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Influence of ethnicity on different aspects of polycystic ovary syndrome: a systematic review

Published:December 16, 2020DOI:https://doi.org/10.1016/j.rbmo.2020.12.006

      Abstract

      This systematic review aimed to assess variations in the clinical presentation and treatment outcomes of patients with polycystic ovary syndrome (PCOS) belonging to different ethnicities. A search was performed for studies comparing various clinical aspects of PCOS in two or more different ethnic groups. After screening 2264 studies, 35 articles were included in the final analysis. In comparison with White women with PCOS (wPCOS), East Asian women with PCOS (eaPCOS) were less hirsute, whereas Hispanic women with PCOS (hPCOS), South Asian women with PCOS (saPCOS) and Middle Eastern women with PCOS (mePCOS) were more hirsute. saPCOS had higher androgen and lower sex hormone-binding globulin (SHBG) concentrations, mePCOS had higher DHEAS concentrations, and hPCOS and Black women with PCOS (bPCOS) had lower SHBG and DHEAS measures than wPCOS. Menstrual disturbances were more frequent in eaPCOS. Both saPCOS and eaPCOS had lower body mass index with increased central adiposity. hPCOS and bPCOS were more obese. saPCOS, mePCOS, hPCOS and bPCOS had a higher prevalence of insulin resistance than wPCOS. bPCOS had a better lipid profile but higher blood pressure and cardiovascular risk. Indigenous Australian women with PCOS were more obese and more insulin resistant with higher androgen concentrations. The clinical phenotype of PCOS therefore shows a wide variation depending on ethnicity.

      Keywords

      Introduction

       Rationale

      Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by clinical and/or biochemical androgen excess, ovulatory dysfunction and polycystic ovarian morphology (PCOM). Women with PCOS have an increased risk of metabolic and cardiovascular comorbidities, infertility, pregnancy complications, psychological disorders and cancer (
      • Azziz R.
      • Carmina E.
      • Chen Z.
      • Dunaif A.
      • Laven J.S.
      • Legro R.S.
      • Lizneva D.
      • Natterson-Horowtiz B.
      • Teede H.J.
      • Yildiz B.O.
      Polycystic ovary syndrome.
      ).
      PCOS is a complex disorder in which the interaction between genetic, epigenetic and environmental factors initiates and perpetuates the syndrome (
      • Azziz R.
      • Carmina E.
      • Chen Z.
      • Dunaif A.
      • Laven J.S.
      • Legro R.S.
      • Lizneva D.
      • Natterson-Horowtiz B.
      • Teede H.J.
      • Yildiz B.O.
      Polycystic ovary syndrome.
      ). Considering these pathophysiological factors, ethnicity might affect the pathogenesis of PCOS. Although many studies have shown that ethnicity has an impact on the prevalence and clinical manifestations of PCOS, information regarding the variability of PCOS in different ethnic groups is scant (
      • Huddleston H.G.
      • Cedars M.I.
      • Sohn S.H.
      • Giudice L.C.
      • Fujimoto V.Y.
      Racial and ethnic disparities in reproductive endocrinology and infertility.
      ;
      • Qiao J.
      Pay more attention to ethnic differences in polycystic ovary syndrome phenotypic expression.
      ;
      • Zhao Y.
      • Qiao J.
      Ethnic differences in the phenotypic expression of polycystic ovary syndrome.
      ;
      • Huang Z.
      • Yong E.L.
      Ethnic differences: Is there an asian phenotype for polycystic ovarian syndrome? Best practice & research.
      ). In 2018, by defining clinical consensus recommendations (CCR), the International PCOS Network recommended that health professionals should consider the individual's ethnicity when assessing a patient with PCOS (
      • Teede H.J.
      • Misso M.L.
      • Costello M.F.
      • Dokras A.
      • Laven J.
      • Moran L.
      • Piltonen T.
      • Norman R.J.
      Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.
      ). However, high-quality evidence regarding the variability of PCOS in individuals from different ethnic backgrounds is currently lacking.

       Objectives

      The main objective of this review was to summarize the available data on the impact of ethnicity on the different aspects of PCOS in patients presenting to clinics. The main research questions were as follows:
      • 1.
        Is there any ethnic difference in women with PCOS in terms of clinical or biochemical hyperandrogenism, menstrual dysfunction and PCOM?
      • 2.
        Is there any ethnic difference in women with PCOS in terms of metabolic and cardiovascular comorbidities?
      • 3.
        Is there any ethnic difference in women with PCOS in terms of infertility and obstetric complications?
      • 4.
        Is there any ethnic difference in women with PCOS in terms of mood disorders and quality of life (QoL)?
      • 5.
        Is there any ethnic difference in women with PCOS in terms of treatment outcomes?

      Materials and methods

      This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (
      • Moher D.
      • Shamseer L.
      • Clarke M.
      • Ghersi D.
      • Liberati A.
      • Petticrew M.
      • Shekelle P.
      • Stewart L.A.
      Preferred reporting items for systematic review and meta-analysis protocols (prisma-p) 2015 statement.
      ).

       Search strategy

      A literature search was performed in the PubMed database. Bibliographies of relevant studies were also searched to identify additional sources. Three different key word sets were used for the search:
      • 1.
        (polycystic ovary syndrome OR pcos OR stein-leventhal syndrome OR hirsutism OR oligomenorrhea OR polycystic ovaries OR hyperandrogenism OR hyperandrogenemia) AND (ethnicity)
      • 2.
        (polycystic ovary syndrome OR pcos OR stein-leventhal syndrome OR hirsutism OR oligomenorrhea OR polycystic ovaries OR hyperandrogenism OR hyperandrogenemia) AND (race)
      • 3.
        (polycystic ovary syndrome OR pcos OR stein-leventhal syndrome OR hirsutism OR oligomenorrhea OR polycystic ovaries OR hyperandrogenism OR hyperandrogenemia) AND (ancestry OR hispanic OR american OR oceanic OR brazilian OR russian OR middle eastern OR turkish OR iranian OR european OR australia OR african OR asian OR black OR white OR thai OR caucasian OR mexican OR latin OR chinese OR arab OR japanese OR indian OR pakistani OR korean OR african american OR american indian OR alaska native OR asian indian OR filipino OR vietnamese OR native hawaiian OR chamorro OR samoan OR jews OR inuits OR other pacific islander OR amish OR other asian OR some other races OR migrant OR indigenous OR aboriginal).

       Inclusion and exclusion criteria

      Articles that were designed to compare two or more different ethnic groups in the same study and were published between April 1990 and February 2020 were included. Only studies that assessed the clinical characteristics of patients with PCOS who were referred (i.e. patients presenting to the clinic but not those in unselected populations) were included. Studies with non-human subjects, those published before 1990 and in languages other than English, and those that were meta-analyses, case reports, case series, editorials or reviews were excluded.

       Data extraction

      Data were extracted on the following: the author of the publication; publication year; number, age and ethnicity of the participants; mean modified Ferriman–Gallwey (mFG) scores or prevalence of subjects with hirsutism; serum androgen concentrations; prevalence of acne; prevalence and type of menstrual disturbances; ovarian morphology; fertility status; mean body mass index (BMI), waist–hip ratio (WHR) or prevalence of obesity; surrogate markers of glucose metabolism such as fasting insulin concentrations and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index; prevalence of acanthosis nigricans; and lipid profile and systolic and diastolic blood pressure (SBP and DBP, respectively).

      Results

      A total of 2916 papers were identified. Of these, 652 were removed because they were duplicates. A further 2220 articles were excluded after the title/abstract screen due to their irrelevant content. Nine more articles were also excluded after a full-text screening due to lack of relevant data. Thirty-five articles were included for the final analyses (Figure 1).

       Clinical and biochemical hyperandrogenism

      The data available from 26 studies regarding clinical and biochemical hyperandrogenism in various ethnic populations are summarized in Table 1. In two studies, it was shown that East Asian women with PCOS (eaPCOS) had lower mFG scores than White women with PCOS (wPCOS) (
      • Carmina E.
      • Koyama T.
      • Chang L.
      • Stanczyk F.Z.
      • Lobo R.A.
      Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome?.
      ;
      • Guo M.
      • Chen Z.J.
      • Eijkemans M.J.
      • Goverde A.J.
      • Fauser B.C.
      • Macklon N.S.
      Comparison of the phenotype of chinese versus dutch caucasian women presenting with polycystic ovary syndrome and oligo/amenorrhoea.
      ). In the other two studies comparing eaPCOS and wPCOS, eaPCOS appeared to have lower mFG scores, although this did not reach statistical significance (
      • Williamson K.
      • Gunn A.J.
      • Johnson N.
      • Milsom S.R.
      The impact of ethnicity on the presentation of polycystic ovarian syndrome.
      ;
      • Legro R.S.
      • Myers E.R.
      • Barnhart H.X.
      • Carson S.A.
      • Diamond M.P.
      • Carr B.R.
      • Schlaff W.D.
      • Coutifaris C.
      • Mcgovern P.G.
      • Cataldo N.A.
      • Steinkampf M.P.
      • Nestler J.E.
      • Gosman G.
      • Guidice L.C.
      • Leppert P.C.
      The pregnancy in polycystic ovary syndrome study: Baseline characteristics of the randomized cohort including racial effects.
      ). The remaining studies did not show a difference in mFG scores between eaPCOS and wPCOS (
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ;
      • Wang E.T.
      • Kao C.N.
      • Shinkai K.
      • Pasch L.
      • Cedars M.I.
      • Huddleston H.G.
      Phenotypic comparison of caucasian and asian women with polycystic ovary syndrome: A cross-sectional study.
      ;
      • Afifi L.
      • Saeed L.
      • Pasch L.A.
      • Huddleston H.G.
      • Cedars M.I.
      • Zane L.T.
      • Shinkai K.
      Association of ethnicity, fitzpatrick skin type, and hirsutism: A retrospective cross-sectional study of women with polycystic ovarian syndrome.
      ). Except for one study in which Black women with PCOS (bPCOS) had higher mFG scores, the severity of hirsutism was comparable in bPCOS and wPCOS (
      • Afifi L.
      • Saeed L.
      • Pasch L.A.
      • Huddleston H.G.
      • Cedars M.I.
      • Zane L.T.
      • Shinkai K.
      Association of ethnicity, fitzpatrick skin type, and hirsutism: A retrospective cross-sectional study of women with polycystic ovarian syndrome.
      ). Although the hirsutism scores did not differ between Hispanic women with PCOS (hPCOS) and wPCOS in one study (
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ), it was in general found that hPCOS were more hirsute than wPCOS (
      • Afifi L.
      • Saeed L.
      • Pasch L.A.
      • Huddleston H.G.
      • Cedars M.I.
      • Zane L.T.
      • Shinkai K.
      Association of ethnicity, fitzpatrick skin type, and hirsutism: A retrospective cross-sectional study of women with polycystic ovarian syndrome.
      ;
      • Engmann L.
      • Jin S.
      • Sun F.
      • Legro R.S.
      • Polotsky A.J.
      • Hansen K.R.
      • Coutifaris C.
      • Diamond M.P.
      • Eisenberg E.
      • Zhang H.
      • Santoro N.
      Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.
      ;
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      ). South Asian women with PCOS (saPCOS) and Middle Eastern women with PCOS (mePCOS) had consistently higher mFG scores than their Caucasian counterparts (
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ;
      • Glintborg D.
      • Mumm H.
      • Hougaard D.
      • Ravn P.
      • Andersen M.
      Ethnic differences in rotterdam criteria and metabolic risk factors in a multiethnic group of women with pcos studied in denmark.
      ;
      • Mani H.
      • Davies M.J.
      • Bodicoat D.H.
      • Levy M.J.
      • Gray L.J.
      • Howlett T.A.
      • Khunti K.
      Clinical characteristics of polycystic ovary syndrome: Investigating differences in white and south asian women.
      ;
      • Afifi L.
      • Saeed L.
      • Pasch L.A.
      • Huddleston H.G.
      • Cedars M.I.
      • Zane L.T.
      • Shinkai K.
      Association of ethnicity, fitzpatrick skin type, and hirsutism: A retrospective cross-sectional study of women with polycystic ovarian syndrome.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ). mFG scores varied even in different Caucasian groups (Icelandic Caucasian versus Boston Caucasian, White American versus Finnish and Norwegian). European Caucasians were less hirsute than their American counterparts (Table 1).
      Table 1Comparison of clinical and biochemical hyperandrogenism between various ethnic groups
      Study (first author, year)DCStudy populationAge (years)mFGAcneSerum androgensComments
      Carmina (1992)NIH25 Hispanic American

      25 Japanese

      25 Italian

      For each ethnic group 10 age-matched controls
      30 ± 2

      24 ± 1

      24 ± 1
      Patients:

      Hispanic American 12 ± 1

      Japanese 3.5 ± 0.2

      Italian 12.5 ± 1

      Controls:

      All <8

      Subjects with hirsutism:

      Hispanic American 60%

      Japanese ns

      Italian 75%

      Controls none
      Serum T and DHEAS concentrations were similar in patients
      The measurements were made in the same laboratory.
      In spite of similar serum androgen concentrations, Japanese patients had a lower mFG score

      mFG scores of Japanese patients and controls were similar

      3α-Androstanediol glucuronide, a marker of skin 5α-reductase activity, was lower in Japanese patients
      Dunaif (1993)NIH13 Caribbean Hispanic

      10 non-Hispanic White

      5 Caribbean Hispanic control

      8 non-Hispanic White control
      25.1 ± 1

      27 ± 2

      28 ± 2

      27 ± 1
      Serum T, fT, A4, DHEAS and SHBG concentrations were similar in patients
      The measurements were made in the same laboratory.
      Similar androgen concentrations
      Norman (1995)NIH11 Indian

      11 White

      11 Indian control

      11 White control
      ∼25

      Age was similar for all groups
      Serum T, A4 and DHEAS concentrations were similar

      Compared with obese White women, SHBG concentrations were higher in obese Indian patients
      Similar androgen concentrations but fT concentrations were not assessed
      Williamson (2001)ns112 White

      16 Maori

      15 Pacific Islander

      19 Indian

      4 Asian

      6 other

      There was an inconsistency between number and percentage of PCOS patients
      27.4 (all)White 8.3 ± 9.0

      Maori 10.5 ± 9.8

      Pacific Islander 9.1 ± 0.2

      Indian 8.3 ± 8.2

      Asian+other 3.1 ± 5.5
      Acne was found in all ethnic groups except Pacific IslandersMaori and Pacific Islander women had the highest T and fT concentrations, with the lowest SHBG
      The measurements were made in the same laboratory.


