**3.2 BMI and POW during follow-up**

The mean BMI was significantly increased after 1 year and increased further afterwards (Fig.1). BMI was higher than the 95th centile in 5 patients (27.8%) at the initiation of therapy, which was also true after 2 years treatment.

Fig. 1. Changes in BMI during GnRHa therapy

Standard Gonadotropin-Suppressive Therapy in Japanese Girls with

baseline and changed little during the GnRHa therapy (Fig. 4).

**0**

**treatment for CA and BA** 

Fig. 4. Changes in POW during GnRHa therapy

r

r

After 1 year or therapy 0.947 After 2 years of therapy 0.926

After 6 months of therapy 0.963 After 1 year of therapy 0.971 After 2 years of therapy 0.975

positively correlated with those during treatment (Table 1, 2).

Table 1. Relationship among BMI SDS for CA during therapy

Table 2. Relationship among BMI SDS for BA during therapy

**4**

**8**

**POW (%)**

**12**

**16**

Idiopathic Central Precocious or Early Puberty Does Not Adversely Affect Body Composition 309

In addition, the POW was higher than 20% (indicating obesity) in 5 patients (27.8%) at the baseline, which was also true after 2 yrs treatment. The mean POW was 8.2 ± 4.0% at the

**Start 6 mo 1 y 2 y**

**3.3 Correlation between the BMI SDS at the start of treatment and that during** 

Regression analysis showed that the BMI SDS for CA and BA at the start of treatment were

The BMI SDS for CA was higher than zero in 14 patients (77.8%) at the initiation of therapy, which was also the case for 13 individuals (72.2%) after 2 years treatment. Furthermore, 5 patients had BMI SDS of higher than 2 SD at the baseline, and 4 patients had BMI SDS of higher than 2 SD after 2 years treatment. The mean BMI SDS for CA was 1.07 ± 0.32 at the baseline and changed little during the therapy (Fig. 2).

Fig. 2. Changes in the BMI SDS for CA during GnRHa therapy

On the other hand, the mean BMI SDS for BA was 0.33 ± 0.25 at the baseline and slightly but not significantly increased during the GnRHa therapy (Fig.3).

Fig. 3. Changes in the BMI SDS for BA during GnRHa therapy

In addition, the POW was higher than 20% (indicating obesity) in 5 patients (27.8%) at the baseline, which was also true after 2 yrs treatment. The mean POW was 8.2 ± 4.0% at the baseline and changed little during the GnRHa therapy (Fig. 4).

Fig. 4. Changes in POW during GnRHa therapy

308 Sex Steroids

The BMI SDS for CA was higher than zero in 14 patients (77.8%) at the initiation of therapy, which was also the case for 13 individuals (72.2%) after 2 years treatment. Furthermore, 5 patients had BMI SDS of higher than 2 SD at the baseline, and 4 patients had BMI SDS of higher than 2 SD after 2 years treatment. The mean BMI SDS for CA was 1.07 ± 0.32 at the

**Start 6 mo 1 y 2 y**

**Start 1 y 2 y**

On the other hand, the mean BMI SDS for BA was 0.33 ± 0.25 at the baseline and slightly but

baseline and changed little during the therapy (Fig. 2).

**0**

**0**

**.5**

**BMI SDS for BA**

**1**

**1.5**

Fig. 2. Changes in the BMI SDS for CA during GnRHa therapy

not significantly increased during the GnRHa therapy (Fig.3).

Fig. 3. Changes in the BMI SDS for BA during GnRHa therapy

**.5**

**BMI SDS for CA**

**1**

**1.5**

## **3.3 Correlation between the BMI SDS at the start of treatment and that during treatment for CA and BA**

Regression analysis showed that the BMI SDS for CA and BA at the start of treatment were positively correlated with those during treatment (Table 1, 2).


Table 1. Relationship among BMI SDS for CA during therapy


Table 2. Relationship among BMI SDS for BA during therapy

Standard Gonadotropin-Suppressive Therapy in Japanese Girls with

Idiopathic Central Precocious or Early Puberty Does Not Adversely Affect Body Composition 311

increased. In addition, their mean BMI SDS was higher than zero at the baseline and increased during treatment. Chiumello et al. treated 14 girls and 2 boys with CPP with leuprolide and triptorelin for at least 1 year. (Chiumello et al., 2000) They concluded that fat mass is increased by GnRHa therapy and that this could lead to obesity; therefore, they suggested that CPP patients undergo a shortened period of pubertal lean mass development and that while the progression of puberty in these patients is associated with increases in fat and lean mass, only the latter is blocked by the "menopausal effect" or the GnRHa therapy itself. van der Sluis et al., who belong to the same group as Boot, reported 47 patients (36 girls and 11 boys) with CPP or early puberty who received leuprolide-acetate for a mean period of 2.7 years. (van der Sluis et al., 2002) In this cohort, BMI SDS increased significantly during treatment, whereas lean body mass decreased significantly during treatment, and percentage body fat increased. Paterson et al. reported 46 girls with CPP or early puberty who received goserelin for a mean period of 1.6 years. (Paterson et al., 2004) In this group, there was a marked increase in BMI following treatment. On average, the girls were fatter than the general population before treatment (BMI SDS: 0.93) and were significantly fatter (BMI SDS: 1.2) than the general population after the completion of therapy. Before treatment, 19 (41%) girls were overweight (BMI > 85th centile), 13 (28%) of whom were obese (BMI > 95th centile), which rose to 27 (59%) overweight patients, of whom 18 (39%) were obese, after the completion of therapy. Wacharasindhu et al. treated 10 Thai girls with CPP for a period of 1 year and reported that their percentage fat values increased significantly.

(Wacharsindhu et al., 2006) So far, this is the only report in an Oriental population.

BMI increase.

during GnRHa therapy.

In contrast, some authors have reported no change throughout the observation period. (Palmert et al., 1999, Herger et al., 1999, Pasuquino et al., 2008) For example, Heger et al. treated 50 girls with CPP with depot triptorelin for a mean period of 4.4 years and reported that their BMI SDS values at pretreatment, at the end of treatment, and at final height were not significantly different. (Herger et al., 1999) Palmert et al. treated 96 girls and 14 boys with CPP with deslorelin or histrelin for 36 months. (Palmert et al., 1999) Among the girls, multiple regression analysis indicated that the BMI SDS for CA at the pretherapy visit was the greatest predictor of the BMI SDS for CA at the end of treatment. They concluded that the administration of GnRHa did not influence the progression of adolescent CPP patients toward obesity. Pasquino et al. reported 87 girls with CPP who received depot triptorelin for a mean period of 4.2 years. (Pasuquino et al., 2008) Their BMI increased markedly during treatment, but their BMI SDS for CA did not change significantly. In addition, 14.3% of the girls were overweight and 9.1 % were obese at the start of therapy, and both categories contained 11.7% of patients at the discontinuation of treatment. Although the patients' overall BMI increased, they remained in the same BMI centile and had the same BMI SDS throughout the treatment period. Regression analysis showed that the BMI SDS for CA at the end of treatment was positively correlated with the BMI SDS for CA at the start of treatment. As a result, they concluded that GnRHa treatment did not result in a significant

On the other hand, Arrigo et al. reported 101 girls with CPP who received decapeptyl depot for over 2 years. (Arrigo et al., 2004) As described above, a quarter of the girls were classified as obese at the start of therapy, and only 4% of them were still obese at the end of therapy. BMI SDS did not increase in any of the patients during the therapy period. In fact, both the mean BMI SDS and obesity prevalence significantly decreased during the treatment period. This is the only report to state that BMI and the prevalence of obesity decreased
