Effect of pre-treatment with deslorelin on the ovarian response of ewes superovulated with FSH.

This study evaluated the use of the GnRH agonist hormone, deslorelin, to control the follicular population before initiating multiple ovulation and embryo transfer (MOET) treatment. Twenty-four cross-bred Santa Inês ewes, aged between 2 and 4 years, were randomly assigned to either a control group (n = 11) or a treated group (n = 13). All ewes received an intravaginal device containing 60 mg of medroxyprogesterone acetate on day 0, and a new device on day 7, which remained in place until day 14. Additionally, the ewes were administered 125 µg of cloprostenol on day 7. The superovulatory treatment involved administering 200 mg of pFSH, divided into eight decreasing doses at 12-h intervals starting on day 12. On day 14, 300 IU of eCG was administered. In the deslorelin group, three doses of 100 µg of deslorelin were administered starting on day 3 after the insertion of the vaginal device, with subsequent doses given at 72-h and 144-h intervals. Natural mating was performed 36 h after the removal of the progesterone implant using males with proven fertility. Embryo collection took place on the 6th day after mating, and the recovered structures were quantified and evaluated for quality and developmental stage. Transrectal ultrasonography was conducted on days 12, 16 and 21 to evaluate the ovaries, specifically to assess the ovarian follicular population and the presence of the corpus luteum. Ewes in the control group had higher embryo recovery rates (p < .01) compared to the treated group (5.2 ± 0.8 vs. 1.1 ± 0.8), with differences observed primarily in the number of morulae. The number of corpus luteum observed during the laparotomy on day 21 was significantly higher (p < .01) in the control group (10.44 vs. 4.5 corpus luteum per ewe). Yet, the treated group had a significantly higher number of follicles (p < .05) on the first day of pFSH application (5.5 vs. 3.0 follicles per ewe). In conclusion, although the inclusion of deslorelin in the superovulation protocol resulted in increased synchronization of oestrus and follicle number, it did not lead to an increase in the number of corpus luteum or harvested embryos.

Adult height of children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND/PURPOSES: Congenital adrenal hyperplasia attributable to 21-hydroxylase deficiency (21-OHD) is a disorder of adrenal steroidogenesis. Achievement of optimal growth by such patients is challenging. We evaluated the adult height of Taiwanese children with 21-OHD and the effect of a gonadotropin-releasing hormone analogue (GnRHa) in patients with central precocious puberty (CPP) complicating 21-OHD. METHODS: Among 116 patients with 21-OHD in Taiwan, 90 who had attained adult height were subjected to an analysis of height outcomes. Nine with progressive CPP were treated with GnRHa and the effects of this therapy on adult height were further analyzed. RESULTS: In the pre-screening era, the percentage of boys with 21-OHD was lower than expected. Although neonatal screening can prevent mortality caused by adrenal crisis, some cases may be missed. The pooled mean adult height of the 78 patients treated with conventional therapy were -1.1 SD and -0.5 SD adjusting for the genetic potential. The disease features affecting height outcomes are the genetic height potential and in boys the simple virilizing type. Nine patients with CPP were treated with GnRHa in addition to conventional therapy; the mean adult height increased from the predicted -4.1 SD to -1.0 SD after 6.0 ± 2.5 years of treatment. CONCLUSION: Patients with 21-OHD had poorer mean adult height. A high caregiver's index of suspicion is required for the early diagnosis of patients with 21-OHD missed on neonatal screening. Adjuvant therapy with GnRHa can improve the adult height of patients with CPP complicating 21-OHD.

An appraisal of current service delivery and future models of care for young people with gender dysphoria.

