Amenorrhea. A Case-Based, Clinical Guide

12. Ethnicity and Amenorrhea

Benjamin M. Lannon1 and Kim L. Thornton

(1)

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology and Reproductive Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

Abstarct

Discussion preceding this chapter has addressed various physiological and pathophysiological states that affect the menstrual cycle. This chapter focuses on the role of race and/or ethnicity on menstrual physiology. Our discussion about the impact of race and ethnicity on amenorrhea focuses on two factors: (1) the physiologic variations in the menstrual cycle among different racial and ethnic groups and (2) variations in cultural attitudes and beliefs about the cessation of menses. While these cultural differences may not always impose specific diagnostic or management dilemmas, awareness may be essential to the goal of providing comprehensive care to our diverse patient population.

Discussion preceding this chapter has addressed various physiological and pathophysiological states that affect the menstrual cycle. This chapter focuses on the role of race and/or ethnicity on menstrual physiology. Our discussion about the impact of race and ethnicity on amenorrhea focuses on two factors: (1) the physiologic variations in the menstrual cycle among different racial and ethnic groups and (2) variations in cultural attitudes and beliefs about the cessation of menses. While these cultural differences may not always impose specific diagnostic or management dilemmas, awareness may be essential to the goal of providing comprehensive care to our diverse patient population.

Ethnic Variations in Menstrual Physiology

Menarche

Failure to recognize interracial variations in the onset of puberty can have a profound effect on subsequent evaluation and management.

An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999–2004, showed a significant decrease in age at menarche in women born in 1920’s compared to 1980’s across Mexican Americans, non-Hispanic Whites, and African Americans [1]. While these data were based on retrospective self-reported age at menarche, the trends are real.

While there may be an overall reduced age for menarche, the generational differences in pubertal onset are not the same across all racial and ethnic groups. Results from the Pediatric Research in Office Settings (PROS) network study in 1997 suggested that black girls in particular had a mean age of menarche more than 6 months earlier than white girls (12.16 vs. 12.88 years) [2]. A subsequent analysis of the data revealed that increases in body mass index (BMI) may have accounted for the earlier onset of puberty in white girls [3]. Unlike white girls, BMI alone did not completely explain the earlier onset of the pubertal transition observed in black girls, leading the authors to speculate that genetic factors such as leptin levels and environmental factors such as nutrition may contribute to interracial differences in pubertal development [3].

Controversy exists regarding the validity of these findings, and the mechanisms underlying racial and ethnic variations in pubertal/menarcheal onset [3]. Nonetheless, these data can clearly impact the evaluation and referral of young girls from different racial and ethnic groups for presumed abnormal pubertal development.

Menstruation

In addition to differences in the timing of menarche, there are also variations in specific menstrual patterns among various racial and ethnic groups. As we discuss later in this chapter, these differences can influence perceived attitudes about menstruation and menstrual cyclicity and management approaches offered to and selected by women from different racial and ethnic groups.

A study by Harlow and colleagues investigated the effect of ethnicity and/or race on the duration, amount, and length of postmenarcheal bleeding [4, 5]. They enrolled 125 African American and 123 European American girls between 12 and 14 years old living in North Carolina in a 2-year study of postmenarcheal bleeding patterns. The participants kept menstrual calendars and records of weight, exercise, and stress. Although they were twice as likely to have an episode of heavy bleeding, African American girls reported a half day shorter mean duration of bleeding [4]. Although mean cycle length was similar in both groups, European American girls had an increased cycle length variability and an increased probability of having a cycle length more than 45 days [5]. These studies were limited by sample size and applicability of results to other age groups. Nonetheless, they suggest that an association between race and variations in the pattern of menstrual cycle length exists. Understanding these variations may help physicians counsel patients and their families about normal and abnormal menstruation patterns and management options.

The role of genetics and the exact biological mechanism giving rise to apparent ethnic and/or racial differences in menstrual duration and flow and menstrual cycle length are unknown. Additional studies are needed to characterize menstrual cycle phenotypes with hormonal profiles and their relation to ovulatory function as a function of ethnicity and/or race.

