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Zhongwei Huang, MBBS, DPhil, AFHEA (UK), MRCOG, M.Med (O&G), Eu-Leong
Yong, MBBS, FRCOG, PhD
PII: S1521-6934(16)30023-2
DOI: 10.1016/j.bpobgyn.2016.04.001
Reference: YBEOG 1609
To appear in: Best Practice & Research Clinical Obstetrics & Gynaecology
Please cite this article as: Huang Z, Yong E-L, Ethnic Differences: Is there an Asian Phenotype for
Polycystic Ovarian Syndrome?, Best Practice & Research Clinical Obstetrics & Gynaecology (2016), doi:
10.1016/j.bpobgyn.2016.04.001.
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Department of Obstetrics & Gynaecology
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National University Health Systems, Tower Block Level 12,
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Email: zhongwei_huang@nuhs.edu.sg
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Contact number: +65 98288725
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Ethnicity has not been accounted for in the diagnostic criteria for polycystic ovary syndrome
(PCOS). It is increasingly recognised that ethnic differences are likely contributors to the differing
manifestations of PCOS. Generally, rates of PCOS may be lower in East Asians. It is clear that East
Asians are less hirsute compared to Caucasians. Hirsutism cut-off thresholds need to be lower in East
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Asian populations compared to Caucasian populations. Despite population-adjusted scoring,
Caucasians have higher hirsutism rates amongst patients diagnosed with PCOS. Rates of
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hyperandrogenaemia do not appear to differ among PCOS subjects, although serum
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androstenedione appeared to be higher in Caucasians in one study. Interestingly, higher prevalence
of the polycystic ovarian morphology has been reported in East Asian PCOS populations compared to
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Caucasian PCOS subjects. Hence, there is a need for comparative studies across different ethnicities
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to establish whether epidemiological differences observed reflect a true ethnic difference in the
definition, based on the 2003 Rotterdam ESHRE/ASRM consensus workshop group, is dependent on
the presence of two out of the following three features: infrequent menstruation (>35 days for cycle
length, or less than 8 cycles a year), hyperandrogenism (manifesting as hirsutism and/or elevated
serum androgens), and the polycystic ovarian morphology on transvaginal ultrasonography [1]. In
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contrast the Androgen Excess – PCOS (AE-PCOS) Society Task Force in 2009 puts hyperandrogenism
at the core of the syndrome, and the co-existence of ovarian dysfunction (as manifested by either
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oligo-anovulation or polycystic ovaries) defines the complete syndrome [2]. In stark contradistinction,
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hyperandrogenism is considered to be much less prevalent in Japanese subjects, and therefore not
used in the Japanese diagnostic criteria for PCOS [3]. Measurement of luteinizing hormone (LH) was
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chosen instead of hyperandrogenism. The diagnostic criteria of PCOS in accordance to the 1993
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Japanese Society for Obstetrics and Gynecology requires the presence of all the following three
criteria: (a) anovulation, (b) presence of the polycystic ovarian morphology, and (c) high serum LH
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levels. Serum testosterone level is used only as a “referential factor”. In 2007, the third criterion is
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revised to allow either the presence of high LH with normal FSH or the presence of
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Based on these criteria, the prevalence of PCOS in various ethnic communities has been
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reported to range from 2–20% [5]. Whether the criteria are appropriate for all ethnicities is a
question that has yet to be fully resolved. Specifically, in this chapter, we will review the evidence on
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ethnic and ecological differences in the prevalence of hirsutism, androgen production and ovarian
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morphology, which can significantly affect the diagnosis of PCOS, and explore the possible existence
of an Asian phenotype.
