Uterine fibroids (UF), also known as uterine myoma or leiomyomas, are a significant health issue among women of reproductive age. These benign pelvic tumors, composed of smooth muscle fibers and an extracellular matrix [1] , affect approximately 30% of women in the United States by age 35 and 70% by age 50, with a higher prevalence among women of color [2] [3] . Fibroids are a leading cause of hospitalizations for gynecological conditions, accounting for nearly 29% of cases among females aged 15 - 54 years [4] , and the leading cause of hysterectomies, representing 40% - 60% of all cases [5] [6] .

Symptoms of uterine fibroids can profoundly affect both physical and mental health, impacting fertility, social life, and work productivity [7] - [11] . Risk factors include obesity, age, nulliparity, family history, and race, with African American women being disproportionately affected [12] . Interestingly, some protective factors have been identified, such as the use of combined oral contraceptives, smoking in women with low BMI, and having children [13] .

The prevalence of uterine fibroids varies across ethnic groups [13] , with African American women experiencing the highest rates at 80%, compared to 70% in Caucasian women, 21.8% in Asian women, and 12.7% in Hispanic women [3] [14] . The increased incidence in African American women may be linked to elevated steroid hormone levels and genetic variations, including differences in the catechol-O-methyltransferase (COMT) gene, though the exact reasons are not fully understood [13] .

Up to 50% of fibroid cases are asymptomatic, particularly those involving small tumors that are discovered during routine exams for other complaints [15] . However, when symptoms do occur, they are influenced by the size, location, and hormonal effects of the fibroids [7] . These tumors can increase the surface area of the endometrium and the overall size and bulk of the uterus, potentially compressing surrounding structures [16] . Clinical manifestations include abnormal uterine bleeding, pelvic pressure, bowel dysfunction, reproductive issues, and low back and pelvic pain, with menorrhagia being the most common symptom [17] - [20] . Less frequently, patients may experience increased urinary frequency and anemia [17] - [20] . However, only about 25% to 30% of women report clinical symptoms.

Diagnosis typically involves assessing symptoms and using ultrasound, with confirmation achieved through surgical excision and pathological analysis. Some patients remain asymptomatic and discover their condition incidentally during physical examinations or imaging. In fact, fibroids are often diagnosed as incidental findings in clinical settings, possibly due to a lack of awareness of characteristic symptoms [18] . Additionally, fibroid symptoms can overlap with those of other gynecologic conditions such as endometriosis, abnormal ovulatory function, or endometrial polyps [18] .

Despite the high incidence and prevalence of uterine fibroids worldwide, there is limited data on their epidemiology among Hispanic women [13] [19] . Some studies suggest Hispanic women are twice as likely to be diagnosed with uterine fibroids compared to White women [21] [22] . One study revealed that Hispanic women, who comprised nearly one-third of the cohort, had significantly higher symptom severity compared to White and Black women [11] . Given the barriers to care and symptoms caused by uterine fibroids, there is a lack of awareness about fibroids and their potential health impacts among the Hispanic/Latino population [11] .

In Puerto Rico, as in many regions, fibroids pose substantial challenges to women’s health, affecting fertility, quality of life, and healthcare utilization. Despite their prevalence and impact, there is a notable gap in research focusing on the specific demographics, clinical presentations, and socioeconomic factors influencing fibroid prevalence and management in women living in Puerto Rico. This paper aims to address these critical aspects, providing a comprehensive overview to guide future research and enhance clinical care strategies tailored to this unique population.

This study is the first to evaluate the clinical and demographic profile of women with uterine fibroids in Puerto Rico. By analyzing an existing clinical research database, we found a prevalence of uterine fibroids at 19.4%. This may be due to many women being undiagnosed or experiencing delayed diagnosis, underscoring the urgent need for increased awareness and education. Delayed diagnosis, often due to a lack of awareness of clinical profiles, results in higher medical expenses. Consequently, it is recommended that routine patient-provider evaluations include assessments for signs and symptoms of uterine fibroids, even in younger women.

In the US, studies have shown that by age 49, over 70% of women have surgically confirmed fibroids, with rates varying among racial groups [24] . The prevalence of self-reported and ultrasound-detected uterine fibroids is higher among non-Hispanic Black women (50%) compared to non-Hispanic White women (25%) [18] . In a systematic review study examining racial disparities in the prevalence of uterine fibroids and endometriosis in the United States, Katon et al. found that among women aged 18 - 30 with no symptoms of fibroids, 26% of Black women and 7% of White women had ultrasound evidence of uterine fibroids [25] .