Ovulation/Anovulation

Even after menarche, variations in ovulatory function and hormonal profiles among various racial and ethnic groups continue to exist. It is important to recognize that these differences may alter the risk of developing other hormonally responsive conditions such as fibroids, breast cancer, and endometrial neoplasia.

Haiman et al. investigated the effect of race and/or ethnicity on the rates of anovulation in groups of students in greater Los Angeles area [6]. They found a trend for a greater frequency of anovulation in white women vs. African American and Latina women. In addition, they noted differences in hormone profiles between the groups with higher follicular phase estradiol (E2) and luteal phase E2 and progesterone levels in African American compared to all other women. Likewise, Latina women had elevated follicular phase E2 and luteal phase E2 and progesterone compared to white women [6]. These differences may account for increased rates of fibroids and invasive breast cancer and breast cancer mortality in African American women [7].

Understanding the role of race and ethnicity in hormonal and menstrual cycle variations may provide a means to assess the risk for future morbidities. For example, Rieder et al., determined markers of insulin resistance and hyperandrogenemia in an unselected group of Caribbean Hispanic and African American women aged 12–21 [8]. The women were grouped according to menstrual regularity and physical exam characteristics. They found that waist circumference, free androgen index, and sex hormone binding globulin (SHBG) levels correlated best with ovulatory and menstrual dysfunction and a hyperandrogenic phenotype. Identification of these young women who are at risk of developing adult polycystic ovarian syndrome (PCOS) may afford an opportunity for intervention and subsequent minimization of the metabolic disruption that frequently plague women with PCOS [8].

Ovarian Insufficiency

Abnormal cessation of ovarian function has also been shown to vary by ethnic group. While many aspects of primary ovarian insufficiency, also known as premature ovarian failure (POF), remain uncertain, there appear to be differences in the prevalence and risk factors among ethnic and racial groups. In a study by Luborsky and colleagues, a part of the Study of Women Across the Nation (SWAN), women aged 40–55 were interviewed at seven sites in the US as part of a multiethnic longitudinal study [9]. The investigators defined POF as spontaneous cessation of menses less than 40 years old with uncertain etiology. In this population, the highest reported rate of POF was in Black and Hispanic women (1.4%) followed by Caucasian (1%) and then Chinese (0.5%) and Japanese (0.14%). Similar trends were observed for women reporting early menopause (age 40–45) as well [9].

A multivariate subgroup analysis of factors associated with POF in African American and Caucasian women suggested the use of female hormones (other than oral contraceptives) was predictive of POF risk. Additionally, in Caucasian women, osteoporosis, severe disability and smoking were significantly associated with POF. While in African American women, higher BMI but not osteoporosis was associated with POF [9].

Although this study was limited by retrospective self-reporting and a cross-sectional design, it still provides some insight into how risk factors for POF vary across ethnic groups as well as information about the overall prevalence of POF in each group.

Menopausal Transition

One of the most studied areas of ethnic variations in amenorrhea is the change during the menopausal transition. As described above, there are differences in hormonal profiles in postmenarchal girls across various racial and ethnic groups. This finding is consistent in women making the menopausal transition and is reflected in studies that evaluate the role of the pituitary, adrenal, and ovarian axes.

Several analyses of the SWAN data have reported racial and ethnic differences in hormone levels in pre- and perimenopausal women. Dehydroepiandrosterone (DHEAS), testosterone (T), and E2 levels in serum collected from 3,029 women in five racial and ethnic groups aged 42–54 for over 2 years suggested DHEAS levels were highest in Chinese and Japanese women and lowest among African American and Hispanics [10]. These differences persisted even after adjusting for age, smoking, and BMI with a multivariate analysis. In some women DHEAS levels exhibited transient elevations, with the greatest increases in Chinese, Hispanic and Japanese women and less for African American and Caucasians. Racial and ethnic changes in T and E2 correlated with changes in DHEAS [10].

A second report from the SWAN study looked at a sub-cohort of 848 women of whom daily urinary hormone levels were measured during the peri-menopausal transition. They found that Chinese- and Japanese American women had lower urinary estrogen conjugates. Other variables including FSH, LH, and progesterone metabolites were not significantly different amongst various racial and ethnic groups when adjusted for BMI [11].

