In a retrospective auxological study of 145 patients seen in Belgium during a 9‐year period for treatment of precocious puberty, 28% appeared to be foreign children (39 girls, one boy) who immigrated 4 to 5 years earlier from 22 developing countries, without any link to a particular ethnic or country background. The patients were either adopted (n = 28) or non‐adopted (n = 12), the latter having normal weight and height at immigration and starting early puberty without evidence of earlier deprivation. This led to the hypothesis that the mechanism of precocious puberty might involve previous exposure to oestrogenic endocrine disrupters. A toxicological plasma screening for eight pesticides detected p, p'‐DDE, which is derived from the organochlorine pesticide DDT. Median p, p'‐DDE concentrations were respectively 1.20 and 1.04 ng/ml in foreign adopted (n = 15) and non‐adopted (n = 11) girls with precocious puberty, while 13 out of 15 Belgian native girls with idiopathic or organic precocious puberty showed undetectable concentrations (<0.1 ng/ml). A possible relationship between transient exposure to endocrine disrupters and sexual precocity is suggested, and deserves further studies in immigrant children with non‐advanced puberty.
Background Cyproterone acetate (CA) is an antiandrogenic progestin commonly used in adult transwomen to suppress endogenous androgens, often in combination with estrogens to induce feminization. Aim To assess the (side) effects and biochemical changes of CA alone and in combination with estrogens in adolescent trans-girls. Methods This study was a retrospective analysis of clinical and biochemical data from 27 trans-girls who presented at Tanner stage G4 and were treated with CA monotherapy for at least 6 months (mean = 12 months) and then in combination with incremental doses of estrogens (CA + E; mean = 16 months). Statistical analysis of data included paired or unpaired Student t-test or Wilcoxon signed-ranks or Mann-Whitney U-test as appropriate. Outcomes Anthropometrics, reported beneficial and side effects, safety parameters, and hormone levels. Results Physical changes included decrease of facial and non-facial hair growth. One third showed breast development under CA (Tanner stages B2–B3), which increased to Tanner stages B3 and B4 in 66.7% and 9.5% respectively, during CA + E. Reported side effects during CA and CA + E were breast tenderness, emotionality, fatigue, and flushes. No relevant weight changes were observed. Main safety parameters showed the following changes. Hemoglobin and hematocrit decreased and liver enzymes transiently and modestly increased during CA. Triglycerides and cholesterol levels slightly decreased during CA but returned to baseline during CA + E; glucose metabolism was unaffected. Relevant hormonal changes included a decrease in gonadotropins during CA + E and in total and free testosterone levels throughout treatment. Prolactin levels increased during CA and were restored during CA + E. Clinical Implications CA produced modest feminizing effects in trans-girls and therefore might be a valuable alternative in situations in which gonadotropin-releasing hormone analogues are not the treatment of choice and/or are not reimbursed. Strengths and Limitations This is the first study to report on the effects of CA in the treatment of trans-girls and one of the few to report on the use of estrogens in this population. Limitations are the modest sample size and the retrospective nature of this study. Conclusion Treatment with CA in late-pubertal trans-girls overall was safe and well tolerated and induced mild clinical and biochemical feminizing changes. Rapid further feminization was observed with incremental doses of E.
BackgroundPrior to the start of cross-sex hormone therapy (CSH), androgenic progestins are often used to induce amenorrhea in female to male (FtM) pubertal adolescents with gender dysphoria (GD). The aim of this single-center study is to report changes in anthropometry, side effects, safety parameters, and hormone levels in a relatively large cohort of FtM adolescents with a diagnosis of GD at Tanner stage B4 or further, who were treated with lynestrenol (Orgametril®) monotherapy and in combination with testosterone esters (Sustanon®).MethodsA retrospective analysis of clinical and biochemical data obtained during at least 6 months of hormonal treatment in FtM adolescents followed at our adolescent gender clinic since 2010 (n = 45) was conducted. McNemar’s test to analyze reported side effects over time was performed. A paired Student’s t test or a Wilcoxon signed-ranks test was performed, as appropriate, on anthropometric and biochemical data. For biochemical analyses, all statistical tests were done in comparison with baseline parameters. Patients who were using oral contraceptives (OC) at intake were excluded if a Mann-Whitney U test indicated influence of OC.ResultsMetrorrhagia and acne were most pronounced during the first months of monotherapy and combination therapy respectively and decreased thereafter. Headaches, hot flushes, and fatigue were the most reported side effects. Over the course of treatment, an increase in musculature, hemoglobin, hematocrit, creatinine, and liver enzymes was seen, progressively sliding into male reference ranges. Lipid metabolism shifted to an unfavorable high-density lipoprotein (HDL)/low-density lipoprotein (LDL) ratio; glucose metabolism was not affected. Sex hormone-binding globulin (SHBG), total testosterone, and estradiol levels decreased, and free testosterone slightly increased during monotherapy; total and free testosterone increased significantly during combination therapy. Gonadotropins were only fully suppressed during combination therapy. Anti-Müllerian hormone (AMH) remained stable throughout the treatment. Changes occurred in the first 6 months of treatment and remained mostly stable thereafter.ConclusionsTreatment of FtM gender dysphoric adolescents with lynestrenol monotherapy and in combination with testosterone esters is effective, safe, and inexpensive; however, suppression of gonadotropins is incomplete. Regular blood controls allow screening for unphysiological changes in safety parameters or hormonal levels and for medication abuse.
