Intro
Racial and ethnic differences in the prevalence of common benign gynecologic conditions and the use of surgical treatments have been reported. These differences may result in significant health disparities among some racial and ethnic groups. Although there are many areas of gynecology to consider, we will focus on uterine fibroids and endometriosis, two of the most common conditions encountered in clinical practice, and hysterectomy, the most frequently performed major gynecologic surgery. Our review will highlight racial and ethnic differences in the burden of disease associated with fibroids and endometriosis, and in the rate, route, and outcomes of hysterectomy. We will emphasize the need for further research to better understand the reasons for these racial and ethnic differences, with the goal of decreasing significant health disparities.
The cause of racial and ethnic differences in these gynecologic conditions and surgeries are not fully understood. A complex set of genetic, physiologic, sociodemographic, cultural, and economic factors likely contribute to racial and ethnic disparities, as has been described in other fields of medicine. 1 , 2 Differences in patient preferences by race and ethnicity may also influence treatment decisions resulting in differential rates of surgery. There are also challenges in the measurement and categorization of race and ethnicity that hinder a complete understanding of racial and ethnic variation for gynecologic conditions. (reference AJOG editorial in press “Health Disparities: definitions and measurements”). We will examine some of the potential causes of gynecologic health disparities and describe limitations in the literature that create significant knowledge gaps.
Uterine
Several studies have found a higher prevalence of fibroids among black women compared with white women. 3 – 5 However, these studies evaluate women undergoing hysterectomy or myomectomy, which may not accurately represent the true distribution of fibroids in the general population; racial and ethnic variation in disease severity, access to non-surgical treatment, or treatment preferences may result in a higher prevalence of surgery among black women. One study attempted to overcome this limitation by screening randomly selected women age 35–49 years for fibroids with pelvic ultrasound. After adjusting for body mass index (BMI) and parity, black women were nearly three times as likely to have fibroids compared with white women (O.R. 2.7, 95%CI 2.3–3.2). 6 Two other studies include women who underwent surgical management of fibroids and those who did not. Among 95,061 premenopausal participants in the Nurses Health Study II, black women had three times the odds of receiving a diagnosis of fibroids by pelvic exam, ultrasound, or hysterectomy compared with white women (O.R. 3.3, 95%CI 3.0, 4.3). 7 Similarly, in adjusted analysis from a case-control study of patients who received either surgical or medical management of fibroids, black women had nine times the odds of clinically apparent fibroids (O.R. 9.4, 95%CI 5.7, 15.7). 8
Although studies of patients undergoing surgery have significant limitations for estimating fibroid prevalence, they are critical for exploring disparities in the surgical burden among women with fibroids. In an uncontrolled nationwide analysis, the rate of hysterectomy for fibroids was 37.6 per 10,000 black women compared with 16.4 per 100,000 white women. 9 In a prospective cohort study of approximately 80,000 women in California, black women had a significantly higher rate of undergoing surgery for fibroids compared with non-Latina white women in a model that controlled for age and family history of fibroids (RR 2.28, 95%CI 1.81–2.87). 5 Several smaller studies have confirmed this higher prevalence of fibroids among black women undergoing hysterectomy and/or myomectomy. 3 , 4
In addition to a higher rate of fibroids, several studies have found that black women present at a younger age with larger, more numerous, and more rapidly growing fibroids compared with white women. Huyck et al. reported a mean age for fibroid diagnosis of 31 years among black women and 37 years among white women (p<.001). 10 Three other studies have confirmed this finding, with black women receiving a diagnosis of fibroids three or more years before white women. 3 , 7 , 11 In a random sample of women, ultrasound detected multiple focal fibroids in 74% of black women but only 31% of white women between age 35 and 39 years. 6 Peddada et al. reported differential fibroid growth by race; the likelihood of rapid tumor growth (>20% increase in volume per 6 months) increased with age in black women, but declined with age among white women (p=.004). 12 Black women undergoing surgery for fibroids may also have larger and/or a greater number of fibroids compared with white women. Among hysterectomy patients, black women had a mean uterine weight of 421 grams compared with 319 grams for white women 3 , and black women undergoing myomectomy were more likely to have >4 fibroids and less likely to have only one (p=.001). 13 However, these differences in fibroid characteristics may be due to variation in patient preference for the timing of surgery, rather than true physiologic differences in fibroid development.
