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Limited Delayed Puberty AdultJia Zhu, MD, Yee-Ming Consequences Chan, MD, PhD of Self- Limited Delayed Pubertyabstract ≥ Delayed puberty is a common condition defined as the lack of sexual maturation by an age 2 SD above the population mean.‍ In the absence of an identified underlying cause, the condition is usually self-limited.‍ Although self-limited delayed puberty is largely believed to be a benign developmental variant with no long-term consequences, several studies have suggested that delayed puberty may in fact have both harmful and protective effects on various adult health outcomes.‍ In particular, height and bone mineral density have been shown to be compromised in some studies of adults with a history of delayed puberty.‍ Delayed puberty may also negatively affect adult psychosocial functioning and educational achievement, and individuals with a history of delayed puberty carry a higher risk for metabolic and cardiovascular disorders.‍ In contrast, a history of delayed puberty appears to be protective for breast and endometrial Division of Endocrinology, Department of Medicine, Boston cancer in women and for testicular cancer in men.‍ Most studies on adult Children’s Hospital, Boston, Massachusetts outcomes of self-limited delayed puberty have been in small series with Dr Zhu conducted the initial literature review, wrote significant variability in outcome measures and study criteria.‍ In this the first draft, and revised the manuscript; Dr Chan article, we review potential medical and psychosocial issues for adults with conceptualized the review and reviewed and revised a history of self-limited delayed puberty, discuss potential mechanisms the manuscript; and both authors approved the final manuscript as submitted. underlying these issues, and identify gaps in knowledge and directions for future research.‍ DOI: https:// doi. org/ 10. 1542/ peds. 2016- 3177 Accepted for publication Jan 6, 2017 Address correspondence to Yee-Ming Chan, MD, Delayed puberty is commonly defined resolves by age 18 years, and in this PhD, Boston Children’s Hospital, 300 Longwood ≥ “ ” as the absence of physical signs of review, this condition is referred to as Avenue, Boston, MA 02115. E-mail: Yee-Ming.Chan@ childrens.harvard.edu puberty by an age 2 SD beyond the self-limited delayed puberty.‍ This population mean for pubertal entry, condition is also called constitutional PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, “ ” 1098-4275). a statistical definition necessitated delay of puberty, development, or by our incomplete understanding maturation, with the word growth Copyright © 2017 by the American Academy of Pediatrics of how the timing1 of puberty is also frequently included (eg, determined.‍ For girls, delayed constitutional delay of growth and FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships puberty [CDGP]).‍ puberty is commonly defined as relevant to this article to disclose. the absence of breast development Self-limited delayed puberty is FUNDING: Dr Chan was supported by a Doris by age 13 years and for boys as the considered by many to be a benign Duke Clinical Scientist Development Award (grant absence of testicular enlargement by developmental variant with no 2013110). age 14 years.‍ Of note, these clinical 14,15 long-term consequences.‍ Thus, POTENTIAL CONFLICT OF INTEREST: The authors conventions do not reflect variation “ ” the mainstay of treatment is an have indicated they have no potential conflicts of in pubertal timing between racial interest to disclose. observational, watchful waiting and ethnic groups or a recent trend approach with reassurance for the toward earlier pubertal timing that – patient and family.‍ However, some has been observed in the United States To cite: Zhu J and Chan YM. Adult Consequences 2 13 reports have suggested that the of Self-Limited Delayed Puberty. Pediatrics. and other developed countries.‍ condition can have lasting physical 2017;139(6):e20163177 In the absence of any identifiable and psychological effects, which raises cause, delayed puberty usually the question whether sex-steroid Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 139, number 6, June 2017:e20163177 STATE-OF-THE-ART REVIEW ARTICLE 34 therapy should be initiated by a these individuals are typically shorter than the 90th percentile) or with certain age in all individuals with during the teenage years than peers a target height that is not short 17, 18 – self-limited delayed puberty to with normal pubertal timing.‍ (defined as37 target height less than prevent or temper any of these Further compounding the short 1.‍5 SDs) were found to reach or effects.‍ These studies were conducted stature during early adolescence is exceed their target height (Tables 1 predominantly in Caucasian the fact that, in addition to having and 2).