Association of Menopause and Rhinitis Among Adult Women in the United States: Findings from the All of Us Research Program

Abstract

Objective:

The inflammatory role of female hormones has been garnering increased attention in the literature. Studies suggest a link between estrogen and inflammatory conditions of the airways and nasal mucosa. However, there remains a paucity of literature regarding the associations of hormones with rhinitis. Given the profound hormonal changes that occur during menopause, we sought to better understand the association between menopause and rhinitis.

Methods:

Data from the All of Us Research Program regarding rhinitis diagnoses, menopause status, demographic variables, socioeconomic status, and comorbidities were extracted for female participants aged 40–60. Crude odds ratios (cORs) and 95% confidence intervals (CIs) were calculated for unadjusted associations between menopause and rhinitis. Variables were then included in multivariable logistic regression models, with separate models for allergic rhinitis (AR) and nonallergic rhinitis (NAR) as the outcome variables. Adjusted odds ratios (aOR) and 95% CI were calculated.

Results:

We identified 40,875 female participants aged 40–60 without any missing data. Compared with participants without rhinitis, a greater proportion of those with AR (51.6% vs. 55.6%; cOR: 1.18; 95% CI: 1.11–1.25) and NAR (51.6% vs. 58.9%; cOR: 1.34; 95% CI: 1.11–1.63) had experienced menopause. However, after controlling for covariates, menopause was associated with a decreased odds of AR (aOR: 0.89; 95% CI: 0.82–0.96) and not associated with NAR (aOR: 0.98; 95% CI: 0.77–1.24).

Conclusion:

Menopause was independently associated with a decreased odds of AR but was not associated with NAR. Research should aim to further examine these relationships and hormonal mechanisms underlying the observed protective associations.

INTRODUCTION

Rhinitis refers to a variety of nasal symptoms such as congestion, runny nose, sneezing, and itching, which arise from inflammation or dysfunction of the nasal mucosa.¹ This condition is categorized into two main types: allergic rhinitis (AR), an immunoglobulin E (IgE)-mediated immune response to allergens, and nonallergic rhinitis (NAR), which encompasses different disorders causing rhinitis symptoms without allergen sensitization.^1,2 The role of sex hormones has become increasingly studied in the pathogenesis of AR and other inflammation-related conditions like asthma. Research highlights testosterone and progesterone as primarily exerting anti-inflammatory effects, whereas estrogen’s impact is more complex, displaying both proinflammatory and anti-inflammatory properties.^3–5 Notably, within the nasal mucosa, both estrogen and progesterone are implicated in promoting inflammation by mechanisms such as eosinophil recruitment, cytokine production, and degranulation.^6,7 This aligns with findings linking estrogenrelated characteristics to a higher incidence of asthma and AR,^8,9 and with the observation that these conditions are more prevalent among adult women.^10–13

Based on the evidence linking sex hormones with nasal mucosal reactivity and conditions like AR, our aim was to investigate whether menopause, characterized by a significant decrease in female sex hormones, correlates with the occurrence of rhinitis. Existing literature has studied the pubertal sex shift in rhinitis, in which the incidence of rhinitis increases among post-pubertal females, potentially suggesting a hormonal role in rhinitis.^14,15 On the contrary, one study conducted in France concluded that menopause is associated with an increased likelihood of rhinitis¹⁶; however, this study did not make a distinction between AR and NAR and may not be generalizable to adults in the United States. To our knowledge, no studies have directly investigated the correlation between menopause and rhinitis in the United States. In addition, the association between menopause and asthma is conflicted. Some studies suggest that menopause is associated with increased rates of asthma,^17,18 while others suggest no correlation.^19,20 Given the well-established link between asthma and rhinitis,^21,22 it is similarly unclear how menopause truly affects the rates of rhinitis. Thus, given the decrease in hormones during menopause, we hypothesize that menopause could be protective against rhinitis.