      Adrenal androgen concentrations were similar
      Hirsutism was an important admission reason for White and Maori women

      Asians had the lowest mFG score but this was not statistically significant
      Kauffman (2002)NIH48 White

      26 Mexican American

      11 White control

      8 Mexican American control
      ∼26
      In this study age was not reported for whole PCOS cohort; however, the mean age of White and Mexican American participants with PCOS was approximately 26 years. White healthy controls were older than Mexican American healthy controls. A4, androstenedione; BMI, body mass index; DC, diagnostic criteria; DHEAS, dehydroepiandrosterone sulfate; FAI, free androgen index; fT, free testosterone; mFG, modified Ferriman–Gallwey score; NIH, National Institutes of Health criteria; ns, not specified; PCOS, polycystic ovary syndrome; R, Rotterdam criteria; SHBG, sex hormone-binding globulin; T, total testosterone.


      ∼30

      ∼25
      Serum T, fT and DHEAS concentrations were similar in patients
      The measurements were made in the same laboratory.
      Despite greater insulin resistance in Mexican American patients, androgen concentrations were similar
      Wijeyaratne (2002)ns47 South Asian

      40 Caucasian

      11 South Asian control

      22 Caucasian control
      26 ± 4

      30.1 ± 5

      31.3 ± 2

      32.9 ± 3
      South Asian 18

      Caucasian 7.5

      South Asian 8

      Caucasian 1.5
      South Asian 66%

      Caucasian 30%
      Serum T values were similar but SHBG concentrations were lower in South Asian women withPCOS
      The measurements were made in the same laboratory.


      SHBG concentrations were similar in controls
      Despite comparable T concentrations, South Asian women with PCOS had higher mFG scores and acne was more frequent in South Asian women

      Compared with White controls, South Asian controls also had higher mFG scores

      Hirsutism started to present at earlier ages in South Asian patients (∼18 versus ∼22 years)
      Carmina (2003)NIH20 non-Hispanic White American

      20 Italian
      29 ± 2

      26.6 ± 2
      Serum T, fT and DHEAS concentrations were similarSimilar androgen concentrations
      Hashimoto (2003)NIH102 Brazilian (predominantly Black)

      31 Austrian
      25.5 ± 3.9

      23.8 ± 4.7
      Brazilians were more hirsute, and hirsutism had a greater impact on the quality of life in Brazilian patients
      Wijeyaratne (2004)ns74 Sri Lankan

      47 British Asian

      40 White

      45 Sri Lankan control

      11 British Asian control

      22 White control
      27.3 ± 1.7

      26 ± 4

      30.1 ± 0.5

      33 ± 4.7

      31.3 ± 2

      32.8 ± 3
      Serum T was similar

      SHBG was lower in Sri Lankan patients but similar in controls

      Despite similar T concentrations, FAI was greater in Sri Lankan patients
      South Asian patients with PCOS had higher FAI measures
      Ehrmann (2005)NIH303 White

      51 Black

      38 Other
      28.8 ± 0.3

      27.6 ± 0.8

      26.7 ± 0.9
      SHBG concentrations in White women with PCOS were higher but the difference was not statistically significant
      The measurements were made in the same laboratory.


      DHEAS concentrations were comparable
      Similar androgen concentrations
      Kumar (2005)NIH186 White

      27 Black

      94 White control

      88 Black control
      27.3 ± 6.6

      28.7 ± 6.2

      28.7 ± 9.1

      30.2 ± 9.1
      White 7.7 ± 4.5

      Black 8.3 ± 4.7

      White 0.2 ± 0.4

      Black 0.2 ± 0.4
      Serum T, fT, DHEAS and SHBG concentrations were similar in PCOS patients
      The measurements were made in the same laboratory.


      White controls had higher DHEAS concentrations
      The severity of hirsutism was similar
      Kauffman (2006)R111 White

      50 Mexican American
      27.3

      26.9
      Serum T and fT concentrations were similar

      Mexican American women had lower DHEAS concentrations
      The measurements were made in the same laboratory.
      In an age- and BMI-matched cohort, DHEAS concentrations were lower in Mexican American women
      Legro (2006)NIH435 Caucasian

      109 African American

      17 Asian

      72 American Indian or Alaska Native
      28.2 ± 3.9

      27.9 ± 4.3

      30.4 ± 3.0

      27.6 ± 4.1
      Caucasian 14.5 ± 8.0

      African American 13.9 ± 7.5

      Asian 12.5 ± 7.2

      American Indian or Alaska Native 15.1 ± 8.2
      T concentrations were higher in Caucasian and African American women
      The measurements were made in the same laboratory.


      FAI and SHBG concentrations were comparable
      mFG scores of Asian women with PCOS were lower but this was not statistically significant
      Welt (2006)NIH105 Iceland Caucasian

      172 Boston Caucasian

      44 Boston African American

      25 Boston Hispanic

      21 Boston Asian

      32 Iceland controls
      30.2 ± 6.2

      28.8 ± 5.5

      28.4 ± 6.7

      26.3 ± 5.2

      25.5 ± 5.3

      32.2 ± 5.5
      Iceland Caucasian 7.1 ± 6.0

      Boston Caucasian 15.4 ± 8.5

      Boston African American 18.5 ± 8.9

      Boston Hispanic 18.2 ± 9.4

      Boston Asian 15.7 ± 11.0

      Iceland controls 3.0 ± 1.4
      Iceland Caucasian 62.1%

      Boston Caucasian 84.8%

      Boston African American 86.0%

      Boston Hispanic 87.0%

      Boston Asian 85.7%
      When compared with Boston Caucasians, A4 concentrations were higher in Icelandic women with PCOS, and T, fT and DHEAS concentrations were lower

      While SHBG concentrations were lower in African Americans and Hispanics, fT concentrations were highest in these ethnic groups
      Icelandic Caucasian PCOS participants had a lower mean mFG score than Boston Caucasian participants

      The percentage of participants with acne was lower in Icelandic Caucasians with PCOS
      Glintborg (2010)R784 Caucasian

      190 Middle Eastern
      32

      25
      Caucasian 11

      Middle Eastern 16
      Serum T, SHBG and fT concentrations were higher in Caucasian women but DHEAS concentrations were lower
      The measurements were made in the same laboratory.
      Despite lower androgen concentrations, Middle Eastern women with PCOS were more hirsute
      Kauffman (2011)R120 White

      71 Mexican American
      27.4

      26.8
      Serum T, SHBG concentrations and FAI were similar but DHEAS concentrations were lower in Mexican American patients
      The measurements were made in the same laboratory.
      In an age- and BMI-matched cohort, Mexican American patients had lower DHEAS concentrations
      Ladson (2011)NIH43 Black

      77 White

      87 Black control

      35 White control
      27.9 ± 5.0

      26.0 ± 6.9

      Age not specified
      Black 17.6 ± 9.2

      White 20.2 ± 8.0
      Serum T and SHBG concentrations were comparable
      The measurements were made in the same laboratory.
      No difference in hirsutism scores and androgen concentrations
      Guo (2012)R547 Chinese

      427 Dutch
      28.3 ± 3.4

      29.0 ± 5.2
      Chinese 3.6 ± 4.9

      Dutch 5.2 ± 5.4
      No difference in terms of the prevalence of biochemical hyperandrogenismChinese women were less hirsute
      Wang (2013)R121 Caucasian

      28 Asian
      28.0 ± 5.4

      29.6 ± 5.9
      Caucasian 8.6 ± 6.5

      Asian 7.4 ± 4.0
      Caucasian 67.9%

      Asian 73.9%
      Serum T, fT, DHEAS and A4 concentrations were measured

      The frequency of individuals with elevated androgen concentrations was comparable
      The total mFG score was similar but Asian women had less hair in the chest region

      The prevalence of acne was similar
      Hilman (2014)R413 non-Hispanic White

      106 non-Hispanic Black
      25.0 ± 6.7

      26.3 ± 7.3
      While serum T and fT concentrations were higher, serum DHEAS concentrations were lower in Black women
      The measurements were made in the same laboratory.
      Differences in androgen concentrations
      Mani (2015)ns929 White

      381 South Asian
      27.1 ± 7.4

      24.3 ± 6.7
      Participants with hirsutism:

      White 77.4%

      South Asian 88.5%
      White 23.9%

      South Asian 16.8%
      Hirsutism was more common in South Asian women

      Acne was more common in White women
      • Chang A.Y.
      • Oshiro J.
      • Ayers C.
      • Auchus R.J.
      Influence of race/ethnicity on cardiovascular risk factors in polycystic ovary syndrome, the dallas heart study.
      R62 Black

      32 White

      23 Hispanic

      113 Black control

      54 White control

      37 Hispanic control
      41

      41

      39

      40

      40

      39
      Serum T, fT and SHBG concentrations were comparable across ethnic groups
      The measurements were made in the same laboratory.
      Similar androgen concentrations
      Afifi (2017)R9 Middle Eastern

      16 Ashkenazi Jewish

      110 Caucasian

      37 East Asian

      5 South Asian

      29 Hispanic

      15 African American

      2 Native American

      20 Other
      28.4 ± 7.5

      28 ± 5.4

      28.2 ± 6.0

      27.1 ± 5.4

      23 ± 6.3

      28.9 ± 6.4

      30.9 ± 6.8

      23 ± 6.3

      28.3 ± 5.3
      Middle Eastern 12.3 ± 8.6

      Ashkenazi Jewish 7.4 ± 5.3

      Caucasian 7.4 ± 5.7

      East Asian 7.9 ± 6.4

      South Asian 9.6 ± 1.5

      Hispanic 12.6 ± 7.5

      African American 9.4 ± 4.4

      Native American 4 ± 4.2

      Other 9.1 ± 6.6
      Hispanic, Middle Eastern, South Asian and African American women with PCOS had higher mFG scores

      Hispanic and African American women had higher facial mFG scores

      Middle Eastern and Hispanic patients had higher truncal and extremity mFG scores
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      R184 American White

      100 American Black

      220 Indian

      233 Brazilian

      94 Finnish

      258 Norwegian
      29

      29

      25

      26

      33

      28.5
      Median mFG:

      American White 11.1

      American Black 10.9

      Indian 15.6

      Brazilian 12.2

      Finnish 7.8

      Norwegian 4.3
      Serum T concentrations were similarIndian women were more hirsute and Norwegian and Finnish women with PCOS were less hirsute
      • Engmann L.
      • Jin S.
      • Sun F.
      • Legro R.S.
      • Polotsky A.J.
      • Hansen K.R.
      • Coutifaris C.
      • Diamond M.P.
      • Eisenberg E.
      • Zhang H.
      • Santoro N.
      Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.
      R476 non-Hispanic White

      98 non-Hispanic Black

      128 Hispanic American
      28.8 ± 4.2

      28.7 ± 4.9

      29.2 ± 4.1
      Non-Hispanic White 17.0 ± 8.7

      Non-Hispanic Black 15.8 ± 8.5

      Hispanic American 17.6 ± 7.5

      Participants with hirsutism:

      Non-Hispanic White 86.8%

      Non-Hispanic Black 82.7%

      Hispanic American 93.8%
      Non-Hispanic White 35.2%

      Non-Hispanic Black 25.5%

      Hispanic American 64.1
      Serum T and A4 concentrations were comparable
      The measurements were made in the same laboratory.


