Post on 30-May-2020
Is Lean PCOS different from Obese PCOS?Kathleen M Hoeger MD MPH
Professor, Obstetrics and Gynecology
University of Rochester
June 18, 2016
International Joint Conference PCOS Society (India) and
AEPCOS
Disclosures
No conflicts of interest to disclose
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Impact of Obesity on PCOS
Teede et al BMC Medicine 2010, Norman et al Lancet 2007, Teede et al MJA 2011
Courtesy Helena Teede MD
What is the prevalence of obesity in PCOS?
Rates vary by region/country
Influenced by environmental factors
Difficult to ascertain accurately--Biased populations who present
for evaluation/management
Obesity rates and PCOS, non selected population
BMI class N (%) PCOS (%)
<18.9 36 (5.3) 8.2
19-24.9 282 (41.8) 9.8
25-29.9 160(23.7) 9.9
30-34.9 87(12.9) 5.2
35-39.9 57(8.5) 12.4
>40 53(7.8) 11.5
Yildiz JCEM 2008
Obesity in PCOS
Lim SS, .. Moran Hum Reprod Update 2012
Australian Longitudinal Study on Women’s Health
0
2
4
6
8
10
12
14
16
BMI < 25 BMI 25-30 BMI > 30
Percentage with PCOS
n=5749
n=1522
n=723
498 women reported PCOS, 60% PCOS women were overweight, longitudinal data 9% inc risk PCOS for 1 unit BMI
Teede, Obesity 2013
Australian Longitudinal Study on Women’s Health
0
2
4
6
8
10
12
14
16
non PCOS PCOS
% Weight gain over 10 years
Teede, Obesity 2013
Impact of obesity on Phenotype
All women
NIH Rotterdam AE-PCOS
Total 100% 6.1% 19.9% 15.3%
Non-obese
90% 5.1% 19% 14.5%
Obese 10.2% 15% 30% 22.5%
Yildiz, Human Reprod 2012
Turkish government employees, prevalence of PCOS by BMI
Diet, Physical Activity and Obesity in PCOS
Looking at diet and exercise data from a cohort of women with
and without PCOS, investigators were able to examine the impact
of diet on the presence of obesity in these populations.
Although the BMI of the PCOS group was on average higher
than the controls, dietary choices and energy intake did not differ
in the overweight or obese groups.
Wright 2004
Diet, Physical Activity and Obesity in PCOS
More control women demonstrated moderate to vigorous
activity levels
Comparing normal weight PCOS to normal weight controls
the caloric intake of lean PCOS was significantly lower (1400
kcal/day compared to 1800 in the weight matched controls)
Wright 2004
Characteristics of women with PCOSAustralian population based study
PCOS Non PCOS p
age 33.5 33.7 0.01
BMI 29.3 25.6 <0.001
Sedentary behavior (h/day)
2.8 2.9 0.008
Kcal/day 2577 2265 0.004
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Moran Hum Rep 2013
Impact of obesity on reproductive phenotype
Is there is evidence that the expression of reproductive features may
vary within BMI categories?
PCOS, infertility and BMI
Joham et al J Womens Health 2015
Pre
vale
nce o
f fe
rtili
ty c
on
cern
s (
%)
PCOS (n=309) Non-PCOS (4547)0
20
40
60
80PCOS (n=309)
Non-PCOS (4547)
BMI category
Pro
ble
ms w
ith
fert
ility
(%
)
25 25 30 > 300
10
20
30
40
50
60
70
80
90PCOS
Non-PCOS
PPCOS II study: PCOS reproductive phenotype by BMI
BMI <30
BMI 30-34.9
BMI 35-39.9
BMI >40 p
Hirsutism 14.4 17.1 18.3 18.9 <0.001
Antral follicle count
51.0 47.0 46.9 42.6 <0.001
Endometrialthickness
6.3 6.3 7.3 7.0 <0.001
AMH 10.0 9.1 7.5 5.7 <0.001
Total T 51.9 58.5 55.9 55.9 0.050
Legro F&S 2015
Obesity and sex steroids
Kiddy et al examined 263 women with PCOS
Compared to lean women, obese women with PCOS had higher rates of
hirsutism (73% vs 56%)
Free testosterone was significantly higher
Kiddy 1990
Geographic variation in obesity and metabolic parameters
Comparison of 210 women with PCOS from Delhi and Srinagar
Evaluated androgens, gonadotropins, cortisol, lipids, OGT and insulin
PCOS women from both communities had similar age, age of menarche,
height and blood pressure
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Ganie et al Gynecol Endocrinol 2016 Feb 15:1-5
Geographic variation in obesity and metabolic parameters
0
5
10
15
20
25
30
35
40
BMI GI FG score HOMA IR
Delhi
Srinagar
%
Kg/m2
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Ganie et al Gynecol Endocrinol 2016 Feb 15:1-5
Influence of Obesity on metabolic phenotype
Obesity has a detrimental impact on metabolic parameters in women
with PCOS
This is likely mediated via worsening insulin resistance seen with obesity
Published in: Evanthia Diamanti-Kandarakis; Andrea Dunaif; Endocrine Reviews 2012, 33, 981-1030.
