Precocious Puberty: Changing Trends in Diagnosis and Treatment

Objective: the complications of precocious puberty may include premature menarche, shortened adult height due to accelerated bane maturation, and psychological distress. With advances in molecular biology and medical imaging techniques, and with a decade and a half of experience with the use of gonadotrophin-releasing hormone (GnRH) agonist analogue therapy to suppress central precocious puberty, the diagnosis and treatment of sexual precocity has been greatly refined. This paper discusses the recent advances in diagnostic and therapeutic interventions for central precocious puberty in girls, with emphasis on the following outcomes: final adult height, ovarian function, and psychological sequelae.Methods: we reviewed the literature on the diagnosis and therapy of precocious puberty. Data were abstracted from reports that included outcome measures of final adult height, ovarian/menstrual function or psychological assessments in treated and untreated female patients.Results: most reports demonstrate increased final adult height in women treated with GnRH analogues when compared to reports of untreated patients or those treated with cyproterone acetate or medroxyprogesterone acetate. This effect appears to be most marked in patients with extremely precocious pubertal onset, before age five to six years. Menarche occurs within two years of treatment cessation in nearly all patients. Limited data exist regarding the psychological consequences of sexual precocity or its treatment.Conclusion: GnRH analogues have become the treatment of choice for girls with central precocious puberty. Their ability to suppress chronically the central activation of the hypothalamic-pituitary-ovarian axis represents a major advance, and results in the slowing of bone maturation and the reversible delay of menarche and the progression of secondary sexual characteristics.     

Comparison of the Clinical and Anthropometric Features of Treated and Untreated Girls with Borderline Early Puberty

Study ObjectiveRisks associated with precocious puberty might be observed in the rapidly progressive form of borderline early puberty (BEP). Differentiating the rate of progression is important for deciding treatment with gonadotropin-releasing hormone analogue (GnRHa). The aim was to examine the treatment characteristics and effect of treatment on predicted adult height (PAH).DesignRetrospective observational study.SettingSingle-center, a pediatric endocrinology unit.ParticipantsA total of 135 girls, pubertal findings starting between 7-10 years of age.InterventionsData were collected via chart review. Patient groups were defined as treated with GnRHa (n = 63) or untreated (n = 72) girls.Main Outcome MeasuresReferral characteristics and anthropometric and pubertal findings of the patients with BEP, effect of treatment on PAH, and final height of the groups were compared.ResultsThe mean (±SD) age of the patients at admission and for the first appearence of pubertal findings was 8.8 ± 1.0 and 8.0 ± 0.8 years, respectively. Target height and PAH-target height values at admission were similar. At initiation of treatment, PAH of the treated girls (157.8 ± 7.2 cm) were significantly lower compared with untreated girls (160.7 ± 6.5 cm). The age at menarche of patients in the treated and untreated groups were 12.3 ± 1.0 and 11.3 ± 1.1 years, respectively. The final height of the groups were similar (157.1 ± 6.6 vs 157.0 ± 5.9 cm; P = .922) despite a lower PAH of the treated group.ConclusionGnRHa treatment resulted in an increase in PAH and normalized the age of menarche in patients with BEP. In selected girls with rapidly progressive BEP, GnRHa treatment may be considered.     

Final height in girls with slowly progressive untreated central precocious puberty

A group of six girls with slowly progressive idiopathic precocious puberty (IPP) and a good initial height prognosis was followed without treatment. At first observation the girls had a bone age advance over chronological age of no more than 18 months, a Δheight age (ΔHA):Δbone age (ΔBA) ratio higher than 0.9 and height prognosis was unimpaired after 6 months. During the first two years of follow-up the girls maintained an acceptable height potential. The ΔHA:ΔBA ratio remained constant at greater than 0.9. Predicted height showed a slight increase or decrease (± 4 cm). The girls were reevaluated after the age of14 years and followed-up until they reached their final height (FH). The mean FH(155.4±2.8 cm) was below the mean target height (159.3 ± 4.2 cm) by 3.9 cm (range -2.1 to -6.7 cm); this difference was not statistically significant. The FH was more than 5 cm below the target height in only one case; this girl had the most precocious onset of puberty, at 6 years of age. In three cases FH was between the 3rd and 10th centiles. These three girls had a target height below 158 cm (< 25th centile). Girls with slowly progressive IPP and a good initial height prognosis preserved height potential with an acceptable final height without therapy.     