Ethnic differences on incidence of PCOS based on the Rotterdam, Japanese and Chinese criteria
The prevalence of PCOS in largely Western populations was reported to be as high as 15%
based on the Rotterdam criteria of 2003 [6]. In contrast, a study of more than 15,000 Chinese
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women noted that the prevalence of PCOS was only 5.6% [7]. The prevalence of PCOS amongst the
Asian populations has been reported to vary from 5.6% in the Southern Chinese population [7], 5.7%
in Thai women [8], 6.3% in Sri Lankan women [9] and 14.3% in Iranian women [10]. Even in studies
One reason for the wide range of reported prevalence of PCOS is likely due to differences in
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the criteria used in the diagnosis of the condition, an enduring controversy further explored in
Chapter 1. Other reasons may be technical, such as subjective variation in clinical assessment of
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hirsutism, lack of reference standards for androgen assays, and inter-observer differences in the
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measurement of ovarian morphology. Nevertheless, divergent prevalence of PCOS in different ethnic
groups suggests the possibility that there may be true ethnic differences (Table 1). In particular, East
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Asian subjects (Korean, Chinese, Thai) appear to have a lower prevalence of PCOS (around 5%) using
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currently accepted diagnostic criteria when compared to Caucasian women (11-20%). Responses to
treatment modalities may differ [12] and therefore ethnic differences may have important
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therapeutic consequences.
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meeting a key diagnostic criterion in both Rotterdam and AE-PCOS definitions. Hirsutism is clinically
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identified by the presence of excessive coarse terminal hair in androgen-responsive areas of the
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female body. The modified Ferriman-Gallwey (mFG) is commonly used to score 9 body areas (upper
lip, chin, chest, upper and lower back, upper and lower abdomen, arm, forearm, thigh, and lower
leg), according to a scale ranging from 0 (no hair) to 4 (similar to that of a well-virilised adult male)
[16]. It has to be kept in mind that the severity of hirsutism does not correlate well with the
magnitude of androgen excess and that hair follicle response to circulating androgens varies
considerably between individuals, explaining why some women with clearly elevated androgen
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levels do not exhibit hirsutism [17]. Despite publication of visual scoring aids, inter-observer
differences may arise due to the subjective nature of visual assessments [18]. An added complexity
is that hirsutism itself may vary with age, with hirsutism scores decreasing with increasing age [19].
Prior treatment for unwanted hair growth may have confounded the results of some studies [20].
The original study by Ferriman and Gallwey defined hirsutism as a score >8 [16]. In most
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Caucasian studies using this definition, the average hirsutism rate was 74.6% in a review of over
6,000 subjects with a range from 17% to 100% [2]. There is evidence that this criterion may not be
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appropriate for all ethnicities. East Asian women (of Chinese, Korean, Thai, Japan ethnicities) have a
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lower prevalence of hirsutism (Table 2). One of the earliest comparative studies indicated that
Japanese PCOS patients have a lower mean hirsutism scores than Italian and American women in
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USA [21].
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Using systematic cluster random sampling and cluster analysis of some 3,000 subjects in a
Southern Chinese population, a mFG score of ≥ 5 was found to be indicative of hair growth above
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the norm [19]. Hirsutism in these women was correlated with higher incidences of acne, menstrual
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irregularity, polycystic ovaries, and acanthosis nigricans. Interestingly, this cut-off value decreased
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with increasing age, being 14.4%, 10.7%, 7.9%, 3.6%, and 1.5%, respectively, in women aged 20–25,
26–30, 31–35, 36–40, and 41–45 years respectively. A large community based study involving 10,120
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Chinese women concluded that mFG score > 4 could be made to diagnose hirsutism [7]. An mFG
score of ≥ 5 indicates hair growth above the norm among Chinese women in the general Southern
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Chinese population, a cut-off value that decreases with increasing age. Based on menstrual
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irregularities and the presence of polycystic ovaries, a mFG score ≥ 5 has been proposed to define
hirsutism in Chinese women [19]. Women diagnosed to have PCOS living in China was reported to be
significantly less hirsute compared to Caucasian PCOS subjects living in Netherlands, with mFG
scores of 3.6 ± 4.9 versus 5.2 ± 5.4 respectively [22]. Differences also exist within East Asian
populations. In Thai women, mFG score > 3 has been proposed based on 97.5th percentile of a
community-based population [23]. In Japanese women, it was suggested to use mFG score of > 6 to
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define hirsutism [24]. On the other hand, some studies involving small number of Asians have found
In South Asians, PCOS subjects were reported to have a higher mean mFG score and in one
study the mean score can be as high as 18 [25]. Another study from an endocrinology clinic in the
United Kingdom demonstrated that in subjects diagnosed with PCOS, women of South Asian descent
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exhibited a rate of hirsutism comparable to White women (88% vs 77% respectively) [26]. A study in
New Zealand indicates about two thirds of women of south Indian descent diagnosed with PCOS has
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hirsutism, similar to the prevalence in women of European, Maori, and Pacific Island descent [27].
