Abstract and Introduction
With the declining age at onset of puberty and increasing prevalence of childhood obesity, early breast development in young obese girls has become a more frequent occurrence. Here, we examine available literature to answer a series of questions regarding how obesity impacts the evaluation and management of precocious puberty. We focus on girls as the literature is more robust, but include boys where literature permits.
Suggestions Include: (1) Age cutoffs for evaluation of precocious puberty should not differ substantially from those used for nonobese children. Obese girls with confirmed thelarche should be evaluated for gonadotropin-dependent, central precocious puberty (CPP) to determine if further investigation or treatment is warranted. (2) Basal luteinizing hormone (LH) levels remain a recommended first-line test. However, if stimulation testing is utilized, there is a theoretical possibility that the lower peak LH responses seen in obesity could lead to a false negative result. (3) Advanced bone age (BA) is common among obese girls even without early puberty; hence its diagnostic utility is limited. (4) Obesity does not eliminate the need for magnetic resonance imaging in girls with true CPP. Age and clinical features should determine who warrants neuroimaging. (5) BA can be used to predict adult height in obese girls with CPP to inform counseling around treatment. (6) Use of gonadotropin-releasing hormone analogues (GnRHa) leads to increased adult height in obese girls. (7) Obesity should not limit GnRHa use as these agents do not worsen weight status in obese girls with CPP.
Traditionally, the onset of secondary sexual characteristics prior to age 8 years in girls and 9 years in boys has been considered precocious. However, data over the past 50 years indicate that puberty is occurring at younger ages than previously. This shift is greater in girls, as the age of onset of breast development (thelarche) has shown the most pronounced decline,[1–7] leading some to recommend lowering the cutoff for precocity to 7 years in girls. While most girls referred for suspected precocious puberty will represent benign variants of normal growth and physical development, the proportion who prove to have true, gonadotropin-releasing hormone (GnRH)-dependent central puberty is not insignificant (up to 20% in some reports), with underlying disorders identified in up to 18% of cases.[9–11] Thus, controversy remains around what ages should be used as cutoffs for diagnostic evaluations among children with early development of secondary sexual characteristics.
A significant rise in the prevalence of pediatric obesity has paralleled the decreasing age of pubertal onset, and multiple studies have demonstrated that overweight and obesity are associated with earlier timing of puberty in girls.[10,12–18] Data are less consistent for boys, implying the relationship between adiposity and pubertal timing may be more complex in males, where the overall effects are not as large. Still, the preponderance of studies in boys do support that earlier pubertal timing is associated with increased indices of adiposity.[19–24] The mechanistic link between overweight and obesity and early puberty is not fully understood, but elevated levels of leptin[25–28] and adipokines have been suggested to play a role. So too have insulin resistance leading to increased adrenal androgen production and increased aromatase activity in adipose tissue leading to peripheral conversion of androgens to estrogen.[30–32] Through these or other mechanisms, increased adiposity could contribute to GnRH-dependent but idiopathic central precocious puberty (CPP) and to isolated early development of androgen and/or estrogen-mediated secondary sexual characteristics.
The effects of overweight and obesity on pubertal development raise the question of how weight status affects evaluation and management of children with early signs of puberty. The general approach to children with early development of secondary sexual characteristics has been reviewed recently.[33–35] The differential diagnosis of early secondary sexual characteristics includes peripheral precocities (such as congenital adrenal hyperplasia, McCune Albright syndrome, and ovarian tumors), benign variants (such as premature thelarche and adrenarche), environmental exposures (such as lavender or tea tree oil), and true, progressive CPP. Depending on the clinical features, all these entities may need to be considered during evaluation, especially if progression is rapid or development is contrasexual.[33–35] In this review, we specifically focus on our approach to the overweight or obese child whose presentation raises concern for CPP, with suggestions summarized in Figure 1. We address the following questions, as they pertain to the most common scenario—a young girl presenting with early breast development:
Evaluation and management algorithm for girls with CPP. Flow diagram for the nonobese girl with early breast development is presented with comments made in righthand panel delineating considerations warranted for the obese (BMI ≥ 85th percentile) girl. * Basal LH ≥ 0.3 mIU/L and LH stim > 5.0 mIU/L pertain to cutoffs used for most assays. Abbreviations: BA, bone Age; BMI, body mass index; CPP, central precocious puberty; FHx, family history; GnRH, gonadotropin-releasing hormone; GnRHa, gonadotropin-releasing hormone analogues; LH, luteinizing hormone; MRI, magnetic resonance imaging; PAH, predicted adult height; PMHx, past medical history.
Affect age cutoffs for the initial evaluation of such patients?
Affect results of diagnostic testing?
Affect criteria for evaluation with magnetic resonance imaging (MRI) in the case of true CPP?
Impact consideration of GnRH analogue (GnRHa) therapy?
Worsen due to GnRHa therapy?
We close with discussion of areas of uncertainty, including whether responses to these questions differ for boys.
J Endo Soc. 2022;6(1) © 2022 Endocrine Society