The third analysis of the SWAN data by Randolph et al., looked at changes in E2 and FSH across the early menopausal transition. They found similarities in age-related E2 reductions and FSH increases across racial and ethnic groups studied. They also found that in Caucasians, FSH levels were lower than African American women, and similar to Chinese and Japanese women. However, Chinese and Japanese women had lower E2 levels, while the African American women were comparable to Caucasians. These findings suggest that ethnic variations in hypothalamic-pituitary-ovarian communication and/or response [12].

The varied relationship between hormone profiles with age across ethnic groups was also supported by data from a 4-year cohort study from the University of Pennsylvania [13]. This study tracked E2, FSH, DHEAS, and T levels in 436 women, equally divided between African American and Caucasian women and found African American women demonstrated an age-related decrease of E2 and DHEAS as compared to Caucasians. Moreover, African American women had decreased E2 and increased DHEAS with increasing BMI [13].

One of the most important concerns raised from all of this data is to what extent do differences in hormone profiles influence racial differences in the rates of hormone sensitive breast cancer. This question was addressed in a subgroup analysis form the Nurse Health Study II. This retrospective study included 116,671 nurses aged 25–42. In a follow up 8–10 years from the initial survey, over 19,000 women submitted a menstrual cycle timed blood sample. A subgroup of women was selected to submit samples over several years. Ultimately, 111 Caucasian women were included and matched with African American and Asian American women. E2, P, prolactin, SHBG, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) were assayed and analyzed across racial and ethnic groups. African American women had higher levels of E2 and IGF-1 and lower levels of SHBG and IGFBP-3 as compared to Caucasian women. Asian Americans had higher E2 and IGF-1 and lower SHBG as compared to Caucasians. There were no differences in P or prolactin across the groups [14].

Variations in Cultural Beliefs and Attitudes Toward Normal and Abnormal Menstrual Cycles

Equally important to the biological differences, are the cultural beliefs and attitudes that can impact the evaluation and subsequent treatment recommendations. A woman’s perception of what is normal and abnormal menstrual function is dictated by a number of factors. These beliefs can modestly affect her decision to seek treatment as well as her choice of management.

Menstrual Symptoms

While a number of anthropologic studies have investigated cultural attitudes toward menses, few have focused on symptom reporting. One such study from England looked at women’s self-assessment of menses across three racial groups. A total of 153 women (48 Afro-Caribbean, 73 Caucasian, and 32 Asian) between the ages of 18 and 48 were enrolled in the study and administered standardized questionnaires about mood, behavior, and menstrual symptoms over a monthly cycle [15]. While intermenstrual symptoms were similar, Caucasian women reported significantly more premenstrual and menstrual related symptoms compared to the other groups. Symptoms reported were primarily attributed to psychological mood, body symptoms and pain categories, rather than mental performance or social behavior [15]. The authors propose that sociocultural mechanism account for racial differences; Caucasian women perceive menstrual bleeding as an aversive event, thereby leading to increased vigilance and more complaints. While these theories are difficult to substantiate, it is hard to deny that there are differences in the way different racial groups report menstrual physiology and symptoms. It remains to be seen whether menstrual cycle and symptom difference across racial groups reflect physiologic or sociologic divergence. Nonetheless, it is important for the physician to recognize perceived or physiological differences in the menstrual cycle and symptoms can ultimately affect a woman’s decision to seek treatment, the type of treatment that she seeks, and whether she is compliant with treatment.

Contraceptive-Induced Amenorrhea

For women seeking treatment for menstrual cycle dysfunction, contraceptive methods are among the most commonly offered. One potential and possibly unintended consequence of treatment is amenorrhea. For some women, this may be a desired effect, while others prefer to maintain monthly menstrual bleeds. Edelman and colleagues assessed whether there were ethnic variations in women’s attitudes toward contraceptive-induced amenorrhea [16]. This study surveyed 292 women with mean age of 27 years in Atlanta, Georgia and Portland, Oregon. They found that 69% of participants welcomed amenorrhea and 58% preferred to have menses every 3 months. However, significantly fewer black women would consider using birth control to induce amenorrhea vs. white women (29 vs. 49%) [16]. The study was limited by the sample size as well as several possible confounders that included education level, geographic location, and prior use of contraception. As a result, the author’s interpretation of their data was limited with regard to the relationship between race and attitude toward amenorrhea. Nonetheless, in light of possible existence of differences in cultural beliefs about menses, race and ethnicity should be seriously considered and cultural attitudes discussed with the patient prior to crafting management plans for menstrual cycle regulation.

