Abstract
Background Prior studies showed that female patients with chronic rhinosinusitis (CRS) suffer a worse disease-specific quality of life (QoL).
Goal The aim of this study is to investigate gender differences in sinonasal QoL outcomes in patients requiring endoscopic endonasal skull base surgeries (EESBS).
Methods Cross-sectional analysis of patients presenting to our clinic from August 2020 to December 2022 with skull base tumors, spontaneous cerebrospinal fluid (CSF) rhinorrhea, or Grave's orbitopathy (for orbital decompression) was performed. Baseline and postsurgical QoL were measured using the 22-item Sinonasal Outcome Test (SNOT-22). Patients' demographics and comorbidities were reviewed. Patients with concomitant CRS were excluded.
Results Eighty-six patients were included (54 with skull base tumors, 17 Grave's orbitopathy, and 15 spontaneous CSF rhinorrhea). The mean age of the patients was 52 years (range: 12.4–81.5 years), and 51.6% of the patients were females. There was no age difference between female and male patients. Smoking history, asthma, and allergic rhinitis were also similar between the two groups. Female patients had a significantly higher incidence of depression (58.3 vs. 32.4%, p = 0.018) and migraine (50.0 vs. 21.6%, p = 0.007). Female patients had a significantly worse overall SNOT-22 scores at baseline (33.6 vs. 18.2, p = 0.001), at the 3-month follow-up (29.7 vs. 15.5, p = 0.002), and at the 6-month follow-up (33.5 vs. 14.9, p = 0.005). This worse QoL was seen mainly in the ear/facial, sleep, and psychological domains. Linear regression of the SNOT-22 scores and its subdomains adjusting for comorbidities showed that migraine was found to be the most significant determinant of gender differences in the QoL.
Conclusion Female patients who undergo EESBS show higher overall SNOT-22 scores secondary to higher incidence of migraine.
Keywords: patient-reported outcome measures, 22-item Sinonasal Outcome Test, skull base surgery, paranasal sinuses, gender
Introduction
Research on gender and sex differences in the quality of life (QoL) of patients with rhinological disorders has mainly focused on chronic rhinosinusitis (CRS). Previous studies have demonstrated that female patients with CRS suffer from a worse disease-specific QoL as measured by the 22-item Sinonasal Outcome Test (SNOT-22). 1 2 Despite the observation of this difference in QoL between genders in patients with CRS, the cause is not well understood at this time. Some studies showed that this difference can be explained by comorbid conditions, such as aspirin sensitivity and depression. 3 However, it is unknown if some of these differences are related to pathophysiological differences in how CRS affects females and males. 4
Endoscopic endonasal skull base surgery (EESBS) is currently the standard treatment for many skull base and orbital pathologies, namely, sellar tumors, spontaneous cerebrospinal fluid (CSF) rhinorrhea, and Grave's orbitopathy requiring endoscopic decompression. A recent systematic review showed improvement in the sinonasal QoL after EESBS. 5 It is important to understand what factors may affect the QoL outcome in patients undergoing EESBS. Does a gender-based difference in disease burden exist in this patient population? Do female patients suffer from worse QoL similar to the CRS female patients? What are the comorbidities that affect QoL in patients undergoing EESBS?
The goal of this study is to investigate the gender differences in QoL outcomes in patients requiring endoscopic endonasal surgeries for skull base pathologies.
Methods
Study Design
This study was approved by West Virginia University's institutional review board. A retrospective longitudinal cohort study of patients who presented to the otolaryngology clinics with skull base pathologies from August 2020 to December 2022 was performed. Patients' subjective assessment and QoL were studied using the SNOT-22 form preoperatively as well as postoperatively at 3 and 6 months. A review of patient demographics, comorbidities, and SNOT-22 scores, and Lund–Kennedy endoscopy scores was performed.
Inclusion/Exclusion Criteria
Skull base pathologies included skull base tumors, spontaneous CSF rhinorrhea, and Grave's orbitopathy (patients referred for endoscopic orbital decompression). Skull base tumors included sellar tumors (pituitary adenoma and Rathke's cyst), suprasellar meningiomas, clival chondrosarcoma, and olfactory neuroblastoma. Patients with preoperative CRS were excluded. Also, patients with inverted papilloma were excluded as these tumors frequently cause obstructive rhinosinusitis, which may affect the sinonasal QoL.
