Gonadotropin-releasing Hormone Analog Treatment Research Articles

Commentary: Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty.

Central precocious puberty (CPP) develops due to premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in early pubertal changes and rapid bone maturation. CPP is associated with lower adult height and increased risk for development of psychological problems. Standard treatment of CPP is based on postponement of pubertal development by blockade of the HPG axis with gonadotropin releasing hormone analogs (GnRHa) leading to abolition of gonadal sex hormones synthesis. Whereas the hormonal and auxological effects of GnRHa are well-researched, there is a lack of knowledge whether GnRHa treatment influences psychological functioning of treated children, despite the fact that prevention of psychological problems is used as one of the main reasons for treatment initiation. In the present study we seek to address this issue by exploring differences in cognitive function, behavior, emotional reactivity, and psychosocial problems between GnRHa treated CPP girls and age-matched controls. Fifteen girls with idiopathic CPP; median age 10.4 years, treated with slow-release GnRHa (triptorelin acetate—Decapeptyl SR® 11.25) and 15 age-matched controls, were assessed with a comprehensive test battery consisting of paper and pencil tests, computerized tasks, behavioral paradigms, heart rate variability, and questionnaires filled in by the children's parents. Both groups showed very similar scores with regard to cognitive performance, behavioral and psychosocial problems. Compared to controls, treated girls displayed significantly higher emotional reactivity (p = 0.016; Cohen's d = 1.04) on one of the two emotional reactivity task conditions. Unexpectedly, the CPP group showed significantly lower resting heart rates than the controls (p = 0.004; Cohen's d = 1.03); lower heart rate was associated with longer treatment duration (r = −0.582, p = 0.037). The results suggest that GnRHa treated CPP girls do not differ in their cognitive or psychosocial functioning from age matched controls. However, they might process emotional stimuli differently. The unexpected finding of lower heart rate that was associated with longer duration of the treatment should be further explored by methods appropriate for assessment of cardiac health.

Effects of pomegranate extract in supplementing gonadotropin-releasing hormone therapy on idiopathic central precocious puberty in Chinese girls: a randomized, placebo-controlled, double-blind clinical trial.

Central precocious puberty (CPP) without organic abnormality is called idiopathic CPP (ICPP). The objective of this trial was to evaluate the effects of pomegranate extract in supplementing gonadotropin-releasing hormone (GnRH) analog therapy on ICPP-affected girls in the Chinese population. 286 girls, diagnosed with ICPP were initially enrolled into this trial, and among them 225 eligible patients were randomized to receive a combinational GnRH analog treatment supplemented with either a placebo or pomegranate extract on a daily basis for a period of 3 months. Their demographics, secondary sexual characteristics and hormone profiles were analyzed at baseline and end of trial. After 3 months of treatment, demographic profiles including bone age, growth velocity and height standard deviation score for bone age, and secondary sexual characteristics including uterus and ovary volume, as well as serum hormone profiles including estradiol, peak luteinizing hormone and insulin-like growth factor 1 were all significantly improved in girls receiving a combinational treatment of both GnRH analog and pomegranate extract. Daily consumption of pomegranate extract was able to supplement and improve the treatment outcomes of the GnRH analog therapy for ICPP in Chinese girls.

Impact of GnRHa pretreatment on the autotransplatation efficacy of cytopreserved rat ovarian tissue.

Pre-therapeutic cryopreservation of ovarian tissue and subsequent transplantation after disease remission has recently emerged as an option to restore endocrinal function and preserve fertility for patients subjected to gonadotoxic treatments such as chemotherapy. However, the relatively low survival rate of follicles after grafting the frozen-thawed ovarian tissue largely limited the application of this technique. Gonadotropin-releasing hormone analogues (GnRHa), owing to their endocrinal regulatory effect, have been successfully used for fertility preservation against gonadotoxic conditions such as cytotoxic agents based anti-cancer therapy. In this study, we evaluated the potential protective effect of precedent GnRHa treatment before cryopreservation on freezing-thawing related follicular damages using a rat autoxenograft model. We have observed that GnRHa significantly increases the fraction of follicles with normal morphology, while presenting negnigible effect on the physiological recovery of the grafted follicular tissue, as demonstrated by the estrous cycle, folliculogenesis and post-autograft vascularization. Our data implicates that GnRHa pretreatment may effectively increase the efficacy of cryopreservation and the subsequent successful rate of transplantation.

Management of Premenstrual Syndrome: Green-top Guideline No. 48.

Management of Premenstrual Syndrome: Green-top Guideline No. 48.

Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents

Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density (BMD) can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT). We aimed to investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents. Gender dysphoria was diagnosed based on diagnostic criteria according to the DSM-IV (TR). Thirty four female-to-male persons (transmen) and 22 male-to-female persons (transwomen)were included. Patients were allocated to a young (bone age of <15years in transwomen or <14 in transmen) or old group (bone age of ≥15years in transwomen or ≥14years in transmen). All were treated with GnRHa triptorelin and CSHT was added in incremental doses from the age of 16years. Transmen received testosterone esters (Sustanon, MSD) and transwomen received 17-β estradiol. P1NP, osteocalcin, ICTP and BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. In addition, BMAD and Z-scores were calculated. We found a decrease of P1NP and 1CTP during GnRHa treatment, indicating decreased bone turnover (young transmen 95% CI −74 to −50%, p=0.02, young transwomen 95% CI −73 to −43, p=0.008). The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of FN and LS, whereas BMAD Z-scores of predominantly the LS decreased especially in the young transwomen. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased in all groups except for the old transmen. During CSHT BMAD increased and Z-scores returned towards normal, especially of the LS (young transwomen CI 95% 0.1 to 0.6, p=0.01, old transwomen 95% CI 0.3 to 0.8, p=0.04). To conclude, suppressing puberty by GnRHa leads to a decrease of BTMs in both transwomen and transmen transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DXA-scans remain important in follow-up of bone health of transgender adolescents.

The assessment of myometrium perfusion in patients with uterine fibroid by arterial spin labeling MRI.

BackgroundIt has been suggested that an inadequate blood supply caused by uterine fibroids may lead to decreasing fertility. Therefore, a quantitative evaluation of blood flow in the uterus might be a good tool for infertility treatments. For the first step, the ability to perform arterial spin labeling (ASL)-MRI in pelvic organs was examined by measuring blood flow in the uterine muscle layer.ResultsThree normal volunteer women, seven patients with one uterine fibroid and four patients treated with GnRH analogue for uterine fibroids, were enrolled in this study. Perfusion of normal uterine myometrium was examined using non-enhanced ASL-MRI. The region of interest was set in the uterine muscle layer, with a point in the iliopsoas or gluteus muscle. The ASL perfusion index was calculated as (ASL value in uterus—ASL value in iliopsoas/gluteus muscle). The ASL perfusion indexes in the secretory phase of all 3 volunteers were significantly lower than the indexes in the proliferative phases (P < 0.05). In patients with fibroids, all three types of fibroids (subserosal, intramural and submucosal types) were included. In seven patients harboring a single uterine fibroid, the ASL perfusion indexes of myometrium on the fibroid-positive side increased 4.9 fold compared with that of the fibroid-negative side. With GnRH analogue treatment, ASL perfusion in myometrium decreased to 39% on average (P < 0.05).ConclusionWe utilized the ASL-MRI technique to evaluate perfusion of uterine myometrium. For clinical use, an inadequate blood supply caused by uterine fibroids is known to lead to decreasing fertility. The ASL-MRI technique might be useful to evaluate blood supply as a quantitative measurement of fertility in patients with uterine fibroids.

ACAN Gene Mutations in Short Children Born SGA and Response to Growth Hormone Treatment.

Some children born small for gestational age (SGA) show advanced bone age (BA) maturation during growth hormone (GH) treatment. ACAN gene mutations have been described in children with short stature and advanced BA. To determine the presence of ACAN gene mutations in short SGA children with advanced BA and assess the response to GH treatment. BA assessment in 290 GH-treated SGA children. ACAN sequencing in 29 children with advanced BA ≥0.5 years compared with calendar age. Four of 29 SGA children with advanced BA had an ACAN gene mutation (13.8%). Mutations were related to additional characteristics: midface hypoplasia (P = 0.003), joint problems (P = 0.010), and broad great toes (P = 0.003). Children with one or fewer additional characteristic had no mutation. Of children with two additional characteristics, 50% had a mutation. Of children with three additional characteristics, 100% had a mutation. All GH-treated children with a mutation received gonadotropin-releasing hormone analog (GnRHa) treatment for 2 years from onset of puberty. At adult height, one girl was 5 cm taller than her mother and one boy was 8 cm taller than his father with the same ACAN gene mutation. This study expands the differential diagnosis of genetic variants in children born SGA and proposes a clinical scoring system for identifying subjects most likely to have an ACAN gene mutation. ACAN sequencing should be considered in children born SGA with persistent short stature, advanced BA, and midface hypoplasia, joint problems, or broad great toes. Our findings suggest that children with an ACAN gene mutation benefit from GH treatment with 2 years of GnRHa.

