 controls) to improve statistical reliability. Detailed calculations are provided in the supplementary material for clarity as S1: Sample Size Calculations.

Inclusion criteria

• Saudi women aged 45 years and above.

• At least 12 months post-menopause.

• A minimum of 8 teeth (including third molars), If a tooth loses its crown and becomes a remaining root, it will still be counted as a tooth and included in the periodontal assessment.

• Cases were defined as those who had generalized periodontitis, characterized by 30% or more sites with periodontitis in the oral cavity. Controls were defined as individuals with 0% periodontitis in the oral cavity, matched to cases by age and location.

Exclusion criteria

• Women who had used HRT but discontinued it before the study were excluded to eliminate potential confounding effects on the study’s outcomes.

• Early menopause onset participants (before 45 years) were excluded to focus on participants with a more typical age range for menopause onset, which may impact hormonal influences on periodontitis.

• History of hysterectomy, as the absence of ovaries or the alteration of hormone production can prevent the use of HRT and affect the results regarding hormonal impacts.

• Cases that couldn’t be matched to controls by age and clinic location. This ensures comparability between cases and controls, eliminating potential confounding factors related to demographics or regional influences.

• Localized incisor-molar periodontitis or localized periodontitis (affecting 1–29% of the oral cavity). By excluding participants with localized periodontitis, the study is less likely to be influenced by factors like genetic predispositions, trauma, or misclassification, which could create bias in the interpretation of results. Focusing on generalized periodontitis, which is more closely related to systemic factors such as hormonal changes, ensures that the study directly examines the relationship between hormonal fluctuations and periodontal health. This reduces bias by narrowing the focus to a more homogenous group, making it easier to interpret the results without the confounding effects of localized, non-systemic influences.

Exclusion criteria were made to improve the reliability of the results and reduce bias. This transparency not only strengthens the validity of the study but also enhances its credibility, as it shows a thoughtful approach to controlling for confounding factors.

Sampling methodology

A systematic random sampling technique was employed. Cases were selected based on their periodontal status, following a pattern (e.g., 1st, 3rd, 5th). Controls were matched to cases by age and clinic location. If matching controls were unavailable, the corresponding cases were excluded.

Data collection

Data collection occurred between July 2023 and August 2023 and involved structured interviews, clinical examinations, and medical file reviews. A single researcher conducted all data collection to ensure consistency and minimize variability. To reduce potential interviewer bias, the researcher underwent standardized training to ensure uniformity in administering the structured questionnaire and performing clinical measurements. The questionnaire (see Supplementary Material S3: Questionnaire) was developed based on known periodontitis predictors and common chronic diseases observed in the elderly Saudi population, as outlined in previous research [1, 5, 6, 11, 12]. It consisted of three sections: (1) sociodemographic and medical information, (2) medical and menopausal history (including chronic diseases, age of menopause, and hormonal replacement therapy usage), and (3) periodontal outcome assessment using the AAP 2017 chart [13]. Clinical attachment loss (CAL) and pocket depths were measured using Williams 15 periodontal probes and radiographs, with precise measurements recorded to ensure accuracy.

Assessment Tools (can be found in supplementary material S2: clinical assessment).

1. Periodontal Health:

• Measured using the American Academy of Periodontology (AAP) 2017 classification [13].

• Clinical attachment loss (CAL) was assessed using the formula: CAL = Pocket Depth (PD) + Distance from Cementoenamel Junction (CEJ) to Gingival Margin.

• CAL and pocket depth were measured at four sites per tooth (mesiobuccal, distobuccal, mesiolingual, and distolingual).

• Bitewing radiographs were used to assess bone loss, defining bone loss as > 15% of bone around the root.

• 2.Secondary Outcomes:

• CAL was measured at four sites per tooth (mesiobuccal, distobuccal, mesiolingual, and distolingual). Then the average attachment loss was measured by dividing the total loss by/ number of sites.

• Salivary Secretion: Stimulated saliva flow was measured using a 5-minute wax-chewing test, with results recorded in ml/min.

• Bone Loss: Measured using radiographs and categorized as < 15% (no bone loss) or > 15% bone loss.