The clinical needs of young people with gender dysphoria (GD) have outpaced the capacity of health services to provide appropriate care. The study aimed to explore the interface of Paediatric Endocrinology and young people with GD, detailing the clinical characteristics and the clinical care provided, in order to inform future service development. Medical records of all young people with GD (n=91, 59 (65%) birth-assigned females and 32 (35%) birth-assigned males) referred to Paediatric Endocrinology during 2011-2019 for puberty suppression were reviewed. Median age at initial assessment was 14.6 years (range 8.8-17.6 years). There was a threefold increase from 2016 (n=22) to 2019 (n=73). Mental health disorders were present in 34 (37%) and autistic spectrum disorder in 21 (23%), while 54 (59%) had at least one comorbidity. Sixty-four (70%) young people fulfilled the criteria for consideration of fertility preservation, with 6 (9%) of them preserving their gametes. Seventy-nine (87%) young people commenced treatment with gonadotrophin-releasing hormone analogue, at a median age of 14.8 years (range 9.7-18.0 years). Six (8%) of those discontinued treatment, following a median duration of 6 months (range 6-18 months). Forty-one young people commenced gender-affirming hormones. One (2%) of those who started gender-affirming hormones discontinued treatment.Conclusions: We have witnessed increasing numbers of young people with GD attending Paediatric Endocrinology, with an over-representation of comorbidities, necessitating provision of an individualised approach to treatment. Addressing young people's acceptability of fertility services and ongoing close collaboration between endocrinology and mental health professionals require innovative models of multidisciplinary care. What is Known: • A worldwide increase in presentation of gender dysphoria has been mirrored in our service, with majority assigned female at birth and post-pubertal. • An over-representation of comorbidities exists, notably mental health disorders and autistic spectrum disorder. What is New: • Coordination of interprofessional care to meet complex needs, at an individual level, while improving efficiency of working, at a systemic level, can be met by the development of specialist centres. • The reasons for low uptake of fertility services demand further exploration.

Role of suppression of endometriosis with progestins before IVF-ET: a non-inferiority randomized controlled trial.

BACKGROUND: Endometriosis affects the responsiveness to ovarian stimulation. This study aimed to assess the role of Dienogest pretreatment for endometriosis suppression as compared to Gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis pursuing IVF treatment. METHODS: In this randomized controlled trial, 134 women with endometriosis-related infertility were randomly allocated to group A (n = 67) who had monthly depot GnRHa for 3 months before ovarian stimulation in IVF treatment (Ultra-long protocol), and Group B (n = 67) who had daily oral Dienogest 2 mg/d for 3 months before starting standard long protocol for IVF. The primary outcome measure was the number of oocytes retrieved. The secondary outcome measures included the number of mature oocytes, fertilization rate, quality of life assessed by FertiQoL scores, cost of treatment, and pregnancy outcomes. RESULTS: Although there was no statistically significant difference between both groups regarding ovarian stimulation, response parameters, and pregnancy outcomes, the Dienogest group had a lower cost of treatment (2773 vs. 3664 EGP, P < 0.001), lower side effects (29.9% vs. 59.7%, P < 0.001), higher FertiQoL treatment scores (33.2 vs. 25.1, P < 0.001) and higher tolerability scores (14.1 vs. 9.4, P < 0.001 < 0.001). CONCLUSION: Our study indicates that Dienogest is a suitable and safe substitute for GnRHa pretreatment in endometriosis patients. TRIAL REGISTRATION: NCT04500743 "Retrospectively registered on August 5, 2020".

Effects of immediate versus delayed frozen embryo transfer in high responder patients undergoing freeze-all cycles.