DOI: 10.1210/er.2011-1034
Copyright © 2012
Published in: Evanthia Diamanti-Kandarakis; Andrea Dunaif; Endocrine Reviews 2012, 33, 981-1030.
DOI: 10.1210/er.2011-1034
Copyright © 2012
Published in: Evanthia Diamanti-Kandarakis; Andrea Dunaif; Endocrine Reviews 2012, 33, 981-1030.
DOI: 10.1210/er.2011-1034
Copyright © 2012
Insulin Resistance in PCOS
WHO criteria for IR<25th centile on clamp studies
65% Obese controls75% lean PCOS
95% obese PCOS women
Overall 85% IR in PCOS
Stepto, Teede Human Reprod 2013
DM2 prevalence in PCOS
Moran L J et al. Hum. Reprod. Update 2010
PPCOS II study: PCOS metabolic phenotype by BMI
BMI <30
BMI 30-34.9
BMI 35-39.9
BMI >40 p
Fasting glucose
82.5 85.7 87.6 88.8 <0.001
Fasting insulin
8.4 16.4 26.3 28.0 <0.001
HDL Chol 41.9 37.7 36.2 34.7 <0.001
TG 92.9 128.3 127.5 128.1 <0.001
MS (%) 9.8 42.5 42.1 49.8 <0.001
Legro F&S 2015
Treatment of PCOS in the setting of obesity
Given the high prevalence of obesity seen in PCOS, what additional
impact does it have on the success of treatments commonly used for
PCOS?
Little data exist for the most common treatment for patients not
seeking fertility—oral contraceptives
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OCP Normal weight vs Obese PCOS(NGT, DSG,GTD)
Mean age 25.4, BMI 20.3 n=28
Pre Post Δ
Acne 2.38 1.46 -0.92p=0.05
FG 9.1 6.9 -2.17p=0.01
T 2.72 1.44 -1.28p=0.001
SHBG 73.0 150.3 77.3p=0.001
Mean age 23.5, BMI 32.3 n=15
Pre Post Δ
Acne 1.67 0.79 -0.88NS
FG 9.8 7.2 -2.58NS
T 2.91 1.65 -1.26p=0.05
SHBG 51.0 105.5 54.5p=0.01
NormalObese
Cibula, Hum Reprod 2001
Oral contraceptive risk and PCOS
No clear indication that PCOS increases the risks of OC use
However obesity may increase the thrombotic risk in OC use
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OCP Risks in PCOS
No clear data on whether OCs have increased risk of DVT in PCOS
There may be independent association of thrombotic risk and PCOS due
to a prothrombotic state and increase activity of PAI-1
• Prevalence of VTE 374.3 vs 193.8/100,000 in PCOS vs controls
irrespective of OC use (Okoroh Am J Obstet Gynecol 2012)
• On OCs PCOS higher 23.7 vs 10.9/10,000 (RR 2.12) (Byrd CMAJ 2013)
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Impact of obesity on fertility treatments
30
Ovulation Induction with CC and obesity
201 women with oligo-ovulation undergoing ovulation induction with
clomid
Best predictors of failure to respond
• Free androgen index
• BMI
Mean BMI of non-responders was 30
Imani 1998
Obesity and FSH ovulation induction Several studies suggest gonadotropin dosing for ovulation induction in PCOS is related to weight
Hamilton-Fairley et al retrospectively examined 100 women with PCOS
Comparison of overweight versus normal weight
Increased dose of FSH required for ovulation but pregnancy rates did not differ
Increased rates of SAB were noted in the heavier group—60% vs 27%
Hamilton-Fairley 1992
Legro RS et al. N Engl J Med 2007;356:551-566.
PPCOS I:Clomiphene, Metformin or Both
Legro RS et al. N Engl J Med 2014;371:119-129.
PPCOS II: Clomiphene versus Letrozole
Obesity and intercourse compliance in PCOS
Conclusions
Women with PCOS demonstrate different phenotypes based on BMI
which may vary considerably by geography
Obesity has a significant impact on the metabolic and reproductive
consequences of PCOS
Women with PCOS who are obese demonstrate lower success with
infertility treatments
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