Pilot study

A pilot study involving 11 participants was conducted to refine the questionnaire and ensure the feasibility of the methodology. Adjustments included switching to interview-based questionnaires due to participants’ limited literacy and adding questions about unlisted illnesses common in the population, not found in previous research. Data collection per participant took approximately 25 min.

Ethical considerations

Ethical approval was obtained from the Ministry of Health’s Institutional Review Board (MOH IRB log A0168, registration number NCBE-KACST, KSA: H-02-J-002). The study adhered to the principles outlined in the Declaration of Helsinki, ensuring the protection of participants’ rights, safety, and well-being. Participants provided informed consent through verbal agreement and fingerprint acknowledgment. Data collection and analysis were anonymous, and questionnaires were destroyed after data entry.

Statistical analysis

The primary outcome, Periodontitis, was coded as a dichotomous variable, then further stratified as ordinal categorical variables arranged according to severity. The sample’s binary socioeconomic and medical data were displayed as percentages, while continuous data were expressed as mean and standard deviation. It was also divided between cases and controls to display any significant difference in the socioeconomic and medical traits between the two groups. The association between exposure (HRT usage) and outcome (periodontitis presence) was measured through odds ratio and Chi-square with significance at 95% CI. The effect of HRT on the severity of periodontitis was measured using a multinomial categorical regression coefficient, with healthy being the reference. A logistic model was created that includes all the variables, showing the significance of each variable in association with periodontitis. It was followed by creating a forward stepwise logistic regression to see significant predictors of periodontitis presence (binary) with entry at (0.05) and exit at (0.051). The primary exposure, which is HRT usage, was lock-termed. The following variables were added to all the logistic model: HRT usage (Binary), duration of HRT usage (continuous), age (continuous), BMI (continuous), employee status (binary), smoking status (binary), monthly income (continuous), an education level (ordinal categorical), age of menopause (continuous), hypertension (binary), diabetes (binary), osteoporosis (binary), vitamin d deficiency (binary), hypothyroidism (binary), malignant tumors (binary), arthritis (binary), asthma (binary), liver diseases (binary), kidney diseases (binary), Salivary flow rate (continuous), cortisone usage (binary), aspirin usage (binary), antidepressant usage (binary). The final model contained: User of HRT (Binary), Age of menopause (continuous), Smoking status (binary), Education level (Categorical ordinal), Diabetes (binary), kidney diseases (binary), with p-value < 0.05 and 95% CI significance. Height and weight were excluded from the model due to BMI and collinearity. A ROC graph for the model area under the curve (AUC) was created to measure the effect of all significant variables in association with HRT. The graph also measures the model’s sensitivity, specificity, and predictability. Secondary outcomes were also measured in association with HRT usage. Clinical attachment loss was measured using a correlation coefficient. A forward stepwise linear regression was created to see possible predictors of CAL (continuous) with entry at (0.05) and exit at (0.051). The primary exposure, which is HRT usage, was lock-termed. All previously mentioned variables (included in the logistic model) were added to the linear regression model with a p-value < 0.05 and 95% CI significance, and R2 was used to assess the model. The Association between HRT salivary secretion was measured once with saliva as a continuous variable using a coefficient and again with saliva as a binary variable (Normal saliva secretion) and (Low saliva secretion) using the odds ratio. The association of bone loss and HRT was also measured using OR.

Results

Sample demographics

A total of 410 female patients attending clinics in Jeddah between July 2023 and August 2023 were examined and interviewed. 5 patients were excluded due to hysterectomy, 3 patients were excluded due to stopping HRT before participating in the study, 2 were excluded due to having localized incisor-molar periodontitis, 6 were excluded due to matching purposes, and 22 were excluded due to having localized periodontitis. 372 people matched the inclusion and exclusion criteria, with 186 cases of periodontitis and 186 controls with healthy periodontium.

Table 1 lists the sociodemographic data of the study population. The age of female participants ranged from 45 to 91, with a mean age of 58.2 years. The age of menopause ranged from 45 to 60 years, for an average duration of 7 years of menopause.

Table 1.

