Differences in Fibroid Symptom Reporting among Asian and Caucasian Patients in a Multidisciplinary Fibroid Center

Introduction: Uterine fibroids are prevalent in reproductive-age Asian women and can have a severe impact on health due to heavy bleeding, pelvic pain, and psychosocial harm. Current treatment, ranging from expectant management to hysterectomy, is aimed at symptom alleviation. Therefore, it is crucial for providers to accurately gauge symptom impact to determine appropriate treatments. A recent study reported differential symptom scores between Asian and Caucasian women treated at the Stanford Fibroid Center (SFC). 1 In this pilot study, we aim to explore potential etiologies contributing to this finding by comparing fibroid size and location, clinical factors, and surveying sociocultural factors. Methods: We utilized a mixed methods approach to uncover potential associations to differential Uterine Fibroid Symptom and Health-Related Quality of Life Symptom Severity Scores (UFS-QoL SSS) between Asian and Caucasian patients at SFC. We quantitatively analyzed fibroid imaging data and clinical risk factors from this cohort and qualitatively compared semi-structured interviews in a representative sub-sample. Results: We found no significant difference in fibroid size or location between groups. However, Asians had significantly lower body mass index ( P < 0.0001) and were more likely non-smokers ( P = 0.0037) compared to Caucasians. After adjusting for these and other risk factors, pretreatment UFS-QoL SSS in Asian patients were still significantly lower ( P < 0.0001). Qualitative interviews with Asian and Caucasian interviewees demonstrated comparable symptom experiences and quality of life, but more Asian participants described a negative impact from family and friends, less access to and distrust of medical providers, and pursuit of alternative therapies for their fibroids. Conclusion: These findings suggest that the UFS-QoL questionnaire may be insufficient for capturing symptom burden in patients of different races. Further understanding on how the above factors modulate symptom reporting is warranted to help design appropriate fibroid treatment recommendations for diverse populations.

The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) questionnaire is a commonly utilized metric for quantifying bleeding, bulk-related symptoms, and quality of life in patients with uterine fibroids. 7Higher scores are associated with more symptom bother.Knowledge of factors that affect symptom impact is limited, but may consist of body mass index (BMI), insurance status, and previous hormonal treatment for fibroids. 1Shaffer et al. 1 described a novel finding in which Asian women reported significantly lower symptom scores compared to Caucasian women.Since then, Murji reiterated this finding in 2020. 8Given that treatment options are aimed at symptom alleviation, symptom underreporting may lead to delays in care.Racial minorities, such as Blacks and Hispanics, tend to have less trust in the healthcare system, which in turn leads to poor clinical relationships, less continuity, reduced medication adherence, worse self-reported health, and underutilization of resources. 9,10However, whether distrust is associated with under-communicating fibroid-related symptoms has not been investigated.Racial and ethnic differences in fibroid-related symptom severity warrant further investigation as they may have a significant impact on access to care and treatment outcomes for Asian women.
In this pilot study, we explore factors that may affect symptom reporting including clinical risk factors, fibroid size and location, and patient sociocultural perspectives.Understanding the origin of lower symptom scores in Asian patients will allow for the development of improved assessment tools and ultimately earlier treatment for uterine fibroids in this population.

Sampling and recruitment
This study was approved by the Stanford University Institutional Review Board, and consent was obtained from all interview participants.
Study participants were identified through the Stanford Fibroid Clinic (SFC), a multidisciplinary center focused on expanding treatment options and optimizing care for women with uterine fibroids.This clinic serves patients in California and across the southwestern US.The SFC population consists of 29% Asian and Pacific Islander patients, providing a robust sample size for analyzing diseases in Asian American communities.
We used the SFC patient database, which includes over 800 fibroid patients from 2013 to 2020 including patients from April 2013 to July 2017 cohort in the Shaffer et al.'s1 study, to retrospectively examine the association between clinical risk factors and UFS-QoL SSS differences between Asian and Caucasian women.The database was used to identify all premenopausal women who (1) self-identified as Asian or non-Hispanic Caucasian in electronic medical records, (2) completed UFS-QoL questionnaires, and (3) had fibroids verified on magnetic resonance imaging (MRI).We defined these patients as the 'parent population' in our study.
To qualitatively explore symptom reporting, we conducted in-depth interviews with patients who consulted with SFC between 2017 and 2020 to reduce potential recall bias.Exclusion criteria for the interviews included hormone therapy use, surgery or treatment within 8 weeks of interview, an incomplete UFS-QoL questionnaire, or pregnant state within 4 weeks of interview to avoid confounding effects on pain or bleeding.Eligible Asian and Caucasian patients were contacted via email.Participants that met all requirements and provided informed consent were interviewed by telephone.Our target sample size for the 'interview cohort' of at least 12 participants per ethnic group for a total of at least 24 participants was based on previous research suggesting thematic saturation can occur within 12 interviews. 11