Effect of suppression of puberty and cross-sex hormone therapy on bone turnover markers and BMAD in transgender adolescents

Background: Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT).Objective: To investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents.Methods: Thirty four female-to-males (FtMs) and 22 male-to-females (MtFs) were divided into a young and old pubertal group, based on the bone age of 14 years in the FtMs and 15 years in the MtFs. All patients received GnRHa triptorelin. CSHT was prescribed in incremental doses from the age of 16 years. FtMs received testosterone ester mixture and MtFs were treated with 17-β estradiol. BTMs P1NP, osteocalcin and ICTP and the BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. Furthermore, BMAD and Z-scores were calculated.Results: P1NP and 1CTP decreased during GnRHa treatment, indicating decreased bone turnover. Osteocalcin showed an aberrant pattern. A low BMAD Z-score of both FN and LS was observed in the MtFs at start of GnRHa treatment. The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of both FN and LS, however BMAD Z-scores of predominantly the LS decreased. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased. During CSHT BMAD Z-scores increased and returned towards normal, especially of the LS.Conclusion: Suppressing puberty by GnRHa leads to a decrease of BTMs in transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24 months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DEXA-scans remain important in follow-up of transgender adolescents.

Changes in Body Mass Index in Girls with Idiopathic Central Precocious Puberty under Gonadotropin-Releasing Hormone Analogue Therapy: The Spanish Registry

Background: The influence of gonadotropin-releasing hormone analogue (GnRHa) treatment on body mass index (BMI) evolution in girls with idiopathic central precocious puberty (CPP) is unclear. Hence, we aimed to evaluate the effect of GnRHa treatment on BMI-standard deviation score (SDS) from diagnosis of idiopathic CPP until adult height. Methods: An observational study of girls diagnosed with CPP in Spain was carried out between January 2008 and December 2014. A computer program was designed to process clinical and biological data from patients treated in 55 departments of pediatric endocrinology throughout the country. The inclusion criteria were (1) girls diagnosed with CPP before 8 years of age; (2) born after 1992; (3) with a difference between bone and chronological age of at least 1 year, and (4) with a luteinizing hormone peak >7 U/l during luteinizing hormone-releasing hormone testing. The influence of GnRHa treatment on BMI-SDS evolution was analyzed. Results: Data from 333 girls (22.2% adopted) were evaluated. We report follow-up data at 6, 12, 24, 36, 48 and 60 months and adult height from 269, 232, 198, 153, 105, 56 and 49 girls, respectively. During treatment, there was an increase in BMI-SDS of 0.43 ± 1.17 (95% CI: 0.20-0.64). At adult height (n = 49), BMI-SDS was 1.51 ± 1.38, which was 0.60 ± 1.09 higher than at diagnosis (95% CI: 0.43-0.75). Conclusions: During treatment with GnRHa, girls experience a significant increase in BMI-SDS that persists after therapy is stopped and adult height has been reached.

Body mass index in girls with idiopathic central precocious puberty during and after treatment with GnRH analogues.

BackgroundIn girls with Idiopathic Central Precocious Puberty (ICPP) concern has been raised by the potential impact of GnRH-analogues (GnRHa) treatment on body weight. We evaluated the effect of GnRHa on Body Mass Index (BMI) in girls with ICPP according to weight status at diagnosis.MethodsOne hundred seventeen ICPP girls were divided according to pretreatment weight status in: normal weight (NW), overweight (OW) and obese (OB). BMI at one and two years of treatment was assessed. BMI-SDS of 60 patients who reached adult height (AH) was compared to that of 33 ICPP untreated girls.ResultsNW girls significantly increased their baseline BMI-SDS at 1 and 2 years of treatment. OW girls only had a significant increment at one year of treatment while OB girls showed no BMI-SDS change. Patients evaluated at AH (at least four years after GnRHa withdrawal) showed a significant decrease on BMI compared to baseline and a significantly lower BMI than the untreated group.ConclusionIn ICPP girls the BMI increase under GnRHa was inversely related to the pretreatment weight status. In the long term follow-up, no detrimental effect of GnRHa on body weight was observed. BMI-SDS was lower in treated than in untreated girls.

Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty.