Serum Makorin ring finger protein 3 values for predicting Central precocious puberty in girls

This study evaluated the serum level of MKRN3 and investigated its diagnostic usefulness in girls with central precocious puberty (CPP). In total, 41 girls with CPP and 35 age-matched normal control girls were enrolled. Serum values of MKRN3 were measured in both groups. Gonadotropin and estradiol concentrations were evaluated after 6 and 12?months of GnRH agonist (GnRHa) treatment in CPP patients. The MKRN3 concentrations were much lower in the patient group than in the control group (p?=?.005). Over 1 year of GnRHa treatment in patients, the gonadotropin concentrations were significantly decreased (p?<?.05), while the MKRN3 concentrations were unchanged (p?>?.05). MKRN3 levels were inversely correlated to standard deviation (SD) in height (r?=??0.46, p?=?.000), SD in weight (r?=??0.32, p?=?.005), Tanner stage (r?=??0.41, p?=?.000), and bone age (r?=??0.46, p?=?.000). Based on ROC analysis, the area under curve was 0.758 for MKRN3, with 82.9% sensitivity and 68.5% specificity. The measurement of serum MKRN3 level may provide some help for CPP prediction, but relatively various values need further validation     

促性腺激素释放激素类似物（曲普瑞林）治疗女童特发性中枢性性早熟23例疗效观察

目的观察促性腺激素释放激素类似物（曲普瑞林）治疗女童特发性中枢性性早熟（ICPP）的临床疗效。方法应用曲普瑞林治疗23例ICPP女童6个月,观察治疗前后第二性征、子宫、卵巢、骨龄（BA）、血清雌二醇（E2）、促性腺激素释放激素（GnRH）激发试验激素水平、预测成人终身高的变化及药物副反应。结果治疗后患儿乳房、子宫、卵巢体积均有缩小,E2、促黄体生成激素（LH）、卵泡刺激素（FSH）峰值均显著降低,骨龄成熟延迟,骨龄/实际生活年龄（BA/CA）值下降,预测成人终身高治疗前为（155.5±0.81）cm,治疗后为（157.0±0.81）cm,较治疗前有改善,差异具有统计学意义（P〈0.01）。结论曲普瑞林治疗ICPP能够抑制性腺轴及性腺发育,延缓BA成熟,最终对改善成人终身高有意义。     

促性腺激素释放激素激动剂治疗与骨量丢失

促性腺激素释放激素激动剂（GnRH-a）已广泛应用于妇科子宫内膜异位症、子宫肌瘤、性早熟等雌激素依赖性疾病的治疗。但其导致的低雌激素血症与骨丢失也愈来愈引起人们的认识和重视。GnRH-a与HRT反向添加疗法可以降低骨丢失、改善生活质量,从而延长GnRH-a治疗时间。     

Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism.

