Individual differences in puberty onset in girls: Bayesian estimation of heritabilities and genetic correlations

We report heritabilities for individual differences in female pubertal development at the age of 12. Tanner data on breast and pubic hair development in girls and data on menarche were obtained from a total of 184 pairs of monozygotic and dizygotic twins. Genetic correlations were estimated to determine to what extent the same genes are involved in different aspects of physical development in puberty. A Bayesian estimation approach was taken, using Markovchain Monte Carlo simulation to estimate model parameters. All three phenotypes were to a significant extent heritable and showed high genetic correlations, suggesting that a common set of genes is involved in the timing of puberty in general. However, gonadarche (menarche and breast development) and adrenarche (pubic hair) are affected by different environmental factors, which does not support the three phenotypes to be regarded as indicators of a unitary physiological factor. © 2006 Springer Science+Business Media, Inc

Puberty induction in Turner syndrome : Results of oestrogen treatment on development of secondary sexual characteristics, uterine dimensions and serum hormone levels

Background: Besides short stature, gonadal dysgenesis leading to a lack of oestrogen is one of the main characteristics of Turner syndrome (TS). In most TS girls, puberty is induced with exogenous oestrogens. Objective: To describe the pubertal development and uterine dimensions achieved by low-dose 17β-oestradiol (17β-E2) orally started at an appropriate age. Additionally, to determine whether serum hormone levels aid evaluation of pubertal progression. Design: In 56 TS girls, we prospectively studied pubertal stage, serum E2, LH, FSH, SHBG and oestrone (E1), starting oestrogen treatment with a low-dose 17β-E2 (5 μg/kg/day) during GH treatment at mean (SD) age 12.7 (0.7) years. Hormone levels were measured at start, 3 months after start and after increasing 17β-E2 dosage. Uterine dimensions were measured in 39 TS women at age 19.9 (2.2) years. Results: Although breast and pubic hair development were similar to that in normal Dutch girls up to Tanner stage B5 and P5, respectively, breast development was 2 years later. Before oestrogen therapy, E2 levels were comparable to those in prepubertal girls. With a 17β-E2 dose of 5 μg/kg/day, these levels increased significantly, becoming comparable to normal late pubertal or adult concentrations, whereas SHBG levels were unchanged. At the adult 17β-E2 dose, SHBG had increased significantly. Uterus shape was juvenile in four (10.2%), cylindrical in four and mature-adult shaped in 31 (79.5%) of TS patients. Conclusions: During GH treatment in TS girls, normal breast development up to B5 can be mimicked, with just a 2-year delay. In a clinical setting, serum hormone levels provide no additional information for evaluating pubertal progression. After age-appropriate pubertal induction, uterine dimensions in women aged nearly 20 years were subnormal. It remains unclear whether this was related to E2 dosage, timing or duration, or factors related to TS

Growth hormone treatment in children with rheumatic disease, corticosteroid induced growth retardation, and osteopenia

Background: In children with severe rheumatic disease (RD), treatment with corticosteroids (CS) is frequently needed and growth retardation and osteopenia may develop. A beneficial effect of human growth hormone (hGH) has been reported but mostly in trials without a control group. Aims: To study the effect of hGH on growth, bone mineral density (BMD), and body composition, taking the disease activity and CS use into account. Methods: Randomised controlled trial on 17 prepubertal RD patients with growth retardation and/or decreased BMD. The hGH group (n = 10) received treatment with hGH 4 IU/m2/day (∼0.045 mg/kg/ day) during two years. The controls (n = 7) received no GH treatment. Results: During the two year study period the disease activity, and use of CS and methotrexate (MTX) did not differ between the groups. There was a significant mean increase in height standard deviation score (HSDS) in the hGH group (0.42±0.16 SDS) and a non-significant decrease in the controls (-0.18±0.11 SDS). Change in BMD did not differ significantly between the groups, although the increase in BMD for lumbar spine within the hGH group was significant. Lean body mass improved significantly in the hGH group compared to controls (0.64±0.19 SDS versus -0.20±0.17 SDS), while the decrease in percentage fat was not significant. Conclusions: There was a significant effect of hGH on growth and lean body mass, but a longer duration of treatment might be necessary to evaluate the effect of hGH on BMD

Anti-mullerian hormone is a sensitive serum marker for gonadal function in women treated for Hodgkin's lymphoma during childhood

Purpose: The aim of this study was to evaluate the long-term effects of combination chemotherapy treatment for girls with Hodgkin's lymphoma ( HL) on gonadal function using anti-Mullerian hormone ( AMH) and inhibin B as ovarian reserve parameters. Patients and Methods: LH, FSH, inhibin B, and AMH were measured in 32 women treated from 1974 to 1998 for pediatric HL with chemotherapy, with the intention to avoid radiotherapy. All patients [ median age 25.0 yr ( range 19.2-40.4 yr)] were in complete remission with a median follow-up time of 14.0 yr ( range 5.7-24.5 yr) after therapy. All patients were treated with combination chemotherapy doxorubicin, bleomycin, vinblastine and dacarbazine ( ABVD) or EBVD with or without mechlorethamine, vincristine, procarbazine, and prednisone ( MOPP). Because of incomplete remission or relapse, involved field radiotherapy was needed in seven of 32 women. Results were compared with a healthy control group. Results: Patients treated with six or more cycles of MOPP combination chemotherapy had significantly higher levels of FSH and lower serum levels of inhibin B and AMH, compared with healthy women [ FSH, 17.0 vs. 6.0 U/liter ( P <0.05); inhibin B, 23.0 vs. 112.5 ng/ liter ( P <0.01); AMH, 0.39 vs. 2.10 mu g/ liter ( P <0.01)]. AMH was also significantly lower, compared with women treated without MOPP ( median 0.39 vs. 1.40 mu g/ liter; P = 0.01). Conclusions: Women treated during childhood for HL with MOPP seem to have a distinctly lower ovarian reserve as measured by lower AMH values at early adulthood, compared with healthy women. Moreover, AMH seems to be the only predictor that is sufficiently sensitive to detect this decrease in ovarian reserv