Quantitative data collection and analysis
Demographic data, relevant clinical risk factors, and UFS-QoL SSS were collected from the electronic health records of eligible participants.The UFS-QoL, first published in 2002, is a validated questionnaire that is effective in identifying symptomatic fibroids and quantifying symptom severity (Spies et al.). 7Fibroid data such as number of fibroids and wall position of dominant fibroid (intramural, subserosal, exophytic, or submucosal/ intracavitary) were collected from pelvic MRIs attained prior to the consult visit at SFC.The volume of the dominant fibroid was calculated with the ellipsoid formula (LxHxWx0.52).
Statistical analyses were performed using R-studio (Version 1.1.463).Data with a P <0.05 were reported as significant.Predictor variables of interest included age, BMI, smoking history, parity,

POPULAR SCIENTIFIC SUMMARY
• There were no significant differences in fibroid size or location between Asian and Caucasian women • Asian women with fibroids had significantly lower BMI and were more likely to be non-smokers

Qualitative data collection and analysis
Eligible interview participants were invited to participate in a 30-45-min semi-structured phone interview.Participants verified demographic information from their Electronic Health Record (EHR) and were asked to self-report their racial background and generational status in the US.The interview guide, which was vetted by an obstetrician-gynecologist (BC) and qualitative researcher (JB), explored participants' presenting symptoms, knowledge about menstruation, fibroid impact on quality of life, impact from family and friends, rapport with healthcare providers, perceptions on their treatment and perceived treatment options, as well as the perception of UFS-QoL questionnaire responses.All interviews were conducted in English by NJR.
Interviews were audio-recorded, transcribed verbatim, and coded by NJR, ZD, and JN.Data analysis was facilitated using Dedoose qualitative software (Version 8.0.35).Using a priori concepts, transcripts were deductively coded and iteratively modified with input from the full research team to promote credibility. 12A pooled Cohen's kappa coefficient (κ) of 0.90 was achieved. 13,14Once all 26 transcripts were coded, a thematic analysis was performed using an iterative and team-based theme analysis process to identify overarching themes across all interview participants and between our Asian and Caucasian subgroups. 13,15Using content analysis, the number of instances in which specific sub-themes were mentioned by participants were counted and analyzed between Asian and Caucasian cohorts. 12,16

Sample characteristics
Clinical risk factor data were collected from 358 SFC patients, who self-identified as Asian (n = 177) and Caucasian (n = 181).The parent populations were similar in age, parity, number of fibroids, volume of largest fibroid, and fibroid location.They differed significantly in their BMI, with Asians having lower average BMIs (-3.6 kg/m 2 ; P < 0.0001), and smoking history, with Asians less likely to be current or former smokers (P = 0.0037) (Table 1).
One hundred fifty-six patients met the inclusion criteria for interview participation.Out of the 43 participants who responded and consented for interviews, 17 were excluded due to the late discovery of an exclusion criterion or 'no show'.A sample representative of the diverse SFC population of Asian and Caucasian participants were interviewed.These were 12 Asian (7 East Asian, 2 South Asian, 3 Southeast Asian, of whom 7 are foreign born, and 4 are first-or second-generation American) and 14 Caucasian (of whom 1 is foreign born).The interview cohort mirrored the parent population in clinical risk factors and fibroid burden.Similar to the observed differences between races in the parent population, Asian interview participants' average UFS scores differed by -13.5 points and BMI by -4.3 kg/m 2 compared to Caucasian interview participants, but neither were statistically significant due to a small sample size (Table 1).

