Pediatric obesity and development of the penis and testis

The prevalence of pediatric obesity is increasing wordwide [1, 2]. The 2022 World Obesity Atlas has estimated that over 100 million children between the age of five to nine will have obesity worldwide by 2030 and that over 150 million children between the age of ten to nineteen will be obese [3]. Increased sedentary time, reduced physical activity time, consumption of poor-nutrient-high-calorie food, and sleep deprivation are some common obesogenic behaviors of pediatric obesity [4].

Childhood obesity is a condition that requires attention at a national level since it can be carried out until adulthood [5]. It is widely known to be related to health problems such as hypertension, cardiovascular diseases, metabolic disorders, and psychosocial problems [6]. The state of being overweight or obese may lead to children being vulnerable to weight-related stigma, which in turn can lead to depression and body dissatisfaction [7].

In association with puberty, several studies have determined the relationship between obesity and sexual maturation. Increasing adiposity is known to be associated with precocious puberty in girls, although results are controversial in boys. Pereira et al. [8] have found that obesity at four to seven years of age and childhood mean body mass index (BMI) standard deviation score (SDS) are associated with precocious gonadarche. They also found that mean age at testicular enlargement was inversely associated with BMI SDS, waist circumference, and percentage of fat mass. In contrast, Lee et al. [9] have conducted a study on 401 boys to determine the relationship between BMI and tanner stage and found that puberty is delayed in obese boys. Effects of obesity on puberty and sexual development are still equivocal up to date. Therefore, our study aimed to determine the relationship between obesity and genital development in boys by comparing anthropometric measures of male external genitalia in pediatric patients without penile or testicular abnormalities.

This study was conducted retrospectively using medical records of 1,499 male patients between the age of two and eighteen who visited our pediatric urology clinic with a renal or bladder complaint between January of 2019 and December of 2022. Their diagnosis included nocturnal enuresis, overactive bladder, vesicoureteral reflux, antenatal hydronephrosis, megaureter, ureteropelvic junction obstruction, urolithiasis, and so on. All data were prospectively collected and recorded after physical examination at the time of visit. Patients who are considered underweight for age were excluded. Patients with abnormalities of the penis or testes, disorder of sex development, developmental disability, endocrinology disorder, and chromosomal anomalies were also excluded from this study.

Parameters collected from each patient included age, height, weight, BMI, baseline penile length (BPL), stretched penile length (SPL), penile circumference (PC), and mean testicular volume of both sides. All measurements were taken by a single urologist to reduce measurement bias. Penile parameters such as BPL, SPL, and PC were measured using a flexible measuring tape. BPL was taken by measuring the linear distance from the pubo-penile junction to the tip of the glans at a flaccid state. SPL was measured from the pubo-penile junction to the tip of the glans at a maximally stretched state. Both measurements were taken while pushing the suprapubic fat inward to reduce error between normal and high BMI groups. PC was measured at the middle of the penile shaft. Mean testicular volume was calculated by measuring bilateral testicular sizes using a Prader orchidometer in milliliter at room temperature [10, 11].

Based on Centers for Disease Control (CDC) definition, BMI was calculated by dividing weight in kilograms by the square of height in meters. For pediatric population, instead of a cut off value, the reference is age and gender specific. CDC growth chart shows BMI-for-age percentile from age two through nineteen years. This was the reason why this study included patients of the same age range. CDC defines underweight as being under 5th percentile, overweight as being in between 85th and 94th percentile, and obese as being in 95th percentile or greater [12]. In this study, patients were divided into two groups: (1) normal BMI group, patients between 5th and 85th percentile for BMI-for-age, and (2) high BMI group, overweight and obese children who exceeded 85th percentile for BMI-for-age. All parameters were analyzed as a whole and within age groups.