Sociodemographic and medical data of study population

Variable	Mean ± SD
Age	58.2 ± 7.10 years
Weight	78.17 ± 12.47 kg
Height	156.13 ± 5.29 cm
BMI	32.06 ± 4.92
Monthly income	5512 ± 5477 Saudi riyals
Age of menopause	51.01 ± 3.27 years
Saliva secretion rate	1.47 ± 0.82 ml/min
Numbe of teeth	22.52 ± 6.74 teeth
Variable	N(%)
Employee Status (Current Worker)	43 (11.56)
Smoking status (Current Smoker)	11 (2.96)
Hypertension	137 (26.83)
Diabetes	109 (29.30)
Osteoporosis	48 (12.90)
Vitamin D deficincy	44 (11.83)
Hypothyrodism	52 (13.98)
Malignant tumors	28 (7.53)
Asthma	31 (8.33)
Artharitis	40 (10.75)
Liver disease	8 (2.15)
Kidney Disease	8 (2.15)
Saliva inssufeciancy	147 (39.50)
Aspirin Usage	81 (21.77)
Anti-depressant Usage	13 (3.49)
Cortisone Usage	4 (1.08)
Education
No Education (Illeterate)	134 (36.02)
Elementry	103 (27.69)
Middle school	57 (15.32)
Highschool	30 (8.06)
University or higher	48 (12.90)
Users of HRT	20 (5.38)

In Table 2, the age of menopause was significantly different between cases and controls, with controls menopausing around one year after cases. Cases had a significantly lower monthly income (4,155 ± 3,453 SAR) compared to controls (6,869 ± 6,674 SAR). Education levels also differed markedly; nearly half of the cases (49.46%) were illiterate, whereas only 22.58% of controls fell into this category. In contrast, university-level education was far more common among controls (22.04%) than cases (3.76%). Employment status followed a similar pattern, with only 4.3% of cases being currently employed compared to 18.82% of controls.

Table 2.

The sociodemographic and medical characteristic distribution between cases and control

Variable	Cases	Controls
Age	58.91 ± 7.60 years	57.47 ± 6.19 years
Weight	77.21 ± 13.49 kg	79.13 ± 11.32 kg
Height	156.12 ± 5.73 cm	156.13 ± 4.84 cm
BMI	31.68 ± 5.2	32.44 ± 4.61
Monthly income*	4155 ± 3453 saudi riyals	6869 ± 6674 saudi riyals
Age of menopause*	50.56 ± 3.44 years	51.45 ± 3.03 years
Saliva secretion rate*	1.23 ± 0.7 ml/min	1.7 ± 0.85 ml/min
Variable	N (%)	N (%)
Employee Status (current worker)*	8 (4.3)	35 (18.82)
Smoking status (Current Smoker)	8 (4.3)	3 (1.61)
Hypertension*	78 (41.94)	59 (31.72)
Diabetes*	78 (41.94)	31 (16.67)
Osteoporosis	24 (12.9)	24 (12.9)
Vitamin D deficincy	20 (10.75)	24 (12.9)
Hypothyrodism	24 (12.9)	28 (15.05)
Malignant tumors	9 (4.84)	19 (10.22)
Asthma	14 (7.53)	17 (9.14)
Artharitis	24 (12.9)	16 (8.6)
Liver disease	8 (4.3)	0
Kidney Disease	7 (3.76)	1 (0.54)
Aspirin Usage	51 (27.42)	30 (16.13)
Anti-depressant Usage	8 (4.3)	5 (2.69)
Cortisone Usage	4 (2.15)	0
Education
No Education (Illeterate)*	92 (49.46)	42 (22.58)
Elementry*	46 (24.73)	57 (30.65)
Middle school*	26 (13.98)	31 (16.67)
Highschool	15 (8.06)	15 (8.06)
University or higher*	7 (3.76)	41 (22.04)
Users of HRT*	5 (2.69)	15 (8.06)

*Significant difference in variable presence between the cases and controls with p-value ≤ 0.05 and CI 95% when using unpaired t-test

Salivary secretion rates were significantly lower in cases (1.23 ± 0.7 ml/min) compared to controls (1.7 ± 0.85 ml/min). Smoking was more prevalent among cases (4.3%) than controls (1.61%). Medical history analysis revealed that hypertension (41.94% vs. 31.72%) and diabetes (41.94% vs. 16.67%) were more common among cases. Additionally, kidney disease (3.76% vs. 0.54%) and liver disease (4.3% vs. 0%) were reported more frequently in cases than in controls. Interestingly, malignant tumors were more prevalent in controls (10.22%) than in cases (4.84%), but this wasn’t significant. Notably, hormone replacement therapy (HRT) usage was significantly lower among cases (2.69%) than in controls (8.06%).