Statistical Analysis
For statistical analysis, group differences on continuous variables were analyzed using the two-sample t -test and group differences by categorical variables were analyzed using the chi-squared test. Linear regression for SNOT-22 and its domain scores was performed to determine if the gender differences can be explained by any of the associated comorbidities. Statistical significance was set at p = 0.05. All statistical analyses were performed using Stata 18 (StataCorp, College Station, TX, United States).
Results
Eighty-six patients in total were included in this study, of which 54 had pituitary tumors, 17 had Grave's orbitopathy, and 15 had spontaneous CSF rhinorrhea. The mean age of the patients was 52 ± 17.3 years and 57% of patients were females. Patient characteristics are summarized in Table 1 . The mean patient body mass index (BMI) was significantly higher in female patients than in male patients (36.4 vs. 30.7, p = 0.003), while male patients had an increased incidence of nasal septal deviation (42.3 vs. 16.3%, p = 0.017). Female patients had a significantly higher incidence of depression (58.3 vs. 32.4%, p = 0.018) and migraine (50.0 vs. 21.6%, p = 0.007). All 86 patients had follow-up SNOT-22 scores available for the 3-month postoperative visit. For the 6-month follow-up visit time point, 44 patients had follow-up visits and completed the SNOT-22 questionnaires (23 female patients and 21 male patients).
Table 1. Patient demographics and comorbidities.
| Overall ( N = 86) | Female ( N = 49) | Male ( N = 37) | p -value | |
|---|---|---|---|---|
| Age (mean, SD) | 52 (17.3) | 51.6 (15.5) | 53.3 (19.6) | 0.658 |
| Body mass index | 34.0 (8.3) | 36.4 (8.4) | 30.7 (7) | 0.003 |
| Septal deviation | 26.1% | 16.3% | 42.3% | 0.017 |
| Allergic rhinitis | 14.0% | 18.4% | 8.1% | 0.174 |
| Asthma | 16.3% | 14.3% | 18.9% | 0.564 |
| Current smoker | 16.3% | 18.4% | 13.5% | 0.546 |
| Past smoker | 33.7% | 36.7% | 29.7% | 0.496 |
| COPD | 5.8% | 2.0% | 10.8% | 0.085 |
| Migraine | 37.7% | 50.0% | 21.6% | 0.007 |
| Depression | 47.1% | 58.3% | 32.4% | 0.018 |
| OSA | 11.6% | 12.2% | 10.8% | 0.837 |
| Postoperative CRS | 6.8% | 10.0% | 2.6% | 0.174 |
| Diagnosis | ||||
| Skull base tumors | 54 (62.8%) | 29 (59.1%) | 25 (67.6%) | 0.685 |
| Grave's orbitopathy with endoscopic orbital decompression | 17 (19.8%) | 11 (22.4%) | 7 (16.2%) | |
| Spontaneous CSF rhinorrhea | 15 (17.4%) | 10 (20.4%) | 5 (13.5%) | |
| Nasoseptal flap | 6 | 5 | 1 | 0.082 |
Abbreviations: COPD, chronic obstructive pulmonary disease; CRS, chronic rhinosinusitis; CSF, cerebrospinal fluid; OSA, obstructive sleep apnea; SD, standard deviation.
Notes: Data expressed as mean ± standard deviation or percentage (%). A two-sample t -test was used for continuous variables, and a chi-squared test was used for categorical variables.
Statistical significance is set at p = 0.05.
The QoL outcomes are summarized in Table 2 . Female patients had a significantly worse overall SNOT-22 scores at baseline (33.6 vs. 18.2, p = 0.001), at the 3-month follow-up (29.7 vs. 15.5, p = 0.002), and at the 6-month follow-up (33.5 vs. 14.9, p = 0.005). This worse QoL was mostly seen mainly in the ear/facial, sleep, and psychological domains ( Fig. 1 ). There was no worsening in the QoL after skull base surgery in any of the two cohorts ( p > 0.05 for all scores).
Table 2. Comparison of baseline and postoperative SNOT-22 scores, subdomain scores, and endoscopy scores between female and male patients.
