Summary:Conditioning for bone marrow transplantation (BMT) may alter viability of germ cells and production of gonadal hormones. We analyzed the risk factors for gonadal failure after 12 Gy total body irradiation (TBI) given as six fractions (n = 31, group 1), 10 Gy (one dose) TBI (n = 20, group 2), 6 Gy (one dose) total lymphoid irradiation (TLI, n = 17, group 3) and chemotherapy alone (n = 7, group 4), given at 7.7 ± 0.4 (0.6-13.6) years. Among the 34 girls, seven (20.6%) had normal ovarian function with regular spontaneous menstruation and normal plasma follicle-stimulating (FSH) and luteinizing (LH) hormones, five (14.7%) had partial ovarian failure with regular menstruation but increased FSH and/or LH, and 22 (64.7%) had complete ovarian failure. The 24 girls with chronological and bone ages Ͼ13 years included similar percentages, with increased FSH or LH in all four groups. There was a positive correlation between age at BMT and FSH (r = 0.54, P Ͻ 0.01), but not with LH, and between FSH and LH (r = 0.8, P = 0.0003). Plasma FSH concentrations had returned to normal spontaneously in six cases, and those of LH in two cases. Among the 41 boys, 16 (39%) had normal testicular function and 25 (61%) had tubular failure and increased FSH. Of these, 10 also had Leydig cell failure (three complete and seven partial). The 18 boys with chronological and bone ages Ͼ15 years included similar percentages with increased FSH or LH in groups 1 to 3, and testicular volume was significantly lower in group 2 than in group 3 (P = 0.008). There was no correlation between age at BMT and FSH, LH or testosterone, but there was a negative correlation between FSH and inhibin B (rho = −0.87, P Ͻ 0.003). We conclude that girls are more likely to suffer ovarian failure the older they are at BMT, and that early ovarian recovery is possible. Keywords: bone marrow transplantation; fertility; inhibin; irradiation; ovary; testis Conditioning for bone marrow transplantation (BMT) may alter the production of gonadal hormones (estradiol and progesterone in girls, testosterone in boys) and the viability of germ cells. 1-3 Gonadal failure results in incomplete sexual development and growth at puberty, and sterility in adulthood. Gonadal hormones are required for the development of secondary sexual characteristics, and for the growth acceleration which normally occurs at puberty.The risk factors for gonadal failure in patients undergoing BMT are difficult to analyze because of the variety of conditioning regimens used, and the possibility of gonadal recovery. 4 This study analyzes the expression and frequency of gonadal failure in both sexes according to the conditioning protocol, and the significance of the age during childhood at which BMT is carried out. We also measured plasma inhibin B concentrations as an additional marker of tubular function in these young patients where semen analysis is not possible. PatientsThe gonadal function of 75 patients (34 girls and 41 boys) who received a BMT during childhood, and who were aged more than 10 years ...

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Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak 410 lg/l. Final height was oÀ2 s.d. in 29 (58%). The height loss between TBI and final height (2.471.1 s.d.) was greater in those who were younger when irradiated (Po0.0001). When the GH-treated and -untreated patients were analyzed separately, this loss was correlated with the age at TBI at 4-8 years for the GHtreated and at 6-8 years for the untreated. Boys showed negative correlations between testicular volume and plasma follicle-stimulating hormone (FSH, P ¼ 0.0008) and between plasma FSH and inhibin B (P ¼ 0.005) concentrations. We concluded that the indications for GH treatment should be mainly based on the age at irradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function.