Table 3 shows a close distribution of different periodontitis stages among cases. The users of HRT were 5.38%, which is 20 participants of the sample. The duration of usage of HRT ranged from 1 to 9 years, with all of them using estradiol 1 gm dose orally once daily.

Table 3.

Stratification of stages of periodontitis

Periodontitis Severity	N (%)
Satge I	43 (23.12)
Stage II	53 (28.49)
Stage III	40 (21.50)
Stage IV	50 (26.88)

Association between HRT usage and periodontitis

In Table 4, the analysis demonstrated that HRT usage was significantly associated with a lower prevalence of periodontitis, with HRT users having 3.2 times lower odds of periodontitis compared to non-users (OR = 0.31, p < 0.05, 95% CI: 0.11–0.89). However, when periodontitis severity was analyzed as an ordinal variable in a multinominal regression, HRT usage did not show a significant effect on the progression of the disease (p > 0.05) as shown in Table 5. Further analysis indicated that the protective effects of HRT may be limited to preventing disease onset rather than altering disease progression. Additionally, the type of HRT used (estradiol 1 mg daily) may not have had a sufficient systemic impact on periodontal tissues to mitigate the inflammatory response in advanced stages of periodontitis. The progression of periodontitis is likely influenced by a complex interplay of systemic inflammation, metabolic factors, and behavioral risks that override any protective effects of estrogen replacement.

Table 4.

Association between HRT usage and periodontitis presence using odds ratio

Usage of HRT	Periodontitis		OR	95% CI
	No	Yes	0.31*	(0.11, 0.89)
No	171	181
Yes	15	5

*p < 0.05

Table 5.

Association between HRT and periodontitis stratified according to severity using categorical regression reference base: healthy periodontium

Periodontitis severity (when using HRT)	Coefficient	95% CI
Stage I	-13.77	(-1002, 975)
Stage II	-0.37	(-1.66, 0.9)
Stage III	-1.23	(-3.29, 0.82)
Stage IV	-1.46	(-3.51, 0.59)

Table 6 is the initial model with all possible variables (the reference for all binary variables is 0, indicating lack of disease and no medication usage), with many variables turning out to be not significantly associated with periodontitis. Table 7 shows a forward stepwise logistic model with entry at (0.05) and exit at (0.051) using all variables and with HRT usage being lock-termed. It is noted that increased education decreased periodontitis, except during high school, which could be due to the small number of participants from that education category. HRT users had approximately six times lower odds of having periodontitis (OR = 0.17, p < 0.05, 95% CI: 0.04–0.81). The area under the curve graph (1) was created to see the sensitivity and specificity of the association between outcome (periodontitis) and all significant exposures for Table 7. The ROC Graph in Fig. 1 shows a model fit at 0.82, an acceptable discrimination of the model.

Table 6.

Logistic regression with all variables in association with periodontitis presence

Periodontitis Presense	OR	95% CI
Users of HRT* (ref no HRT)*	0.23	(0.04–0.99)
Age	0.99	(0.95–1.03)
BMI	0.91	(0.95–1.03)
Monthly income	0.69	(0.99–1)
Age of menopause*	0.9	(0.82–0.99)
Saliva secretion rate***	0.47	(0.31–0.71)
Employee Status (current worker)	0.42	(0.05–3.66)
Smoking status (Current Smoker)**	19.13	(2.54–143)
Hypertension	0.69	(0.34–1.42)
Diabetes***	3.37	(1.72–6.61)
Osteoporosis	1.91	(0.46–6.90)
Vitamin D deficincy	1.09	(0.25–4.68)
Hypothyrodism	0.75	(0.31–1.82)
Malignant tumors*	0.26	(0.07–0.98)
Asthma	0.62	(0.23–1.68)
Artharitis	0.82	(0.32–2.09)
Liver disease	1	1
Kidney Disease*	11.95	(1.21–118)
Aspirin Usage	1.33	(0.6–2.98)
Anti-depressant Usage	1.46	(0.36–5.97)
Cortisone Usage	1	1
Duration of Usage	4.05	(0.99–16.20)
Education (ref: no education)
Elementry***	0.3	(0.15–0.62)
Middle school***	0.27	(0.12–0.59)
Highschool	0.93	(0.31–2.81)
University or higher*	0.2	(0.02–2.14)

*p < 0.05, ** p < 0.01, ***p < 0.001

Table 7.