OBJECTIVE: To compare pulsatile gonadotropin-releasing hormone (GnRH) therapy with gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. DESIGN: Prospective study. Patients had free choice between the two forms of therapy. SETTING: Patients were treated on an outpatient basis in our department. PATIENTS: Eighteen patients of matched age (mean [+/- SD] age: 21.1 +/- 3.0 years and 23.6 +/- 7.3 years) and similar testicular volume were treated in each group. INTERVENTIONS: Pulsatile GnRH therapy was started with 4 micrograms GnRH subcutaneously every 2 hours using a portable pump and gonadotropin therapy with 3 x 2,500 IU human chorionic gonadotropin (hCG) weekly injected intramuscularly. After 8 to 12 weeks of hCG treatment, 150 IU human menopausal gonadotropin two to four times weekly were added. RESULTS: Testosterone (T) and estradiol (E2) levels increased significantly higher (T: P less than 0.03; E2; P less than 0.001) in the gonadotropin group than in the GnRH group (T: 22.5 +/- 8.1 versus 16.8 +/- 5.5 nmol/L; E2: 150 +/- 70 versus 88. +/- 59 pmol/L). Five patients developed gynecomastia during gonadotropin therapy. The rise of testicular volume was significantly more pronounced (P less than 0.001) in the GnRH group (delta testicular volume = 8.1 +/- 2.0 mL) than in the gonadotropin group (delta testicular volume = 4.8 +/- 1.8 mL). Ten patients of the GnRH and 8 of the gonadotropin group had positive sperm counts, ranging from 1.5 to 26 x 10(6) spermatozoa/mL. The latter was achieved more rapidly in the GnRH group (12 +/- 1.6 versus 20 +/- 2.3 months: P less than 0.02). CONCLUSIONS: Endocrine and exocrine testicular function can be normalized by both forms of therapy. Gonadotropin therapy has more side effects. Gonadotropin-releasing hormone leads to a higher testicular volume and a more rapid initiation of spermatogenesis compared with gonadotropin therapy.     

Adult height of patients with classical congenital adrenal hyperplasia.

BACKGROUND AND PURPOSE: Data on factors that affect the final height of patients with classical congenital adrenal hyperplasia (CAH) are limited. This study investigated the factors that can affect height outcome of patients with classical CAH. METHODS: A retrospective study of 44 patients (16 males, 28 females) with classical CAH who had attained the adult height without gonadotropin-releasing hormone analog therapy was conducted. Adult height standard deviation scores (AHSDS) and target height standard deviation scores (THSDS) were determined. The impact of type, gender, control of disease activity or occurrence of precocious puberty on height was analyzed. RESULTS: The difference between AHSDS and THSDS of the 44 patients was -0.7 +/- 1.0 and was greatest in simple-virilizing males (-1.1 standard deviation score [SDS]). However, no significant differences in height outcomes were identified between genders and types. The differences between AHSDS and THSDS of patients with good control of disease activity or normal puberty were -0.3 SDS and -0.4 SDS, respectively, which were better height outcomes than those of the other groups (p < 0.05). CONCLUSIONS: Classical CAH can lead to reduced adult height. Good control of disease activity and the prevention of the occurrence of precocious puberty is important to achieving normal adult height outcome.     

不同初治年龄对先天性肾上腺皮质增生症患儿发育的影响

目的了解不同初治年龄对先天性肾上腺皮质增生症(CAH)患儿身高、骨龄、性早熟等方面的影响。 方法将1982~2004年在上海新华医院和上海市儿科医学研究所内分泌、遗传代谢病专科诊治的32例CAH患儿(年龄：女≥8岁，男≥9岁)，按初治年龄分为≤3岁组(14例)和>3岁组(18例)，观察两组间末次复诊时骨龄与身高龄之差、性早熟例数及男女患儿发生性早熟的不同。 结果14例初治年龄≤3岁患儿末次复诊时骨龄与身高龄之差\[(30±20)岁\]与18例>3岁组\[(46±16)岁\]比较差异有显著性(P<005)，初治年龄>3岁组发生真性性早熟(9例)与≤3岁组(2例)比较差异有显著性(χ2=4453，P<005)。男性患儿发生真性性早熟(9例)与女性患儿(2例)比较差异有显著性(χ2=4794，P<005)。 结论CAH患儿≤3岁得到诊治者其预测终身高较>3岁方诊治者明显改善，其性早熟发生率明显减少，男性CAH患儿较女性CAH患儿更易发生性早熟。     