However, there is limited information regarding Hispanic/Latino women in the US or Latin America. Marsh et al., found that only 47% of Hispanic women in their cohort had heard of fibroids compared to 60% of Black women [11] . Consistent with other studies, many women delay seeking a diagnosis because they believe their symptoms are normal [17] . Borah et al. found that in their large survey study of U.S. women living with uterine fibroids, waited an average of 3.6 years after experiencing symptoms before seeking a diagnosis, with 32% waiting more than 5 years before seeking treatment [17] . Cultural perceptions, economic status, health literacy, healthcare system, and other psycho-biosocial factors specific to Latin American communities may limit access to care and diagnosis, leading to underestimation of the true prevalence of uterine fibroids [25] . This further establishes the importance of awareness and education about uterine fibroids.

Our findings align with existing research showing that the prevalence of uterine fibroids increases with age during the reproductive years and decreases during post menopause [26] - [29] . In our cohort, fibroids were most common among women aged 40 – 49 years, with a notable decline of 4.2% among women over 50. Previous studies have established that uterine fibroid primarily develop during the reproductive years when estrogen and progesterone are cyclically secreted, with production decreasing after menopause [30] . These observations underscore the significant roles of ovarian hormones, particularly estrogen and progesterone, in promoting uterine fibroid growth [30] . Therefore, it appears that the occurrence of fibroids is influenced by age and hormone levels [31] [32] .

Contrary to previous reports [33] - [36] , our study found no association between the presence of uterine fibroids and age of menarche, menstrual cycle length, or duration of menstruation. These results align with earlier research that also did not identify an association between early menarche and the risk of developing uterine fibroids [37] [38] . Interestingly, a majority of women in our sample who had fibroids reported regular menstrual cycles and normal menstruation lengths, which contrasts with conventional understanding of how fibroids typically affect menstrual patterns. However, symptoms such as dysmenorrhea, dyspareunia, and challenges with conception were significantly prevalent among women without uterine fibroids in our cohort, highlighting their substantial impact compared to women with uterine fibroids.

While previous studies have indicated that higher parity may have a protective effect against uterine fibroids [39] [40] , our findings revealed an unexpected trend. Within our cohort, women with uterine fibroids tended to have higher parity (≥2) compared to the controls. Several mechanisms potentially explain this inverse relationship between parity and uterine fibroids. Full-term pregnancies can lead to reduced menstrual cycling, alterations in sex hormone levels, and decreased estrogen receptor expression, thereby potentially modifying fibroid sensitivity to hormonal stimulation and influencing uterine remodeling [41] [42] .

Additionally, consistent with various studies, OCPs have been suggested as a protective factor against uterine fibroids [2] [43] [44] . Our study similarly indicated a significantly lower current use of OCPs among women with fibroids, potentially influenced by the predominance of women aged 40 - 49 years in this group, who typically decrease OCP usage. Interestingly, while not statistically significant, our observation of previous OCP use among women with uterine fibroids suggests a potential trend that warrants further investigation. This is particularly important given the conflicting results in existing literature regarding the relationship between OCP use and fibroid development [27] .

Furthermore, our study identified a higher prevalence of miscarriages among women with uterine fibroids compared to controls [45] [46] , consistent with findings from Pritts et al., 2009 review, which documented reduced clinical pregnancy and live births in women with uterine fibroids [31] . However, recent studies have reported no association between uterine fibroids and miscarriages [45] , contrary to earlier research linking fibroids with adverse pregnancy outcomes [46] [47] .

In our study, we found that gynecological infections were present in 32% of women with uterine fibroids, abnormal pap smears in 25%, ovarian cysts in 52% and abnormal uterine bleeding in 38%. These rates were notably higher compared to the control group, consistent with findings from previous studies [48] [49] . The association of uterine fibroids with conditions such as abnormal uterine bleeding aligns with current guidelines and diagnostics recommended by the American College of Obstetricians and Gynecologists (ACOG) [50] . This underscores the clinical relevance of our findings in understanding the broader impact of uterine fibroids on women’s health.

Recent research has increasingly spotlighted diabetes and uterine fibroids, driving a deeper exploration into their common risk factors, such as obesity and insulin resistance, that may contribute to their co-occurrence. Insulin resistance, a characteristic of Type 2 diabetes, often leads to hyperinsulinemia, a key feature of metabolic syndrome [51] . Hyperinsulinemia is also linked to increased levels of serum insulin-like growth factor-1 (IGF-1) and epidermal growth factor, which are believed to play a role in the formation of uterine fibroids by increasing the secretion of ovarian hormones or promoting the proliferation of smooth muscle cells in the uterine lining [51] - [53] . Research has demonstrated that insulin can affect uterine fibroid maintenance by triggering a hormone cascade and disrupting the interaction between sex hormones and globulins, leading to elevated estrogen levels and other factors that promote fibroid persistence [51] - [53] . Interestingly, a study found that metformin, a first-line treatment for Type 2 diabetic patients, has been shown to reduce the risk of uterine leiomyomas in this patient population [54] .