Forward Stepwise logistic regression model with lock-term exposure (user of HRT) to assess predictors of periodontitis

Periodontitis Presense	OR	95% CI
Users of HRT* (ref no HRT)*	0.18	(0.04–0.81)
BMI***	0.91	(0.86–0.96)
Age of menopause**	0.89	(0.82–0.96)
Saliva secretion rate***	0.54	(0.38–0.76)
Smoking status (ref: no smoker)**	16.18	(2.35–111)
Diabetes***	3.72	(2.05–6.78)
Kidney Disease*	11.95	(1.21–118)
Education (ref: no education)
Elementry***	0.3	(0.15–0.62)
Middle school***	0.27	(0.12–0.59)
University or higher*	0.2	(0.02–2.14)

*p < 0.05, ** p < 0.01, ***p < 0.001

Fig. 1.

ROC graph of last fitted logistic model predicting periodontitis in Table 7

Association between HRT usage and secondary outcome (CAL)

A t-test comparing clinical attachment loss (CAL) between HRT users and non-users initially showed that HRT users had, on average, 1.13 mm less CAL than non-users (p < 0.05, 95% CI: -2.26 to -0.02). However, after adjusting for covariates using a forward stepwise linear regression model with HRT usage as a locked-term as shown in Table 8, the effect of HRT on CAL lost significance (p > 0.05, 95% CI: -1.49 to 0.94). The regression model revealed that several other variables were significant predictors of CAL. Smoking (coefficient = 2.3, 95% CI: 0.86 to 3.73), diabetes (coefficient = 1.1, 95% CI: 0.57 to 1.63), and lower education levels were found to have significant positive associations with CAL, likely due to their impact on inflammation, tissue healing, and bone metabolism. Furthermore, higher BMI (coefficient = -0.07, 95% CI: -0.12 to -0.02) and lower saliva secretion rate (coefficient = -0.45, 95% CI: -0.78 to -0.11) were associated with decreased CAL. Education level also emerged as an important predictor, with individuals having higher education levels exhibiting lower CAL scores, with university-level education showing the strongest protective association (coefficient = -2.0, 95% CI: -2.79 to -1.22). The model’s R² was 0.25, and the adjusted R² was 0.22, indicating that the model explained only 22% of the variability in CAL, suggesting that additional unaccounted factors may contribute to CAL.

Table 8.

A forward Stepwise linear regression model with lock term exposure (user of HRT) to assess predictors of increased CAL in Ml

CAL	Coef	95% CI
Users of HRT (ref no HRT)	-0.27	(-1.49, 0.94)
BMI***	-0.07	(-0.12, − 0.02)
Saliva secretion rate***	-0.45	(-0.78, -0.11)
Smoking status (ref: no smoker)**	2.3	(0.86, 3.73)
Diabetes***	1.1	(0.57, 1.63)
Kidney Disease*	1.78	(0.23, 3.33)
Malignant Tumor*	-1.28	(-2.38, -0.18)
Anti-depressant usage*	1.38	(0.33, 2.63)
Education (ref: no education)
Elementry*	-0.69	(-1.27, -0.10)
Middle school***	-1.53	(-2.22, -0.84)
Highschool***	-1.88	(-2.78, -0.98)
University or higher***	-2	(-2.79, -1.22)

*p < 0.05, ** p < 0.01, ***p < 0.001

Association between HRT usage and secondary outcome (Saliva and Bone)

In the categorical analysis of saliva secretion shown in Table 9, HRT usage was not significantly associated with normal or low saliva secretion (OR = 1.23, 95% CI: 0.48 to 3.15). Similarly, in the continuous saliva secretion model in Table 10, HRT usage showed no significant relationship (coefficient = 0.13, 95% CI: -0.23 to 0.5), suggesting that HRT does not significantly affect saliva secretion levels.

