Pubertal development in PWS is characterized by normal adrenarche, variable hypothalamic dysfunction, and hypogonadism due to a unique testicular defect. Primary testicular dysfunction is a major component of hypogonadism in PWS.

Objective: The variable hypogonadism in Prader-Willi syndrome (PWS) has generally been attributed to hypothalamic dysfunction. Recent studies have documented primary testicular dysfunction in PWS males. Our aims were to characterize sexual development and reproductive hormones in PWS females and to investigate the etiology of hypogonadism. Design: A cross-sectional study. Methods: Physical examination was performed on 45 PWS females (aged 6 weeks to 32 years) and blood samples were obtained for hormonal analyses. Results: Age of onset and progression of puberty varied; most adults had incomplete sexual development. Spontaneous menarche was reported in four (aged 15-30 years) but all had subsequently developed secondary amenorrhea or oligomennorrhea. Anti-Mullerian hormone levels were within the normal range in all age groups. Inhibin B was consistently low or undetectable; only five women had levels in the low-normal range (20-54 pg/ml). LH was normal in most children, but low (!1.0 IU/l) in 9 of 15 adults. FSH was within the normal range for age in most children, but low (!0.5 IU/l) in 10 and high in four adults. Estradiol levels were normal-low and androgen levels were normal in the majority. Conclusions: Pubertal development in PWS females, as in males, is characterized by normal adrenarche, pubertal arrest, and hypogonadism due to variable combinations of a unique primary gonadal defect and hypothalamic dysfunction.

Objective: To assess the efficacy of oral ketamine versus oral midazolam for sedation during laceration repair at a pediatric emergency department.Methods: Children between 1 and 10 years requiring laceration repair were randomly assigned to 2 groups, treated either with oral midazolam (0.7 mg/kg) or with oral ketamine (5 mg/kg).Main outcomes measured were level of pain during local anesthesia, as assessed by the parent on a 10-cm visual analog scale (VAS) and the number of children who required intravenous sedation. Secondary outcomes included VAS by physician, pain assessment by child, maximal sedation depth assessed by the University of Michigan Sedation Scale, time until University of Michigan Sedation Scale 2 or more, general satisfaction of a parent and treating physician, length of procedure, total sedation time, and the incidence of any adverse events.Results: Sixty-eight children were recruited of which 33 were girls. Average age was 5.08 ± 2.14 years. Thirty-seven children were treated with ketamine and 31 with midazolam. Parent-assessed VAS in ketamine treated patients was 5.07 ± 0.75 compared with 3.68 ± 0.7 in midazolam treated patients [mean difference = 1.39 95% confidence interval (CI) –0.47 to 3.26]. Twelve (32%) of the children treated with ketamine required the addition of IV sedation compared to only 2 children (6%) of the children treated with midazolam [odds ratio (adjusted for age and gender) 6.1, 95% CI: 1.2 to 30.5]. The rest of the measured variables were similar between the groups, with no statistical significance.Discussion: No difference in the level of pain was found between ketamine and midazolam treated patients. Compared with oral midazolam (0.7 mg/kg), oral ketamine (5 mg/kg) was associated with higher rates of sedation failure, and thus is not recommended as a single agent for oral sedation in children requiring laceration repair.

Background/Aims: To investigate the etiology of hypogonadism in women with Prader-Willi Syndrome (PWS). Methods: Ten women aged 23 ± 5.5 years with PWS and 10 age- and BMI-matched controls were included. Blood samples were drawn and abdominal ultrasounds were performed on days 2–4 of spontaneous cycles or at random from amenorrheic women. Anti-Müllerian hormone (AMH), inhibin B (INB), gonadotropins, sex steroids, TSH, prolactin, ovarian volume and antral follicle count (AFC) in PWS women were compared with results from controls and the reference ranges. Results: Compared to controls, PWS women had lower INB (mean ± SD = 17.6 ± 12.8 pg/ml vs. 110.6 ± 54.5; p = 0.0002) and AMH levels (1.18 ± 0.86 ng/ml vs. 3.53 ± 2.42; p = 0.01). INB levels were exceptionally low in all PWS women, but individual AMH levels overlapped with the levels in the controls. Ovarian volume (mean ± SD = 3.7 ± 2.3 ml vs. 30.5 ± 28.8; p = 0.03) and AFC (6.4 ± 6.9 vs. 14.0 ± 8.2; p = 0.01) were lower in the PWS group compared to the controls. Three PWS patients had abnormally high follicle-stimulating hormone levels, while only 1 had hypogonadotropic hypogonadism. Conclusions: Our results suggest a unique follicular stage-specific insult in women with PWS. Thus, primary ovarian dysfunction is a major component of hypogonadism in PWS.

Background: Hypogonadism is a major feature of PraderWilli syndrome (PWS), but clinical manifestations are variable. Sexual interests and behavior in this population have not been previously described. Objectives: We studied PWS adolescents and young adults to assess 1) satisfaction with physical and sexual development, 2) frequency of romantic and sexual experiences, 3) aspirations and expectations regarding marriage, 4) possible relationships between sexual interests and hormone levels, and 5) the desire for hormonal replacement therapy. Methods: The study population consisted of 27 individuals (13 males) ages 17 -32 (mean 23.5) years with genetically confi rmed PWS. Mean intelligence quotient (IQ) was 75 (range 50 -100). We conducted structured interviews using questionnaires specifi cally designed for this study. Results: There was a signifi cant negative correlation between IQ and body image in both males and females. IQ showed a positive correlation with interest in dating and romantic activities. Approximately half of PWS males and females reported having been on a date and kissing romantically. All males and 64 % of the females wished to be married. Seventy-seven per cent of PWS males wanted hormonal treatment to increase phallic size. We found no correlation between hormone levels and sexual interests. Only 43 % of PWS females wanted hormonal medication to achieve regular menstruation. Conclusion: Despite documented hypogonadism, PWS young adults are interested in sexual and romantic issues.