The mean age of a total of 1,499 patients was 81.34±44.45 months. The mean height of all age groups of this study showed similar growth trends with 2017 Korean National Growth Charts for children and adolescents [13]. Patients were divided into two groups based on their BMI: normal BMI group (n=851, 56.8%) and high BMI group (n=648, 43.2%). Within the high BMI group, 253 patients were overweight (16.9%) and 395 patients were obese (26.4%). The mean age and height for the two groups were similar (82.32±45.79 months vs. 80.08±42.61 months, p=0.333; 119.87±24.44 cm vs. 120.07±24.56 cm, p=0.876). Weight and BMI were significantly greater in the high BMI group as expected (24.55±13.80 kg vs. 32.38±18.65 kg, 16.49±1.82 kg/m² vs. 20.50±3.68 kg/m², p<0.05) (Table 1, Supplementary Table 1). Weight and BMI were also significantly greater in the high BMI group in all age groups (Table 2).

Table 1
Comparison of patient characteristics, penile parameters, and testicular volume according to BMI

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Table 2
Height, weight, and BMI within age groups

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Patients of the normal BMI group showed longer BPL and SPL than patients with a high BMI (3.76±1.65 cm vs. 3.52±1.37 cm, 5.17±1.77 cm vs. 4.99±1.48 cm, respectively, p<0.05). Although PC and mean testicular volumes showed a greater tendency in the normal BMI group, they were not significantly different between the two groups (4.80±1.48 cm vs. 4.70±1.29 cm, 3.87±4.43 mL vs. 3.55±4.04 mL, p>0.05).

When the same parameters were assessed within age groups, BPL did not show significant difference between the two groups until age ten where normal BMI group showed significantly longer BPL. SPL of the normal BMI group showed a tendency to be longer starting at age eleven, although the difference was not statistically significant throughout all age groups. PC and mean testicular volume did not show any significant difference among age groups (Table 3, Fig. 1).

Fig. 1
Figure shows the growth charts of (A) baseline penile length (BPL), (B) stretched penile length (SPL), (C) penile circumference, and (D) mean testicular volume between boys with normal body mass index (BMI) for age and high BMI for age. Statistically significant differences are denoted with asterisks. Normal BMI, 5th–85th percentile; High BMI, ≥85th percentile.

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Table 3
Penile parameters and mean testicular volume within age groups

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Nowadays, pediatric obesity is becoming a pandemic problem where increasing obesogenic behaviors make the pediatric population vulnerable to obesity globally. Pediatric obesity is an important issue to be solved since it usually carries out until adulthood. Obesity is already proven to be associated with hypertension, cardiovascular diseases, metabolic disorders, and psychosocial problems [6]. Many studies have shown a positive relationship between precocious puberty and obesity in girls. However, studies regarding obesity and puberty timing in boys are equivocal [8, 9]. With this in mind, our study aimed to observe how obesity could affect the male pediatric population from a urological point of view, making development of external genitalia as the primary outcome.

To the best of our knowledge, this is the first study to analyze the relationship of obesity with the development of external genitalia among a large population of pediatric patients including both prepubertal and pubertal boys. This study further elaborated the finding by comparing within different age groups. Results of our study showed that BMI had negative relationship with penile length. When compared within age groups, penile length was significantly longer in normal weight boys starting from age ten to eleven years. However, the mean testicular volume did not show significant difference between boys with normal BMI and high BMI.