Table 9.

Association between HRT usage and saliva secretion as a categorical variable using OR

	Normal Saliva	Low Saliva	OR	95% CI
User of HRT	13	7	1.23	(0.48 - 3.15)
Non-user of HRT	212	140

Table 10.

Association between HRT usage and saliva secretion level as a continuous variable using liner regression compared to non-users

Saliva ml/min	Coef	95% CI
User of HRT	0.13	(-0.23, 0.5)

Regarding bone loss in Table 11, HRT users showed a slight increase in the likelihood of experiencing bone loss (OR = 1.8, 95% CI: 0.67 to 5.08), but this finding did not reach statistical significance. This indicates that, while there is a slight association between HRT use and bone loss, it is not strong enough to draw conclusive results.

Table 11.

Association between HRT usage and bone loss using OR

	No bone loss	Bone loss	OR	95% CI
User of HRT	15	5	1.8	(0.67–5.08)
Non-user of HRT	220	132

Discussion

Several studies have investigated the relationship between hormone replacement therapy (HRT) and periodontal health, yet findings remain inconsistent due to methodological variations. Some studies found no significant association between HRT and periodontal disease, likely due to small sample sizes, short follow-up periods, and inadequate control for confounding factors [6, 7]. In contrast, larger studies, such as Haas et al. [14]. and Lee et al. [15]. reported a significant reduction in periodontitis prevalence among HRT users. These studies adjusted for key confounders like smoking and socioeconomic status, similar to our analysis. However, differences in sample sizes, HRT formulations, and participant demographics across studies suggest a need for further research on how different HRT regimens impact periodontal health.

Our study contributes to this body of research by demonstrating that postmenopausal women using HRT had significantly lower odds of periodontitis compared to non-users. However, while HRT use was associated with lower disease prevalence, it did not influence periodontitis severity. This suggests that estrogen’s protective effects may be limited to delaying disease onset rather than altering its progression. The progression of periodontitis is likely influenced by a complex interplay of systemic inflammation, metabolic factors, and behavioral risks that override any protective effects of estrogen replacement.

In analyzing secondary outcomes, we initially found that HRT users exhibited lower clinical attachment loss (CAL), suggesting a possible protective effect. However, after adjusting for confounders such as smoking, diabetes, and socioeconomic factors, this association lost statistical significance. While estrogen may contribute to periodontal integrity, systemic and behavioral factors play a more dominant role in periodontal health. Similarly, no significant association was found between HRT use and either saliva secretion rates or bone loss, reinforcing the idea that HRT alone may not be sufficient to mitigate these aspects of periodontal deterioration, found in previous research [16].

From a biological perspective, estrogen appears to exert protective effects on periodontal tissues through multiple mechanisms. It modulates immune responses by downregulating pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), reducing chronic inflammation in periodontal tissues. Additionally, estrogen enhances collagen synthesis, improves wound healing, and plays a crucial role in maintaining bone metabolism. These effects may explain why HRT users had a lower prevalence of periodontitis in our study. However, the absence of a significant impact on disease severity suggests that once periodontitis develops, factors like bacterial dysbiosis, metabolic disorders, and chronic inflammation may play a more critical role in disease progression than hormonal influences.

These findings highlight important clinical implications. Given the association between HRT use and lower periodontitis prevalence, healthcare providers should consider integrating oral health assessments into menopause management protocols. Gynecologists prescribing HRT could collaborate with dental professionals to monitor periodontal health in postmenopausal women, identifying those at risk for disease progression. Additionally, the strong influence of smoking and diabetes on periodontitis severity underscores the need for targeted prevention strategies, such as patient education, smoking cessation programs, and better glycemic control for diabetic patients.

Overall, this study provides valuable insights into the relationship between HRT and periodontal health. While estrogen replacement may help reduce the prevalence of periodontitis, its effects on disease progression remain unclear. Further research is necessary to clarify its long-term impact, optimize treatment strategies, and explore the interplay between hormonal therapy and other systemic health factors.