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Mediterranean and Middle Eastern women also tend to have higher prevalence of hirsutism and this
was observed in a study comparing Middle Eastern and Caucasian women with PCOS [28].
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Even within Caucasian populations ethnic differences have been reported. Ferriman-Gallwey
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score was lower (7.1 ± 6.0 vs. 15.4 ± 8.5, p< 0.001) in Icelandic women with PCOS compared to
Boston women with PCOS [29]. On the other hand, no significant differences in mFG scores were
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noted between White and Black women (195 Black and 174 White) in a study conducted in south-
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Studies in the literature suggest that the appropriate mFG score to define hirsutism in Asian
women, excluding those from the Indian subcontinent, is less than 8. Recognising these differences
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investigators have used mFG cut-offs threshold for hirsutism from 3 to 6 in East Asian populations
(Table 2). Using these race-specific cut-offs, the mean prevalence of hirsutism in Caucasian
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populations was 2.7 fold higher in Caucasian compared to East Asian PCOS subjects (76.3% versus
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28.4% respectively) (Table 2). For these reasons, it is clear that ethnic differences in hirsutism among
PCOS do exist, and such differences may contribute to varying rates of PCOS in different populations.
measured androgen for diagnostic purposes is total testosterone [37]. Some 97-98% of testosterone
is bound to plasma proteins especially sex hormone binding globulin (SHBG) and therefore not
biologically active. Determination of SHBG levels allows the calculation of bioactive free androgen
index, reflecting the amount of bioavailable testosterone. Other androgens in clinical use include
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androstenedione, and the adrenal androgen dehydroepiandrosterone (DHEA) and its sulphated
metabolite (DHEA-S).
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Diagnosis of biochemical hyperandrogenism is fraught with controversy. When interpreting
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and evaluating androgen assays in women, the following considerations should be kept in mind [38].
The concentration of testosterone varies with the time of the day and there is cross-reaction
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between the androgens in serum. Plasma total concentrations of testosterone in women are in the
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lower sensitivity ranges of assays in clinical use and thus are at their lower limits of accuracy. There
using different kits making comparisons between different ethnic groups difficult, unless assays are
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performed with one assay in one laboratory. The cut-off levels for high testosterone in different
ethnic communities ranged from 2.94 nmol/L in a South-eastern United States [5] to 1.63 nmol/L in
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There is abundant data that there are ethnic differences in oestrogen levels. It is relevant to
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consider oestrogen levels; since testosterone is metabolized to oestrogens and abnormalities in the
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aromatase enzyme activity has been reported in PCOS patients. Asians have lower plasma oestradiol
levels compared to Caucasians irrespective of whether the specimens were collected during the
follicular or luteal phase [39]. The lower oestradiol concentrations in Asians were observed even
after adjustment for differences in body size. Women in the USA had the adjusted mean values of
urinary oestrone, oestradiol, and oestriol that were 162% (p < 0.0001), 152% (p < 0.0001), and 92%
(p < 0.0009) higher, respectively, than in Singapore Chinese women [40]. The question arises
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whether there are differences in androgen levels in the Asian population when compared to
Evidence for ethnic differences in androgen production is scanty and unclear. The Japanese
Society for Obstetrics and Gynaecology specifically precludes the use of serum androgens for the
diagnosis of PCOS because of the low prevalence of raised androgens in the Japanese population.