Larger size and a greater number of fibroids may result in worse symptoms and surgical outcomes for black women. In a multivariable model that controlled for fibroid risk factors, black women were more likely to have severe disease based on age at diagnosis, severity of menstrual symptoms, and history of fibroid-related surgery (O.R. 5.2, 95%CI 2.0–13.7). 10 In a study of 1,200 women with fibroids undergoing hysterectomy, black women were more likely to report severe pelvic pain (59% vs. 41% for whites) and have anemia (56% vs. 38% for whites). 3 Roth et al. reported that among 225 women undergoing myomectomy, black women were twice as likely to have a complication compared with white women (OR 2.5, 95% CI 1.5,,4.8) and more frequently required a blood transfusion (OR 2.3, 95% CI 1.1,5.0). 13 However, these differences appeared to be related to the larger size, greater number, and increased co-morbidities among black women. After controlling for these clinical factors, the risk of complications or blood transfusion was not significantly different between black and white women. 13
There are multiple possible etiologies for a higher prevalence and more severe presentation of fibroids among black women. Fibroids are hormonally-responsive tumors and some genetic studies have found that black women have unique gene polymorphisms for estrogen synthesis or metabolism, and aberrant expression of micro-RNAs that may lead to gene dysregulation in fibroids. 14 , 15 For example, the estrogen receptor (ER)-α PP variant has a higher prevalence among black women and has been associated with an increased risk of fibroids. 16 One investigation found more polymorphisms in catechol-O-methytransferase, an enzyme involved in estrogen metabolism 17 , among black women although another study did not confirm this finding. 18 Lifestyle and clinical factors such as diet, BMI, smoking, alcohol intake, exercise, diabetes, and hypertension have also been reported in some studies to increase the risk of fibroids. 5 , 7 , 19 , 20 Higher rates of these risk factors among black women compared to other racial and ethnic groups may contribute to the incidence of fibroids. 21 – 24 Finally, exposure to bisphenol A has been found to have transcriptional activation and mitogenic effects on fibroids in the Eker rat and CD-1 mouse models. 25 – 28 Differential exposure to these or other environmental factors by race and ethnicity may contribute to variations in the prevalence of fibroids. 29
There is scarce literature on differences in fibroid presentation or treatment among racial and ethnic groups other than black and white women. In the Nurses Health Study II, there were no statistically significant differences in the likelihood of a fibroid diagnosis among Hispanic and Asian women compared with white women. 7 Conversely, Templeman et al. , applying similar multivariable models, found that Hispanic women had a higher risk of undergoing surgery for fibroids compared with white women (OR 1.3, 95%CI 1.1–1.6). 5 In this study, there were no significant differences in the prevalence of fibroids between Asian and white women. 5 Future research is needed to examine the prevalence, prognosis, and treatment of fibroids among Hispanic and Asian women to clarify these preliminary findings. Studies are also needed to explore potential genetic causes of fibroid development among Asian and Hispanic women, as have been found among black women.
Conclusions
Table 1 demonstrates the significant knowledge gaps on racial and ethnic disparities in fibroids, endometriosis, and hysterectomy. There are high quality and consistent data demonstrating that black women have a higher prevalence of fibroids and present at a younger age compared with white women. Some studies indicate that fibroids in black women are larger, more numerous, cause worse symptoms, and increase myomectomy complications. However, for Hispanic and Asian women, there are extremely limited data on fibroid prevalence and no studies that examine differences in the presentation or prognosis of fibroids. Although several investigators have examined racial and ethnic differences in the prevalence of endometriosis, conflicting results preclude a definitive conclusion. Large national databases have consistently found higher rates of hysterectomy among black women. However, the data are less robust on racial and ethnic differences in the route of hysterectomy, complications, and concomitant oophorectomy.
Future research should focus on further examining possible differences in the prevalence of fibroids and endometriosis by race and ethnicity, as well as exploring potential disparities in the natural history, treatment, and long term morbidity of these conditions. Understanding why some racial and ethnic groups carry an increased burden of disease for these conditions may provide insights into disease mechanisms, and assist in creating new approaches for assessment and treatment. The multi-factorial etiology of racial and ethnic differences in hysterectomy rate and route and the greater surgical morbidity among black women also requires further study with well-designed multivariable models. Although differences in patient preferences and attitudes may in part underlie variations in hysterectomy use, undue physician influence or limited access to hysterectomy alternatives may also play a role. Overall, the current literature on gynecologic health disparities is limited by both quantity and quality. More well-designed studies that examine differences in disease prevalence and surgical rates by race or ethnicity will enrich our understanding of racial and ethnic variation, and lead to further investigations to reduce health disparities.
Hysterectomy
Several studies have found an increased risk of hysterectomy complications among black women compared with white women. Among 53,000 hysterectomies in Maryland, 20% of black women and 13% of white women had one or more peri-operative complications. 62 After adjusting for age, hysterectomy route, a diagnosis of cancer or fibroids, co-morbidities, payer, and hospital characteristics, black women were still more likely to have complications (OR 1.4, 95%CI 1.3–1.5) with a significantly increased risk of mortality (OR 3.1, 95% CI 2.0–4.8). 62 Hakim et al. also found a higher risk of hysterectomy complications among black women independent of multiple demographic and clinical risk factors (OR 1.7, 95% 1.3–2.1), but the risk among Hispanics was not statistically different from the risk among whites. 69 Among nearly 650,000 hysterectomies in California, black and Asian women were more likely to have a surgical complication, irrespective of age, insurance, indication, co-morbidities or other surgeries. 77 Hispanic women were less likely to have a surgical complication following vaginal (OR 0.92, 95%CI 0.88–0.96) or total abdominal hysterectomy (OR 0.95, 95%CI 0.93–0.98), but had a slightly increased risk following subtotal hysterectomy (OR 1.11, 95%CI 1.01–1.22). 77 Racial and ethnic differences in uterine volume, preoperative health status, or postoperative follow-up care may contribute to disparities in hysterectomy complications and these factors have not been fully evaluated in the current literature.
