Pre- and peripubertal sex steroids are inversely associated with birth weight in preterm boys.

OBJECTIVE: The relationship between sex hormone concentrations during childhood and birth weight (BW) is poorly understood. We aimed to investigate this relationship and the associations with anthropometric data at 5, 6, 7, 8, and 10 years of age in preterm boys. DESIGN: A prospective longitudinal single-centre study, including 58 boys with a BW of 1325-3320 g and gestational age (GA) of 32 + 2 to 36 + 6 weeks. PATIENTS AND MEASUREMENTS: Data on GA, BW and anthropometric data between 5 and 10 years of age were recorded. Testicular development was assessed at 8 and 10 years of age. Serum concentrations of sex steroids were analysed with gas chromatography-tandem mass spectrometry at 5-10 years and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with immunoassays at 10 years of age. RESULTS: At 8 years of age, testosterone and estrone correlated negatively with BW, (ρ = -0.35, p = .021) and (ρ = -0.34, p = .024), respectively. At 10 years of age, testosterone, dihydrotestosterone, estrone and estradiol correlated negatively with BW (ρ = -0.39, p = .010), (ρ = -0.38, p = .013), (ρ = -0.44, p = .003) and (ρ = -0.36, p = .019), respectively. Weight gain from birth correlated with testosterone at 5 years (ρ = 0.40, p = .002), 7 years (ρ = 0.30, p = .040), 8 years (ρ = 0.44, p = .003) and 10 years (ρ = 0.40, p = .008) of age. At 10 years of age, testosterone correlated with LH (ρ = 0.42, p = .006) and FSH (ρ = 0.33, p = .033) but not with testicular volume. CONCLUSIONS: Lower BW was associated with increased sex steroid concentrations from 8 years of age, independently of clinical signs of puberty.

Mini review shows that a testicular volume of 3 mL was the most reliable clinical sign of pubertal onset in males.

AIM: We aimed to evaluate aspects of pubertal development to identify the most reliable clinical sign of pubertal onset in males. METHODS: We performed a mini review of the literature. RESULTS: In 1951 Reynolds and Wines categorised pubic hair growth and genital development in five stages by visual inspection. Today the Tanner scale is used to assess the five stages of pubertal development, The second genital stage, characterised by enlargement of the scrotum defines pubertal onset in males. Testicular volume may be evaluated by using a calliper or by ultrasound scan. The Prader orchidometer, described in 1966, offers a method for evaluating testicular growth by palpation. Pubertal onset is commonly defined as testicular volume >3 or ≥4 mL. The development of sensitive laboratory methods has enabled studies analysing hormonal activity in the hypothalamus-pituitary-gonadal axis. We review the relationships between physical and hormonal signs of puberty. We also discuss the results of studies assessing different aspects of pubertal development with a focus on identifying the most reliable clinical sign of pubertal onset in males. CONCLUSION: A substantial amount of evidence supports testicular volume of 3 mL as the most reliable clinical sign of male pubertal onset.

Adrenal androgen trajectories are established during childhood in preterm boys.

AIM: We investigated longitudinal adrenal androgen concentrations and any relationship between gestational age, birth size, anthropometric parameters and adrenal androgen concentrations during childhood in boys born moderate to late preterm. METHODS: This longitudinal, prospective study included 58 boys born at 32+0 to 36+6 weeks of gestation. Dehydroepiandrosterone sulphate and androstenedione were analysed by liquid chromatography-tandem mass spectrometry, and anthropometric data were recorded from 5 to 10 years of age. RESULTS: Dehydroepiandrosterone sulphate concentrations correlated with weight standard deviations scores (SDS) from 7 to 10 years of age and waist-to-height ratios at seven and 10 years of age. Androstenedione correlated with weight SDS from 7 to 10 years of age and waist-to-height ratios at 10 years of age. Longitudinal analysis showed a relationship between weight SDS and waist-to-height SDS and dehydroepiandrosterone sulphate (p < 0.001 and p < 0.001, respectively) and androstenedione (p = 0.002 and p = 0.003, respectively), independently of age. CONCLUSION: The trajectories of anthropometric parameters and adrenal androgen secretion were consistent from 5 to 10 years of age in this cohort. The body composition reflected by current weight and the waist-to-height ratio, rather than gestational age and birth size, was associated with adrenal androgen secretion.