Insight: prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist: a proposed mechanism and management plan

We have previously described our data collected after administration of gonadotropin releasing hormone-agonist (GnRH-a) to delay sexual maturation, in premenarchal girls suffering from idiopathic central precocious puberty.¹ We have explained the recurrent episodes of bleeding due to discontinuation of the estrogen support of the proliferative and stable endometrium. The recognition in recent years of the extra-pituitary functions of GnRH-a, the ability of GnRH to stimulate prostaglandin production and the known role of prostaglandins in irregular vaginal bleeding prompted us to seek alternative explanations to our data.We suggest considering a potential clinical use of combination therapies of GnRH agonists and prostanoid receptor antagonists to treat central precocious puberty.     

32例性早熟临床分析

目的　分析女性真性性早熟 (ICPP)患者的临床特点、探讨该病的诊断、治疗方法。方法　对1984年以来的 32例ICPP患者进行回顾性分析。结果　绝大多数ICPP患儿在月经来潮前都有不同程度的乳房发育、阴道分泌物增加等早期征象 ;而且身高也大多超出同龄人。结论　应重视ICPP患儿的早期临床征象 ,对疑似者尽早行GnRH兴奋试验。促性腺激素释放激素的衍生物 (GnRH -A)治疗ICPP ,不仅疗效显著 ,而且可明显改善患者的身高。     

Effect of growth hormone therapy on adult height of children with turner syndrome

Background/Purpose: Short stature is a common manifestation of Turner syndrome. The purpose of this study was to evaluate the effect of growth hormone (GH) therapy alone on the adult height of children with Turner syndrome. Methods: From 1987 to 2006, 21 Turner syndrome patients who had been treated with GH for > 2 years and had reached adult height were enrolled in the study. The dosage of GH was 0.33 mg/kg/week. Estrogen replacement therapy was prescribed at the age of 15.6 +/- 0.9 years, if indicated. The patients had been followed-up until they reached their adult height. During the same period, 28 Turner syndrome patients who were not treated with growth-promoting agents were enrolled for comparison. Mann-Whitney U test and Wilcoxon signed rank test were used for comparison. Results: Twenty-one patients in the study group started GH therapy at the age of 11.5 +/- 1.8 years. The duration of GH therapy was 4.0 +/- 1.5 years. The growth rate before treatment was 3.8 +/- 0.7 cm/year, which increased to 7.1 +/- 1.4, 5.4 +/- 1.4 and 4.7 +/- 0.9 cm/year during the first 3 years of GH therapy, respectively. Patients who received GH reached an adult height of 150.0 +/- 5.1 cm, which was significantly higher than the 144.7 +/- 5.9 cm of the control group (p < 0.05). The adult height of the study group was 6.3 +/- 3.3 cm taller than their projected adult height upon enrolment. No major adverse events were detected during GH therapy. Conclusion: GH alone is safe and effective for the promotion of growth in children with Turner syndrome in Taiwan.     

Do Most 7- to 8-Year-Old Girls with Early Puberty Require Extensive Investigation and Treatment?