Thus, our study aims to further investigate this association using a large national dataset from the All of Us Research Program (AoURP). Understanding the association between menopause and rhinitis is crucial for optimizing therapeutic strategies for post-menopausal women with rhinitis. This study may also lend additional evidence to the growing body of literature linking female sex hormones with inflammatory conditions and diseases of the nasal mucosa. To our knowledge, this study is the first to investigate the association between menopause and rhinitis in the United States.

METHODS

This study utilized data from AoURP’s Controlled Tier Dataset v7, available to authorized users on the Researcher Work-bench. AoURP is a national dataset of adults in the United States that integrates participant information from various sources such as surveys, electronic health records, biosamples, and physical measurements, specifically targeting populations historically underrepresented in biomedical research.²³ Participants are invited to enroll in AoURP via partner healthcare provider organizations, including academic centers, Veterans Affairs medical centers, and community health centers. Given that AoURP is a deidentified public dataset, the institutional review board determined this study to be exempt from review.

For our study, we included individuals assigned female sex at birth. To focus specifically on menopause as the variable of interest, we restricted our sample to participants aged 40–60 years. We excluded individuals who were pregnant at the time of data collection, had a history of oophorectomy, or were using hormonal medications. We then extracted data on rhinitis diagnosis as the primary outcome, encompassing both AR and NAR. In AoURP, medical diagnoses are based on participant medical records using Systemized Nomenclature of Medicine (SNOMED) and International Classification of Diseases codes (ICD-9 and ICD-10). AoURP translates these codes into a unified standardized vocabulary. For our primary outcome, we extracted data on rhinitis diagnoses by including any condition from this standardized vocabulary that contained the term “rhinitis.” We classified these diagnoses as AR if they included the terms “allergic” or “allergy,” while all other diagnoses were categorized as NAR. A manual review was conducted to ensure accurate classification.

Our primary exposure was natural menopause, denoted by participant response to the survey question “Why did your periods stop?”. We also extracted covariate data, including demographic factors (age, race/ethnicity), socioeconomic status indicators (income, education, and insurance status), and relevant comorbidities (such as asthma and gastroesophageal reflux disease [GERD]), guided by extensive literature supporting their association with rhinitis.^24,25 Participants with any missing outcome, exposure, or covariate data were excluded from the study. Of the 249,565 adult women included in AoURP data, we identified a total of 40,875 participants meeting our inclusion and exclusion criteria.

Statistical Analysis

We calculated participant characteristics stratified by rhinitis diagnosis using proportions for categorical variables and means for continuous variables. Chi-square or t-test was conducted as appropriate to compare participant characteristics between those with and without rhinitis. Crude odds ratios (cORs) and 95% confidence intervals (CIs) were calculated for unadjusted associations between menopause and rhinitis. Covariate data were subsequently incorporated into multivariable logistic regression models to evaluate the independent association of menopause and rhinitis, controlling for participant characteristics. Separate models were developed for both AR and NAR, calculating adjusted odds ratios (aORs) and 95% CIs for the association between exposure and outcome variables. Statistical significance was set at p < 0.05. Analyses were conducted using R version 4.4.0 (R Foundation for Statistical Computing, Vienna, Austria) within the AoURP cloud analysis environment.

RESULTS

Participant characteristics are shown in Table I. Among our full identified cohort, the mean age was 50.4 years old, a majority had undergone menopause (52.2%), participants were primarily non-Hispanic White (54.3%), had some college education (51.7%), and were insured through private/employer plans (57.5%). After stratification by rhinitis diagnosis and type, 5,457 participants (13.4%) had rhinitis and 35,418 (86.6%) did not have rhinitis. Of those with rhinitis, 5,007 (91.8%) had AR while 450 (8.2%) had NAR. Compared with participants without rhinitis, a greater proportion of those with AR (51.6% vs. 55.6%, respectively; cOR: 1.18; 95% CI: 1.11–1.25) and NAR (51.6% vs. 58.9%, respectively; cOR: 1.34; 95% CI: 1.11–1.63) had experienced natural menopause. In terms of covariates, the rhinitis cohort had a higher proportion of participants who were middle income, college educated, insured (private/employer plans or Medicare/Medicaid), and diagnosed with asthma or GERD. Participants with AR were more likely to be White or Black, whereas there was no statistically significant difference in race/ethnicity between the NAR cohort and those without rhinitis.