Association between clinical risk factors and UFS score
Asian patients at SFC had significantly lower UFS-QoL SSS compared to Caucasian patients (-12.3,P < 0.0001, Table 1), despite the lack of differences in fibroid bulk and location.On multivariate linear regression analysis, race and a diagnosis of anemia had a statistically significant effect on UFS-QoL SSS (β = 11.96;P < 0.0001 and β = 15.48;P < 0.0001, respectively).An increase in BMI had a weak effect on UFS-QoL SSS (β = 0.65; P = 0.001).When Asian and Caucasians were treated as separate groups, BMI was no longer a significant risk factor in Caucasian patients and had increased significance in Asian patients (β = 0.36; P < 0.1648 and β = 1.28;P < 0.0023, respectively; Fig. 1, Table 2).Multivariate linear regression models on these three significant factors also showed that BMI, anemia, and race had statistically significant interactions affecting UFS-QoL SSS.

Qualitative findings
Several key themes developed from participant understanding of their uterine fibroids including fibroid impact on quality of life, impact from family and friends, and rapport with medical providers.Across these thematic areas, we examined perceptions between Asian and Caucasian interview participants. 11We used findings from the content analysis to indicate the number of participants indicating a particular level of impact, support, or interaction with their provider.

Fibroid impact on quality of life
Asian and Caucasian participants had a generally similar insight on the impact of fibroids on quality of life when stratified by low, moderate, or high UFS-QoL SSS The most bothersome symptoms reported by both groups were bleeding and pain.When asked about their general understanding of fibroids, many women did not know what fibroids were until their diagnosis.Many participants questioned their own culpability in the development of their fibroids and others became accustomed to their symptoms over the years.Participants, particularly those with higher symptom scores, mentioned social and psychological impact including missed work and depression, which they perceived to be worse than their physical symptoms.Participants in both groups said their symptoms caused anxiety because they were unable to predict their heavy periods (or urinary urgency) because of their fibroids.Multiple participants noticed a lump or mass, with some noting concern that fibroids made them appear pregnant, overweight, or worried over malignancy (Table 3).

Impact of family and friends
Overall, participants in both groups looked to their spouses and mothers for support and treatment decisions.Others found reassurance in friends who shared similar symptoms.Supportive family and friends provided comfort and reassurance and encouraged them to seek medical care (Table 4).Nevertheless, despite feeling supported by people close to them, more Asian participants (n = 5) noted negative or unsupportive interactions with their family and friends compared to Caucasians (n = 2).Moreover, Asian participants cited different reasons why these experiences were negative, such as feeling overwhelmed or misinformed  by family and friends.On the contrary, two Caucasian participants mentioned unsupportive interactions with family and friends, citing feeling let down or being blamed for not being able to provide for their family anymore (Table 4).Multiple women, in particular in the Asian group (n = 5, Caucasians n = 4), felt it was inappropriate and avoided talking about their symptoms to support people (Table 4).Members of both groups did not think it would be helpful to share their perspectives with support people.Participants mentioned shame or disgust toward their symptoms and specifically in the Asian cohort, not wanting to scare family and friends.