BackgroundDespite the number of reported data concerning idiopathic central precocious puberty (CPP) in girls, major questions remain including its diagnosis, factors, and indications of gonadotropin releasing hormone (GnRH) analog treatment.MethodsA retrospective, single-center study was carried out on 493 girls with CPP.ResultsEleven girls (2.2%) were aged less than 3 years. Breast development was either isolated (Group 0, n = 99), or associated with one sign, pubic hair development, growth rate greater than 2 standard deviation score (SDS) or bone age (BA) >2 years above chronological age, (Group 1, n = 187), two signs (Group 2, n = 142) or three signs (Group 3, n = 65). The interval between onset of puberty and evaluation, body mass index (BMI) SDS, plasma luteinising hormone (LH) concentrations (basal and peak) and LH/ follicle-stimulating hormone (FSH) peak ratio after GnRH test, plasma estradiol and uterus length were significantly greater in Groups 2 and 3 than in Groups 0 and 1 respectively. 211 (42.8%) patients were obese and/or had excessive weight gain during the year before puberty. Obese girls more often had BA advance of >2 years (p = 0.0004) and pubic hair development (p = 0.003) than the others. BMI did not correlate with LH or with LH/FSH peak ratio. Girls with familial history of early puberty (41.4%) had greater frequencies of pubertal LH/FSH peak ratios (p = 0.02) than the others. During the 31 years of the study, there was no increase in the frequency of CPP or variation in its characteristics.ConclusionObesity is associated with a higher BA advance and higher frequency of pubic or axillary hair development but not with LH secretion, suggesting that obesity accelerates adrenarche but not the maturation of the hypothalamic-pituitary-ovarian axis. The LH/FSH peak ratio was more frequently pubertal in girls with a familial history of early puberty, suggesting that this maturation depends on genetic factors.

The type of CNS lesion influences the presentation of CPP. This is probably caused by differences in the mechanisms inducing puberty and to the hypothalamic-pituitary deficiencies associated with the CPP as a result of a lesion and/or its treatment.

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Data concerning the effects of GnRHa on weight gain are scarce. Objective: To assess the variation of the body mass index (BMI) in girls during GnRHa treatment for idiopathic central precocious puberty (CPP). Patients and Methods: Semestral anthropometric data from 176 girls treated with goserelin or leuprorelin were analyzed. Results: BMI z-score increased from 1.5 ± 0.1 SD before treatment (n = 176) to 1.7 ± 0.2 SD after 24 months (n = 61, ρ = 0.008). In girls with normal weight before treatment, this variation was greater (n = 112,0.2 ± 0.1 SD, ρ = 0.01) than in those who were overweight (n = 63, -0.9 ± 0.2 SD, ρ = 0.7). In the goserelin group the weight change adjusted for bone age was greater (n = 28, 0.4 ± 0.1 SD) than in the leuprorelin group (n = 5, 0.04 ± 0.1 SD, ρ = 0.05). Conclusions: A slight increase in BMI was noted, mainly in girls with normal weight before treatment. The influence of different GnRHa on weight must be further investigated.We studied the BMI follow-up of girls treated with GnRHa for CPP. PATIENTS AND METHODSThe aim of this longitudinal retrospective study was to evaluate semestral changes in BMI of 176 Brazilian girls treated with GnRHa for idiopatic central precocious puberty (ICPP), regularly seen at a public health reference center (CEDEBA) in the state of Bahia, Brazil, during a 6-year period (1998)(1999)(2000)(2001)(2002)(2003)(2004).

BackgroundIt is difficult to predict the reproductive capacity of children given hematopoietic cell transplantation (HCT) before pubertal age because the plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are not informative and no spermogram can be done.MethodsWe classified the gonadal function of 38 boys and 34 girls given HCT during childhood who had reached pubertal age according to their pubertal development and FSH and LH and compared this to their plasma inhibin B and anti-Müllerian hormone (AMH).ResultsTen (26%) boys had normal testicular function, 16 (42%) had isolated tubular failure and 12 (32%) also had Leydig cell failure. All 16 boys given melphalan had tubular failure. AMH were normal in 25 patients and decreased in 6, all of whom had increased FSH and low inhibin B.Seven (21%) girls had normal ovarian function, 11 (32%) had partial and 16 (47%) complete ovarian failure. 7/8 girls given busulfan had increased FSH and LH and 7/8 had low inhibin B. AMH indicated that ovarian function was impaired in all girls.FSH and inhibin B were negatively correlated in boys (P < 0.0001) and girls (P = 0.0006). Neither the age at HCT nor the interval between HCT and evaluation influenced gonadal function.ConclusionThe concordance between FSH and inhibin B suggests that inhibin B may help in counselling at pubertal age. In boys, AMH were difficult to use as they normally decrease when testosterone increases at puberty. In girls, low AMH suggest that there is major loss of primordial follicles.