THE CHILDREN’S HOSPITAL ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE
Effect of Body Mass Index on Gonadal Axis
Junfen Fu
Children’s Hospital of Zhejiang University school of Medicine
THE CHILDREN’S HOSPITAL ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE
Contents
1 Prevalence of Childhood Obesity and Precocious Puberty
2 Relationship Between Body Mass Index and Sexual development
3 Body Mass Index and Gonadal Hormone Levels
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Childhood Obesity ---the consequences of
overnutrition and the prevalent trend worldwide
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Diabetes
Liver and
Renal
disease
Reproductive
Dysfunction
Pubertal development
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内容
Contents:
1、流行病学与机制
Epidemiology and Pathogenesis
2、诊断新技术
New Diagnostic Technologies
3、治疗新进展
Update Treatment
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Our recent multicenter study
(National project 2009BAI80B01,2012BAI02B03)
22071 students (11638 were boys and 10433 were girls) aged 7–16
years old from 6 representative geographical areas, showed the
prevalence of overweight was 11.0 % and the prevalence of obesity
was 8.9 %.
Chinese Journal of Pediatrics 2013, 51(6): 409-413.
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The increasing trend of
childhood obesity in China
Figure 2 Empirical changes in the prevalence of
overweight and obesity combined category among
females aged 7-18 years in four city groups.
▲Group I Big coastal cities: 32.6% (2010). The annual
growth rate is 1.15%
■ Group II Other big cities - : 26.1% (2010). The annual
growth rate is 1.02%
●Group III+IV Middle-sized and small cities: 21.2%
(2010). The annual growth rate is 0.82%
Biomed Environ Sci, 2013; 26(1): 1-12
THE CHILDREN’S HOSPITAL ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE
Global prevalent trend of
precocious puberty
1940-1994 statistical data of USA shows that women breast development and menarche begin
at an earlier age
(Susan Y. Euling et al. 2008, Pediatrics )
From 19th century to mid-20th century in the USA and Northern European countries, the
average age of menarche in female shifts from 16-17 years old to 12.5 years old ahead of time
(Jacobsen, B.K. et al. 2007 , J. Epidemiol.)
The prevalence of precocious puberty in Chinese children also show the trend of increasing
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Annual Precocious Puberty Inpatients
in our Hospital
1סידרה
THE CHILDREN’S HOSPITAL ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE
A representative sample involving
18,707 (9812 boys and 8895 girls )
children and adolescents aged 6 to 18
years who participated in Chinese
Children and Adolescent Metabolic
Syndrome Epidemiologic Study (2009.7-
2010.7) were surveyed.
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The median age for girls of
the Tanner stage 2 was 9.69
(95%CI: 9.63-9.75) years,
The median age for boys of
Tanner stage 2 was 11.25
(95%CI: 11.19-11.30) years.
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2.56% of 7-year-old girls,
2.91% of 8-year-old girls,
10.77% of 9-year-old girls,
appeared B2, respectively.
1.12% of 9-year-old girls began
to appear B3 or more (Fig. 1).
0.61% of 8-year-old boys,
1.74% of 9-year-old boys,
3.67% of 10-year-old boys,
appeared G2, respectively.
0.78% of 10-year-old boys began
to appear G3 or more (Fig. 2).
THE CHILDREN’S HOSPITAL ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE
Contents
1 Prevalence of Childhood Obesity and Precocious Puberty
2 Relationship Between Body Mass Index and Sexual Development
3 Body Mass Index and Gonadal Axis Hormone Levels
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The effect of obesity on the
female sexual initiation
The female sexual
initiation starts at
an earlier age
The increase of
childhood obesity
incidence
Accidental
?
Inevitable?
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Study on the correlation between obesity and
female’s earlier sexual development
Figure 2. White girls aged 6-9 years with
breast development and without breast
development
Figure 3. The association between mean
BMI z scores and Tanner stage in girls
aged 7-12 years, among whom white girls
account for 90% and black girls account
for 10%.
The research of Kaplowitz, P.B. shows that among white people aged 6-9 years, mean BMI z
score of those with breast development is significantly higher than that of the girls without
puberty initiation of the same age; among the girls aged 7-12 years, the Tanner stage is
positively related to BMI z score in the girls of the same age (Pediatrics. 2001;108(2):347–353)
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Study on the correlation between obesity and
female’s earlier sexual development
The research of Freedman DS et al. shows that the age at menarche is negatively
related to BMI, and the earlier menarche girls with BMI at the 75th percentile is 1.79
times higher than that of the girls with BMI at the25th percentile, the earlier menarche
probability of girls with skin-fold thickness at 75th percentile is 1.4-1.5 times higher
than that of the girls with skin-fold thickness at the 25th percentile.(Pediatrics.