Rapport with medical providers
Asian (n = 12) and Caucasian (n = 13) participants both expressed trust in their medical providers at comparable levels, but cited different reasons.Both groups described trusted knowledgeable providers, but Asians cited trust in caring and reassuring providers, while Caucasians had more positive experiences when they felt they were taken seriously, were closely followed, and were involved in decision-making.For example, one participant described feeling heard when a provider allowed her to take time to wait and see but also offered her new options when she was ready to make a change (Table 5).
Both Asians and Caucasians expressed distrust in their medical providers prior to reaching SFC.Both Asians and Caucasians cited a lack of validation from their providers, that providers had ulterior motives or were not knowledgeable, had inadequate follow-up, or had negative interactions with hospital staff.Patients in both groups expressed a desire for primary care providers to inquire more about their menstrual health.These negative interactions more often present in the Asian cohort (n = 9) compared to Caucasians (n = 7) led some participants to avoid further care, seek alternative care, and experience worsening symptoms prior to reaching SFC.
Participants in both groups cited issues with insurance and long waiting periods prior to their initial appointment with a specialist, as well as seeing multiple providers prior to reaching SFC.Notably, Asian participants (n = 10) mentioned problems accessing providers more often than Caucasian participants (n = 7).One Asian patient required an ED visit for heavy bleeding while she waited.Asian participants attributed difficulties with provider access as one of the factors for feeling less comfortable with providers (Table 5).
Multiple participants expressed frustration toward providers prior to reaching SFC for lacking treatment options.They mentioned that some of their providers were unaware of newer treatment options such as uterine artery embolization or MRI-guided focused ultrasound and instead could only provide hysterectomies or D&C.These options were very limiting, especially to those who wished to get pregnant.A significant few believed that hysterectomy was their only option for treatment.Participants cited fear of long recovery and worry over risks and complications such as decreased sex drive and infertility as factors against hysterectomy.Their fears and feelings of lack of options impeded them from getting timely treatment.Members of both groups mentioned avoiding care (4 Asians and 4 Caucasians), thinking it was not worth getting treated or normalized their symptoms (Table 5).
There were more mentions of exploring alternative therapies to conventional treatments before visiting SFC in Asians (n = 6) compared to Caucasians (n = 4).In the Asian cohort, acupuncture was most mentioned as an alternative treatment, followed by dietary changes and supplements (Table 5).

DISCUSSION
The UFS-QoL is a validated questionnaire that is effective in identifying symptomatic fibroids and quantifying symptom severity. 7Although it was recently translated, - Asian participant culturally adapted, and validated in Chinese, 17 there is no current data describing racial discrepancies with the use of the UFS-QoL questionnaire.Our previous study revealed a significant difference in UFS-QoL symptom severity scores between Asian and Caucasian women.
There is scant data demonstrating differences in fibroid symptom impact among Asian women.Prior gynecological studies have shown that East and Southeast Asian women report fewer symptoms related to menopause and endometriosis relative to their prevalence, suggesting a cultural tendency to under-report symptoms compared to other ethnicities. 18,19The patients in the latter report were also older and had more severe stages of endometriosis, 19 highlighting the need to better understand symptom under-reporting and its potential effects on under-treatment.
To further understand the racial discrepancies in UFS-QoL SSS, we sought to examine differences in clinical factors and fibroid burden between groups that may be associated with differential symptom reporting.We found that there are no significant differences between Asian and Caucasian patients in fibroid number, size, and location, as well as parity and diagnosis of anemia.However, Asians had a significantly lower BMI and were less likely smokers than their Caucasian counterparts.Adjusting for these differences, UFS-QoL SSS continued to be significantly different between groups.In previous studies, BMI was associated with an increased risk of uterine fibroids. 2,5Smoking, on the contrary, has been weakly linked to a decreased risk of uterine fibroids. 2owever, there are no publications on how these two risk factors affect fibroid symptom reporting.Curiously, this study revealed modest, but significant interactions between BMI, a history of anemia and race in predicting UFS-QoL SSS, suggesting symptom scores in Asians were more affected by changes in BMI and anemia than in their Caucasian counterparts.These observations warrant further study of this possible interaction, especially with concurrent research suggesting lower BMI cutoffs in East Asian patient risk for hypertension. 20We also qualitatively queried patient experiences to explore if this discrepancy may be cultural, environmental, or social in nature.Qualitative data were acquired from representative samples within the Asian and Caucasian populations at the SFC to maximize content saturation and methodically analyzed under current qualitative research standards. 11,12Interviews suggest that patients in both Asian and Caucasian groups had similar insight in the realms of fibroid impact on the quality of life when stratified by UFS-QoL SSS, while their relationships with healthcare and their perception of support by loved ones differed.
On average, both Asian and Caucasian participants that were interviewed saw more than one provider for their fibroids before reaching the SFC, in concordance with Borah et al. 21Still, more Asian interview participants reported issues with accessing medical providers either for their consultation visits or for follow-ups after fibroid treatments.More Asian participants also mentioned distrust of prior medical practitioners compared to Caucasians.Previous research has shown that distrust in healthcare, which is reportedly greater in minority groups, may be correlated with lower utilization of healthcare, which in turn may lead to a decreased sense of reliability for the medical system. 10,22However, whether distrust is associated with under-communicating symptoms has not been investigated.The Asian interview cohort in this study lacked knowledgeable, accessible healthcare providers, close monitoring and treatment autonomy, bringing into question whether there is physician bias or even paternalistic tendencies from providers that should be further explored.Our findings of greater distrust among Asian patients compared to their Caucasian counterparts warrant further investigation into the impact on symptom reporting, since it has been established that distrust of physicians can alter patient narrations of illness experience. 10,23nterviewed Asian patients reported seeking alternative treatment methods more often than Caucasians.Whether alternative treatments such as diet changes, acupuncture, and supplements may play a role in reducing symptom impact or whether these patients benefit from stress relief of the perceived treatment is a subject for further exploration.Currently, there is no robust evidence for acupuncture as an effective treatment for fibroids, 24,25 but some studies suggest that acupuncture might reduce menstrual pain and associated symptoms more effectively than no treatment or NSAIDs. 26On the contrary, the observation that more Asians tend to seek alternative treatment could suggest a lesser reliance on the healthcare system than Caucasian participants, which could result in a lower emphasis on symptom reporting to providers if less is expected of them.
This was an exploratory study to provide data for hypothesis generation.There are limitations given the descriptive nature of our study.Because the study draws from the SFC patient population, it fails to capture patients managed by their primary care providers or gynecologists, and those who lack access to tertiary care.The interview methodology is qualitative, which is not designed to test hypotheses but rather to identify patterns across consistent themes to develop and inform hypotheses. 12Furthermore, although all eligible patients were contacted, those who participated self-selected, introducing selection bias.This overall hinders our ability to make greater generalizations to women with symptomatic fibroids.Additionally, although representative of our Asian patient population as a whole, our study was not equipped to separate interview participants into the different Asian ethnic groups.This is something that should be further explored in future prospective studies as differences within this diverse group may also help explain the UFS score discrepancy.Furthermore, the cohort consisted of one immigrant from the Caucasian cohort and 11 first-or second-generation immigrants from the Asian cohort, who were all English speaking.Within the interview cohort, immigrants tended to have lower UFS scores.Taking into account first-and secondgeneration immigrants who may have differing views on medical interventions may be especially important since Asian immigrants are more likely to be uninsured and therefore less likely to access care than their USborn counterparts. 27