Study ObjectiveTo investigate the etiology, progression, and treatment of precocious puberty in 7- to 8-year-old girls with breast development. Additionally, we evaluated the value of diagnostic tests in differentiating rapidly progressive precocious puberty (RP-PP) and slowly progressive precocious puberty (SP-PP) in these girls.DesignAmbispective cohort study.SettingSingle-center, pediatric endocrinology unit.ParticipantsGirls with breast development between the ages of 7 and 8 years and assessed between July 2016 and July 2018.InterventionsCollected of clinical data and followed-up for 2 to 3 years. Girls were divided into RP-PP and SP-PP groups.Main Outcome MeasuresDescribed the etiology, rate of progression of puberty, and proportion intervened and compared the results of auxiliary examinations between the groups.ResultsA total of 212 girls were enrolled, of which 211 (99.53%) were diagnosed with central precocious puberty (CPP) and 1 with peripheral precocious puberty (PPP). Hypophysis magnetic resonance imaging revealed that none had pathological brain lesions requiring surgical intervention. A total of 95 girls (44.81%) developed RP-PP, and 117 girls (55.19%) developed SP-PP. A total of 31 girls (14.62%) with RP-PP received treatment due to deteriorated predicting adult height. As compared with the SP-PP group, the RP-PP group showed more advanced bone age (BA), a higher level of basal luteinizing hormone (LH), and larger ovarian volume and uterine volumes. Receiver operating characteristic analyses revealed that BA was the best at identifying girls with RP-PP.ConclusionThe majority of girls with breast development between the ages of 7-8 years do not need treatment. BA is a useful preliminary test for identifying girls with RP-PP who are more likely to require treatment.     

Gonadotropin-releasing hormone infusion test in the distinction of hypopituitary patients from normal subjects.

We undertook a pilot study to determine whether infusion of gonadotropin-releasing hormone (GnRH) might improve the distinction of hypogonadotropinism from the normal state and might permit gonadotropin deficiency to be diagnosed in the prepubertal child. Normal prepubertal and pubertal boys had a greater luteinizing hormone (LH) reaction (delta LH 54 +/- 15 [SD] ng/ml and 165 +/- 23 ng/ml, respectively) to a 4-hour infusion (100 microgram/hour) than to a 100-microgram bolus of GnRH (19 +/- 9 and 52 +/- 35 ng/ml). These augmented responses were observed in boys with delayed puberty, but not in apparently hypogonadotropic males greater than or equal to 12 years old. LH (delta LH 445 to 1602 ng/ml) and FSH (delta FSH 718 to 2112 ng/ml) surges were induced consistently by GnRH infusion only in normal, postmenarchial females. In all, of 13 hypopituitary cases classified as hypogonadotropic on the basis of a subnormal response to GnRH infusion, 31% had a normal response to the GnRH bolus (P = 0.05). Thus, GnRH infusion testing seems to improve the distinction of hypogonadotropic patients from normal individuals, including boys with delayed puberty.     

简化促性腺激素释放激素兴奋试验在女性同性性早熟症诊断中的应用

目的 探讨简化促性腺激素释放激素(GnRH)兴奋试验用于女性同性性早熟症发病原因的诊断及指导治疗的价值。方法 对42例女性同性性早熟患者施行简化GnRH兴奋试验,其中38例患者平均随访26(3～78)个月,观察患者的临床表现及病情发展情况。结果 42例患者对GnRH兴奋试验反应分为黄体生成激素(LH)优势型、卵泡刺激素(FSH)优势型及无反应型3类。其中LH优势型14例(33％,14/42),包括下丘脑错构瘤1例、特发性性早熟13例;14例中生长过速或骨成熟过早各10例。FSH优势型13例(31％,13/42),包括生长过速2例、骨成熟过早1例。无反应型15例(36％,15/42),8例为外周性性早熟症,包括卵巢颗粒泡膜瘤1例、自主性功能性卵巢滤泡囊肿2例、McCune-Albright综合征2例、外源性性早熟症3例;15例中生长过速4例、骨成熟过早5例。FSH优势型13例及无反应型的其余7例,未发现明确的发病原因,考虑为一过性性早熟症或乳房早发育。结论 简化GnRH兴奋试验有助于女性同性性早熟症发病原因的诊断,及客观判断下丘脑-垂体-卵巢轴是否被激活,较临床指标更为可靠。     