Racial Differences in Hysterectomy

Another commonly offered treatment modality for menstrual dysfunction is hysterectomy. Whether racial differences in the decision to seek definitive treatment exist is an area of active investigation. However, race and/or ethnicity may affect counseling received by patients regarding management options for menstrual dysfunction. These differences may reflect underlying disparities in access to healthcare between groups or disparities in physician attitudes rather than differences in racial and/or ethnic physiology or cultural attitudes.

Hysterectomy is the most frequently performed surgery on women in the US. Epidemiological data has suggested that over the past decade, while overall hysterectomy rates have declined, there was an increase in its use for treatment of leiomyoma. For women aged 40–44, there is a significant difference in the hysterectomy rate among African American women [17]. Some have speculated that increased rates of fibroids in African American women explain increased hysterectomy rates, however definitive studies are needed.

Using SWAN data, Powell et al., investigated racial/ethnic differences in hysterectomy for benign conditions [17]. After adjusting for adjusted for age, education, fibroids, BMI, marital status, smoking, geography, and country of education, Powell et al., found that race and ethnicity was associated with past hysterectomy. Increased odds in African American (1.66) and Hispanic (1.64) women, and decreased odds in Asian American (0.44) women compared to Caucasians were specifically noted. The authors contend that the highest rates of hysterectomy occurred in disadvantaged African American and Hispanic groups. More importantly, because the differences could not be explained by other factors, the authors conclude that this could reflect health disparity resulting in the overuse of hysterectomy in this groups [17].

Interestingly, a recent analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Women’s Study addressed the potential issue of health disparity as well [18]. This cohort study included 1,863 black and white women in the US from 2000 to 2002, 15 years after the baseline study. Again black women were more likely (3.5 times) to undergo hysterectomy than white women. This association was observed after the adjustment for age, educational status, perceived barriers to medical care, BMI, PCOS, tubal ligation, age at menarche, depressive symptoms and geographic location [18]. Further analysis of a subset of women in whom fibroids were directly visualized by ultrasound revealed only a minimal reduction in the difference between the two groups, implying that fibroids alone did not explain the racial differences in hysterectomy. They speculate that while biologic factors may contribute to these racial disparities, there may be nonclinical modifiers such as education about alternative treatments, cultural beliefs, communication issues, or other psychosocial factors.

Menopause

Just as ethnicity and race appears to modify how some women experience menstruation, attitudes about menopause and the climacteric are also effected by ethnicity and race. A subgroup of the SWAN dataset analyzed attitudes toward menopause in over 12,000 women aged 40–55 years. They were surveyed by telephone using standardized questionnaires to assess whether they had positive or negative attitudes about menopause [19]. The five racial and ethnic groups included were African American, White, Chinese American, Japanese American, and Hispanic. All of the groups tended to report a positive attitude toward menopause, while slightly more positive in African American and less so in Chinese- and Japanese Americans. Group attitudes did not vary significantly across the stages of menopause [19].

Another SWAN report studied symptom reporting across the groups [20]. They used factor analysis to identify two consistent factors affecting menopausal women; vasomotor symptoms (hot flashes and night sweats) and psychosomatic symptoms. In a regression analysis, controlling for age, education, health, and economic strain, they found that Caucasian women reported more psychosomatic symptoms than all other groups, while African American women reported more vasomotor symptoms [20]. This suggests that race and ethnicity may differentially affect the way menopause and the climacteric manifests and thus counseling and treatment may need to be tailored accordingly.

Summary

In this chapter, we have discussed ethnic differences in amenorrhea, the menstrual cycle and the menopause. These range from biologic variations in hormone profiles and endocrine function, to complex cultural and psychosocial interactions. While the majority of these studies may be limited by sample size, retrospective review, or reporting biases, the overall theme is the same and suggests that the physical and psychological experience of amenorrhea varies across different racial and ethnic groups and that this could negatively impact the effectiveness of a “one size fits all” approach to counseling, treatment, and healthcare policy.

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