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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


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


Childhood Obesity ---the consequences of

overnutrition and the prevalent trend worldwide


Diabetes

Liver and

Renal

disease

Reproductive

Dysfunction

Pubertal development


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


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.


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


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

514 635

883

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1255

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2010 2011 2012 2013 2014 2015

Annual Precocious Puberty Inpatients

in our Hospital

1סידרה


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.


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.


2.56% of 7-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,



appeared G2, respectively.

0.78% of 10-year-old boys began

to appear G3 or more (Fig. 2).


Contents


2 Relationship Between Body Mass Index and Sexual Development

3 Body Mass Index and Gonadal Axis Hormone Levels


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？


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）


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.）


Is obesity the cause or result of

female gonad initiation?

Obesity has a "switch" effect on the gonad initiation of the female.

Click to edit your text Click to edit your text Click to edit your text

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


OBESITY PUBERTY

Effect of obesity on male sexual initiation


Obesity is possitively

associated with sexual

maturation in both boys

and girls, but it is more

stronger in girls than in

boys.



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


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



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?


Contents


2 Relationship Between Body Mass Index and Sexual development

3 Body Mass Index and Gonadal Hormone Levels


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


Among other factors, adequate nutritional status appears to be

requisite for the central initiation of puberty.


Reproductive axis and obesity

related hormones


Reproductive Field

Leptin Adiponectin


A simplified model of the

leptin-signaling pathway

Endocrinol Metab Clin N Am 38 (2009) 525–548.


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


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


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.


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.


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


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


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


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.


Obesity (Silver Spring). 2015 Mar;23(3):637-43.


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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