2002;110(4).)(Addo OY, Pediatr Res. 2014 Dec;76(6):564-70.)
The research on 147 black girls by Himes JH et al. shows that breast development
level is positively related to BMI, waist circumference, fat mass and percentage of
body fat, compared with the age-matched prepubertal girls, adolescent girls with over
95th percentile of BMI is 8 times higher. Obes Res. 2004;12(suppl):64S–72S.)
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Is obesity the cause or result of
female gonad initiation?
Obesity has a "switch" effect on the gonad initiation of the female.
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A longitudinal study
on 354 girls by Lee JM
et al. shows that high
BMI at age 3, or BMI
increase during 3-6
years old is a
significant risk factor
for whether the sexual
development of girls
starts earlier or not.
Pediatrics. 2007;119(3).
A longitudinal study in
Pennsylvania of USA
shows that for the girls
with a high body mass
or a high BMI percentile
at age 5 and 7, the
possibility of earlier
sexual development at
age of 9 increases
significantly. Davison KK, Pediatrics.
2003;111(4 pt 1):815–821.
A study of France shows
that, for the girls aged 4
to 8 years who have pubic
hair ahead of time, 32.5%
of the infant patients have
a BMI≥2 SD, and BMI z
score is significantly
correlated to serum
DHEA-S levels.
Charkaluk ML,Eur J Pediatr.
2004;163:89–93.
1 2 3
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OBESITY PUBERTY
Effect of obesity on male sexual initiation
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Obesity is possitively
associated with sexual
maturation in both boys
and girls, but it is more
stronger in girls than in
boys.
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Effect of obesity on male sexual initiation
In dispute
• The study of Hae Sang Lee et al
shows that the sexual
development of the obese boys
starts at an earlier age than that
of the boys with normal weight
Sandhu J et al make follow-up
observation of 1520 boys from
9-18 years of age to adulthood
who are born in 1927-1956, and
they find those with high BMI in
childhood are prone to have
precocious puberty.
Neuroendocrinology,2012 Sep 20.
Int J Obes 2006;30:14-22.
The sexual development study on
582 German obese boys by Denzer
C shows that the age of the
appearance of the public hair, testis
size and the appearance of gonad
function in the obese patients have
no obvious differences from those
of the normal group.
Int J Obes 2007;31:1509-1519.
Clin Endocrinol (Oxf). 2015 ;82:550-6.
• A statistics from III NHANES
(1988-1994, 1520 boys aged 8-14
years) shows that the obese
children have a later sexual
initiation than the boys with
normal weight
Int J Obes (Lond) 2007;31:1509-
1519.
Biro FM et al. think that boys with
high BMI have a later puberty
than the boys with normal
weight.
Int J Androl 2006;29:272-277.
Promote Irrelevant
Delay
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Mildly increased BMI earlier puberty
Very high BMI later puberty
A nonlinear relationship between BMI as
a measure of obesity and male puberty
Fat percentage better describe the relationship between obesity
and puberty in normal to overweight boys, in whom BMI is more
strongly associated with lean mass than with fat mass
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Effect of obesity on male sexual initiation
Male sexual precocity judgment relies mainly on testis and penis size,
voice change and other indicators, which is somewhat subjective and
lacks objective indicators such as female menarche.
Using BMI as an alternative indicator to obesity is misleading because the
association between body fat and BMI of the male is smaller than that of
the female.
After the onset of puberty in the male, because the neohombreol F
promotes the anabolic effect, the muscle growth can result in the
increase of body weight and BMI instead of the simple accumulation of
body fat.
Therefore, more reasonable indicators are needed to judge obesity, and
using of Dual-energy X-ray to determine the amount and percentage of
body fat in some studies may be more reasonable.
Why controversial?