Adrenal and Gonadal Activity, Androgen Concentrations, and Adult Height Outcomes in Boys With Silver-Russell Syndrome.

Background: We have previously shown that adult height (AH) in males with Silver-Russell syndrome (SRS) correlated negatively with prepubertal estradiol concentrations. We aimed to identify the source of estradiol by analyzing androgen secretion profiles and measuring anti-Müllerian hormone (AMH) and inhibin B concentrations during childhood and puberty in this group of patients. Methods: In a retrospective longitudinal single-center study, 13 males with SRS were classified as non-responders (NRs = 8) or responders (Rs = 5), depending on the AH outcome. From 6 years of age, androgens were determined by mass spectrometry, and AMH, inhibin B and sex hormone-binding globulin concentrations were analyzed by immunoassays. Results: AH outcome correlated negatively with dehydroepiandrosterone-sulfate (DHEAS) at 8 (r = -0.72), 10 (r = -0.79), and 12 years (r = -0.72); testosterone at 10 (r = -0.94), 12 (r = -0.70) and 14 years (r = -0.64); dihydrotestosterone (DHT) at 10 (r = -0.62) and 12 years; (r = -0.57) and AMH at 12 years (r = 0.62) of age. Compared with Rs, NRs had higher median concentrations of DHEAS (µmol/L) at 10 years (2.9 vs. 1.0); androstenedione (nmol/L) at 10 (1.1 vs. 0.6) and 12 years (1.7 vs. 0.8); testosterone (nmol/L) at 10 (0.3 vs. 0.1), 12 (7.8 vs. 0.2) and 14 years (15.6 vs. 10.4); and DHT (pmol/L) at 10 (122 vs. 28) and 12 years (652 vs. 59) of age. AMH (ng/mL) was lower in NRs than in Rs at 12 years of age (11 vs. 50). No significant differences were observed in the inhibin B concentrations at any age. Conclusions: The elevated androgen concentrations before and during puberty, originated from both adrenal and gonadal secretion and correlated negatively with AH outcomes in males with SRS.

Hyperestrogenism Affects Adult Height Outcome in Growth Hormone Treated Boys With Silver-Russell Syndrome.

Background: Intrauterine growth retardation and short stature are common features in Silver-Russell syndrome (SRS). Despite recombinant growth hormone (rGH) treatment, poor pubertal height gain, affecting adult height (AH), is common. This study investigated whether growth patterns and estrogen concentrations are associated with AH outcome in rGH treated SRS males. Methods: In this retrospective longitudinal single-center study, 11 males with SRS were classified as non-responders (NR = 6) or responders (R = 5), depending on AH adjusted for midparental height. Epigenetic analysis and longitudinal growth measures, including bone age, rGH related parameters, pubertal development, gonadotropins and estrogen concentrations, were analyzed until AH. Results: Pubarche before 9 years was only observed in one NR. At 10 years of age, there was no difference in gonadotropins between NR and R. However, estradiol (E2) concentrations at 10 years of age showed a strong association to AH adjusted for MPH (r = -0.78, p < 0.001). Serum E2 (pmol/L) was significantly higher in NR at ages 10 years [median (range) 2 (<2-5) vs. <2 (<2)], 12 years [23 (10-57) vs. 2 (<2-2)] and 14 years [77 (54-87) vs. 24 (<2-38)] but not at 16 years. Birth weight standard deviation score (SDS) was lower in NR [-4.1 (-4.7 to -2.1) vs. -2.7 (-3.3 to -1.7)]. Weight gain (SDS) until pubertal onset was greater in NR [2.4 (1.4-3.5) vs. 0.8 (-0.4 to 1.7)] and pubertal height gain (SDS) was lower in NR [-1.0 (-2.7-0.4) vs. 0.1 (-0.1 to 1.1)]. At AH, a number of NR and R had high E2 concentrations and small testes. Conclusion: Increased E2 concentrations at age 10, 12, and 14 years were associated to less pubertal height gain, thus affecting AH. Due to the small number of patients, the results need to be confirmed in larger cohorts. The finding of impaired testicular development stresses the need of hormonal evaluation as a complement to clinical and radiological assessment when predicting AH in males with SRS.