Penile length dramatically increases during the first three months after birth. This period is called “minipuberty.” During this time, there is a gonadotropin surge due to the loss of inhibitory effects of maternal estrogen. Penile length goes through another significant increase during adolescence. Its final size is reached when the hypothalamic pituitary gonadal axis is re-activated [14, 15]. As a result, gonadotropin-releasing hormone (GnRH) is released to stimulate the release of other hormones such as gonadotrophins, luteinizing hormone (LH), and follicle stimulating hormone (FSH). LH can stimulate Leydig cells on testosterone production, while FSH can stimulate spermatogenesis in Sertoli cells [16]. Testis is composed of seminiferous tubules which consist of Sertoli cells and germ cells surrounded by peritubular myoid cells [17]. Leydig cells exist in the interstitial tissue around seminiferous tubules. They make up for about 20% to 30% of total testicular volume [18]. When preparing for puberty, Sertoli cells proliferate and cause elongation of seminiferous tubules, which in turn leads to testicular enlargement [19]. Thus, the beginning of puberty can be estimated by testicular enlargement of greater than 3 mL termed gonadarche that precedes increase in penile length [20]. Sex steroids, including testosterone and estrogen, play an important role in masculinization of pubertal boys, such as increasing penile length and circumference, scrotal development, male hair pattern development, and appropriate changes in the musculoskeletal system [21].

Although research on obesity’s effect on pediatric testosterone level is scarce, research studies about obesity’s effect on testosterone level in adult males are readily available. Aromatase is an enzyme that converts testosterone into estradiol. It is expressed in the hypothalamus and peripheral adipose tissue. Abundant aromatase activity can lead to an increase in estrogen, which in turn suppresses testosterone secretion from gonads through a cascade of reactions [22]. The conversion of testosterone into estradiol itself also lowers androgen level, thus forming a hypogonadal-obesity cycle [23]. Many studies have shown that lower testosterone levels in prostate cancer patients undergoing androgen deprivation therapy can result in increased weight and body fat [24]. Therefore, abundance of fat in body composition can lower androgen levels, which in turn cam increase body fat, causing a favorable state to become obese. In turn, decreased androgen may lead to delayed or inefficient genital development.

There has been one study in the pediatric field reporting an inverse correlation between pediatric penile length and testosterone level [25]. Mancini et al. [25] have used a similar penile measuring technique as our BPL measurement in which the length is taken by measuring the penis from the pubic angle to the top of the glans at a flaccid state without pushing the suprapubic fat. They found that obese boys had significantly lower testosterone levels and shorter penile lengths than normal weight boys. They also found a positive correlation between penile length and testosterone level, but not between penile length and BMI. This finding was the opposite of our finding where BMI showed a negative correlation with penile length. Our study compared between normal BMI and high BMI, which included overweight and obese boys according to CDC definition. However, their study included overweight boys in the normal weight group. Their results have confirmed that testosterone plays a key role in penile growth and suggested that obesity in pediatrics might lead to lower testosterone level which in turn can lead to shorter penile length.

Our findings suggest that BMI does not affect testis growth. However, there was a significant gap in penile growth between normal BMI and high BMI boys. Thus, it is necessary to search for the difference in testosterone in terms of synthesis and metabolism between boys of normal versus high BMI. The biggest limitation of our study was that serum testosterone was not included. Future research that includes hormone levels in underway. This upcoming study may further elucidate the effect BMI on genital development. Another limitation of this study was possible error in measuring flaccid and stretched penis. Although all measurements were taken by a single urologist to reduce interobserver bias, measurement of penile length is vulnerable to error due to suprapubic fat in high BMI patients or severe phimosis in all patients. A novel universal method that is less influenced by patient factors might be needed for better analysis. Lastly, although our study encompassed boys of all ages older than two years, the sample size decreased as the age increases, making the data not representative of that specific age group.

Our study confirmed that pediatric obesity had a negative effect on penile length during puberty. Overall, overweight and obese boys had shorter BPL than that of normal boys. BPL was found to be significantly longer in the normal BMI group starting at age ten. SPL tends to be longer in the normal BMI group starting at age eleven. However, there was no significant relationship between BMI and PC or testis volume. Results of this study suggest that childhood obesity does not affect the growth of testis, but the growth of penile length. Our upcoming research includes testosterone level and will take into consideration the onset of puberty and metabolism of hormones which affect external genital development.

Supplementary material can be found via https://doi.org/10.4111/icu.20230287.

Supplementary Table 1

Comparison of patient characteristics, penile parameters, and testicular volume according to exact BMI categories