Does the incidence of metabolic syndrome vary between the diﬀerent phenotypes of PCOS in adolescents?

(1)

Does the incidence of metabolic syndrome vary between the diﬀerent phenotypes of PCOS in

adolescents?

Derya Akdağ Cırık, M.D.

Etlik Zübeyde Hanım Women’s Health Training and Research Hospital

MSRM 2016

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PCOS in adolescents

•  PolycysDc ovary syndrome (PCOS) is the most

frequent endocrine disorder in reproducDve-‐aged women.

•  Well-‐known triad of PCOS includes -‐ chronic anovulaDon,

-‐ hyperandrogenism, -‐ polycysDc ovaries

•  RoQerdam criteria à 4 reproducDve phenotypes

(3)

PCOS in adolescents

•  Exact cause is unknown

•  Evidence suggest geneDc origin

•  Excess androgens produced in ovaries during puberty is supposed to be the iniDaDng factor

Roe et al, 2011

•  Androgens promote insulin resistance that might lead to metabolic dysfuncDon in later years.

•  PCOS is accepted as both reproducDve and metabolic disorder

(4)

Metabolic Syndrome (MS)

•  MS is the end point of this metabolic dysfuncDon in PCOS.

•  MS à Coronary artery disease à Mortality

•  MS incidence à as high as 38% even in adolescence with PCOS.

Coviello et al, 2006

•  The screening and detecDon is vital and -‐ AES (Androgen Excess Society) recommends

screening to decrease future cardiovascular event.

Salley et al, 2007

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ObjecFve of the study

•  To determine whether the incidence and

parameters of metabolic syndrome diﬀer in four PCOS phenotypes in adolescents.

•  Phenotype A: H + A + P

•  Phenotype B: H + A

•  Phenotype C: H + P

•  Phenotype D: O + P

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Study Design

SeIng: At the Youth Center clinic at a terDary referral hospital in Ankara, Turkey.

ParFcipants and study protocol:

•  114 consecuDve adolescents with newly diagnosed PCOS (n=144) with RoQerdam

criteria were classiﬁed into four phenotypes.

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Study Design

Measurements and Lab Tests

•  Body mass index, waist circumference

•  Blood pressure, Sonographic examinaDon

•  Lipid Proﬁle (TG, Cholesterol, HDL, LDL)

•  Hormone Proﬁle (FSH, LH, E2, T, DHEAS, 17OHP)

•  FasDng glucose, HOMA-‐IR

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Study Design

Metabolic syndrome -‐ IDF criteria

•  Central obesity, deﬁned as a WC ≥ 80 cm(absolute)

•  The presence of two of following four criteria was required

(1) TG ≥ 150 mg/dl;

(2) HDL < 50 mg/dl;

(3) FasDng plasma glucose ≥100 mg/dl;

(4) Systolic/diastolic blood pressure ≥ 130/85 mmHg.

(9)

Results

•  The mean age was 17.25 ± 1.22, and the ages are similar in all phenotypes.

Of all,

•  Oligomenorrhea (76.4%),

•  HirsuDsm (75.7%).

•  History of PCOS in their family (43.2%).

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Table 1: Metabolic and hormonal characterisFcs of adolescents with PCOS

CharacterisFcs Phenotype A Phenotype B Phenotype C Phenotype D p value

BMI 27.16 ± 4.14 25.14 ± 3.87 24.98 ± 4.05 25.32 ± 4.14 p=0.006^a

WC (cm) 0.84 (0.08) 0.77 (0.14) 0.78 (0.15) 0.79 (0.10) p=0.007^b

FasDng glucose (mg/dl) 90 (9.0) 87 (10.0) 86 (9.0) 88 (8.0) p=0.016

Insulin (µIU/ml) 9.98 (2.32) 10.20 (2.08) 9.76 (2.10) 9.15 (3.08) p=0.427

HOMA-‐IR 2.17 (0.77) 2.15 (0.84) 2.14 (0.60) 1.94 (0.68) p=0.122

Systolic BP (mmhg) 115.0 (10.0) 110.0 (10.0) 110 (10.0) 110 (10.0) p=0.262

Diastolic BP (mmhg) 73.7 (10.0) 71.3 (5.0) 72.6 (10.0) 69.7 (5.0) p=0.192

a: A vs BCD, b: A vs BCD

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Table 1: Metabolic and hormonal characterisFcs of adolescents with PCOS

CharacterisFcs Phenotype A Phenotype B Phenotype C Phenotype D p value

Testosterone (ng/ml) 0.8 (0.4) 0.8 (0.2) 0.7 (0.3) 0.6 (0.2) p<0.001^d

FSH (IU/L) 5.19 (2.12) 5.60 (2.12) 5.03 (2.59) 5.40 (1.87) p=0.621

LH (IU/L) 9.88 (2.76) 10.55 (2.77) 9.16 (4.70) 8.33 (2.68) p=0.002^e

DHEAS (µg/dl) 221.0 (94.0) 201.5 (136.0) 171.5 (118.0) 174.5 (108.0) p=0.42

17 OH Prog (ng/ml) 0.98 (0.18) 0.96 (0.25) 0.95 (0.20) 0.89 (0.34) p=0.48

Cholesterol (mg/dl) 176.0 (42.0) 160 (39.0) 182.5 (45.0) 154.5 (39.0) p=0.11

TG (mg/dl) 134.0 (74.0) 95.0 (28.0) 100.5 (57.0) 100.0 (35.0) p=0.12

LDL (mg/dl) 87.5 (24.0) 88.0 (19.0) 90.0 (19.0) 78.0 (19.0) p=0.10

HDL (mg/dl) 37.0 (9.0) 39.0 (10.0) 39.5 (11.0) 39.0 (7.0) p=0.29

d: ABC vs D, e: ABC vs D

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Table 2: Parameters of metabolic syndrome in four PCOS phenotypes (n=144, %)