      Hispanic women had higher FAI and lower SHBG measures
      Hispanic women were more hirsute and had a severe hyperandrogenic profile

      Acne scores were higher in Hispanic women
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      R256 non-Hispanic American

      47 Hispanic American
      28.1

      28.5
      Participants with hirsutism:

      Non-Hispanic American 49%

      Hispanic American 75.6%
      Non-Hispanic American 63.4%

      Hispanic American 70.5%
      Serum T, A4, DHEAS, SHBG and FAI measures were comparableHirsutism was more common in Hispanic women

      The prevalence of acne was similar
      Age: values are mean ± SD, mean or median; mFG: values are mean ± SD.
      a The measurements were made in the same laboratory.
      b In this study age was not reported for whole PCOS cohort; however, the mean age of White and Mexican American participants with PCOS was approximately 26 years. White healthy controls were older than Mexican American healthy controls.A4, androstenedione; BMI, body mass index; DC, diagnostic criteria; DHEAS, dehydroepiandrosterone sulfate; FAI, free androgen index; fT, free testosterone; mFG, modified Ferriman–Gallwey score; NIH, National Institutes of Health criteria; ns, not specified; PCOS, polycystic ovary syndrome; R, Rotterdam criteria; SHBG, sex hormone-binding globulin; T, total testosterone.
      A comparison of total mFG scores was available in all studies, and two studies also reported on regional mFG score comparisons. Wang and colleagues showed that despite the similar total mFG scores, eaPCOS had less hair on the chest (
      • Wang E.T.
      • Kao C.N.
      • Shinkai K.
      • Pasch L.
      • Cedars M.I.
      • Huddleston H.G.
      Phenotypic comparison of caucasian and asian women with polycystic ovary syndrome: A cross-sectional study.
      ). Moreover, Afifi and co-workers found that while hPCOS and bPCOS had higher facial mFG scores, mePCOS and hPCOS had higher truncal and extremity mFG scores (
      • Afifi L.
      • Saeed L.
      • Pasch L.A.
      • Huddleston H.G.
      • Cedars M.I.
      • Zane L.T.
      • Shinkai K.
      Association of ethnicity, fitzpatrick skin type, and hirsutism: A retrospective cross-sectional study of women with polycystic ovarian syndrome.
      ). When compared with wPCOS, hirsutism started to present at earlier ages in saPCOS (approximately 18 versus approximately 22 years) (
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ). Excess hair growth was an important reason for wPCOS to present to clinics and had greater impact on QoL in Brazilian than Austrian women (
      • Williamson K.
      • Gunn A.J.
      • Johnson N.
      • Milsom S.R.
      The impact of ethnicity on the presentation of polycystic ovarian syndrome.
      ;
      • Hashimoto D.M.
      • Schmid J.
      • Martins F.M.
      • Fonseca A.M.
      • Andrade L.H.
      • Kirchengast S.
      • Eggers S.
      The impact of the weight status on subjective symptomatology of the polycystic ovary syndrome: A cross-cultural comparison between brazilian and austrian women.
      ).
      Controversial results were available from seven studies that assessed acne prevalence among various ethnic groups. Acne was found to be more frequent in saPCOS than wPCOS in one study, whereas in another study the percentage of subjects with acne was higher in wPCOS compared with saPCOS (
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ;
      • Mani H.
      • Davies M.J.
      • Bodicoat D.H.
      • Levy M.J.
      • Gray L.J.
      • Howlett T.A.
      • Khunti K.
      Clinical characteristics of polycystic ovary syndrome: Investigating differences in white and south asian women.
      ). Acne scores in hPCOS were higher than in wPCOS in one study (
      • Engmann L.
      • Jin S.
      • Sun F.
      • Legro R.S.
      • Polotsky A.J.
      • Hansen K.R.
      • Coutifaris C.
      • Diamond M.P.
      • Eisenberg E.
      • Zhang H.
      • Santoro N.
      Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.
      ) but the prevalence of acne was similar in another (
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      ). A direct comparative study of wPCOS and eaPCOS showed that these two groups had similar frequencies of acne (
      • Wang E.T.
      • Kao C.N.
      • Shinkai K.
      • Pasch L.
      • Cedars M.I.
      • Huddleston H.G.
      Phenotypic comparison of caucasian and asian women with polycystic ovary syndrome: A cross-sectional study.
      ). Welt and colleagues found a lower prevalence of acne in Icelandic Caucasians than Boston Caucasians (
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ).
      Androgen concentrations were assessed in 23 studies. In 15 out of the 23, hormone measurements were made in the same laboratory. Twelve studies did not reveal any differences in serum androgen based on ethnicity (Table 1) (
      • Carmina E.
      • Koyama T.
      • Chang L.
      • Stanczyk F.Z.
      • Lobo R.A.
      Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome?.
      ;
      • Dunaif A.
      • Sorbara L.
      • Delson R.
      • Green G.
      Ethnicity and polycystic ovary syndrome are associated with independent and additive decreases in insulin action in caribbean-hispanic women.
      ;
      • Kauffman R.P.
      • Baker V.M.
      • Dimarino P.
      • Gimpel T.
      • Castracane V.D.
      Polycystic ovarian syndrome and insulin resistance in white and mexican american women: A comparison of two distinct populations.
      ;
      • Carmina E.
      • Legro R.S.
      • Stamets K.
      • Lowell J.
      • Lobo R.A.
      Difference in body weight between american and italian women with polycystic ovary syndrome: Influence of the diet.
      ;
      • Ehrmann D.A.
      • Kasza K.
      • Azziz R.
      • Legro R.S.
      • Ghazzi M.N.
      Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome.
      ;
      • Kumar A.
      • Woods K.S.
      • Bartolucci A.A.
      • Azziz R.
      Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (pcos).
      ;
      • Ladson G.
      • Dodson W.C.
      • Sweet S.D.
      • Archibong A.E.
      • Kunselman A.R.
      • Demers L.M.
      • Williams N.I.
      • Coney P.
      • Legro R.S.
      Racial influence on the polycystic ovary syndrome phenotype: A black and white case-control study.
      ;
      • Guo M.
      • Chen Z.J.
      • Eijkemans M.J.
      • Goverde A.J.
      • Fauser B.C.
      • Macklon N.S.
      Comparison of the phenotype of chinese versus dutch caucasian women presenting with polycystic ovary syndrome and oligo/amenorrhoea.
      ;
      • Wang E.T.
      • Kao C.N.
      • Shinkai K.
      • Pasch L.
      • Cedars M.I.
      • Huddleston H.G.
      Phenotypic comparison of caucasian and asian women with polycystic ovary syndrome: A cross-sectional study.
      ;
      • Chang A.Y.
      • Oshiro J.
      • Ayers C.
      • Auchus R.J.
      Influence of race/ethnicity on cardiovascular risk factors in polycystic ovary syndrome, the dallas heart study.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ;
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      ). In two studies that assessed wPCOS and saPCOS, serum testosterone concentrations were comparable but sex hormone-binding globulin (SHBG) concentrations were lower and free androgen index was higher in saPCOS (
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ;
      • Wijeyaratne C.N.
      • Nirantharakumar K.
      • Balen A.H.
      • Barth J.H.
      • Sheriff R.
      • Belchetz P.E.
      Plasma homocysteine in polycystic ovary syndrome: Does it correlate with insulin resistance and ethnicity?.
      ). In contrast, another study reported higher SHBG concentrations in obese saPCOS than obese wPCOS (
      • Norman R.J.
      • Mahabeer S.
      • Masters S.
      Ethnic differences in insulin and glucose response to glucose between white and indian women with polycystic ovary syndrome.
      ). Looking at dehydroepiandrosterone sulphate (DHEAS) concentrations in comparison to wPCOS, some studies noted lower DHEAS concentrations in hPCOS (
      • Kauffman R.P.
      • Baker V.M.
      • Dimarino P.
      • Castracane V.D.
      Hyperinsulinemia and circulating dehydroepiandrosterone sulfate in white and mexican american women with polycystic ovary syndrome.
      ;
      • Kauffman R.P.
      • Baker T.E.
      • Graves-Evenson K.
      • Baker V.M.
      • Castracane V.D.
      Lipoprotein profiles in mexican american and non-hispanic white women with polycystic ovary syndrome.
      ) and bPCOS (
      • Hillman J.K.
      • Johnson L.N.
      • Limaye M.
      • Feldman R.A.
      • Sammel M.
      • Dokras A.
      Black women with polycystic ovary syndrome (pcos) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with pcos [corrected].
      ), and higher concentrations in mePCOS (
      • Glintborg D.
      • Mumm H.
      • Hougaard D.
      • Ravn P.
      • Andersen M.
      Ethnic differences in rotterdam criteria and metabolic risk factors in a multiethnic group of women with pcos studied in denmark.
      ). Legro and colleagues found that, compared with eaPCOS, testosterone concentrations were higher in wPCOS and bPCOS but the free androgen index and SHBG measures were similar (
      • Legro R.S.
      • Myers E.R.
      • Barnhart H.X.
      • Carson S.A.
      • Diamond M.P.
      • Carr B.R.
      • Schlaff W.D.
      • Coutifaris C.
      • Mcgovern P.G.
      • Cataldo N.A.
      • Steinkampf M.P.
      • Nestler J.E.
      • Gosman G.
      • Guidice L.C.
      • Leppert P.C.
      The pregnancy in polycystic ovary syndrome study: Baseline characteristics of the randomized cohort including racial effects.
      ). Differences were reported even within various Caucasian populations. Whereas serum testosterone, free testosterone and DHEAS concentrations were lower, serum androstenedione measures were higher in Icelandic Caucasian women with PCOS when compared with Boston Caucasian women with PCOS (
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ).

       Menstrual disturbances

      The data regarding menstrual disturbances among various ethnic populations are summarized in Table 2. There were only seven studies that compared menstrual patterns in women with PCOS in different ethnic groups. Generally, no differences were noted (
      • Hashimoto D.M.
      • Schmid J.
      • Martins F.M.
      • Fonseca A.M.
      • Andrade L.H.
      • Kirchengast S.
      • Eggers S.
      The impact of the weight status on subjective symptomatology of the polycystic ovary syndrome: A cross-cultural comparison between brazilian and austrian women.
      ;
      • Hillman J.K.
      • Johnson L.N.
      • Limaye M.
      • Feldman R.A.
      • Sammel M.
      • Dokras A.
      Black women with polycystic ovary syndrome (pcos) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with pcos [corrected].
      ;
      • Mani H.
      • Davies M.J.
      • Bodicoat D.H.
      • Levy M.J.
      • Gray L.J.
      • Howlett T.A.
      • Khunti K.
      Clinical characteristics of polycystic ovary syndrome: Investigating differences in white and south asian women.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ). However, Wijeyaratne and colleagues showed that menstrual irregularities tended to be seen at earlier ages in saPCOS (
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ). Furthermore, two studies indicated that, compared with wPCOS, the prevalence of menstrual disturbance was higher in eaPCOS (
      • Guo M.
      • Chen Z.J.
      • Eijkemans M.J.
      • Goverde A.J.
      • Fauser B.C.
      • Macklon N.S.
      Comparison of the phenotype of chinese versus dutch caucasian women presenting with polycystic ovary syndrome and oligo/amenorrhoea.
      ;
      • Wang E.T.
      • Kao C.N.
      • Shinkai K.
      • Pasch L.
      • Cedars M.I.
      • Huddleston H.G.
      Phenotypic comparison of caucasian and asian women with polycystic ovary syndrome: A cross-sectional study.
      ).
      Table 2Comparison of menstrual disturbances between various ethnic groups
      Study (first author, year)DCStudy populationAge (years) mean± SD, mean or medianCriteriaComments
      Wijeyaratne (2002)ns47 South Asian

      40 Caucasian

      11 South Asian control

      22 Caucasian control
      26 ± 4

      30.1 ± 5

      31.3 ± 2

      32.9 ± 3
      Menstrual disturbance: cycle length >35 days and lack of ovulationAge at menarche and number of periods per year were similar (∼13 years and ∼5 periods/year, respectively)

      Menstrual irregularity tended to be seen in earlier ages in South Asian women (16.2 versus 18.4 years)
      • Hashimoto D.M.
      • Schmid J.
      • Martins F.M.
      • Fonseca A.M.
      • Andrade L.H.
      • Kirchengast S.
      • Eggers S.
      The impact of the weight status on subjective symptomatology of the polycystic ovary syndrome: A cross-cultural comparison between brazilian and austrian women.
      NIH102 Brazilian (predominantly Black)

      31 Austrian
      25.5 ± 3.9

      23.8 ± 4.7
      Menstrual disturbance frequencies were similar (∼70%) but had a greater impact on quality of life in Brazilian women
      Guo (2012)R547 Chinese

      427 Dutch
      28.3 ± 3.4

      29.0 ± 5.2
      Oligomenorrhoea: cycles between 35 and182 days

      Amenorrhoea: cycles ≥182 days
      Chinese women presented more often with amenorrhoea (75% versus 27%)
      Wang (2013)R121 Caucasian

      28 Asian
      28.0 ± 5.4

      29.6 ± 5.9
      Oligomenorrhoea was more frequent in Asian women
      Hilman (2014)R413 non-Hispanic White

      106 non-Hispanic Black
      25.0 ± 6.7

      26.3 ± 7.3
      Menstrual disturbance: 9 or fewer menses/yearMenses per year were similar (∼4 ± 3 menses/year)
      Mani (2015)ns929 White

      381 South Asian
      27.1 ± 7.4

      24.3 ± 6.7
      Oligomenorrhoea: 9 or fewer menses/year

      Amenorrhoea: not specifically stated
      Whereas oligomenorrhoea was more common in South Asian women, the percentage of women with amenorrhoea was higher in White women even though the menstrual disturbance rate was similar
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      R184 American White

      100 American Black

      220 Indian

      233 Brazilian

      94 Finnish

      258 Norwegian
      29

      29

      25

      26

      33

      28.5
      Oligomenorrhoea: intermenstrual interval of >35days and <8 menstrual bleeds/year

      Amenorrhoea: absent menstrual bleeding in the past 90 days
      The frequency of oligomenorrhoea/amenorrhoea was similar
      DC, Diagnostic criteria; NIH, National Institutes of Health criteria; ns, not specified; R, Rotterdam criteria.