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Although testosterone levels were significantly higher in PCOS subjects compared to controls, there
was a lot of overlap in the distribution between these two populations. Testosterone was
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recommended only as a complementary factor for diagnosis of PCOS. Based on a two standard
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deviations (+2SD) of normal menstruating women cut-off for serum testosterone, only 10% of
Japanese PCOS subjects would have raised serum testosterone levels [41]. Using this cut-off value,
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the receiver operator curve for testosterone was 0.72. This value was considered insufficiently
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discriminatory to diagnose PCOS with high sensitivity and specificity. Using a cut-off level of
testosterone of 2.5% of the normal population, the prevalence of hyperandrogenaemia ranged from
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A population-based study of 3250 rural Chinese women and 300 British women, aged 35 to
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64 years, indicated that Chinese women might have significantly less testosterone [43]. On the other
hand, there were no differences in the levels of testosterone between Chinese and Dutch women
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diagnosed with PCOS (2.3 ± 1.3 versus 2.3 ± 2.1 nmol/L respectively) [22]. Another study in United
states comparing Caucasian women and Asian women with PCOS did not reveal any differences in
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serum androgen levels, although only 28 women were studied and their ethnicity was not clearly
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described [20]. Additionally, a study comparing the levels of androgens in Japanese women with
PCOS to women from United States and Italy, observed that the level of testosterone was similar
amongst the 3 groups of women, but levels of 3α-androstanediol glucuronide, which was elevated in
women from the United States and Italy, was normal in women from Japan. The adrenal androgens,
DHEA-S and 11 β-hydroxyandrostenedione although were elevated in women with PCOS, but the
was significantly lesser in South Asians (35 ± 3·3 versus 55 ± 9·4 nmol/L p < 0.05). Although serum
testosterone was similar (2·69 ± 0·11 versus 2·64 ± 0·13 nmol/L), differences in SHBG might
contribute to differences in the free androgen index [44]. Looking at Caucasian women with PCOS
and Middle Eastern women with PCOS living in Denmark, the level of testosterone was higher in
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Caucasian women but the levels of DHEA-S was noted to be higher in Middle eastern women [28].
Even within the Caucasian populations, androstenedione (4.0 ± 1.3 ng/dL versus 3.5 ± 1.2 ng/dL, p
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<0.01) was higher and testosterone (54.0 ± 25.7 ng/dL versus 66.2 ± 35.6 ng/dL, p < 0.01) was lower
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when Caucasian Icelandic women (N=105) with PCOS were compared with Boston women (N=262)
with PCOS [29]. Differences in androgen levels have been reported between African-American
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women and their Caucasian counterparts in the USA. After controlling for differences in BMI, insulin
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resistance, and waist hip ratio, Black women had lower androgen levels (androstenedione, total
women versus Caucasian women (Table 3) although the threshold for total testosterone levels
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differs amongst the East Asian population with one study from Japan being a significant outlier. Not
all studies examined the use of other androgens; amongst the studies that examine
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androstenedione levels, it appears that Caucasian women with PCOS may have higher levels of when
compared to East Asian women (Table 3). Thus, given the heterogeneity and scarcity of studies
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directly comparing ethnic differences in androgen levels, definite conclusions cannot be made as to
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whether ethnic differences in androgen levels exist in the same manner as observed for oestradiol in
women with PCOS and further studies are necessary to examine this.
common finding in healthy young women and is not pathognomonic of PCOS [49]. Based on the
Rotterdam criteria 2003, ultrasound features of PCOS include the following observations - (A) more
than 12 follicles throughout the ovary measuring 2 – 9 mm in diameter and/or (B) increased ovarian
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Issues with assessment of ovarian morphology by transvaginal ultrasound have been
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mind that ovarian volume increases through childhood, achieves its maximum volume shortly after
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puberty and declines significantly with each decade of life from age 30 to age 70 in the physiological
state [50], [51]. According to the normative model developed by Kelsey and colleagues, 69% of the
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variation in ovarian volume is due to age alone [52]. The rate of decline in anthral follicle count (AFC)
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among women with PCOS was linear, while in those who did not have PCOS, it was exponential until
30 years of age, and then became similar to that of women with PCOS. The rate of follicle loss per
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year was significantly slower in women with PCOS compared with that in women with normal
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ovaries. In both groups, the fastest period of follicle loss was between the ages of 18 and 30 years.