Overall Data:

Seventy-‐nine (54.9%) of 144 paDents in cohort were overweight.

Thirty-‐seven (25.7%) of 144 paDents were diagnosed as metabolic syndrome

Phenotype A Phenotype B Phenotype C Phenotype D p value

Abdominal obesity 31 (81.6%) 30 (76.9%) 27 (79.4%) 28 (24.1%) 0.85

Hypertension 8 (21.1%) 4 (10.3%) 5 (14.7%) 2 (6.1%) 0.27

TG ≥ 150 (mg/dl) 17 (44.7%) 8 (20.5%) 8 (23.5%) 5 (15.2%) 0.023

HDL < 50 (mg/dl) 33 (86.9%) 31 (79.5%) 28 (82.4%) 30 (90.9%) 0.56

Glu ≥ 100 (mg/dl) 7 (18.4%) 2 (5.1%) 4 (11.8%) 1 (3.0%) 0.11

Mets (IDF) 15 (39.5%) 8 (20.5%) 9 (26.5%) 5 (15.2%) 0.10

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Table 3: Comparison of the endocrinologic and metabolic parameters in PCOS adolescents with and without metabolic syndrome (n=144)

CharacterisFcs Adolescents without Metabolic syndrome

Adolescents with Metabolic Syndrome

p value

Age (years) 17.26 ± 1.22 17.21 ± 1.25 0.84

BMI (kg/m2) 24.46 ± 3.30 29.63 ± 3.26 <0.001

WC (cm) 68.0 (15.0) 88.0 (8.0) <0.001

FasDng glucose (mg/dl) 87.0 (8.0) 94.0 (14.0) <0.001

Insulin (µIU/ml) 9.2 (2.61) 10.8 (2.08) <0.001

HOMA-‐IR 1.98 (0.58) 2.56 (0.79) <0.001

Cholesterol (mg/dl) 158.0 (36.0) 197.0 (21.0) <0.001

Triglyceride (mg/dl) 92.0 (28.0) 153.0 (12.0) <0.001

LDL (mg/dl) 80.0 (20.0) 92.5 (19.0) 0.003

HDL (mg/dl) 40.0 (10.0) 35.0 (9.0) <0.001

Testosterone (ng/ml) 0.70 (0.24) 0.82 (0.35) 0.004

DHEA-‐S (ng/ml) 205.0 (135.0) 221.0 (117.0) 0.95

FSH (IU/L) 5.25 (2.10) 5.35 (2.27) 0.59

LH (IU/L) 9.37 (3.87) 10.11 (3.18) 0.21

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Discussion

•  In this study, overweight 54.9 %,

metabolic syndrome 25.7 %.

•  30 Iranian adol à overweight 52.0 %

metabolic syndrome 33 %

Rahmanpour et al.

•  128 Chinese adol à metabolic syndrome 4.7%

Huang et al.

Healthy Turkish girls à metabolic syndrome 4.0 % Agirbasli et al, 2009

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Discussion

•  Although, insulin resistance and HDL levels are similar in all phenotypes.

•  Obesity and waist circumference are higher in phenotype A.

•  MS incidence highest in phenotype A (39.5 %) lowest in phenotype D (15.2 %)

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Discussion

•  In this study, the incidence of metabolic syndrome in

normal-‐weight adolescents was 6.1%;

increased to 25.5% in overweight adolescents and 67.7% in obese adolescents (data not shown).

•  Obesity deteriorates metabolic dysfuncDon in adolescents with PCOS.

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Discussion

•  The PCOS adolescents with metabolic syndrome were also found to have higher testosterone levels than those without metabolic syndrome.

•  Higher free testosterone levels in adolescent PCOS with metabolic syndrome

Coviello et al, 2006

•  More severe lipid proﬁle in androgenic

phenotypes

FruzeF et al, 2009

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Strenghts and limitaFons

•  This is the ﬁrst study that has invesDgated the incidence of metabolic syndrome in four PCOS phenotypes

•  The endocrinologic and metabolic parameters were compared in detail.

•  Single center study

•  Cross secDonal study, not comment on

whether metabolic proﬁle will change unDl adulthood.

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Conclusion

•  One in four adolescents with PCOS in our populaDon had metabolic syndrome.

•  Obesity and hyperandrogenism worsen the MS.

•  MulDcenter studies with diﬀerent ethnic

populaDons and follow-‐up studies are required to evaluate the risk factors for metabolic

syndrome and further development of cardiovascular disease.

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Thank you for your a]enFon