       PCOM

      In 10 studies, ovarian morphology was compared between different ethnic groups. The data regarding ovarian morphology among various ethnic populations are summarized in Table 3. Despite the selection of different criteria to determine PCOM and PCOS, in most studies there was no difference between ethnic groups in terms of ovarian morphology. Although eaPCOS had a lower ovarian volume and follicle count, the prevalence of PCOM did not differ (
      • Legro R.S.
      • Kunselman A.R.
      • Dodson W.C.
      • Dunaif A.
      Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: A prospective, controlled study in 254 affected women.
      ;
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ). However, Wang and co-workers determined no difference between eaPCOS and wPCOS in ovarian volume and follicle number (
      • Wang E.T.
      • Kao C.N.
      • Shinkai K.
      • Pasch L.
      • Cedars M.I.
      • Huddleston H.G.
      Phenotypic comparison of caucasian and asian women with polycystic ovary syndrome: A cross-sectional study.
      ). Interestingly, the frequency of PCOM, ovarian volume and follicle number differed in various Caucasian populations. Icelandic subjects with PCOS had smaller ovaries and fewer follicles (although the frequency of PCOM was similar) and the prevalence of PCOM was higher in Norwegian and Finnish women with PCOS when compared with American White participants (
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ). In the only study that compared the prevalence of PCOM between wPCOS and mePCOS, Glintborg and colleagues found a higher frequency of PCOM in Caucasians (
      • Glintborg D.
      • Mumm H.
      • Hougaard D.
      • Ravn P.
      • Andersen M.
      Ethnic differences in rotterdam criteria and metabolic risk factors in a multiethnic group of women with pcos studied in denmark.
      ).
      Table 3Comparison of ovarian morphology between various ethnic groups
      Study (first author, year)DCStudy populationAge (years)PCO criteriaPercentage of PCOS women with PCOComments
      Carmina (1992)NIH25 Hispanic American

      25 Japanese

      25 Italian

      For each ethnic group 10 age-matched controls
      30 ± 2

      24 ± 1

      24 ± 1
      10 or more cysts 2–8 mm in diameter arranged either peripherally around a dense core of stroma or scattered throughout an increased amount of stromaHispanic American 80%

      Japanese 68%

      Italian 76%
      Similar frequency of PCO (∼75%)
      Wijeyaratne (2002)ns47 South Asian

      40 Caucasian

      11 South Asian control

      22 Caucasian control
      26 ± 4

      30.1 ± 5

      31.3 ± 2

      32.9 ± 3
      10 or more cysts 2–8 mm in diameter with a thickened echo dense stromaMean ovarian volumes were comparable (∼12 ml)
      Legro (2006)NIH435 Caucasian

      109 African American

      17 Asian

      72 American Indian or Alaska Native
      28.2 ± 3.9

      27.9 ± 4.3

      30.4 ± 3.0

      27.6 ± 4.1
      Multiple cysts (≥10) of 2–8 mm in diameter distributed evenly around the ovarian periphery with an increased amount of stroma, or multiple small cysts 2–4 mm in diameter distributed throughout abundant stromaCaucasian 89.4%

      African American 97.2%

      Asian 100%

      American Indian or Alaska Native 100%

      Mean right ovarian volume (ml):

      Caucasian 12.1 ± 6.7

      African American 13.4 ± 9.2

      Asian 10.9 ± 5.5

      American Indian or Alaska Native 10.1 ± 4.3

      Mean left ovarian volume (ml):

      Caucasian 11.6 ± 6.7

      African American 11.3 ± 6.1

      Asian 7.7 ± 5.3

      American Indian or Alaska Native 8.7 ± 4.3
      PCO was less frequent in Caucasian women with PCOS

      Asians and Native Americans had lower ovarian volumes

      Right and left ovary volumes were different
      Welt (2006)NIH105 Iceland Caucasian

      172 Boston Caucasian

      44 Boston African American

      25 Boston Hispanic

      21 Boston Asian

      32 Iceland controls
      30.2 ± 6.2

      28.8 ± 5.5

      28.4 ± 6.7

      26.3 ± 5.2

      25.5 ± 5.3

      32.2 ± 5.5
      Presence of ≥12 follicles in each ovary measuring 2–9 mm in diameter, and/or increased ovarian volume (>10 ml)Iceland Caucasian 92.5%

      Boston Caucasian 99.3%

      Boston African American 97.4%

      Boston Hispanic 95.0%

      Boston Asian 100%

      Maximum ovarian volume (ml):

      Iceland Caucasian 12.2 ± 5.6

      Boston Caucasian 15.8 ± 7.2

      Boston African American 18.2 ± 7.4

      Boston Hispanic 14.4 ± 4.4

      Boston Asian 13.3 ± 3.8

      Maximum follicle no (count):

      Iceland Caucasian 11.6 ± 3.9

      Boston Caucasian 14.5 ± 3.8

      Boston African American 14.8 ± 4.6

      Boston Hispanic 13.7 ± 3.8

      Boston Asian 12.0 ± 2.9
      When compared with Boston Caucasian subjects, Icelandic women with PCOS had smaller ovaries and fewer follicles but the frequency of PCO was similar

      Ovarian volume and follicle number were lower in Asian women
      Glintborg (2010)R784 Caucasian

      190 Middle Eastern
      32

      25
      10 or more cysts 2–8 mm in diameter with a thickened echo-dense stromaCaucasian 47%

      Middle Eastern 29%
      PCO was less frequent in Middle Eastern patients
      Ladson (2011)NIH43 Black

      77 White

      87 Black control

      35 White control
      27.9 ± 5.0

      26.0 ± 6.9

      Age not specified
      Left and right ovarian volumes were comparable
      Guo (2012)R547 Chinese

      427 Dutch
      28.3 ± 3.4

      29.0 ± 5.2
      Presence of ≥12 follicles in each ovary measuring 2–9 mm in diameter, and/or increased ovarian volume (>10 ml)The prevalence of PCO did not differ
      Wang (2013)R121 Caucasian

      28 Asian
      28.0 ± 5.4

      29.6 ± 5.9
      Presence of ≥12 follicles in each ovary measuring 2–9 mm in diameter, and/or increased ovarian volume (>10 ml)Percentage of PCOS women with antral follicle count ≥12:

      Caucasian 85.1%

      Asian 82.1%

      Percentage of PCOS women with ovarian volume ≥10 ml:

      Caucasian 44.6%

      Asian 50.0%
      Both groups had similar ovarian morphology
      Chan (2017)R184 American White

      100 American Black

      220 Indian

      233 Brazilian

      94 Finnish

      258 Norwegian
      29

      29

      25

      26

      33

      28.5
      Presence of ≥12 follicles in each ovary measuring 2–9 mm in diameter, and/or increased ovarian volume (>10 ml)American White 68.5%

      American Black 76%

      Indian 78.6%

      Brazilian 67.4%

      Finnish 100%

      Norwegian 90.3%
      When compared with American White patients with PCOS, the prevalence of PCO was higher in Indian, Finnish and Norwegian participants
      • Engmann L.
      • Jin S.
      • Sun F.
      • Legro R.S.
      • Polotsky A.J.
      • Hansen K.R.
      • Coutifaris C.
      • Diamond M.P.
      • Eisenberg E.
      • Zhang H.
      • Santoro N.
      Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.
      R476 non-Hispanic White

      98 non-Hispanic Black

      128 Hispanic American
      28.8 ± 4.2

      28.7 ± 4.9

      29.2 ± 4.1
      Presence of ≥12 follicles in each ovary measuring 2–9 mm in diameter, and/or increased ovarian volume (>10 ml)Non-Hispanic White 99.4%

      Non-Hispanic Black 99.0%

      Hispanic American 100%
      Frequency of PCO, mean right ovarian volume and mean left ovarian volume were comparable
      Age: values are mean ± SD, mean or median.
      DC: diagnostic criteria; NIH, National Institutes of Health criteria; ns, not specified; PCO, polycystic ovarian morphology; PCOS, polycystic ovary syndrome; R, Rotterdam criteria.

       Metabolic and cardiovascular comorbidities

      Thirty studies evaluated and compared the metabolic and cardiovascular properties of individuals with PCOS belonging to different ethnicities. There was wide variability in the metabolic and cardiovascular comorbidities between different ethnic groups (Table 4). When compared with wPCOS, hPCOS and bPCOS were more obese. saPCOS and eaPCOS had lower BMI measures (
      • Carmina E.
      • Koyama T.
      • Chang L.
      • Stanczyk F.Z.
      • Lobo R.A.
      Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome?.
      ;
      • Williamson K.
      • Gunn A.J.
      • Johnson N.
      • Milsom S.R.
      The impact of ethnicity on the presentation of polycystic ovarian syndrome.
      ;
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ;
      • Wijeyaratne C.N.
      • Nirantharakumar K.
      • Balen A.H.
      • Barth J.H.
      • Sheriff R.
      • Belchetz P.E.
      Plasma homocysteine in polycystic ovary syndrome: Does it correlate with insulin resistance and ethnicity?.
      ;
      • Al-Fozan H.
      • Al-Futaisi A.
      • Morris D.
      • Tulandi T.
      Insulin responses to the oral glucose tolerance test in women of different ethnicity with polycystic ovary syndrome.
      ;
      • Legro R.S.
      • Myers E.R.
      • Barnhart H.X.
      • Carson S.A.
      • Diamond M.P.
      • Carr B.R.
      • Schlaff W.D.
      • Coutifaris C.
      • Mcgovern P.G.
      • Cataldo N.A.
      • Steinkampf M.P.
      • Nestler J.E.
      • Gosman G.
      • Guidice L.C.
      • Leppert P.C.
      The pregnancy in polycystic ovary syndrome study: Baseline characteristics of the randomized cohort including racial effects.
      ;
      • Lo J.C.
      • Feigenbaum S.L.
      • Yang J.
      • Pressman A.R.
      • Selby J.V.
      • Go A.S.
      Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome.
      ;
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ;
      • Koval K.W.
      • Setji T.L.
      • Reyes E.
      • Brown A.J.
      Higher high-density lipoprotein cholesterol in african-american women with polycystic ovary syndrome compared with caucasian counterparts.
      ;
      • Ladson G.
      • Dodson W.C.
      • Sweet S.D.
      • Archibong A.E.
      • Kunselman A.R.
      • Demers L.M.
      • Williams N.I.
      • Coney P.
      • Legro R.S.
      Racial influence on the polycystic ovary syndrome phenotype: A black and white case-control study.
      ;
      • Guo M.
      • Chen Z.J.
      • Eijkemans M.J.
      • Goverde A.J.
      • Fauser B.C.
      • Macklon N.S.
      Comparison of the phenotype of chinese versus dutch caucasian women presenting with polycystic ovary syndrome and oligo/amenorrhoea.
      ;
      • Hillman J.K.
      • Johnson L.N.
      • Limaye M.
      • Feldman R.A.
      • Sammel M.
      • Dokras A.
      Black women with polycystic ovary syndrome (pcos) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with pcos [corrected].
      ;
      • Mani H.
      • Davies M.J.
      • Bodicoat D.H.
      • Levy M.J.
      • Gray L.J.
      • Howlett T.A.
      • Khunti K.
      Clinical characteristics of polycystic ovary syndrome: Investigating differences in white and south asian women.
      ;
      • Chang A.Y.
      • Oshiro J.
      • Ayers C.
      • Auchus R.J.
      Influence of race/ethnicity on cardiovascular risk factors in polycystic ovary syndrome, the dallas heart study.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ;
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      ). However, WHR, an indicator of central adiposity, was higher in saPCOS and eaPCOS (
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ;
      • Wijeyaratne C.N.
      • Nirantharakumar K.
      • Balen A.H.
      • Barth J.H.
      • Sheriff R.
      • Belchetz P.E.
      Plasma homocysteine in polycystic ovary syndrome: Does it correlate with insulin resistance and ethnicity?.
      ;
      • Guo M.
      • Chen Z.J.
      • Eijkemans M.J.
      • Goverde A.J.
      • Fauser B.C.
      • Macklon N.S.
      Comparison of the phenotype of chinese versus dutch caucasian women presenting with polycystic ovary syndrome and oligo/amenorrhoea.
      ). mePCOS had similar or lower BMI values compared with wPCOS (
      • Al-Fozan H.
      • Al-Futaisi A.
      • Morris D.
      • Tulandi T.
      Insulin responses to the oral glucose tolerance test in women of different ethnicity with polycystic ovary syndrome.
      ;
      • Glintborg D.
      • Mumm H.
      • Hougaard D.
      • Ravn P.
      • Andersen M.
      Ethnic differences in rotterdam criteria and metabolic risk factors in a multiethnic group of women with pcos studied in denmark.
      ). The results were contradictory in terms of obesity among various Caucasian populations. While Northern Europeans had a similar BMI to American White participants, Southern Europeans were leaner (
      • Carmina E.
      • Legro R.S.
      • Stamets K.
      • Lowell J.
      • Lobo R.A.
      Difference in body weight between american and italian women with polycystic ovary syndrome: Influence of the diet.
      ;
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ;
      • Essah P.A.
      • Nestler J.E.
      • Carmina E.
      Differences in dyslipidemia between american and italian women with polycystic ovary syndrome.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ).
      Table 4Comparison of metabolic and cardiovascular risk factors between various ethnic groups
      Study (first author, year)DCStudy populationAge (years)ObesityIR/prediabetes/diabetesAcanthosis nigricansDyslipidaemiaHypertensionComments
      Carmina (1992)NIH25 Hispanic American

      25 Japanese

      25 Italian

      For each ethnic group 10 age-matched controls
      30 ± 2

      24 ± 1

      24 ± 1
      Percentage of ideal body weight:

      Hispanic American 122%

      Japanese 111%

      Italian ns
      FIC were lower in Japanese

      Similar IR
      Hispanic patients were more obese

      FIC were lower in Japanese women

      Despite lower weight in Japanese women, all groups were similar in terms of IR
      Dunaif (1993)NIH13 Caribbean Hispanic