| Overall ( N = 86) | Female ( N = 49) | Male ( N = 37) | p -value | ||
|---|---|---|---|---|---|
| SNOT-22 (mean, SD) | Baseline | 27.5 (21.3) | 33.6 (19.7) | 18.2 (20.4) | 0.001 |
| 3 mo | 23.2 (20.1) | 29.7 (19) | 15.5 (18.8) | 0.002 | |
| p -value a | 0.188 | 0.338 | 0.569 | ||
| 6 mo | 24.6 (22.6) | 33.5 (21.3) | 14.9 (20.3) | 0.005 | |
| p -value a | 0.464 | 0.975 | 0.555 | ||
| Domains | |||||
| Rhinologic (mean, SD) | Baseline | 6 (5.7) | 6.1 (5.5) | 5.9 (6.2) | 0.829 |
| 3 mo | 6.4 (5.6) | 7.3 (4.6) | 5.4 (6.4) | 0.162 | |
| p -value | 0.649 | 0.293 | 0.773 | ||
| 6 mo | 6.3 (6.1) | 8.2 (6.2) | 4.3 (5.5) | 0.038 | |
| p -value | 0.797 | 0.157 | 0.353 | ||
| Extra-rhinologic (mean, SD) | Baseline | 2.4 (3.2) | 2.6 (3.4) | 1.9 (3) | 0.296 |
| 3 mo | 2.8 (3.2) | 3 (2.7) | 2.6 (3.6) | 0.613 | |
| p -value | 0.34 | 0.567 | 0.382 | ||
| 6 mo | 2.5 (2.7) | 3.3 (2.6) | 1.7 (2.6) | 0.05 | |
| p -value | 0.816 | 0.439 | 0.752 | ||
| Ear/facial (mean, SD) | Baseline | 4.5 (4.5) | 5.7 (4.7) | 2.8 (3.6) | 0.002 |
| 3 mo | 4.4 (4.3) | 6.2 (4.3) | 2.2 (3.1) | <0.001 | |
| p -value | 0.796 | 0.635 | 0.531 | ||
| 6 mo | 4.5 (4.5) | 6.4 (4.1) | 2.5 (4) | 0.003 | |
| p -value | 0.979 | 0.553 | 0.827 | ||
| Sleep (mean, SD) | Baseline | 9.1 (7.9) | 11.7 (7.6) | 5.3 (6.7) | <0.001 |
| 3 mo | 6.8 (6.5) | 8.7 (6.5) | 4.6 (5.9) | 0.007 | |
| p -value | 0.048 | 0.053 | 0.675 | ||
| 6 mo | 7.9 (7.7) | 10.6 (7.5) | 5 (7) | 0.015 | |
| p -value | 0.394 | 0.578 | 0.894 | ||
| Psychological (mean, SD) | Baseline | 11.1 (9.8) | 14.4 (9.3) | 6.1 (8.3) | <0.001 |
| 3 mo | 7.4 (8.1) | 10.1 (8.2) | 4.2 (6.9) | 0.002 | |
| p -value | 0.011 | 0.024 | 0.329 | ||
| 6 mo | 8.3 (9.3) | 11.9 (9.3) | 4.6 (7.8) | 0.008 | |
| p -value | 0.129 | 0.289 | 0.523 | ||
| Endoscopy scores (mean, SD) | Baseline | 0.7 (1.4) | 0.6 (1.2) | 0.9 (1.6) | 0.399 |
| 3 mo | 1.1 (2) | 1.2 (2) | 1.1 (2.2) | 0.882 | |
| p -value | 0.157 | 0.124 | 0.698 | ||
| 6 mo | 1.3 (2.5) | 1.7 (3.1) | 0.7 (1.3) | 0.279 | |
| p -value | 0.125 | 0.052 | 0.757 | ||
Abbreviations: SD, standard deviation; SNOT-22, 22-item Sinonasal Outcome Test.
Note: Sample size for 6 months of follow-up was 44 patients, comprising 23 female patients and 21 male patients.
Comparison between baseline and follow-up.
Fig. 1.
Box plots showing baseline quality-of-life measures (SNOT-22 scores and its domains) by gender. All, except the rhinologic and extra-rhinologic domains, showed statistically significant difference between female and male patients. SNOT-22, 22-item Sinonasal Outcome Test.
Linear regression of SNOT scores and its subdomains adjusting for BMI and nasal septal deviation is summarized in Table 3 (baseline data) and Supplementary Table S1 (available in the online version only; at the 3-month follow-up) and Supplementary Table S2 (available in the online version only; at the 6-month follow-up). Migraine was found to be the most significant determinant of gender differences in the QoL.