Central precocious puberty (CPP) develops due to premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in early pubertal changes and rapid bone maturation. CPP is associated with lower adult height and increased risk for development of psychological problems. Standard treatment of CPP is based on postponement of pubertal development by blockade of the HPG axis with gonadotropin releasing hormone analogs (GnRHa) leading to abolition of gonadal sex hormones synthesis. Whereas the hormonal and auxological effects of GnRHa are well-researched, there is a lack of knowledge whether GnRHa treatment influences psychological functioning of treated children, despite the fact that prevention of psychological problems is used as one of the main reasons for treatment initiation. In the present study we seek to address this issue by exploring differences in cognitive function, behavior, emotional reactivity, and psychosocial problems between GnRHa treated CPP girls and age-matched controls. Fifteen girls with idiopathic CPP; median age 10.4 years, treated with slow-release GnRHa (triptorelin acetate—Decapeptyl SR® 11.25) and 15 age-matched controls, were assessed with a comprehensive test battery consisting of paper and pencil tests, computerized tasks, behavioral paradigms, heart rate variability, and questionnaires filled in by the children's parents. Both groups showed very similar scores with regard to cognitive performance, behavioral and psychosocial problems. Compared to controls, treated girls displayed significantly higher emotional reactivity (p = 0.016; Cohen's d = 1.04) on one of the two emotional reactivity task conditions. Unexpectedly, the CPP group showed significantly lower resting heart rates than the controls (p = 0.004; Cohen's d = 1.03); lower heart rate was associated with longer treatment duration (r = −0.582, p = 0.037). The results suggest that GnRHa treated CPP girls do not differ in their cognitive or psychosocial functioning from age matched controls. However, they might process emotional stimuli differently. The unexpected finding of lower heart rate that was associated with longer duration of the treatment should be further explored by methods appropriate for assessment of cardiac health.

The effects of gonadotropin-releasing hormone analog on yellowtail kingfish Seriola lalandi (Valenciennes, 1833) spawning and egg quality

Communal spawning behaviour in marine aquaculture species often results in a few individuals contributing disproportionate amounts of gametes. This can lead to a reduction in genetic variability and increases the risk of inbreeding among successive generations. Therefore, long term sustainability of captive breeding programmes for such species partly depends upon maintaining a sufficiently high proportion of parents contributing high quality gametes during spawning. The current study was conducted to evaluate if the use of slow-release gonadotropin-releasing hormone analog (GnRHa) implants could increase the number of females spawning high quality gametes, and thus increase genetic variation in a captive population of yellowtail kingfish Seriola lalandi (Valenciennes, 1833). Broodstock fish received implants with or without 500μg of GnRHa during the spawning season. GnRHa treatment was associated with a higher proportion of females contributing to spawning. However, compared to eggs from non-GnRHa-treated broodstock, GnRHa significantly decreased the floating rate, fertilisation rate, number of viable eggs and egg oil globule diameter. Overall, the use of slow-release GnRHa implants is a useful tool to increase parental contribution to spawning, but this benefit must be carefully balanced against lower egg quality.

Gonadotropin-Releasing Hormone Analogue Treatment in Females with Moderately Early Puberty: No Effect on Final Height

Objective: To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age.Methods: Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ≤10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height.Results: Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold.Conclusion: We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty.

Impact of intervention treatment on body mass index in girls with idiopathic central precocious puberty

Objective To study the impact of intervention treatment on body mass index(BMI) in girls with idiopathic central precocious puberty(ICPP). Methods One hundred and fifty-six cases girls with ICPP had a long-term follow-up study, and 106 out of the 156 girls were treated with gonadotropin-releasing hormone analogs(GnRHa) for (25.30±1.43)months.And their height, weight, and BMI were measured before treatment, at the end of the treatment and after reaching near adult height, which was compared with those in the untreated 50 girls(control group), and t test was used to analyze the differences between the 2 groups. Results (1)The age BMI standard deviation score(BMISDS) in the GnRHa treatment group before treatment, at the end of the treatment and after reaching near adult height remained in the normal range; among them, the age BMISDS before treatment was similar to that at the end of the treatment, and was slightly higher than that after reaching near adult height, but there was no significant difference(all P>0.05); in the control group, the age BMISDS before treatment was similar to that after reaching near adult height, compared with the treatment group the difference was not significant(all P>0.05). (2) In the GnRHa treatment group, the proportion of overweight before treatment, at the end of the treatment and after reaching near adult height, was 18.8%, 15.0%, 9.4%, and obesity was 8.4%, 6.6%, 4.7%, in the control group, the proportion of overweight before treatment and after reaching near adult height was 14.0%, 6.0%, and obesity was 8.0%, 4.0%, there was no significant difference between 2 groups and by tournament method before and after treatment(all P>0.05). (3) The age BMISDS in 2 groups showed a positive correlation between after reaching near adult height and before treatment(r=0.708, 0.671, all P<0.01). Conclusions GnRHa treatment has no effect on BMI, no obvious tendency to leading to obesity, and a few children with obesity are related to its initial BMI. Key words: Gonadotropin-releasing hormone analogs; Idiopathic central precocious puberty; Girl; Body mass index

Puberty and Pubertal Growth in GH-treated SGA Children: Effects of 2 Years of GnRHa Versus No GnRHa.