TABLE I.

Participant Characteristics of Cohort for Menopause Analysis after Inclusion/Exclusion Criteria.

	Full cohort (N = 40,875)	No rhinitis (N = 35,418)	Rhinitis
			All rhinitis (N = 5457)	Allergic rhinitis (N = 5007)	Nonallergic rhinitis (N = 450)
Menopause, n (%)
No	19,553 (47.8%)	17,147 (48.4%)	2,406 (44.1%)	2,221 (44.4%)	185 (41.1%)
Yes	21,322 (52.2%)	18,271 (51.6%)	3,051 (55.9%)	2,786 (55.6%)	265 (58.9%)
p-value	-	-	< 0.001*	< 0.001*	0.002*
Age, mean (SD)	50.4 (5.9)	50.3 (5.9)	51.1 (5.7)	51.1 (5.7)	51.4 (5.8)
p-value	-	-	< 0.001*	< 0.001*	< 0.001*
Race/Ethnicity, n (%)
Non-Hispanic White	22,179 (54.3%)	19,155 (54.1%)	3,024 (55.4%)	2,761 (55.1%)	263 (58.4%)
Non-Hispanic Black	8,931 (21.8%)	7,688 (21.7%)	1,243 (22.8%)	1,149 (22.9%)	94 (20.9%)
Hispanic	7,651 (18.7%)	6,703 (18.9%)	948 (17.4%)	877 (17.5%)	71 (15.8%)
Other	2,114 (5.2%)	1,872 (5.3%)	242 (4.4%)	220 (4.4%)	22 (4.9%)
p-value	-	-	0.001*	0.002*	0.245
Annual Income (USD), n (%)
Less than 10,000	7,352 (18.0%)	6,409 (18.1%)	943 (17.3%)	884 (17.7%)	59 (13.1%)
10,000–25,000	5,774 (14.1%)	4,950 (14.0%)	824 (15.1%)	744 (14.9%)	80 (17.8%)
25,000–35,000	3,342 (8.2%)	2,921 (8.2%)	421 (7.7%)	388 (7.7%)	33 (7.3%)
35,000–50,000	3,467 (8.5%)	2,990 (8.4%)	477 (8.7%)	434 (8.7%)	43 (9.6%)
50,000–75,000	4,740 (11.6%)	4,073 (11.5%)	667 (12.2%)	605 (12.1%)	62 (13.8%)
75,000–150,000	9,495 (23.2%)	8,184 (23.1%)	1,311 (24.0%)	1,206 (24.1%)	105 (23.3%)
More than 150,000	6,705 (16.4%)	5,891 (16.6%)	814 (14.9%)	746 (14.9%)	68 (15.1%)
p-value	-	-	0.002*	0.016*	0.025*
Education, n (%)
Less than high school	3,648 (8.9%)	3,227 (9.1%)	421 (7.7%)	398 (7.9%)	23 (5.1%)
High school or GED	6,920 (16.9%)	6,030 (17.0%)	890 (16.3%)	827 (16.5%)	63 (14.0%)
Some college	21,113 (51.7%)	18,141 (51.2%)	2,972 (54.5%)	2,713 (54.2%)	259 (57.6%)
Advanced degree	9,194 (22.5%)	8,020 (22.6%)	1,174 (21.5%)	1,069 (21.4%)	105 (23.3%)
p-value	-	-	< 0.001*	< 0.001*	0.003*
Health Insurance, n (%)
None	3,328 (8.1%)	3,040 (8.6%)	288 (5.3%)	268 (5.4%)	Hidden†
Medicare/Medicaid	12,161 (29.8%)	10,482 (29.6%)	1,685 (30.9%)	1,538 (30.7%)	147 (32.7%)
Private/Employer	23,483 (57.5%)	20,239 (57.1%)	3,231 (59.2%)	2,959 (59.1%)	272 (60.4%)
Other	1,903 (4.7%)	1,657 (4.7%)	253 (4.6%)	242 (4.8%)	Hidden†
p-value	-	-	< 0.001*	< 0.001*	0.001*
Asthma, n (%)
No	35,569 (87.0%)	32,355 (91.4%)	3,214 (58.9%)	2,891 (57.7%)	323 (71.8%)
Yes	5,306 (13.0%)	3,063 (8.6%)	2,243 (41.1%)	2,116 (42.3%)	127 (28.2%)
p-value	-	-	< 0.001*	< 0.001*	< 0.001*
GERD, n (%)
No	33,538 (82.1%)	30,853 (87.1%)	2,685 (49.2%)	2,436 (48.7%)	249 (55.3%)
Yes	5,306 (17.9%)	4,565 (12.9%)	2,772 (50.8%)	2,571 (51.3%)	201 (44.7%)
p-value	-	-	< 0.001*	<0.001*	<0.001*