      10 non-Hispanic White

      5 Caribbean Hispanic control

      8 non-Hispanic White control
      25.1 ± 1

      27 ± 2

      28 ± 2

      27 ± 1
      mBMI:

      Hispanic 35.6 ± 1.5

      White 37.1 ± 1.8
      In the euglyaemic clamp test, Caribbean Hispanic women had lower IS than non-Hispanic White womenIn an age-, weight- and body composition-matched cohort, Caribbean Hispanic patients were more insulin resistant
      Norman (1995)NIH11 Indian

      11 White

      11 Indian control

      11 White control
      ∼25

      Age was similar for all groups
      In an age- and BMI-matched cohort, Indian PCOS patients had higher insulin responses than White patients on an OGTT
      Ehrmann (1999)NIH63 Caucasian

      44 African American

      10 Asian

      5 Hispanic
      nsFrequency of IGT or type 2 DM:

      Caucasian 41%

      African American 50%

      Asian 40%

      Hispanic 50%
      The study was not specifically designed to assess ethnic differences

      Numbers of Asian and Hispanic participants were low

      African Americans had a slight preponderance of type 2 DM

      No difference between ethnicities in terms of glucose tolerance
      Williamson (2001)ns112 White

      16 Maori

      15 Pacific Islander

      19 Indian

      4 Asian

      6 other

      There was an inconsistency between number and percentage of PCOS patients
      27.4mBMI:

      White 27.5 ± 6.6

      Maori 32.3 ± 4.3

      Pacific Islander 34.0 ± 6.0

      Indian 28.7 ± 7.4

      Asian+other 24.3 ± 4.6
      FIC were higher in Maori and Pacific IslanderMaori and Pacific Islander women had higher TG and lower HDL concentrationsSBP and DBP were similarMaori and Pacific Islander women had the worst metabolic profile while Asian women had a mild metabolic phenotype
      Kauffman (2002)NIH48 White

      26 Mexican American

      11 White control

      8 Mexican American control
      ∼26
      In this study age was not reported for whole PCOS cohort; however the mean age of White and Mexican American participants with PCOS was approximately 26 years. White healthy control participants were older than Mexican American healthy controls. AUC, area under the curve; BMI, body mass index (kg/m2); DBP, diastolic blood pressure; DC, diagnostic criteria; DM, diabetes mellitus; FIC, fasting insulin concentration; FPG, fasting plasma glucose; HbA1c, glycated haemoglobin; HDL, high-density lipoprotein; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance; HT, hypertension; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; IR, insulin resistance; IS, insulin sensitivity; LDL, low-density lipoprotein; mBMI, mean body mass index (kg/m2); mDBP, mean diastolic blood pressure; mSBP, mean systolic blood pressure; NIH, National Institutes of Health criteria; ns, not specified; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; QUICKI, quantitative insulin sensitivity check index; R, Rotterdam criteria; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; WHR, waist–hip ratio.


      ∼30

      25
      mBMI was higher in insulin-resistant Mexican American women with PCOS (40 versus 36)FIC and HOMA-IR measures were higher in Mexican American women while glucose/insulin ratios were lower

      IR White 43.8%

      IR Mexican American 73.1%
      After adjustment for BMI, Mexican American women still had higher FIC and HOMA-IR values but lower glucose/insulin ratios

      These ethnic difference were negligible at BMI values of ≤24

      Ethnicity influenced the normative values of IR screening
      Wijeyaratne (2002)ns47 South Asian

      40 Caucasian

      11 South Asian control

      22 Caucasian control
      26 ± 4

      30.1 ± 5

      31.3 ± 2

      32.9 ± 3
      mBMI:

      South Asian 30.6 ± 7.5

      Caucasian 32.1 ± 5.9

      WHR:

      South Asian 1.04 ± 0.02

      Caucasian 0.92 ± 0.01
      FIC in South Asian patients were higher

      IS calculated by the QUICKI method was lower in South Asians
      South Asian 55%

      Caucasian 7%
      Serum TC, TC/HDL and TG concentrations were similarAfter adjustment for age, SBP and DBP were higher in CaucasiansDespite similar BMI and WHR, South Asians had lower IS than Caucasians

      Almost half of the South Asian women with PCOS had acanthosis nigricans
      Carmina (2003)NIH20 non-Hispanic White American

      20 Italian
      29 ± 2

      26.6 ± 2
      mBMI:

      White American 40.3 ± 1

      Italian 29.7 ± 1

      WHR:

      White American 0.85 ± 0.02

      Italian 0.83 ± 0.04
      FIC were higher in Americans

      American women had lower glucose/insulin ratios
      TC and LDL were comparable

      Serum TG concentrations were higher in American women while HDL concentrations were lower
      SBP and DBP were similarAfter adjustment for BMI, American women still had a worse metabolic profile

      Consumption of saturated fat was higher in Americans
      • Hashimoto D.M.
      • Schmid J.
      • Martins F.M.
      • Fonseca A.M.
      • Andrade L.H.
      • Kirchengast S.
      • Eggers S.
      The impact of the weight status on subjective symptomatology of the polycystic ovary syndrome: A cross-cultural comparison between brazilian and austrian women.
      NIH102 Brazilian (predominantly Black)

      31 Austrian
      25.5 ± 3.923.8 ± 4.7mBMI:

      Brazilian 27.5 ± 6.6

      Austrian 23.7 ± 4.3
      Austrian PCOS patients were leaner but obesity had a greater impact on the quality of life in Austrians
      Wijeyaratne (2004)ns74 Sri Lankan

      47 British Asian

      40 White

      45 Sri Lankan control

      11 British Asian control

      22 White control
      27.3 ± 1.7

      26 ± 4

      30.1 ± 0.5

      33 ± 4.7

      31.3 ± 2

      32.8 ± 3
      mBMI:

      Sri Lankan 26.3 ± 0.9

      British Asian 30.6 ± 7.5

      White 32.1 ± 5.9

      WHR:

      Sri Lankan 0.97 ± 0.01

      British Asian 1.04 ± 0.02

      White 0.92 ± 0.01
      Sri Lankan women with PCOS had higher FPG and FIC but lower IS assessed by QUICKITC and TG concentrations were higher in Sri Lankan patientsSouth Asian women were younger

      Sri Lankan women had lower BMI

      Sri Lankan women had the highest homocysteine concentrations

      Despite lower BMI and comparable WHR, Sri Lankan women had a worse metabolic profile

      Sri Lankan women with PCOS may have increased cardiovascular disease risk compared with their White counterparts
      • Al-Fozan H.
      • Al-Futaisi A.
      • Morris D.
      • Tulandi T.
      Insulin responses to the oral glucose tolerance test in women of different ethnicity with polycystic ovary syndrome.
      ns41 Western European

      18 Middle Eastern

      15 African American

      9 East Indian

      9 South American
      33.3 ± 5.7

      32.1 ± 4.9

      33.8 ± 6.6

      34.2 ± 4.8

      28.8 ± 4.3
      mBMI:

      Western European 30.2 ± 4.5

      Middle Eastern 31.4 ± 5.0

      African American 29.9 ± 4.8

      East Indian 27.3 ± 5.5

      South American 28.8 ± 4.3
      Middle Eastern women had higher glucose and insulin concentrations than Western European womenIndependent of BMI, Middle Eastern women had worse glucose tolerance than Western Europeans
      Ehrmann (2005)NIH303 White

      51 Black

      38 Other
      28.8 ± 0.3

      27.6 ± 0.8

      26.7 ± 0.9
      mBMI:

      White 36.3 ± 0.5

      Black 37.1 ± 1.2

      Other 32.6 ± 1.1

      WHR:

      White 0.87 ± 0.01

      Black 0.91 ± 0.01

      Other 0.88 ± 0.01
      Black women had higher FIC, higher HbA1c and were more IR by HOMA-IRBlack women with PCOS were more IR
      Kumar (2005)NIH186 White

      27 Black

      94 White control

      88 Black control
      27.3 ± 6.6

      28.7 ± 6.2

      28.7 ± 9.1

      30.2 ± 9.1
      mBMI:

      White 36.0 ± 9.3

      Black 36.0 ± 8.9

      WHR:

      White 0.84 ± 0.08

      Black 0.84 ± 0.10
      FIC and FPG were similarNo differences in terms of carbohydrate metabolism
      Kauffman (2006)R111 White

      50 Mexican American
      27.3

      26.9
      mBMI:

      White 33.7

      Mexican American 35.4
      FPG concentrations were similar

      Mexican American patients had higher FIC and were higher IR
      Mexican American patients had a worse metabolic profile
      Legro (2006)NIH435 Caucasian

      109 African American

      17 Asian

      72 American Indian or Alaska Native
      28.2 ± 3.9

      27.9 ± 4.3

      30.4 ± 3.0

      27.6 ± 4.1
      mBMI:

      Caucasian 35.4 ± 8.8

      African American 36.0 ± 8.4

      Asian 29.1 ± 6.3

      American Indian or Alaska Native 34.3 ± 8.0
      Glucose/insulin ratios were lowest in Asian women, and Asian women tended to have more normal HOMA-IR valuesmSBP:

      Caucasian 122.2 ± 13.7

      African American 123.6 ± 12.6

      Asian 111.4 ± 9.1

      American Indian or Alaska Native 122.5 ± 15.0

      mDBP:

      Caucasian 77.6 ± 9.9

      African American 76.8 ± 10.5

      Asian 73.1 ± 6.8

      American Indian or Alaska Native 74.4 ± 9.2
      Asian women with PCOS tended to be older and lighter

      After adjustment for weight, blood pressures were similar

      Asian women had a better metabolic profile
      Lo (2006)ns3778 White

      552 Black

      1117 Asian

      1324 Hispanic

      432 other
      32.6 ± 7.4

      31.7 ± 7.9

      32.2 ± 6.4

      30.8 ± 6.7

      31.7 ± 6.5
      BMI ≥30:

      White 67.5%

      Black 80.3%

      Asian 45.1%

      Hispanic 73.8%

      Other 68.9%
      DM:

      White 9.5%

      Black 8.9%

      Asian 11.9%

      Hispanic 11.9%

      Other 13.9%
      HT:

      White 13.9%

      Black 21.7%

      Asian 14.2%

      Hispanic 12.2%

      Other 13.9%
      Asian women with PCOS had the lowest BMI

      Black and Hispanic women were more obese

      After adjustment for BMI and age, Asian and Hispanic women had an increased risk of DM

      After adjustment for BMI, age and DM status, Black women had an increased risk of HT
      Welt (2006)NIH105 Iceland Caucasian

      172 Boston Caucasian

      44 Boston African American

      25 Boston Hispanic

      21 Boston Asian

      32 Iceland controls
      30.2 ± 6.2

      28.8 ± 5.5

      28.4 ± 6.7

      26.3 ± 5.2

      25.5 ± 5.3

      32.2 ± 5.5
      mBMI:

      Iceland Caucasian 31.5 ± 7.7

      Boston Caucasian 30.7 ± 9.2

      Boston African American 36.3 ± 7.9

      Boston Hispanic 32.3 ± 10.3

      Boston Asian 26.3 ± 5.9
      DM:

      Iceland Caucasian na

      Boston Caucasian 2%

      Boston African American 11.9%

      Boston Hispanic 4.3%

      Boston Asian 0%

      FIC and HOMA-IR measures were higher in African American and Hispanic women
      Iceland Caucasian 47.4%

      Boston Caucasian 62.9%

      Boston African American 76.7%

      Boston Hispanic 69.6%

      Boston Asian 70%
      TC, LDL and TG concentrations were comparable across all ethnic groups but HDL concentrations were lower in Icelandic CaucasiansmSBP of Icelandic PCOS subjects was higherAfrican American women had the highest BMI and Asian women had the lowest BMI

      African American and Hispanic participants had a worse metabolic profile

      The percentage of participants with acanthosis nigricans was lower in Icelandic Caucasians
      Essah (2008)NIH106 American (92% White)

      108 Italian
      29.9 ± 7.5

      24.7 ± 5.2
      mBMI:

      American 36.1 ± 8.6

      Italian 28.1 ± 5.8

      BMI >30:

      American 73.6%

      Italian 30.6%
      While HDL concentrations were lower, TC, LDL and TG concentrations were higher in American womenmSBP of Italian PCOS patients was higherAfter adjustment for BMI and age, serum TG concentrations remained higher in American participants
      Glintborg (2010)R784 Caucasian

      190 Middle Eastern
      32

      25
      mBMI:

      Caucasian 27.0

      Middle Eastern 25.7
      Middle Eastern women had higher FIC

      Middle Eastern PCOS patients had higher 2 h glucose and AUC insulin during OGTT
      After adjustment for BMI and age, lipid profiles were comparablemSBP and mDBP were higher in Caucasian women even after correcting for BMI and ageWhen compared with Middle Eastern women, Caucasian women with PCOS had higher IS but an increased cardiovascular disease risk
      Koval (2010)NIH94 Caucasian

      32 African American
      30.5 ± 6.8

      30.6 ± 7.6
      mBMI:

      Caucasian 37.0 ± 7.1

      African American 41.0 ± 9.6
      After adjustment for BMI, age and HOMA-IR, African American women had higher HDL, lower TG and non-HDL cholesterolAfrican American women with PCOS had a more favourable lipid profile
      Kauffman (2011)R120 White

      71 Mexican American
      27.4

      26.8
      mBMI:

      White 34.8

      Mexican American 34.3
      HOMA-IR, 2 h insulin concentrations and AUC insulin during OGTT

      were higher in Mexican American participants with PCOS

      Matsuda and Strumvoll IS index values were higher in Whites
      TC, TG, HDL, LDL and non-HDL cholesterol concentrations were similarIn an age- and BMI-matched cohort, Mexican American women had higher IR but lipid concentrations were similar
      Ladson (2011)NIH43 Black

      77 White

      87 Black control

      35 White control
      27.9 ± 5.0

      26.0 ± 6.9

      Age not specified
      mBMI:

      Black 39.0 ± 9.3

      White 37.7 ± 6.3

      WHR:

      Black 0.88 ± 0.08

      White 0.88 ± 0.06
      FIC and HOMA-IR values were higher in Black participantsBlack women with PCOS had higher HDL and lower TG concentrationsmSBP and mDBP were comparableLipid profile was more favourable in Black women with PCOS
      Guo (2012)R547 Chinese

      427 Dutch
      28.3 ± 3.4

      29.0 ± 5.2
      mBMI:

      Chinese 25.3 ± 4.3

      Dutch 26.3 ± 6.9

      WHR:

      Chinese 0.85 ± 0.06

      Dutch 0.82 ± 0.08
      FPG was lower but FIC were higher in Chinese

      HOMA-IR values were similar
      TC and TG concentrations were similar

      Chinese participants had higher LDL and lower non-HDL cholesterol concentrations
      mSBP and mDBP were higher in Dutch womenAlthough mBMI values of Chinese women were lower, WHR of Chinese women was higher

      Chinese women were more prone to central obesity
      Wang (2013)R121 Caucasian

      28 Asian
      28.0 ± 5.4

      29.6 ± 5.9
      mBMI:

      Caucasian 30.4 ± 8.1

      Asian 30.1 ± 7.4
      FPG, 2 h glucose concentrations and FIC were similarTC, TG, HDL and LDL concentrations were similarGroups were similar in terms of metabolic profile
      Hilman (2014)R413 non-Hispanic White

      106 non-Hispanic Black
      25.0 ± 6.7

      26.3 ± 7.3
      BMI >30:

      White 47%

      Black 72.3%
      FIC and FPG were higher in Black womenTC, TG and HDL concentrations were lower in Black womenmSBP and mDBP were higher in Black womenBlack women were more obese and had higher IR, had higher blood pressure values

      Despite the relatively favourable lipid profile, Black individuals with PCOS had a higher prevalence of metabolic syndrome and 10-year cardiovascular disease risk

      After adjustment for age and BMI, Black women had low HDL and high glucose concentrations
      Mani (2015)ns929 White

      381 South Asian
      27.1 ± 7.4

      24.3 ± 6.7
      mBMI:

      White 31.5 ± 7.9

      South Asian 29.3 ± 6.8
      DM:

      White 5.6%

      South Asian 8.1%
      White 3.1%

      South Asian 16.8%
      mSBP and mDBP were higher in White womenSouth Asian women presented at earlier ages

      Despite lower BMI, acanthosis nigricans and DM were more common in South Asian women
      • Chang A.Y.
      • Oshiro J.
      • Ayers C.
      • Auchus R.J.
      Influence of race/ethnicity on cardiovascular risk factors in polycystic ovary syndrome, the dallas heart study.
      R62 Black

      32 White

      23 Hispanic

      113 Black control

      54 White control

      37 Hispanic control
      41

      41

      39

      40

      40

      39
      mBMI:

      Black 32.3

      White 28.2

      Hispanic 31.7

      WHR:

      Black 0.87

      White 0.83

      Hispanic 0.86
      FIC were lower in White women with PCOS even after adjustment for BMI

      Hispanic women had a higher frequency of IFG
      Prevalence of hypertriglyceridaemia was higher in White women

      TC concentrations were lower in Black women
      mSBP and the prevalence of HT were higher in Black individualsBlack and Hispanic women were more obese

      Black women had higher FIC

      Hypertension was more common in Black women

      Hispanic women had a higher frequency of IFG

      The lipid profile of Black women was more favourable

      Ethnicity influences cardiovascular risk factors in both individuals with and without PCOS but no synergistic effect on cardiovascular risk factors that varied by ethnicity was noted
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      R184 American White

      100 American Black

      220 Indian

      233 Brazilian

      94 Finnish

      258 Norwegian
      29

      29

      25

      26

      33

      28.5
      Median BMI:

      American White 30.6

      American Black 37.5

      Indian 26.7

      Brazilian 29.3

      Finnish 29.4

      Norwegian 31.1
      Despite lower BMI, FPG concentrations were highest in Indian participantsWhen compared with American White women with PCOS, Black women had lower and Indian women had higher TG concentrations

      HDL concentrations were lower both in Indian and Black women
      When compared with American White women with PCOS, Black participant had higher mSBP and mDBP

      mDBP was also higher in Brazilian, Finnish and Norwegian women with PCOS
      Black individuals had the highest rate of obesity

      The prevalence of metabolic syndrome was higher in Black (52%) and Norwegian (41.1%) women compared with American White women (28.3%)

      In an age- and BMI-adjusted analysis, Indian and Norwegian women had elevated odds of metabolic syndrome
      • Engmann L.
      • Jin S.
      • Sun F.
      • Legro R.S.
      • Polotsky A.J.
      • Hansen K.R.
      • Coutifaris C.
      • Diamond M.P.
      • Eisenberg E.
      • Zhang H.
      • Santoro N.
      Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.
      R476 non-Hispanic White

      98 non-Hispanic Black

      128 Hispanic American
      28.8 ± 4.2

      28.7 ± 4.9

      29.2 ± 4.1
      mBMI:

      non-Hispanic White 35.1 ± 9.8

      non-Hispanic Black 35.7 ± 7.9

      Hispanic American 36.4 ± 7.9
      FIC, FPG and HOMA-IR measures were higher in Hispanic participantsTG concentrations were highest in Hispanic and lowest in Black women

      LDL concentrations were comparable
      Black women had higher mSBPMetabolic syndrome was more prevalent in Hispanic women

      Despite the comparable BMI and waist circumference, Hispanic women had the most severe metabolic disturbance
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      R256 non-Hispanic American

      47 Hispanic American
      28.1

      28.5
      median BMI:

      non-Hispanic American 26.0

      Hispanic American 31.2
      HOMA-IR measures were higher in Hispanic womenNon-Hispanic American 34.3%

      Hispanic American 65.2%
      Whereas TG concentrations were higher, HDL concentrations were lower in Hispanic womenHispanic women had an unfavourable metabolic profile

      Non-alcoholic steatohepatitis was more common in Hispanic women, and Hispanic ethnicity was an independent risk factor for this in multivariate analysis
      Age: values are mean ± SD, mean or median.
      a In this study age was not reported for whole PCOS cohort; however the mean age of White and Mexican American participants with PCOS was approximately 26 years. White healthy control participants were older than Mexican American healthy controls.AUC, area under the curve; BMI, body mass index (kg/m2); DBP, diastolic blood pressure; DC, diagnostic criteria; DM, diabetes mellitus; FIC, fasting insulin concentration; FPG, fasting plasma glucose; HbA1c, glycated haemoglobin; HDL, high-density lipoprotein; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance; HT, hypertension; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; IR, insulin resistance; IS, insulin sensitivity; LDL, low-density lipoprotein; mBMI, mean body mass index (kg/m2); mDBP, mean diastolic blood pressure; mSBP, mean systolic blood pressure; NIH, National Institutes of Health criteria; ns, not specified; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; QUICKI, quantitative insulin sensitivity check index; R, Rotterdam criteria; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; WHR, waist–hip ratio.
      Considering glucose metabolism, when compared with wPCOS, hPCOS and bPCOS were more insulin resistant (
      • Dunaif A.
      • Sorbara L.
      • Delson R.
      • Green G.
      Ethnicity and polycystic ovary syndrome are associated with independent and additive decreases in insulin action in caribbean-hispanic women.
      ;
      • Kauffman R.P.
      • Baker V.M.
      • Dimarino P.
      • Gimpel T.
      • Castracane V.D.
      Polycystic ovarian syndrome and insulin resistance in white and mexican american women: A comparison of two distinct populations.
      ;
      • Ehrmann D.A.
      • Kasza K.
      • Azziz R.
      • Legro R.S.
      • Ghazzi M.N.
      Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome.
      ;
      • Kauffman R.P.
      • Baker V.M.
      • Dimarino P.
      • Castracane V.D.
      Hyperinsulinemia and circulating dehydroepiandrosterone sulfate in white and mexican american women with polycystic ovary syndrome.
      ;
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ;
      • Kauffman R.P.
      • Baker T.E.
      • Graves-Evenson K.
      • Baker V.M.
      • Castracane V.D.
      Lipoprotein profiles in mexican american and non-hispanic white women with polycystic ovary syndrome.
      ;
      • Ladson G.
      • Dodson W.C.
      • Sweet S.D.
      • Archibong A.E.
      • Kunselman A.R.
      • Demers L.M.
      • Williams N.I.
      • Coney P.
      • Legro R.S.
      Racial influence on the polycystic ovary syndrome phenotype: A black and white case-control study.
      ;
      • Hillman J.K.
      • Johnson L.N.
      • Limaye M.
      • Feldman R.A.
      • Sammel M.
      • Dokras A.
      Black women with polycystic ovary syndrome (pcos) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with pcos [corrected].
      ;
      • Engmann L.
      • Jin S.
      • Sun F.
      • Legro R.S.
      • Polotsky A.J.
      • Hansen K.R.
      • Coutifaris C.
      • Diamond M.P.
      • Eisenberg E.
      • Zhang H.
      • Santoro N.
      Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.
      ;
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      ). Moreover, Hispanic ethnicity was determined as an independent risk factor for non-alcoholic steatohepatitis (
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      ). Despite lower or comparable BMI values, saPCOS and mePCOS also had higher glucose concentrations in different settings (
      • Wijeyaratne C.N.
      • Nirantharakumar K.
      • Balen A.H.
      • Barth J.H.
      • Sheriff R.
      • Belchetz P.E.
      Plasma homocysteine in polycystic ovary syndrome: Does it correlate with insulin resistance and ethnicity?.
      ;
      • Al-Fozan H.
      • Al-Futaisi A.
      • Morris D.
      • Tulandi T.
      Insulin responses to the oral glucose tolerance test in women of different ethnicity with polycystic ovary syndrome.
      ;
      • Glintborg D.
      • Mumm H.
      • Hougaard D.
      • Ravn P.
      • Andersen M.
      Ethnic differences in rotterdam criteria and metabolic risk factors in a multiethnic group of women with pcos studied in denmark.
      ;
      • Mani H.
      • Davies M.J.
      • Bodicoat D.H.
      • Levy M.J.
      • Gray L.J.
      • Howlett T.A.
      • Khunti K.
      Clinical characteristics of polycystic ovary syndrome: Investigating differences in white and south asian women.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ). Conflicting results were available for eaPCOS. In general, eaPCOS were leaner but more prone to central adiposity. Three studies revealed no difference between eaPCOS and wPCOS. While Carmina and colleagues used the percentage ideal body weight for comparison, BMI values were measured in other studies (
      • Carmina E.
      • Koyama T.
      • Chang L.
      • Stanczyk F.Z.
      • Lobo R.A.
      Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome?.
      ;
      • Guo M.
      • Chen Z.J.
      • Eijkemans M.J.
      • Goverde A.J.
      • Fauser B.C.
      • Macklon N.S.
      Comparison of the phenotype of chinese versus dutch caucasian women presenting with polycystic ovary syndrome and oligo/amenorrhoea.
      ;
      • Wang E.T.
      • Kao C.N.
      • Shinkai K.
      • Pasch L.
      • Cedars M.I.
      • Huddleston H.G.
      Phenotypic comparison of caucasian and asian women with polycystic ovary syndrome: A cross-sectional study.
      ). In the study conducted by Legro and co-workers, it was shown that eaPCOS tended to have lower HOMA-IR measures (
      • Legro R.S.
      • Myers E.R.
      • Barnhart H.X.
      • Carson S.A.
      • Diamond M.P.
      • Carr B.R.
      • Schlaff W.D.
      • Coutifaris C.
      • Mcgovern P.G.
      • Cataldo N.A.
      • Steinkampf M.P.
      • Nestler J.E.
      • Gosman G.
      • Guidice L.C.
      • Leppert P.C.
      The pregnancy in polycystic ovary syndrome study: Baseline characteristics of the randomized cohort including racial effects.
      ). Nevertheless, in the largest study based on a health database review including 3778 wPCOS, 552 bPCOS, 1117 eaPCOS, 1324 hPCOS and 432 individuals with PCOS belonging to other ethnic groups, Lo and colleagues showed that, after adjustment for BMI and age, eaPCOS had an increased risk of diabetes mellitus (
      • Lo J.C.
      • Feigenbaum S.L.
      • Yang J.
      • Pressman A.R.
      • Selby J.V.
      • Go A.S.
      Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome.
      ). Four studies evaluating acanthosis nigricans reported that this finding was more common in ethnic populations that were more insulin resistant (hPCOS and saPCOS; Table 4) (
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ;
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ;
      • Mani H.
      • Davies M.J.
      • Bodicoat D.H.
      • Levy M.J.
      • Gray L.J.
      • Howlett T.A.
      • Khunti K.
      Clinical characteristics of polycystic ovary syndrome: Investigating differences in white and south asian women.
      ;
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      ).
      Seventeen studies evaluated lipids in different ethnic groups with PCOS. It was not the ethnicity but the fat mass (especially the central fat mass) that determined serum triglyceride and high-density lipoprotein (HDL) concentrations. In association with BMI or WHR, serum triglyceride concentrations were higher and serum HDL concentrations were lower in more obese (especially centrally obese) ethnic groups (
      • Williamson K.
      • Gunn A.J.
      • Johnson N.
      • Milsom S.R.
      The impact of ethnicity on the presentation of polycystic ovarian syndrome.
      ;
      • Carmina E.
      • Legro R.S.
      • Stamets K.
      • Lowell J.
      • Lobo R.A.
      Difference in body weight between american and italian women with polycystic ovary syndrome: Influence of the diet.
      ;
      • Wijeyaratne C.N.
      • Nirantharakumar K.
      • Balen A.H.
      • Barth J.H.
      • Sheriff R.
      • Belchetz P.E.
      Plasma homocysteine in polycystic ovary syndrome: Does it correlate with insulin resistance and ethnicity?.
      ;
      • Essah P.A.
      • Nestler J.E.
      • Carmina E.
      Differences in dyslipidemia between american and italian women with polycystic ovary syndrome.
      ;
      • Engmann L.
      • Jin S.
      • Sun F.
      • Legro R.S.
      • Polotsky A.J.
      • Hansen K.R.
      • Coutifaris C.
      • Diamond M.P.
      • Eisenberg E.
      • Zhang H.
      • Santoro N.
      Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.
      ;
      • Sarkar M.
      • Terrault N.
      • Duwaerts C.C.
      • Tien P.
      • Cedars M.I.
      • Huddleston H.
      The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome.
      ). Exceptionally, bPCOS had a more favourable lipid profile. In particular, serum triglyceride concentrations were lower in bPCOS. Moreover, bPCOS had higher HDL concentrations when compared with their White counterparts (
      • Koval K.W.
      • Setji T.L.
      • Reyes E.
      • Brown A.J.
      Higher high-density lipoprotein cholesterol in african-american women with polycystic ovary syndrome compared with caucasian counterparts.
      ;
      • Ladson G.
      • Dodson W.C.
      • Sweet S.D.
      • Archibong A.E.
      • Kunselman A.R.
      • Demers L.M.
      • Williams N.I.
      • Coney P.
      • Legro R.S.
      Racial influence on the polycystic ovary syndrome phenotype: A black and white case-control study.
      ). Conversely, Hilman and colleagues reported lower HDL concentrations in bPCOS even after adjusting for BMI and age (
      • Hillman J.K.
      • Johnson L.N.
      • Limaye M.
      • Feldman R.A.
      • Sammel M.
      • Dokras A.
      Black women with polycystic ovary syndrome (pcos) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with pcos [corrected].
      ) (Table 4).
      Although bPCOS had a low prevalence of dyslipidaemia, they presented with higher blood pressure. When compared with wPCOS, bPCOS had higher SBP and DBP values (
      • Lo J.C.
      • Feigenbaum S.L.
      • Yang J.
      • Pressman A.R.
      • Selby J.V.
      • Go A.S.
      Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome.
      ;
      • Hillman J.K.
      • Johnson L.N.
      • Limaye M.
      • Feldman R.A.
      • Sammel M.
      • Dokras A.
      Black women with polycystic ovary syndrome (pcos) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with pcos [corrected].
      ;
      • Chang A.Y.
      • Oshiro J.
      • Ayers C.
      • Auchus R.J.
      Influence of race/ethnicity on cardiovascular risk factors in polycystic ovary syndrome, the dallas heart study.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ). Blood pressure measurements were higher among European White women, followed by American White participants, with the values for other ethnic groups (saPCOS, mePCOS and eaPCOS) being lower than in White participants (
      • Wijeyaratne C.N.
      • Balen A.H.
      • Barth J.H.
      • Belchetz P.E.
      Clinical manifestations and insulin resistance (ir) in polycystic ovary syndrome (pcos) among south asians and caucasians: Is there a difference?.
      ;
      • Welt C.K.
      • Arason G.
      • Gudmundsson J.A.
      • Adams J.
      • Palsdottir H.
      • Gudlaugsdottir G.
      • Ingadottir G.
      • Crowley W.F.
      Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.
      ;
      • Essah P.A.
      • Nestler J.E.
      • Carmina E.
      Differences in dyslipidemia between american and italian women with polycystic ovary syndrome.
      ;
      • Glintborg D.
      • Mumm H.
      • Hougaard D.
      • Ravn P.
      • Andersen M.
      Ethnic differences in rotterdam criteria and metabolic risk factors in a multiethnic group of women with pcos studied in denmark.
      ;
      • Guo M.
      • Chen Z.J.
      • Eijkemans M.J.
      • Goverde A.J.
      • Fauser B.C.
      • Macklon N.S.
      Comparison of the phenotype of chinese versus dutch caucasian women presenting with polycystic ovary syndrome and oligo/amenorrhoea.
      ;
      • Mani H.
      • Davies M.J.
      • Bodicoat D.H.
      • Levy M.J.
      • Gray L.J.
      • Howlett T.A.
      • Khunti K.
      Clinical characteristics of polycystic ovary syndrome: Investigating differences in white and south asian women.
      ;
      • Chan J.L.
      • Kar S.
      • Vanky E.
      • Morin-Papunen L.
      • Piltonen T.
      • Puurunen J.
      • Tapanainen J.S.
      • Maciel G.a.R.
      • Hayashida S.a.Y.
      • Soares Jr., J.M.
      • Baracat E.C.
      • Mellembakken J.R.
      • Dokras A.
      Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: A regional cross-sectional study.
      ) (Table 4).