2~10岁性早熟女童骨密度检测分析

目的探讨性早熟对2~10岁女童骨密度的影响。 方法选择2003 01—2006 01在湖南省儿童医院内分泌专科就诊的2~10岁性早熟(明确诊断、并排除影响骨代谢性疾病)女童237例，根据真、假性性早熟(CPP、PPP)分为2组，各组再按年龄组分层，采用单光子骨矿物质密度测定仪测量左手桡骨中远1/3处桡、尺骨密度(BMD)，并与同龄健康女童进行对比和分析。 结果CPP、PPP和健康组BMD均随年龄增长而增加，3组各年龄桡骨BMD均高于尺骨；CPP桡、尺骨BMD均相对较高，8~10岁组中CPP较对照组约高6.4%~8.6%；3组桡、尺骨BMD均在8~10岁增长加速，特别是尺骨(P<0.05)，分别较6~7岁组增长20.4%、17.8%和14.3%；以CPP组增幅最大，明显高于健康组，与健康组(6~7岁)增长比较差异有显著性(桡骨P<0.05、尺骨P<0.001)。PPP组则与健康女童差异不显著。 结论健康女童骨矿化自9岁起开始青春期加速，CPP女童青春期尺骨生长加速的年龄提早，BMD相应增加，而PPP不像CPP那样明显影响女童的正常骨骼发育。     

Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls.

Children born small for gestational age (SGA) may present advanced bone maturation in childhood and reduced final height. The objectives of the study were to evaluate adrenarche, pubertal development, age at menarche and final height in full-term born-SGA girls. Twenty-four girls (12 born-SGA and 12 matched controls) were evaluated at 6-7.5 years of age for clinical signs of puberty and dehydroepiandrosterone sulfate (DHEAS) levels, as a marker of adrenarche. Thirty-eight girls (19 born-SGA and 19 matched controls) were evaluated at 17.5-18.5 years of age to assess final height, sexual maturation and age at menarche. SGA girls had a mean final height (160.1 cm vs 165.8 cm, p < 0.01) and mean weight (52.1 kg vs 56.5 kg, p < 0.05) significantly lower than controls. Controls had a mean final height significantly higher than their mean target height. Sexual maturation was at stage 5 of Tanner's staging in SGA girls and control subjects. SGA girls had a slightly anticipated puberty (9.9 vs 10.4 years for initial breast development) and a lower age at menarche (11.9 vs 12.3 years). At 6-7.5 years of age, SGA females and controls did not show any difference for clinical signs of puberty; however, DHEAS levels (0.75 + 0.18 microgram/ml vs 0.57 + 0.22 microgram/ml, p < 0.05) were significantly higher in SGA girls than in control subjects. We concluded that full-term born-SGA females have impaired final height and weight in adolescence but substantially normal sexual maturation and age at menarche. Increased DHEAS levels before puberty in born-SGA girls may predispose to increased bone maturation in childhood with a reduced final height. In our population a progressive increment in final stature is evident.     

Bone density in adolescents treated with a GnRH agonist and add-back therapy for endometriosis

STUDY OBJECTIVE: To evaluate the bone density of adolescents with endometriosis treated with a GnRH-agonist and "add-back" therapy with norethindrone acetate. DESIGN: Retrospective chart review. SETTING: Pediatric gynecology clinic at a tertiary care center. PARTICIPANTS: 36 adolescents, ages 13 to 21 years, with endometriosis. MAIN OUTCOME MEASURES: Bone mineral density (BMD, g/cm(2)) by dual energy x-ray absorptiometry (DXA); BMD Z-scores of hip and spine. RESULTS: The mean BMD Z-score at the total hip was -0.24 +/- 1.0, with a range of -2.4 to 1.7. At this site, 6 subjects had a BMD Z-score between -1.0 and -2.0 SD, while 2 had a Z-score < or = -2.0 SD. The mean BMD Z-score at the lumbar spine was 0.55 +/- 1.1, with a range of -2.8 to 1.4. At the spine, 11 subjects had a BMD Z-score between -1.0 and -2.0 SD, while 3 had a Z-score < or = -2.0 SD. There was no correlation noted between duration of therapy with the GnRH-agonist plus add-back and BMD at the hip or spine. CONCLUSION: BMD at the hip was normal in most adolescents with endometriosis who were receiving a GnRH-agonist plus add-back therapy with norethindrone acetate. Almost one third of subjects exhibited skeletal deficits at the spine. These data suggest that BMD should be carefully monitored in adolescents receiving treatment with GnRH agonists.     