In a retrospective auxological study of 145 patients seen in Belgium during a 9-year period for treatment of precocious puberty, 28% appeared to be foreign children (39 girls, one boy) who immigrated 4 to 5 years earlier from 22 developing countries, without any link to a particular ethnic or country background. The patients were either adopted (n = 28) or non-adopted (n = 12), the latter having normal weight and height at immigration and starting early puberty without evidence of earlier deprivation. This led to the hypothesis that the mechanism of precocious puberty might involve previous exposure to oestrogenic endocrine disrupters. A toxicological plasma screening for eight pesticides detected p,p'-DDE, which is derived from the organochlorine pesticide DDT. Median p,p'-DDE concentrations were respectively 1.20 and 1.04 ng/ml in foreign adopted (n = 15) and non-adopted (n = 11) girls with precocious puberty, while 13 out of 15 Belgian native girls with idiopathic or organic precocious puberty showed undetectable concentrations (<0.1 ng/ml). A possible relationship between transient exposure to endocrine disrupters and sexual precocity is suggested, and deserves further studies in immigrant children with non-advanced puberty.
Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in PTPN11, KRAS, SOS1, and RAF1. We performed SOS1, RAF1, BRAF, MEK1, and MEK2 mutation analysis in a cohort of 102 PTPN11- and KRAS-negative NS patients and found pathogenic SOS1 mutations in 10, RAF1 mutations in 4, and BRAF mutations in 2 patients. Three novel SOS1 mutations were found. One was classified as a rare benign variant and the other remains unclassified. We confirm a high prevalence of pulmonic stenosis and ectodermal abnormalities in SOS1-positive patients. Three patients with SOS1 mutations presented with tumors (embryonal rhabdomyosarcoma, Sertoli cell testis tumor, and granular cell tumors of the skin). One patient with a RAF1 mutation had a lesion suggestive for a giant cell tumor. This is the first report describing different tumor types in NS patients with germ line SOS1 mutations.
Objective: Since the availability of recombinant human growth hormone (rhGH) all children with growth hormone deficiency (GHD) living in Belgium are offered rhGH treatment after approval by a peer -review board. In this study, we evaluated the prevalence and demographic features of childhood GHD in Belgium during the period 1986 -2001 and we compared them with the data from other countries. Methods: Diagnostic, demographic and baseline auxological data of 714 children diagnosed as having GHD between 1986 and 2001 were retrieved from the database of the Belgian Study Group for Paediatric Endocrinology. Results: The prevalence of GHD in Belgium was estimated to be 1/5600. The origin of GHD was idiopathic (idGHD) in 41% of the patients, congenital (congGHD) in 20% and acquired (acqGHD) in 35%. During the first 4 years (1986 -1989) more patients were classified as idGHD; thereafter the distribution between the three aetiology groups did not change. In all groups, boys outnumbered girls but this preponderance was especially pronounced in congGHD patients (male:female ¼ 4:1) with a central malformation that associates an anterior pituitary hypoplasia, a missing, fine or normal pituitary stalk and an ectopic posterior pituitary. Thirteen percent of the patients with idGHD, 50% with congGHD and 52% with acqGHD had multiple pituitary deficiencies. Patients with congGHD were the youngest (mean^S.D. age: 6.5^4.7 years) and were the shortest (2 3.0^1.3 standard deviation score (SDS)) at the start of rhGH treatment. There was no time trend over the studied period for age and height at onset of GH therapy. Conclusion: In Belgium, the prevalence of childhood GHD can be estimated as 1/5600 which is comparable to other recent surveys. The yearly number of new patients for the different aetiologies and the auxological parameters have remained relatively constant over the last 16 years.
Background: Our primary purpose was to determine the normal range and variability of blood volume (BV) in healthy children, in order to provide reference values during childhood and adolescence. Our secondary aim was to correlate these vascular volumes to body size parameters and pubertal stages, in order to determine the best normalisation parameter.
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