       Sub-infertility and pregnancy obstetric complications

      No data currently exist regarding fertility outcomes in PCOS across various ethnic groups. In the only study that assessed the risk of gestational diabetes mellitus during pregnancy in PCOS including diverse ethnic groups (White, Black, Hispanic, Asian and others), Lo and co-workers reported East Asian ethnicity as a predictor for gestational diabetes mellitus with an odds ratio of 3.5 (95% confidence interval 2.3–5.5) in relation to the White population (
      • Lo J.C.
      • Yang J.
      • Gunderson E.P.
      • Hararah M.K.
      • Gonzalez J.R.
      • Ferrara A.
      Risk of type 2 diabetes mellitus following gestational diabetes pregnancy in women with polycystic ovary syndrome.
      ).

       Mood disorders and QoL

      Only two studies compared QoL parameters across different ethnicities. Hashimoto and colleagues compared Brazilian (Predominantly black) women with PCOS and Austrian women with PCOS. The rates of infertility and menstrual disturbances were similar. Hirsutism and obesity were more common among Brazilian participants. Overall, Brazilian women with PCOS had lower QoL scores. When compared with Austrian women with PCOS, hirsutism, infertility and menstrual disturbances had a more negative impact on QoL in Brazilian women with PCOS. Austrian women with PCOS were leaner. However, despite lower BMI measures, obesity had a greater impact on QoL in Austrian women with PCOS (
      • Hashimoto D.M.
      • Schmid J.
      • Martins F.M.
      • Fonseca A.M.
      • Andrade L.H.
      • Kirchengast S.
      • Eggers S.
      The impact of the weight status on subjective symptomatology of the polycystic ovary syndrome: A cross-cultural comparison between brazilian and austrian women.
      ). In the other study, Jones and co-workers compared saPCOS and wPCOS for health-related QoL scores and did not find any differences in mean scores (
      • Jones G.L.
      • Palep-Singh M.
      • Ledger W.L.
      • Balen A.H.
      • Jenkinson C.
      • Campbell M.J.
      • Lashen H.
      Do south asian women with pcos have poorer health-related quality of life than caucasian women with pcos? A comparative cross-sectional study.
      ). Although it was not a direct comparison of different ethnic groups, Schmid and co-workers illustrated a decreased QoL in Moslem immigrants in Austria. Moslem women had more concerns about infertility (
      • Schmid J.
      • Kirchengast S.
      • Vytiska-Binstorfer E.
      • Huber J.
      Infertility caused by pcos–health-related quality of life among austrian and moslem immigrant women in austria.
      ).

       Treatment outcomes

      No studies were found regarding treatment outcomes of PCOS in different ethnic populations.