‍ These studies suggest that populations and used traditional a delayed pubertal growth spurt, individuals with familial short stature cutoffs for delayed puberty and individuals with self-limited delayed in combination with self-limited may thus be limited in their puberty often have a slow19 growth delayed puberty are particularly generalizability; nonetheless, they velocity before puberty.‍ When likely to fall short of their target provide insight into the potential these individuals do eventually heightCorrelations.‍ With Prepubertal consequences of self-limited delayed undergo a pubertal growth spurt, Growth puberty.‍ In this review, we examine the conventional teaching is that this “ ” consequences of self-limited pubertal growth spurt, albeit delayed, allows delay on height, bone mineral density them to catch up and attain20 their Another factor that has been (BMD), psychosocial functioning, Conflictingfull genetic height Observations potential.‍ suggested to play a role in and educational achievement, as well determining adult height in as associations between delayed individuals with self-limited delayed puberty and the risks for adult puberty is the rate of growth during Consistent with this teaching, several cancers and cardiovascular disorders.‍ the childhood years before puberty, observational studies report that with a slow rate of prepubertal METHODS children with self-limited delayed growth associated with failure to puberty eventually achieve their attain target height in both boys and genetic height potential, with no girls with an otherwise unremarkable The PubMed database was searched significant difference between 36,39 medical evaluation.‍ In boys, using the following medical subject measured adult height and predicted ∼ – such individuals had adult heights heading terms and keywords: adult height (ie, midparental target 21 25 0.‍63 SD ( 4 cm) less than predicted, delayed puberty, adult height, BMD, height) (Tables 1 and 2).‍ whereas those with normal rates fracture, depression, substance use, However, other studies suggest that ∼ of prepubertal growth had no such self-esteem, educational achievement, these individuals fall short of their – height deficits (Fig 1).‍ Height gain breast cancer, endometrial cancer, target height by 0.‍6 to 1.‍5 SD, 4 to 26 32 during the pubertal growth spurt testicular cancer, prostate cancer, 11 cm (Tables 1 and 2).‍ These was comparable between the 2 cardiovascular disease, myocardial disparate findings may be due to groups, and thus the growth during infarction, peripheral arterial disease, variation in study populations due puberty did not compensate for stroke, hypertension, and metabolic to ascertainment criteria, inclusion the prepubertal growth deficit in syndrome.‍ All relevant articles criteria (which sometimes include individuals with slow prepubertal published from 2006 to 2016 were growth delay), and/or use of sex- 36 growth (Table 1).‍ In both boys and included in the review.‍ Articles steroid treatment.‍ Thus, these girls, individuals with slower growth published before 2006 were included findings have prompted attempts to rates in childhood also had shorter if they provided key background identify features that may predict parents, which support previous information, demonstrated a new or which individuals will fail to meet conclusions that familial short stature significant finding in the field, and/ their genetic height potential.‍ Role of Familial Short Stature may limit individuals from reaching or summarized previous findings their target height and suggests a in a review and/or meta-analyses.‍ possible genetic component to the References of selected articles were 34, 37 One factor that appears to influence slowEffects growth of Sex-Steroid rate.‍ Therapy reviewed for additional articles not whether target height is ultimately identified on the initial search.‍ attained in self-limited delayed HEIGHT puberty is the target height itself.‍ Sex-steroid therapy (eg, testosterone Delayed puberty is often (although in boys, estradiol in girls) can be not always) seen in the context of offered to ameliorate psychosocial 1 Puberty is marked by a period of familial short stature, which can distress related to delayed puberty.‍ rapid skeletal 16growth, the pubertal exacerbate1 concerns regarding short Several observational studies and growth spurt.‍ Because this growth stature.‍ Individuals with self-limited 2 randomized trials have examined acceleration is delayed in individuals delayed puberty with at least 1 tall the effects of sex-steroid therapy with self-limited delayed puberty, parent (defined as height greater on height in boys with self-limited Downloaded from
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