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Contents
1 Prevalence of Childhood Obesity and Precocious Puberty
2 Relationship Between Body Mass Index and Sexual development
3 Body Mass Index and Gonadal Hormone Levels
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Factors initiating and regulating puberty development are unclear at present
Key acceptable factors: Kisspeptin family, and the receptor GPR54;
Other important factors: Insulin, Leptin, NeuropeptideY, Gamma-aminobutyric acid,
Transforming Growth Factor-α , Ghrelin and IGFs;
Puberty Onset
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Among other factors, adequate nutritional status appears to be
requisite for the central initiation of puberty.
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Reproductive axis and obesity
related hormones
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Reproductive Field
Leptin Adiponectin
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A simplified model of the
leptin-signaling pathway
Endocrinol Metab Clin N Am 38 (2009) 525–548.
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Obesity promotes the female sexual
initiation mechanism
Mäntyselkä A,
J Clin Endocrinol Metab.
2014 Oct;99(10):3889-94.
Ahmed ML ,Trends
Endocrinol Metab.
2009 Jul;20(5):237-42
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Effect of BMI on sex hormones level
The study on the effect of BMI on sex hormones in adolescent girls
by Christopher R. McCartney et al. finds that :
J Clin Endocrinol Metab, February 2007, 92(2):430–436
T is 2-9 times higher in adolescent obese girls than that of the girls with normal weight
The insulin resistance of Tanner1-3 obese girls is 3 times higher than that of the girls with
normal weight
The average level of LH of Tanner1-2 obese girls decreases, but there is
no similar difference in late adolescent girls
P、T concentration of Tanner 1 - 3 girls with normal weight increases significantly
overnight, the difference in the obese girls is not so obvious than that of the former.
3
2
1
4
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Effect of BMI on sex hormones level
N H Birkebæk et al. find in the study on sex hormone levels after the weight loss in Caucasus obese children :
BMI↓
Neohombreol F :boys↑,girls↓。
Insulin sensitivity and SHBG↑。
FSH:boys↑,girls↑ 。
LH:boys↑, no obvious change in girls
European Journal of Endocrinology.2010;163:895–900.
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The effect of BMI on the secretion level of LH
Research subject: healthy prepubertal girls aged 6.4-9.5 (prepubertal, pre, n = 20)
and pubertal premenarcheal volunteers aged 9.4-13 (pubertal premenarcheal
volunteers, pub, n = 20) are divided into excessive-weight (EW) group and normal-
weight (NW) group according to BMI ≥ the 85th percentile
J Clin Endocrinol Metab. April 2009, 94(4):1168–1175
Brian Bordini et al find that the sleep related LH secretion weakens
in obese pubertal premenarcheal girls.
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The effect of BMI on the secretion level of LH
The sleep related LH secretion in EW-PUB group is not statistically
significant compared with that of NW-PUB group .
Conclusion
1
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The effect of BMI on the secretion
frequency and peak of LH
NW-PUB 组中睡眠相关LH分泌显著增加,EW-PUB 组增加不具有统计学差异;与NW-PUB组相比
,睡眠相关的LH分泌增加在EW-PUB组中显著减弱。
Conclusion
2 The frequency and peak of sleep related LH pulse secretion in the EW-PUB group are lower than those in the NW-PUB group
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The effect of BMI on LH secretion
The study of Christopher R. McCartney et al. on LH secretion in the
adolescent period also has similar results:
1 For the Tanner1-2 obese patients, the nocturnal LH secretion frequency and peak both ↓
For the Tanner3-5 obese patients, the nocturnal LH secretion frequency ↑ , but the peak↓. 2
The nocturnal LH secretion ↑ exists in Tanner3-5 people with normal weight, but does not exist in obese people. 3
J Clin Endocrinol Metab. January 2009, 94(1):56–66
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Impact of BMI on GnRH-Stimulated LH Peak
The study of Hae Sang Lee, MD. et al. finds that BMI is negatively related to
GnRH-Stimulated LH peak in male with precocious puberty.
Neuroendocrinology. 2012 Sep 20.
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Obesity (Silver Spring). 2015 Mar;23(3):637-43.
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Summary
Excess adiposity during childhood may influence pubertal development.
(advance in girls, while dispute in boys].
It is possible that Excess adiposity related abnormalities may affect the
hypothalamic-pituitary unit and promote both early puberty and early,
abnormal weight gain
Obesity has an important effect on the sex hormones level, studies has
showed nocturnal LH secretion in obese and overweight children is
weaker than that of children with normal weight, and BMI is negatively
related to GnRH-Stimulated LH peak in children with precocious puberty.
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