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The average follicle loss was 0.8 follicles/year in women with PCOS women and 1.7 follicles/year in
those without PCOS (P < 0.001). This study concluded that age-related decline in AFC among women
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Given the physiological variations in ovarian development, it is pertinent to find out if any
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ovarian parameters are likely to be affected by ethnic differences. Interestingly, the occurrence of
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polycystic ovaries (68% to 80%) in Japanese women diagnosed with PCOS was comparable between
women with PCOS from United States and Italy [21]. However, for Chinese women with PCOS, when
their ovaries were assessed sonographically, it was noted that they tend to have significantly lower
stromal volume and vascularity when compared to Caucasian women and it seemed that the best
threshold to diagnose PCOS in Chinese women based on ovarian morphology appeared to be less
than 6.3 cm3 for ovarian volume and 10 follicles for mean follicular number [46]. In contrast, Wang
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and colleagues conducted a study comparing Caucasian women with PCOS and Chinese women with
PCOS but they concluded that there was no difference in ovarian morphology noted on ultrasound
[20]. Another study attempted to assess the differences in ovarian volume and follicle number in
Turkish women versus the Western population and noted that the threshold value to diagnose PCOS
for Turkish women was an ovarian volume of 6.43 cm3 and a follicle count of 8 and above [54].
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Comparing data from East Asian women with PCOS, it appears that most East Asian women
(92.9%) met the criteria for polycystic ovary syndrome based on the Rotterdam criteria 2003 (Table 4)
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Surprisingly, in studies examining Caucasian women with PCOS, albeit given the differences in
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diagnostic criteria for polycystic ovary morphology on ultrasound, the proportion of East Asian
women with PCOS having polycystic ovary morphology on ultrasound appeared to be higher (92.9%
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versus 69.9%) when compared to Caucasian women with PCOS (Table 4). However, this observation
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may not be conclusive given lower threshold levels for ovarian volume and follicle numbers found in
Chinese [46] and Turkish women with PCOS [54]. Therefore, further studies directly comparing
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Caucasian and Asian women with PCOS are needed to affirm ethnic differences in polycystic ovarian
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morphology on ultrasound.
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Although Insulin resistance and associated metabolic syndrome is not part of the currently
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accepted diagnostic criteria for PCOS, the presence of hyperinsulinism exacerbates the symptom of
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PCOS and its response to therapy [12], [26]. Furthermore, there is a direct relationship between
bioactivity of serum androgens and SHBG levels. SHBG varies with body weight and therefore could
affect the bioavailability of androgens. These metabolic and endocrine changes can impact the
diagnosis of PCOS and even the subsequent management of these women. These issues will be
Although ethnicity and its impact on the prevalence of PCOS is not currently accounted for in
the diagnostic criteria for PCOS, it is increasingly being recognised that “geographic location, ethnic
origin, and cultural/social practices are likely contributors to the differing manifestations of PCOS
and should be recognized in routine clinical practice’’ [6], [58]. Generally, rates of PCOS may be
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lower in East Asians (Table 1). It is clear that East Asians are less hirsute compared to Caucasians.
Hirsutism cut-off thresholds need to be lower in East Asian populations compared to Caucasian
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populations. Despite population-adjusted scoring, Caucasians have higher hirsutism rates amongst
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patients diagnosed with PCOS (Table 2). Rates of hyperandrogenaemia do not appear to differ
among PCOS subjects, although serum androstenedione appeared to be higher in Caucasians in one
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study (Table 3). Interestingly, higher prevalence of the polycystic ovarian morphology has been
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reported in East Asian PCOS populations compared to Caucasian PCOS subjects (Table 4). Henceforth,
there is a need for comparative studies across different ethnicities to establish whether
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epidemiological differences observed reflect a true ethnic difference in the phenotype of PCOS.