Most studies on puberty in children born small for gestational age (SGA) report height and age at onset of puberty. GH-treated SGA children with an adult height (AH) expectation below -2.5 SDS at onset of puberty can benefit from an additional 2 years of GnRH analog (GnRHa) treatment. There are no data on puberty and growth after discontinuation of GnRHa treatment in GH-treated SGA children. This study aimed to investigate the effects on puberty and pubertal growth of 2 years GnRHa vs no GnRHa in GH-treated SGA children. This was a GH trial involving 76 prepubertal short SGA children (36 girls) treated with GH. Thirty-two children received additional GnRHa for 2 years. Pubertal stages were 3-monthly assessed according to Tanner. Age, bone age, and median height at pubertal onset were lower in girls and boys in the GH/GnRHa group compared with the GH group. In girls and boys treated with GH/GnRHa, pubertal duration after stop of GnRHa treatment was shorter than pubertal duration in those with GH only (40.9 vs 46.7 mo; P = .044; 50.8 vs 57.5 months; P = .006; respectively). Height gain from onset of puberty until AH, including height gain during 2 years of GnRHa treatment, was 25.4 cm in girls and 33.0 cm in boys, which was 6.6 cm more than girls and boys treated with GH only. AH was similar in children treated with GH/GnRHa compared with those with GH only. GH-treated SGA children who start puberty with an AH expectation below -2.5 SDS and are treated with 2 years of GnRHa have a shorter pubertal duration after discontinuation of GnRHa compared with pubertal duration in children treated with GH only. Height gain from onset of puberty until AH is, however, more due to adequate growth during 2 years of GnRHa treatment resulting in a similar AH as children treated with GH only.

MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty.

GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP), with the main objective to recover the height potential compromised by the premature fusion of growth cartilages. The aim of this review was to analyze long-term effects of GnRHa on height, body weight, reproductive function, and bone mineral density (BMD) in patients with CPP, as well as the potential predictors of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are not available, only qualified conclusions about the efficacy of interventions can be drawn. GnRHa treatment appears to improve adult height in girls with CPP, especially if diagnosed before the age of 6, whereas a real benefit in terms of adult height is still controversial in patients with the onset of puberty between 6 and 8 years of age. No height benefit was shown in patients treated after 8 years. Gonadal function is promptly restored in girls after cessation of treatment, and reproductive potential appears normal in young adulthood. Data are conflicting on the long-term risk of polycystic ovarian syndrome in both treated and untreated women. Fat mass is increased at the start of treatment but normalizes thereafter, and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does not appear to have a negative impact on BMD. Owing to the paucity of data available, no conclusions can be drawn on the repercussions of CPP and/or its treatment on the timing of menopause and on the health of the offspring.

Pharmacological treatment of sex offenders

Most people recognize that incarceration alone will not solve sexual violence. Indeed, treating the offenders is critical in an approach to preventing sexual violence and reducing victimization. In most cases, a diagnosis of paraphilia is associated with sexual violence. This review is intended to present and summarize the first recently published international guidelines about pharmacological treatment of paraphilias. Pharmacological interventions should be part of a more comprehensive treatment plan including psychotherapy and, in most cases, behavior therapy. Antiandrogens, and mostly GnRH analogues, significantly reduce the intensity and frequency of deviant sexual arousal and behavior. GnRH analogue treatment constitutes the most promising treatment for sex offenders at high risk of sexual violence, such as pedophiles or serial rapists, however informed consent is necessary. SSRIs remain an interesting option in adolescents, in patients with depressive or OCD disorders, or in mild paraphilias such as exhibitionism.Disclosure of interestThe author has not supplied his declaration of competing interest.