p-values calculated using chi-square or t-test as appropriate comparing each group to the cohort without rhinitis.

Percentage values represent column percentages.

GED = general educational development; SD = standard deviation; USD = US Dollars.

^*p < 0.05.

^†Values hidden in accordance with AoURP policy requiring values less than 20 to be hidden to protect participant privacy.

Table II shows the results of the multivariable logistic regression model analyzing the independent association of menopause with rhinitis. Menopause was protective against rhinitis (aOR: 0.89; 95% CI: 0.83–0.97). However, when assessing both AR and NAR individually, menopause was found to be protective against AR (aOR: 0.89; 95% CI: 0.82–0.96) but not NAR (aOR: 0.98; 95% CI: 0.77–1.24). Older age (aOR: 1.02; 95% CI: 1.01–1.03), some college education (aOR: 1.22; 95% CI: 1.07–1.40), or advanced degree compared with less than high school education (aOR: 1.28; 95% CI: 1.10–1.50), asthma (aOR: 4.81; 95% CI: 4.47–5.18), and GERD (aOR: 4.84; 95% CI: 4.53–5.18) were associated with an increased likelihood of any rhinitis, and were associated with both AR and NAR individually. Private/employer insurance was associated only with AR (aOR: 1.43; 95% CI: 1.22–1.68).

TABLE II.

Adjusted Associations Between Menopause and Rhinitis.

	All rhinitis (N = 5457)	Allergic rhinitis (N = 5007)	Nonallergic rhinitis (N = 450)
Menopause
No	Ref	Ref	Ref
Yes	0.89 (0.83–0.97)	0.89 (0.82–0.96)	0.98 (0.77–1.24)
Age	1.02 (1.01–1.03)	1.02 (1.01–1.03)	1.03 (1.01–1.05)
Race/Ethnicity
Non-Hispanic White	Ref	Ref	Ref
Non-Hispanic Black	1.04 (0.95–1.13)	1.05 (0.96–1.15)	0.97 (0.74–1.25)
Hispanic	0.98 (0.89–1.07)	0.98 (0.89–1.08)	0.88 (0.66–1.16)
Other	0.99 (0.85–1.15)	0.98 (0.84–1.15)	1.00 (0.62–1.52)
Annual Income (USD)
Less than 10,000	Ref	Ref	Ref
10,000–25,000	1.08 (0.96–1.21)	1.04 (0.93–1.18)	1.51 (1.06–2.16)
25,000–35,000	0.97 (0.84–1.13)	0.96 (0.83–1.12)	1.17 (0.73–1.83)
35,000–50,000	1.01 (0.86–1.17)	0.98 (0.83–1.15)	1.39 (0.87–2.19)
50,000–75,000	1.00 (0.86–1.16)	0.97 (0.83–1.14)	1.41 (0.89–2.22)
75,000–150,000	1.01 (0.87–1.17)	1.00 (0.86–1.17)	1.19 (0.75–1.88)
More than 150,000	0.92 (0.78–1.09)	0.92 (0.78–1.09)	1.08 (0.66–1.78)
Education
Less than high school	Ref	Ref	Ref
High school or GED	1.05 (0.91–1.21)	1.03 (0.89–1.19)	1.33 (0.83–2.22)
Some college	1.22 (1.07–1.40)	1.18 (1.02–1.35)	1.90 (1.22–3.08)
Advanced degree	1.28 (1.10–1.50)	1.22 (1.04–1.44)	2.10 (1.28–3.57)
Health insurance
None	Ref	Ref	Ref
Medicare/Medicaid	0.94 (0.81–1.08)	0.91 (0.79–1.06)	1.32 (0.84–2.19)
Private/Employer	1.43 (1.22–1.68)	1.43 (1.22–1.68)	1.43 (0.88–2.43)
Other	1.17 (0.96–1.43)	1.21 (0.99–1.49)	0.68 (0.31–1.41)
Asthma
No	Ref	Ref	Ref
Yes	4.81 (4.47–5.18)	5.02 (4.66–5.41)	2.45 (1.94–3.08)
GERD
No	Ref	Ref	Ref
Yes	4.84 (4.53–5.18)	4.87 (4.54–5.22)	4.18 (3.39–5.15)