Likewise, hypertension has been recognized as a possible risk factor for uterine fibroid development. A longitudinal cohort study revealed that individuals with newly diagnosed hypertension had a 45% higher risk of reporting fibroids [55] . Fischer and colleagues further demonstrated the link between hypertension and uterine fibroids through the angiotensin-converting enzyme (ACE) pathway, which regulates blood pressure [56] . By comparing women with hypertension, with or without coexisting uterine fibroids, and the use of ACE inhibitors, they found that those prescribed ACE inhibitors had a more than 30% reduced risk of fibroid diagnosis [56] . These findings suggest a complex interaction between hypertension and fibroid growth, with potential involvement from hormonal factors like estrogen, whose effects may be more pronounced during hormonal fluctuations such as pregnancy or menopause [57] .

It has been established that a considerable number of women with uterine fibroids are asymptomatic [18] [28] , highlighting the challenge of accurately estimating prevalence and incidence through clinical symptoms alone. Therefore, epidemiologic studies utilizing ultrasound screening should provide more reliable estimates. A limitation of our study is its reliance on self-reported surveys, which may result in underestimation if participants are unaware of their condition until symptomatic or diagnosed by a physician. Additionally, retrospective data collection is susceptible to recall bias, impacting the accuracy of reported medical histories. Despite these challenges, self-reported data remains a valuable tool in initial epidemiological assessments across various disciplines due to its cost-effectiveness and adaptability [11] [19] .

For instance, Myers et al. conducted a study comparing self-reported and ultrasound measurements of uterine fibroid status, highlighting the method’s high sensitivity in epidemiological contexts [38] . Despite these acknowledged limitations, our study’s findings align with previously reported prevalence rates ranging from 5% to 35%, consistent with studies like Flores et al., which found a 12% prevalence among Latin American women [2] [11] [19] [20] [27] [58] .

Furthermore, a significant limitation of our study was the lack of access to participants’ medical records, which would have provided critical clinical details such as uterine size, fibroid characteristics, and surgical findings. However, it is essential to recognize the valuable roles of descriptive studies like ours in identifying epidemiological variations among different demographic groups. Such studies offer valuable insights into the diverse clinical presentations of uterine fibroids across populations.

In conclusion, this study provides a comprehensive analysis of the clinical, demographic, and gynecological profiles of women with uterine fibroids residing in Puerto Rico compared to those without uterine fibroids. With a documented prevalence of 19.4% among women living in Puerto Rico, including those under 40 years old, our findings underscore the significant impact of factors such as age, parity, and comorbidities such as diabetes and hypertension within our cohort.

Our research underscores the urgent need to address underdiagnosis resulting from inadequate awareness of the typical signs and symptoms of uterine fibroids. By examining the epidemiological profile of affected women living in Puerto Rico, our study contributes to a better understanding of its impacts on women’s health, quality of life, and overall well-being. These insights highlight the critical importance of recognizing and addressing uterine fibroids as a significant public health concern, paving the way for improved diagnostic strategies, patient care, and health outcomes.

We thank Dr. Raymond L. Tremblay for supporting our group in the statistical analysis of our data and the evaluation of the manuscript. We also thank Dr. Estela S. Estapé for the review of the manuscript and the support of the San Juan Bautista School of Medicine. Finally, we want to thank Tiffany Sánchez for her contribution to this work.

Generated Statement: The data analyzed in this study is subject to the following licenses/restrictions: The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Requests to access these datasets should be directed to mcolondiaz@sanjuanbautista.edu.

MC, IF, ES, SA, GM, GR. PC, AN and AJ contributed to the conception and design of the study. ES organized the database. MC, AJ and ES performed the statistical analysis and wrote the first draft of the manuscript. IG, SA, AJ, ES, GR, GM and PC wrote sections of the manuscript. All authors contributed to manuscript revision, editing, and approved the submitted version.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

This paper was presented at the 12th Scientific Day 2023 of the Hispanic Alliance for Clinical and Translational Research as a poster presentation with interim findings. The poster abstract was published in the Scientific Day Abstract Supplement of the Puerto Rico Health Science Journal, PRHSJ Vol. 42 (Scientific Day Abstract Supplement) 2023.