Oophorectomy
Several studies have found higher rates of bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy among white women compared to other racial and ethnic groups. In the Women’s Health Initiative Observational Study, 50% of white women with a prior hysterectomy had BSO compared with 44% of black women and 40% of Hispanic women, but Asian women had the highest rate of BSO (59%). 65 In the CARDIA study, 45% of white women who underwent hysterectomy had a BSO compared with 29% of black women. 61 However, these studies did not account for the younger age at hysterectomy among non-white women which decreases the likelihood of undergoing a BSO.
To address the limitations of the uncontrolled studies, a nationwide analysis of approximately 520,000 hysterectomies utilized multivariable models with demographic, clinical, and health system factors to examine race and ethnicity as an independent predictor of BSO. 64 In this study, black, Asian, and Hispanic women were less likely to undergo BSO compared with white women. There was a significant interaction between racial and ethnic groups and income with lower income increasing the odds of BSO among white and black women, but not among other groups ( Fig. 2 ). The lower rate of BSO among black women may be associated with a lower use of hormone therapy. 78 , 79 Estrogen is frequently used to manage vasomotor symptoms following BSO and a decreased inclination to use estrogen may diminish the desire to undergo BSO among black women. However, there are no studies that specifically examine the cause of racial and ethnic differences in BSO rates; further investigation is needed to determine what patient and provider factors may influence BSO practice patterns.
Endometriosis
Endometriosis is a common estrogen-dependent condition that may cause dysmenorrhea, chronic pelvic pain, and infertility. 30 The gold standard for diagnosing endometriosis is a biopsy of abnormal tissue visualized during surgery. Historically, many gynecologists believed that endometriosis was a disease confined almost exclusively to white women. 31 Most early studies reported at least double the prevalence of endometriosis among white women and many authors propagated the belief that endometriosis was an extremely rare condition among black gynecology patients. 32 – 35 In the 1970s, several studies reported that over 20% of black women undergoing diagnostic laparoscopy had endometriosis and suggested that endometriosis was overlooked as a cause of pelvic pain due to clinicians’ misperceptions of the low incidence in black women 36 , 37 However, this early literature was significantly limited by lack of multivariable models to account for clinical and demographic factors that have been associated with receiving a diagnosis of endometriosis.
More recent studies have had conflicting results for racial and ethnic differences in endometriosis. In a study of 330 women undergoing laparoscopic tubal sterilization that accounted for age, parity, income, and payment source in multivariable models, Asian women had almost 9 times greater odds of endometriosis (OR 8.6, 95%CI 1.4–20.1) compared with white women, while the findings for black and Hispanic women were not statistically significant. 38 Several other studies of women undergoing infertility evaluation or laparoscopy for pelvic pain have also reported an increase in the prevalence of endometriosis among Asian women compared with white women. 39 , 40 However, in a prospective cohort study of 90,000 women enrolled in the Nurses Health Study II, Asian women did not have a statistically significant difference in the odds of self-reported endometriosis in a model that controlled for age, parity, and BMI (OR 0.6, 95%CI 0.4–0.9). 41 In the same study, black and Hispanic women were each 40% less likely to be diagnosed with endometriosis (OR 0.6, 95%CI 0.4–0.9 for black women, OR0.6, 95%CI 0.4,1.0 for Hispanic). 41 Two other studies have found no statistically significant differences in the prevalence of endometriosis between any racial or ethnic group. 42 , 43
The heterogeneity in findings for differences in the prevalence of endometriosis by race or ethnicity may reflect the diversity of study designs. Some studies have focused on symptomatic patients with infertility or pelvic pain which may under-represent medically-underserved women in racial or ethnic minority groups with poorer access to gynecologic services. Other studies have assessed asymptomatic patients at the time of laparoscopy with variation in the design of multivariable models. Although the epidemiologic evidence is inconclusive, genetic studies have sought an etiology for racial and ethnic differences in endometriosis. Some authors have identified gene mutations among Asian women that may make them more susceptible to endometriosis. 44 – 46 However, a recent literature review found weak data to support an association between genetic polymorphisms and endometriosis. 47 Additional research is needed to better understand possible genetic mechanisms associated with racial and ethnic differences in the prevalence of endometriosis. Endometriosis has also been associated with environmental exposures such as in utero cigarette smoke and diethylstilbestrol, dioxin, and serum polychlorinated biphenyl congeners (PCB) in some, but not all, studies. 48 – 55 Racial and ethnic differences in these environmental exposures may contribute to variations in endometriosis. However, data is limited for serum levels of these chemicals among Asian women compared to other groups. 56 Further research is needed to elucidate possible racial and ethnic differences among women with endometriosis and to determine how these differences affect gynecologic outcomes.
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