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• Ethnic differences exist amongst the Asian population in the diagnostic criteria for PCOS –
clinical and/or biochemical proof of androgen excess, menstrual irregularities and number of
• There are clear ethnic differences in hirsutism rates amongst East Asian compared to
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Caucasian populations. The normative cut-off value to define hirsutism in Asian women,
excluding those from the Indian subcontinent and Middle east, is a mFG score <8
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• Data is lacking to conclude convincingly that there are ethnic differences in androgen levels
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and polycystic ovarian morphology in Asian and Caucasian women with PCOS.
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Research Agenda
• Population-based studies to guide clear evidence based criteria for diagnosis of PCOS as a
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disease entity.
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• To determine the ethnic and population specific cut-off values on the morphology of the
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• To define the phenotype of the Asian women with PCOS based on specific
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Table 1
of subjects
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Korea NIH 203 4.9% Byun et al, 2005 [13]
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Chinese Rotterdam 15 924 5.6% Li et al, 2013[7]
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Sri Lankan Rotterdam 2915 6.3 % Kumarapeli et al, 2008[9]
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≥5 10.5% (314/2988) Zhao et al, 2011[19]
>2 62.6% (553/883) Zhao et al, 2010 [31]
>8 34.8% (95/273) Li et al, 2007 [32]
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Taiwan Chinese >8 43.7% (66/151) Chen et al, 2007 [34]
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Takai et al, 1991[33]
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33.9% (293/865) Kim et al, 2014 [35]
Korean ≥6
60.0% (24/40) Hong et al, 2015 [36]
28.4 % (2263/7961)
clinical hirsutism
Average as high as 18
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>2.81 nmol/L >3.12 ng/mL a 80.2% (708/883) b Li et al, 2013 [7]
>1.80 nmol/La 24.1% (173/719) b Zhang et al, 2012 [47]
Thai >2.80 nmol/La >2.7 ng/ml 37.1% (23/62) c Vutyavanich et al, 2007[8]
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60.0% (24/40) b Hong et al, 2015 [36]
>2.4nmol/La
Korean 47.4% (410/865) b Kim et al, 2014 [34]
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60.7% (645/1062) b Sung et al, 2014 [48]
>2.3nmol/La
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PCOS has biochemical hyperandrogenism 58.9% (2742/4656)
a
Conversion from nmol/L to ng/ml or vice versa
b
PCOS Rotterdam criteria 2003
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PCOS NIH Criteria 1990
d
Japanese Society of Obstetrics and Gynecology PCOS criteria 2007
e
Androgen Excess and PCOS society for PCOS criteria 2009
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Table 4
Prevalence of polycystic ovary morphology of women with PCOS
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Thai Rotterdam Criteria a 76.9% (40/62) Vutyavanich et al, 2007[8]
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86.1% (143/166) Chae at al, 2008 [57]
Korean Rotterdam Criteria a 96.5% (835/865) Kim et al, 2014 [34]
84.2% (895/1062) Sung et al, 2014 [48]
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82.1% (23/28) #
Asian * Rotterdam Criteria a Wang et al, 2013 [20]
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polycystic ovary morphology
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Definition of polycystic ovary Percentage of PCOS women with
Ethnicity Reference
morphology polycystic ovary morphology
Middle Eastern Adams et al, 1986 [59] b 29.0% (50/172) Glintborg et al, 2010 [28]
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ovary > 10 ml
b
Polycystic ovaries had multiple cysts (10 or more) 2-8 mm in diameter arranged either peripherally around a dense core of stroma or
scattered throughout an increased amount of stroma
*Asian population comprises of Asian/Asian American, East Asian and Pacific Islander
#
Asian or Caucasian women with PCOS had follicular count ≥ 12
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• Difference in incidence of hirsutism in women with PCOS of East Asian and Caucasian
ethnicities
• Ethnic differences in androgen excess and polycystic ovarian morphology in women with
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PCOS
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