Effect of exogenous hormones on ovulation and gonadal steroid plasma levels in starry flounder, Platichthys stellatus

The present study was designed to examine the potential for inducing ovulation in starry flounder (Platichthys stellatus) using gonadotropin-releasing hormone analog (GnRHa) and human chorionic gonadotropin (hCG) to assess whether starry flounder are differentially responsive to GnRHa and hCG. Female starry flounder were injected or implanted with different doses of hCG or GnRHa pellets to examine their ovulation-inducing potential and effects on plasma levels of testosterone (T), 17β-estradiol (E2), and 17,20β-dihydroxy-4-pregnen-3-one (17,20βP). Blood samples were collected for up to 10 or 25 days post-injection or post-implantation in two separate experiments designed to mimic the early and middle stages of spawning, respectively. Fish treated with the GnRHa pellets (100 µg) showed a significant increase in the total number of stripped eggs relative to the controls. GnRHa administration had no effect on the floating rate or fertilization rate of ovulated eggs in the both experiments, whereas hCG injection affected both of these rates. Plasma T levels were not significantly different between the exogenous hormone-treated and control fish. In contrast, the plasma E2 level was elevated in those fish treated with GnRHa, regardless of injection or implantation, and was accompanied by increased numbers of stripped eggs in both experiments. Treatment with GnRHa resulted in higher 17,20βP levels compared to the controls, and there was a positive relationship between elevated plasma 17,20βP and an increase in ovulated eggs in response to GnRHa treatment. The implantation of starry flounder with GnRHa-containing pellets was effective at inducing sustained ovulation compared to hCG treatment.

Gonadotropin-Releasing Hormone Agonist Treatment in Sexual Precocity.

Depot gonadotropin-releasing hormone (GnRH) analogs represent the first-line therapy in sexual precocity due to central precocious puberty. GnRH analogs desensitize the pituitary and account for the suppression of luteinizing hormone and follicle-stimulating hormone leading to a decrease of sex steroid levels. The conventional indications are central puberty starting before the age of 8 years in girls and 9 years in boys. These indications can be extended to difficult conditions with poor adult height prognosis or marked psychosocial impact. This includes children after irradiation, international adoption, and children with a physical handicap or mental disabilities. There are different formulations of depot preparations of GnRH analogs; long-acting 1- or 3-month forms are widely used in Europe and all are well tolerated with minor side effects. Overweight is often present at the onset of precocious puberty and some etiologies such as hamartomas predispose to obesity, requiring appropriate care for weight control during and after the cessation of GnRH analog treatment. Many studies have reported on the effects on adult height, which seems to be especially beneficial when treatment is started before the age of 6; however, few studies have focused on the establishment of the 1st menstruation, 1st sexual intercourse, socioprofessional outcome and subsequent fertility.

Insulin Sensitivity and β-Cell Function in SGA Children Treated With GH and GnRHa: Results of a Long-Term Trial.

Pubertal children born small for gestational age with a poor adult height (AH) expectation can benefit from treatment with GH 1 mg/m(2)/d (∼0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with GH 2 mg/m(2)/d. Because both GH and GnRHa can negatively influence insulin sensitivity, combining these treatments has raised concerns. The long-term GH dose effects on insulin sensitivity in children treated with combined GH/GnRHa are unknown. The purpose of this study was to investigate insulin sensitivity and β-cell function by a very precise method during long-term GH treatment, either with or without 2 years of additional GnRHa and to study differences in insulin sensitivity during treatment until AH between GH at 1 or 2 mg/m(2)/d. This was a randomized, dose-response GH trial involving 110 short small for gestational age children (59 girls) treated with GH until AH (GH randomized to 1 or 2 mg/m(2)/d). Sixty-seven children received additional GnRHa treatment. Frequently sampled intravenous glucose tolerance tests were performed and insulin sensitivity (Si), acute insulin response (AIR), and disposition index (DI) were calculated using Bergman's MINMOD. The GH dose effect was evaluated in a subgroup of 48 children who started GH treatment in early puberty (randomized to 1 or 2 mg/m(2)/d) combined with 2 years of GnRHa. At AH, after 5.9 years of GH treatment, Si, AIR, and DI were similar between children treated with combined GH/GnRHa and those treated with GH only. In the subgroup of children who started GH treatment in early puberty (randomized to 1 or 2 mg/m(2)/d) together with 2 years of GnRHa treatment, there were no significant differences in Si, AIR, or DI between the GH dose groups during the treatment. Combined GH/GnRHa treatment has no long-term negative effects on insulin sensitivity and β-cell function compared with GH only. Started in early puberty, a GH dose of 2 mg/m(2)/d results in a similar insulin sensitivity at AH as a GH dose of 1 mg/m(2)/d.