Body fat distribution and body composition during GnRH agonist therapy

OBJECTIVE: To identify the effects of GnRH agonist therapy on body composition (lean and fat mass components) and body fat distribution. METHODS: Fifteen women with uterine leiomyomas were given a GnRH agonist (leuprorelin acetate, 3.75 mg) monthly for 4 months. Weight, height, and body mass index (BMI, weight/height) were recorded. Regional and total body composition, trunk-leg fat ratio, bone mineral density of the lumbar spine (L2-L4), and total body were assessed by whole-body scanning with dual-energy x-ray absorptiometry before and after treatment. Uterine volume was measured by transabdominal ultrasonography. RESULTS: The mean (+/- standard deviation [SD]) lean mass of total body, trunk, and leg decreased significantly (36.3 +/- 4.9 to 35.4 +/- 4.4 kg, P <.01; 18.8 +/- 2.8 to 18.1 +/- 2.8 kg, P <.05; and 11.4 +/- 1.8 to 11.1 +/- 1.6 kg, P <.05; respectively), whereas body fat mass, percentage of body fat, and trunk fat mass increased significantly (20.8 +/- 4.8 to 21.8 +/- 4.6 kg, P <.01; 34.9 +/- 5.9 to 36.5 +/- 5.2%, P <.01; and 8.6 +/- 3.0 to 9.3 +/- 3.0 kg, P <.01; respectively). Trunk-leg fat ratio increased significantly (1.03 +/- 0.32 to 1.12 +/- 0.33, P <.05). Weight, BMI, arm tissue composition (lean and fat mass components), and leg fat mass did not change during 4 months of GnRH agonist therapy. Bone mineral density and uterine volume decreased significantly. CONCLUSION: Hypogonadism by GnRH agonist therapy induces lean mass loss, increased adiposity overall, and upper body fat accumulation.     

Adrenarche,pubertal development,age at menarche and final height of full-term,born small for gestational age (SGA) girls

Children born small for gestational age (SGA) may present advanced bone maturation in childhood and reduced final height. The objectives of the study were to evaluate adrenarche ,pubertal development ,age at menarche and final height in full-term born-SGA girls. Twenty-four girls (12 born-SGA and 12 matched controls) were evaluated at 6-7.5 years of age for clinical signs of puberty and dehydroepiandrosterone sulfate (DHEAS) levels ,as a marker of adrenarche. Thirty-eight girls (19 born-SGA and 19 matched controls) were evaluated at 17.5-18.5 years of age to assess final height ,sexual maturation and age at menarche. SGA girls had a mean final height (160.1 cm vs 165.8 cm ,p < 0.01) and mean weight (52.1 kg vs 56.5 kg ,p < 0.05) significantly lower than controls. Controls had a mean final height significantly higher than their mean target height. Sexual maturation was at stage 5 of Tanner's staging in SGA girls and control subjects. SGA girls had a slightly anticipated puberty (9.9 vs 10.4 years for initial breast development) and a lower age at menarche (11.9 vs 12.3 years). At 6-7.5 years of age ,SGA females and controls did not show any difference for clinical signs of puberty; however, DHEAS levels (0.75 + 0.18μg/ml vs 0.57 + 0.22μg/ml ,p < 0.05) were significantly higher in SGA girls than in control subjects. We concluded that full-term born-SGA females have impaired final height and weight in adolescence but substantially normal sexual maturation and age at menarche. Increased DHEAS levels before puberty in born-SGA girls may predispose to increased bone maturation in childhood with a reduced final height. In our population a progressive increment in final stature is evident.