p < 0.05. Values represent OR (95% CI).

GED = general educational development; USD = US Dollars.

DISCUSSION

Our study found that menopause was independently associated with a lower odds of AR, while there was no association between menopause and NAR after adjusting for covariates.

Given the decrease in hormone levels during menopause, in addition to the fact that AR is primarily inflammation-mediated, our results could lend support to a role of hormones in the pathogenesis of AR and related inflammatory conditions. On the contrary, NAR is a more heterogeneous condition mediated by predominantly non-inflammatory mechanisms. The most common form of NAR, nonallergic rhinopathy (or vasomotor rhinitis), which comprises at least two thirds of NAR,²⁶ is thought to be mediated by an imbalance in parasympathetic and sympathetic inputs to the autonomic nervous system in response to changes in environmental conditions, weather, strong emotions, smells, or hormones.^27,28 Other less common forms of NAR may be attributed to tachyphylaxis, as in the case of rhinitis medicamentosa, or progressive atrophy of the nasal mucosa, as in the case of atrophic rhinitis.¹ This lack of inflammation in the pathogenesis of many of the common forms of NAR may explain why no association between menopause and NAR was found in our study.

Although some prior research has examined the relationship between rhinitis and factors such as hormone replacement therapy and long-term estrogen exposure in postmenopausal women,^8,29,30 we are not aware of any studies specifically exploring the connection between menopause and rhinitis in the United States. Our findings contradict those of Lund et al., which found that menopause was associated with an increased likelihood of rhinitis symptoms among adult women in France.¹⁶ This study is the first to investigate the relationship between menopause and both AR and NAR in the United States. We additionally utilized a large and diverse national dataset, incorporating participants of various demographic and socioeconomic backgrounds.

Although more research is needed, establishing menopause as a protective factor against AR could have significant implications in clinical management. Understanding that menopause may reduce the risk of AR could lead to more personalized treatment strategies for women by allowing clinicians to explore treatments that consider a woman’s menopausal status. From a public health perspective, women could be encouraged to seek care for AR symptoms earlier in their reproductive years, fostering better management strategies. These insights could also be applied to healthcare policy aimed at improving care for women dealing with allergic conditions throughout different life stages.

Our study has certain limitations. Menopause history and the socioeconomic variables in the AoURP dataset, including income, education, and insurance status, were self-reported by participants, making them potentially subject to bias. Additionally, because NAR is a heterogeneous category that includes various pathologies, our findings may not apply to all types of NAR. Furthermore, due to the cross-sectional design of this study, causation could not be determined.

CONCLUSION

In conclusion, our study found that menopause is independently associated with a decreased odds of AR while having no association with NAR. Our findings contribute to the paucity of the literature investigating the effect of endogenous hormonal changes and estrogen-related characteristics on rhinitis. Future research should investigate this association longitudinally to establish causation, and additional studies could aim to establish an association between objective laboratory values of hormone levels and rhinitis. Further investigations into the role of hormones in inflammatory conditions of the nasal mucosa are also needed to deepen our understanding of these processes.