Table 3. Multivariate linear regression for SNOT-22 scores and its subdomains at baseline adjusting for body mass index and nasal septal deviation.
| SNOT-22 | Coefficient | p -value | 95% CI |
|---|---|---|---|
| Total score | |||
| Gender | 3.9 | 0.46 | –6.6 to 14.4 |
| Migraine | 17.1 | 0.013 | 3.8–30.5 |
| Depression | 9.4 | 0.082 | –1.2 to 20 |
| Ear/facial domain | |||
| Gender | 0.6 | 0.604 | –1.6 to 2.8 |
| Migraine | 3.2 | 0.03 | 0.3–6.0 |
| Depression | 1.9 | 0.09 | –0.3 to 4.2 |
| Sleep domain | |||
| Gender | 3.7 | 0.076 | –0.4 to 7.9 |
| Migraine | 3.2 | 0.232 | –2.1 to 8.4 |
| Depression | 4.5 | 0.036 | 0.3–8.7 |
| Psychological domain | |||
| Gender | 3.9 | 0.103 | –0.8 to 8.6 |
| Migraine | 5.7 | 0.059 | –0.2 to 11.7 |
| Depression | 4.5 | 0.06 | –0.2 to 9.2 |
Abbreviations: CI, confidence interval; SNOT-22, 22-item Sinonasal Outcome Test.
Discussion
Prior data have consistently shown that adult female patients with CRS have worse QoL as evidenced by higher overall SNOT-22 scores, with the difference being mainly accounted for by the nonrhinologic domains. 1 2 6 One large, multicenter study has found that females reported a significantly higher health-related QoL outcomes compared with the male cohort despite similar objective measures of disease severity. 1 Mendolia-Loffredo et al described worse scores on patients' QoL measures (Rhinosinusitis Disability Index and the Chronic Sinusitis Survey) in female patients with CRS. 3 In this study, authors attributed the difference to higher incidence of acetylsalicylic acid intolerance and depression in the female patients in their study population. 3 Lal et al also found that, despite equal numbers of women and men electing for endoscopic sinus surgery, women had higher total SNOT-22 symptom scores and lower burden of disease on CT than men. 2
The QoL outcomes after EESBS have been reported in several other studies. 5 7 8 The main focus in these studies has been on the sinonasal outcomes because of the use of the sinonasal corridor during EESBS. SNOT-22 is the most commonly used disease-specific patient-reported outcome measure (PROM) in patients with CRS. It is a powerful instrument as it measures several domains including the rhinologic, extra-rhinologic, ear/facial, sleep, and psychological domains. Choi et al studied the QoL outcomes with SNOT-22 in patients undergoing simple sellar approaches and extended beyond the sella approaches for skull base pathologies and did not note any significant worsening in the sinonasal QoL outcomes. 8
In this study, we aimed to investigate the gender differences in the QoL of patients undergoing EESBS. We found that female patients have significantly worse overall SNOT-22 scores than male patients. This difference was mainly seen in the nonrhinologic domains. Similar findings were also seen in the 3- and 6-month postoperative follow-ups. Two recent studies also identified gender differences in QoL after skull base surgery. 9 10 The first study by Buchlak et al in 2022 found that low preoperative QoL is negatively associated with female gender in endoscopic pituitary surgery using the anterior skull base surgery (ASBS) questionnaire. Another study by Fleseriu et al in 2023 also found worse baseline rhinologic QoL in female patients using the SNOT-22 rhinologic domain in patients with sinonasal malignancy. None of these studies looked at other contributing factors to explain this gender differences in the QoL. Our study shows that gender difference in the QoL can be attributed to the higher incidence of migraine as a comorbidity in the female cohort, rather than the disease itself or the surgical treatment.
Another important finding in our study is that the sinonasal QoL is not worse after EESBS. This was true in the overall cohort and in the female and male cohorts separately. These findings are similar to the studies by Choi et al 8 and McCoul et al 7 who found that the SNOT-22 scores and the subdomains are not different at 3 and 6 months postoperatively. However, a systematic review by Bhenswala et al in 2019 showed overall improvement in the QoL after EESBS in several of the included studies using the SNOT-22 questionnaire. 5
Our study had several limitations. First, this is a retrospective study, which has inherent bias regarding data collection. However, the SNOT-22 surveys were prospectively completed at the beginning of the patients. Another limitation is that our sample size is relatively small, but it is comparable to several of the prior studies published on the QoL in patients undergoing EESBS. Finally, although the SNOT-22 survey is not a validated instrument for patients with skull base pathologies, it is commonly used to measure the sinonasal QoL in this patient population.
Conclusion
Female patients who undergo EESBS for skull base pathologies show a higher overall SNOT-22 score, which is secondary to nonrhinologic symptomatology. This can be attributed to the higher incidence of migraine. This difference is specific to neither the skull base pathology nor the surgical treatment. Further studies with larger sample sizes are needed to confirm these findings.
Footnotes
Conflict of Interest None declared.
Supplementary Material
References
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