      Discussion

      For this review, the literature was systematically searched to identify ethnic differences in the clinical presentation of PCOS and it was found that the phenotype of PCOS varies widely depending on the ethnicity.
      Clinical hyperandrogenism is included in the definition of PCOS in all three sets of recommended diagnostic criteria (
      • Zawadzki J.k.
      • Dunaif A.
      Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach.
      ;
      • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
      Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
      ;
      • Azziz R.
      • Carmina E.
      • Dewailly D.
      • Diamanti-Kandarakis E.
      • Escobar-Morreale H.F.
      • Futterweit W.
      • Janssen O.E.
      • Legro R.S.
      • Norman R.J.
      • Taylor A.E.
      • Witchel S.F.
      Positions statement: Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An androgen excess society guideline.
      ). Hirsutism is used to define clinical hyperandrogenism, although acne or androgenic alopecia can accompany hirsutism in PCOS. Along with serum androgen concentrations, individual sensitivity of the pilosebaceous unit to androgens determines the degree of hair growth (
      • Yilmaz B.
      • Yildiz B.O.
      Endocrinology of hirsutism: From androgens to androgen excess disorders.
      ). The mFG system is the gold standard method to diagnose and quantify hirsutism, scoring hair density in the nine body areas from 0 to 4. In the original study conducted in Caucasian women, a cut-off score of ≥8 was determined as defining hirsutism (
      • Hatch R.
      • Rosenfield R.L.
      • Kim M.H.
      • Tredway D.
      Hirsutism: Implications, etiology, and management.
      ). However, subsequent studies performed in diverse ethnic populations showed ethnic variations in the mFG cut-off. While lower cut-off values were recommended for East Asian women, higher mFG cut-off values have been proposed even in healthy Hispanic and Middle Eastern subjects owing to the higher hair density (
      • Escobar-Morreale H.F.
      • Carmina E.
      • Dewailly D.
      • Gambineri A.
      • Kelestimur F.
      • Moghetti P.
      • Pugeat M.
      • Qiao J.
      • Wijeyaratne C.N.
      • Witchel S.F.
      • Norman R.J.
      Epidemiology, diagnosis and management of hirsutism: A consensus statement by the androgen excess and polycystic ovary syndrome society.
      ). The findings of this review suggest lower mFG scores in eaPCOS and higher mFG scores in hPCOS, saPCOS and mePCOS compared with Caucasians (Figure 2). All available data regarding bPCOS came from studies conducted in the USA and in these studies, in general, bPCOS had comparable mFG scores to their American non-Hispanic White counterparts. It is also worth emphasizing that there were differences in hirsutism even within Caucasian populations (European versus American) (Table 1).
      Figure 2
      Figure 2Variations in the clinical presentation of polycystic ovary syndrome patients belonging to different ethnicities. AN, acanthosis nigricans; BP, blood pressure; DHEAS, dehydroepiandrosterone sulphate; FAI, free androgen index; fT, free testosterone; GDM, gestational diabetes mellitus; HDL, high-density lipoprotein; IR, insulin resistance; SHBG, sex hormone-binding globulin; T, testosterone; TG, triglyceride.
      Total mFG scores were used for the comparison of hirsutism between different ethnic groups in all but two studies. Although total mFG scores give an estimation of the total amount of body hair, excessive hair growth might occur only in some parts of the body. Some body areas may be more sensitive to androgen action and this might be more evident in some ethnic groups. In support of this idea, in the only two studies that also compared site-specific mFG scores, researchers pointed out ethnic differences in site-specific mFG scores (Table 1). mFG scores decrease with age (
      • Zhao X.
      • Ni R.
      • Li L.
      • Mo Y.
      • Huang J.
      • Huang M.
      • Azziz R.
      • Yang D.
      Defining hirsutism in chinese women: A cross-sectional study.
      ), but not all studies directly comparing different ethnicities in the current review were age matched, and age groups were heterogeneous (Table 1). This may lead to errors of interpretation. Moreover, there is no comparative study investigating how hair density changes with ageing in different ethnicities. Therefore, when using the mFG score to determine clinical androgen excess, the individual's ethnicity and age should be taken into consideration.
      Acne can be observed in patients with hyperandrogenism. Although the available data are contradictory, some differences may exist in the biological characteristics of skin among various ethnic groups (
      • Davis E.C.
      • Callender V.D.
      A review of acne in ethnic skin: Pathogenesis, clinical manifestations, and management strategies.
      ). For instance, the density of Propionibacterium acnes was found to be higher in African American individuals compared with Caucasian patients (
      • Warrier Ag K.A.
      • Harper Ra
      • Bowman J
      • Wickett Rr
      A comparison of black and white skin using noninvasive methods.
      ). Hence, the prevalence of acne may differ in various ethnic groups. In this review, the results for acne were discordant and not sufficient to conclude whether ethnicity has any impact on the prevalence of acne among different ethnicities in PCOS. It should also be noted that there are no universally accepted visual tools to evaluate acne.
      Evidence for ethnic differences in hyperandrogenemia was scarce and unclear. There are no studies specifically evaluating and rogens and their cut-off levels in different ethnic groups with different ages. Most studies had a limited sample size and did not assess the same androgens. Despite these limitations, androgen concentrations seemed to be similar in diverse ethnic populations, with a few exceptions for ethnic differences in SHBG and adrenal androgens (Table 1).
      Ovulatory dysfunction is a diagnostic criterion for PCOS, and the clinical detection of ovulatory dysfunction is based on menstrual irregularity. Only seven studies were identified that compared the menstrual patterns of women with PCOS belonging to different ethnicities (Table 2). Menstrual disturbances appeared to be more common in eaPCOS. eaPCOS has a mild androgenic phenotype and menstrual disturbances may be a major complaint in clinical presentation. Considering that all studies enrolled patients presenting to clinics, this finding might be due to selection bias. Whether there are frank differences in menstrual irregularity between eaPCOS and other ethnic groups warrants further multiethnic comparative studies in unselected populations.
      The 2003 Rotterdam consensus proposed PCOM as a diagnostic criterion for PCOS, defining it as the presence of 12 or more follicles in each ovary measuring 2–9 mm in diameter, and/or increased ovarian volume (>10 ml) on ultrasound (
      • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
      Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
      ). This criterion was also included in the Androgen Excess and PCOS (AE-PCOS) Society recommendations for the diagnosis of PCOS (
      • Azziz R.
      • Carmina E.
      • Dewailly D.
      • Diamanti-Kandarakis E.
      • Escobar-Morreale H.F.
      • Futterweit W.
      • Janssen O.E.
      • Legro R.S.
      • Norman R.J.
      • Taylor A.E.
      • Witchel S.F.
      Positions statement: Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An androgen excess society guideline.
      ). However, PCOM is not included as a diagnostic criterion by the National Institutes of Health (NIH) criteria (
      • Zawadzki J.k.
      • Dunaif A.
      Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach.
      ). Accordingly, using NIH criteria to diagnose PCOS may exclude some individuals with PCOM and may yield an underrepresentation of this group. In the current review, 15 studies had used NIH criteria. In general, the frequency of PCOM did not show a difference for different ethnic groups in the available studies. However, there were subtle differences in ovarian morphology even though the prevalence of PCOM was similar between ethnic groups. For instance, eaPCOS had lower follicle counts and ovarian volume in two studies (see Table 3). Further studies are needed to determine whether PCOM differs in different ethnic groups.
      Obesity is prevalent in women with PCOS presenting to clinics. In this review, obesity was more frequent in hPCOS and bPCOS compared with Caucasian patients. On the other hand, eaPCOS and saPCOS had lower BMI values with increased central fat and a comparable or higher metabolic risk compared with Caucasian PCOS women. The most common method for assessing excessive fat is BMI calculation. A BMI value higher than 30 kg/m2 was proposed to diagnose obesity in Caucasian populations. However, BMI is a crude indicator and does not reflect the increased metabolic and cardiovascular disease risk in certain ethnic populations (
      • Heymsfield S.B.
      • Peterson C.M.
      • Thomas D.M.
      • Heo M.
      • Schuna Jr., J.M.
      Why are there race/ethnic differences in adult body mass index-adiposity relationships? A quantitative critical review.
      ). Accordingly, different BMI thresholds were determined to define obesity in various ethnic groups. BMI cut-offs have been lowered to 25 and 23 kg/m2 to reflect the risk in South Asian and East Asian populations, respectively (
      • Misra A.
      • Chowbey P.
      • Makkar B.M.
      • Vikram N.K.
      • Wasir J.S.
      • Chadha D.
      • Joshi S.R.
      • Sadikot S.
      • Gupta R.
      • Gulati S.
      • Munjal Y.P.
      Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for asian indians and recommendations for physical activity, medical and surgical management.
      ;
      • Chen X.
      • Ni R.
      • Mo Y.
      • Li L.
      • Yang D.
      Appropriate bmi levels for pcos patients in southern china.
      ). Considering the propensity of East Asian and South Asian individuals to develop central adiposity, the lowered thresholds of BMI may still not be appropriate for these ethnic populations. Therefore, for evaluating the increased adiposity in women of various ethnic origins with PCOS, the use of population-specific anthropometric measures such as WHR may provide a better assessment of metabolic risk.
      Many women with PCOS are insulin resistant and the incidence of prediabetes and diabetes mellitus is increased in women with PCOS independent of age and BMI (
      • Moran L.J.
      • Misso M.L.
      • Wild R.A.
      • Norman R.J.
      Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: A systematic review and meta-analysis.
      ). Some ethnic groups have a propensity to insulin resistance and therefore prediabetes/diabetes mellitus (
      • Raygor V.
      • Abbasi F.
      • Lazzeroni L.C.
      • Kim S.
      • Ingelsson E.
      • Reaven G.M.
      • Knowles J.W.
      Impact of race/ethnicity on insulin resistance and hypertriglyceridaemia.
      ). Thus, one might expect variable degrees of insulin resistance in PCOS patients with different ethnicities. In this systematic review, it was found that hPCOS, bPCOS, mePCOS and saPCOS were more insulin resistant and predisposed to glucose intolerance compared with wPCOS. Moreover, the prevalence of acanthosis nigricans was higher in the ethnic groups with a higher level of insulin resistance. However, the methods to assess glucose homeostasis showed variations (Table 4). Other cardiovascular risk factors, including dyslipidaemia and hypertension, also varied among different ethnic populations. Dyslipidaemia was more prevalent in more obese ethnic groups. bPCOS had better lipid measures but higher blood pressure. High blood pressure values were also noted in European and American Caucasians when compared with saPCOS, mePCOS and eaPCOS (Table 4). Hence, the components of the metabolic syndrome were widely variable in women with PCOS of different ethnicities. The current data regarding the differences in clustering components of metabolic syndrome in different ethnic populations emphasize that ethnic variables should also be taken into consideration when evaluating patients’ metabolic status.
      PCOS is the main cause of anovulatory subfertility. Evidence suggests that both natural and assisted fecundity rates differ between various ethnic groups and that ethnicity may affect the success of fertility treatments and their outcomes (
      • Huddleston H.G.
      • Cedars M.I.
      • Sohn S.H.
      • Giudice L.C.
      • Fujimoto V.Y.
      Racial and ethnic disparities in reproductive endocrinology and infertility.
      ;
      • Dimitriadis I.
      • Batsis M.
      • Petrozza J.C.
      • Souter I.
      Racial disparities in fertility care: An analysis of 4537 intrauterine insemination cycles.
      ). However, this literature search did not reveal any study comparing fertility outcomes across various ethnic groups that included only women with PCOS. Women with PCOS are at increased risk of pregnancy complications and adverse obstetric outcomes (
      • Roos N.
      • Kieler H.
      • Sahlin L.
      • Ekman-Ordeberg G.
      • Falconer H.
      • Stephansson O.
      Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: Population based cohort study.
      ). The diverse reproductive and metabolic presentation of PCOS in diverse ethnic populations may persist during pregnancy and influence the obstetric and neonatal outcomes. Therefore, it can be expected that pregnancy-associated complications may vary in different ethnic groups. In the current review, only one study was found showing that eaPCOS had a higher risk of gestational diabetes mellitus during pregnancy compared with wPCOS (
      • Lo J.C.
      • Yang J.
      • Gunderson E.P.
      • Hararah M.K.
      • Gonzalez J.R.
      • Ferrara A.
      Risk of type 2 diabetes mellitus following gestational diabetes pregnancy in women with polycystic ovary syndrome.
      ).
      Psychological disorders are common in PCOS and several symptoms related to PCOS may have a negative impact on QoL (
      • Dokras A.
      • Stener-Victorin E.
      • Yildiz B.O.
      • Li R.
      • Ottey S.
      • Shah D.
      • Epperson N.
      • Teede H.
      Androgen excess- polycystic ovary syndrome society: Position statement on depression, anxiety, quality of life, and eating disorders in polycystic ovary syndrome.
      ). The patient's ethnic and cultural background may also affect the perception of the disorder (
      • Hashimoto D.M.
      • Schmid J.
      • Martins F.M.
      • Fonseca A.M.
      • Andrade L.H.
      • Kirchengast S.
      • Eggers S.
      The impact of the weight status on subjective symptomatology of the polycystic ovary syndrome: A cross-cultural comparison between brazilian and austrian women.
      ;
      • Schmid J.
      • Kirchengast S.
      • Vytiska-Binstorfer E.
      • Huber J.
      Infertility caused by pcos–health-related quality of life among austrian and moslem immigrant women in austria.
      ). Two studies were found that assessed the QoL scores of PCOS patients with different ethnicities, and in a separate study individuals from different religions were compared (
      • Kumar A.
      • Woods K.S.
      • Bartolucci A.A.
      • Azziz R.
      Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (pcos).
      ;
      • Jones G.L.
      • Palep-Singh M.
      • Ledger W.L.
      • Balen A.H.
      • Jenkinson C.
      • Campbell M.J.
      • Lashen H.
      Do south asian women with pcos have poorer health-related quality of life than caucasian women with pcos? A comparative cross-sectional study.
      ;
      • Wang E.T.
      • Kao C.N.
      • Shinkai K.
      • Pasch L.
      • Cedars M.I.
      • Huddleston H.G.
      Phenotypic comparison of caucasian and asian women with polycystic ovary syndrome: A cross-sectional study.
      ). More data are needed on the potential role of ethnicity in psychological disorders and QoL in patients with PCOS.
      Lifestyle intervention is the first-line treatment for PCOS, and medical treatment aims to improve reproductive and metabolic dysfunction (
      • Teede H.J.
      • Misso M.L.
      • Costello M.F.
      • Dokras A.
      • Laven J.
      • Moran L.
      • Piltonen T.
      • Norman R.J.
      Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.
      ). There was no study that compared the outcomes of lifestyle intervention and medical treatment among different ethnic populations with PCOS. Ethnic variations can be important for treatment outcomes. For instance, interindividual variations in metformin response due to genetic heterogeneity have been reported in patients with diabetes (
      • Mofo Mato E.P.
      • Guewo-Fokeng M.
      • Essop M.F.
      • Owira P.M.O.
      Genetic polymorphisms of organic cation transporter 1 (oct1) and responses to metformin therapy in individuals with type 2 diabetes: A systematic review.
      ). Moreover, the ethnic or cultural background of an individual may affect drug preferences. Rocca and colleagues reported significant ethnic disparities in use of the contraceptive pill (

      Rocca, C.H., Harper, C.C., 2012. Do racial and ethnic differences in contraceptive attitudes and knowledge explain disparities in method use? Perspectives on sexual and reproductive health. 44, 150-8

      ). Accordingly, the potential influence of ethnicity on response to lifestyle interventions or medical treatment in PCOS is an area of interest for future research.
      Overall, ethnicity plays an important role in the phenotypic presentation of PCOS and its individual components. For example, independent of PCOS, mFG cut-off scores for defining hirsutism and the severity of hirsutism vary by ethnicity. Scores of ≥4 and ≥6 define hirsutism in White and Black women and Han Chinese women, respectively. Accordingly, in 2018, the International PCOS Network suggested that ethnic variation should be considered in the management of PCOS (
      • Teede H.J.
      • Misso M.L.
      • Costello M.F.
      • Dokras A.
      • Laven J.
      • Moran L.
      • Piltonen T.
      • Norman R.J.
      Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.
      ). However, the studies included in our review did not compare phenotypic variations in PCOS using ethnicity-specific recommendations. Future studies on the impact of ethnicity are needed to inform the guidelines (Table 5).
      Table 5Areas for future research regarding impact of ethnicity on PCOS
      • Development of age- and ethnicity-specific visual tools and cut-off values for assessment and definition of clinical hyperandrogenism, including hirsutism and acne
      • Comparative analysis of biochemical hyperandrogenism in multiethnic cohorts with high-quality assays
      • Assessment of phenotypic variation including prevalence of prediabetes/diabetes and risk of cardiovascular disease in multiethnic longitudinal studies of unselected populations
      • Evaluation of the impact of ethnicity on fertility, obstetric and neonatal outcomes in comparative studies of women with PCOS
      • Determination of the role of ethnicity on perception of PCOS and emotional well-being and quality of life
      • Assessment of the role of ethnicity on long-term medical management of PCOS
      PCOS, polycystic ovary syndrome.
      There are some limitations to the current systematic review. First, the review included studies that were performed in clinics. The clinical presentation and ethnic characteristics of PCOS may vary in unselected populations (
      • Ezeh U.
      • Yildiz B.O.
      • Azziz R.
      Referral bias in defining the phenotype and prevalence of obesity in polycystic ovary syndrome.
      ). Therefore these findings on clinical referral populations might not be able to be extrapolated to unselected populations. Second, in all studies, ethnicity was assessed by self-reported data. However, self-reported ethnicity might be subjective and biased. Using genetic ancestry instead of self-reported ethnicity may provide a better ethnic determination (
      • Louwers Y.V.
      • Lao O.
      • Fauser B.C.
      • Kayser M.
      • Laven J.S.
      The impact of self-reported ethnicity versus genetic ancestry on phenotypic characteristics of polycystic ovary syndrome (pcos).
      ). Finally, although in some studies the participants lived in the same environment, in others study participants were recruited from different countries. Considering the effect of environmental factors on PCOS, the disparities between different ethnic groups might not be attributable to ethnic factors per se.

      Conclusion

      Based on the limited data available, the clinical presentation of PCOS shows a wide variation among different ethnic populations. Larger multiethnic comparative studies specifically assessing the role of ethnicity in the diagnosis and management of PCOS are needed for developing ethnicity-specific guidelines.

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      Biography

      Suleyman Nahit Sendur completed his training in internal medicine and endocrinology at Hacettepe University, Turkey. He was appointed as an Assistant Professor at the same institution in 2020. His research and clinical interests are in pituitary, adrenal and gonadal disorders.
      Key message
      Ethnicity affects the clinical presentation of PCOS and needs to be taken into consideration in evaluating and managing the syndrome.