Conclusion and recommendation

This study highlights a significant association between HRT usage and reduced periodontitis prevalence in postmenopausal women. While the protective effects of HRT on periodontal health are evident, further research is needed to clarify its broader implications and mechanisms. These findings contribute to a growing body of evidence supporting the systemic benefits of HRT and underscore its potential role in oral health management. The findings emphasize the need for interdisciplinary collaboration between gynecologists and dentists in managing postmenopausal women’s health. Healthcare providers should consider the potential oral health benefits of HRT when advising on menopausal treatment options. Educating patients on the systemic interplay between hormonal changes and oral health may further enhance prevention and management strategies for periodontitis.

A key strength of this study is the clinical assessment of periodontitis in real-time, as opposed to relying on stored data, which enhances the accuracy and reliability of periodontal health measurements. Additionally, the study utilized a reproducible questionnaire and adhered to the American Academy of Periodontology (AAP) classification criteria, ensuring consistency in diagnosis. The inclusion of sociodemographic and medical predictors further strengthens the analysis by adjusting for potential confounders.

However, certain limitations should be acknowledged. The case-control study design may introduce selection bias, as participants were recruited from healthcare facilities, potentially overrepresenting individuals who seek medical or dental care more frequently. Recall bias is another concern, as menopausal data were self-reported, which may have affected the accuracy of information regarding age at menopause, duration of menopause, and HRT usage. To mitigate this, recall-related questions, including last childbirth and prior gynecologist visits, were incorporated to improve data reliability. A more objective method of verifying menopausal status and HRT history could enhance future studies. One notable limitation is the small proportion of HRT users (5.38%) in the sample, which may impact statistical power and the generalizability of findings. A larger sample of HRT users in future research would allow for more definitive conclusions regarding its effects on periodontal health. Furthermore, this study focused on a single HRT formulation (oral estradiol 1 mg daily). Future studies should explore various HRT types, dosages, and administration routes (e.g., transdermal patches) to assess potential differences in their periodontal effects.

Expanding research to examine the interaction between HRT and systemic factors, such as metabolic syndrome, inflammatory markers, and genetic predispositions, is essential for understanding the underlying biological mechanisms. Additionally, investigating the role of lifestyle factors, including oral hygiene behaviors, dietary habits, and access to dental care, could provide further insights into the association between HRT and periodontal health. Strengthening collaboration between gynecologists and dental professionals could enhance patient care by integrating periodontal assessments into menopause management strategies, ensuring early detection and prevention of periodontal disease in postmenopausal women.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

The author Dr. Raneem Ageel with initials (R.A.) has contributed to the ethical approval application, design of the study, the acquisition of data, analysis, tables and figures creation, interpretation of data, have drafted the work and substantively revised it, and submitted it. Author Dr. Bahaa Abalkhail (B. A.) has contributed to the ethical approval application, design of the study, data analysis, tables creation, interpretation of data; and revised the written work. The author Dr. Zuhair Natto (Z. N.) has contributed to the design of the study and tools used, data analysis and interpretation, tables and figures creation, and has contributed in writing the research work.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

The original paper questionnaires and periodontal charts were destroyed through incineration after anonymized data were recorded. As such, the datasets generated and/or analysed during the current study are not publicly available due to privacy protection protocols, but summary data are available from the corresponding author on reasonable request.

Declarations

Ethical approval and consent to participate

Ethical approval was given from the institutional review board of the Ministry of Health in Saudi Arabia (MOH) IRB log A0168 with national registration number NCBE-KACST, KSA: (H-02-J-002) in 2023, which follows the responsibilities and recommendations of GDRS. All participants were shown the consent form, which was read to those who could not read. Consent explained the study and its aim; it also contained the tools used in the examination and the length of the examination it had the patient’s rights, and the researchers’ contact information. If subjects showed clear understanding, they were asked to consent verbally and by applying the index finger’s fingerprint to the first page of the questionnaire. After the study was completed, data from the questionnaire and fingerprint paper were destroyed through incineration.

Consent for publication

Not applicable, as there are no identifying images or other personal or clinical details of participants that compromise anonymity.

Competing interests

The authors declare no competing interests.