CONCLUSION
Uterine fibroids display a wide range of manifestations that underline the complexity of how the treatment is approached.Our study found that Asian patients at the Stanford Fibroid Clinic had significantly lower UFS symptom scores than Caucasian patients despite having similar fibroid characteristics.BMI, history of smoking, and race appeared to interact with UFS-QoL scores.Interviews highlighted possible issues with accessibility, provider rapport, and increased use of alternative therapies in Asian patients.These findings suggest that the UFS-QoL questionnaire may be insufficient for capturing symptom burden in patients of different races.Further understanding on how the above factors modulate symptom reporting is warranted to help design appropriate fibroid treatment recommendations for diverse populations.

Figure. 1 .
Figure. 1. Multivariate linear regression of UFS score.(a) Pooled data from both groups.(b) Multivariate linear regression by race reveals BMI and diagnosis of anemia as modulators of UFS-QoL SSS in the Asian population in this study. 12

Table 2 . Multivariate linear regression on UFS-QoL SSS by common risk factors by race.
*P < 0.05 is significant.

Table 3 . Impact of fibroid symptom burden between Asian and Caucasian participants stratified by UFS score. Low (0-33; n = 9) Medium (34-66; n = 11) High (67-100, n = 6) Asian
'My case is probably simple because there's only one big one and it's growing towards outside of the uterus, so, for a long time …it didn't bother me'.'You just learn to manage your symptoms.… [menses] happens every month.I couldn't take a day off every month, like that wouldn't work out.I managed to get through the day….because it's so regular … You sort of learn to deal with it yourself'.'It's just overwhelming the amount of mental anguish people experience and I just, it's not something that [can] be understood unless you've really experienced that on a daily basis, for over a year.It's just crazy … and it wasn't really until I was on the other side of the surgery that I realized how much I suffered'.