BACKGROUND: Frozen embryo transfer (FET) can greatly improve the pregnancy outcomes for high responder patients. However, it is not known whether the timing of FET is a risk factor on pregnancy outcomes in high responder patients undergoing freeze-all cycles. METHODS: A retrospective cohort study to compare the pregnancy outcomes of the immediate and delayed FET groups in high responder patients undergoing freeze-all cycles. The two groups were defined as that FET took place either within the first menstrual cycle following oocyte retrieval or afterwards. Propensity score matching was used to make the potential risk factors of the two groups comparable. Multivariable regression analysis was used to study the effect of the timing of FET on pregnancy outcomes in the entire cohort and propensity score-matched cohort, even in different controlled ovarian hyperstimulation protocol cohorts as subgroup analysis. RESULTS: We obtained 1130 patients in immediate FET group and 998 patients in delayed FET group, and the average age of the two groups were 30.30 and 30.63. We showed that the immediate FET group were equivalent to delayed FET group in the entire cohort [clinical pregnancy rate (CPR), 61.0% versus 63.4%, adjusted odd ratio (OR), 0.939, 95% confidence interval (CI), 0.781-1.129; spontaneous abortion rate (SAR), 10.1% versus 12.6%, adjusted OR, 0.831, 95% Cl (0.628-1.098); live birth rate (LBR), 49.9% versus 49.2%, adjusted OR, 1.056, 95% Cl (0.883-1.263)]. The same results were obtained by χ2 test in the propensity score-matched cohort (CPR, 60.5% versus 63.5%; SAR, 11.6% versus 12.3%; LBR, 48% versus 49.3%) (P > 0.05). Subgroup analysis indicated that pregnancy outcomes of immediate FET were no difference to delayed FET in gonadotropin-releasing hormone agonist (GnRH-a) protocol (P > 0.05). The SAR of the immediate FET group were lower than that of the delayed FET group in GnRH antagonist protocol (adjusted OR, 0.645, 95% CI, 0.430-0.966) (P < 0.05), no differences were observed in CPR and LBR (P > 0.05). CONCLUSIONS: The pregnancy outcomes of immediate FET were no difference to delayed FET in high responder population undergoing freeze-all cycles.

Testicular effects of a postnatal GnRH antagonist in domestic cats.

The aim of this study was to describe the histological effects of two high postnatal doses of the potent third-generation GnRH antagonist, acyline in the domestic cat testicle. Secondly, the physical, endocrine, and steroidogenic findings of this pharmaceutical protocol are also reported. Twelve postnatal littermate male kittens were administered acyline in a dose of 2.2 mg/100 g SC weekly for 2 weeks (ACY; n = 6), or placebo (PL; n = 6). All the animals were followed up until puberty when they were castrated. Serial faecal samples were collected until the age of 10 weeks for testosterone (T) measurement. The kittens achieved puberty without either age (236.5 ± 19.7 vs. 221.7 ± 23.7 days) or body weight (3.05 ± 0.15 vs. 2.78 ± 0.28 kg, P > 0.05) differences between ACY and PL, respectively. Acyline suppressed faecal T concentrations for 3 weeks (P < 0.01). From the fourth week on, both groups had low concentrations up to the end of the follow-up period (P > 0.05). Histological assessment of the testes showed that ACY cats presented a reduced height of the epithelium (P < 0.01) due to the diminished number of germinal cells accompanied by an enlarged luminal area (P < 0.01) with cellular debris (P < 0.01). The immunostaining of P450c17 also appeared partially diminished in ACY testes.

[Support for transgender adolescents and preadolescents: the role of the pediatric endocrinologist]. / Rôle de l'endocrino-pédiatre dans l'accompagnement des adolescents et préadolescents transgenres.

Since the end of the 1990s, the management of transgender adolescents has developed in many countries following the Dutch Approach initiated in the Netherlands. Dedicated consultations have been developed in France since 2013, welcoming a growing number of children and adolescents. What kind of support is offered to children and their families?

Progestins versus GnRH analogues for pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and meta-analysis.

This systematic review and meta-analysis of comparative studies investigated whether progestins are as effective as gonadotrophin releasing hormone (GnRH) analogues for pituitary suppression in assisted reproduction. The primary outcome was live birth rate per woman. Secondary outcomes were live birth or ongoing pregnancy per woman and per embryo transfer, ongoing pregnancy, clinical pregnancy, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotrophin consumption. Adverse events included miscarriage, ectopic pregnancy and multiple pregnancy rates. The GRADE system was used to assess the quality of evidence. Seven studies involving a total of 2047 women were included. Three studies compared a progestin with a GnRH antagonist and four studies compared a progestin with a GnRH agonist. Most studies are non-randomized and report outcomes per embryo transfer, rather than per woman. Although progestins were similar to GnRH antagonists in effectiveness and safety parameters, they were associated with significantly higher live birth or ongoing pregnancy per embryo transfer compared with the short GnRH agonist protocol (RR 1.49, 95% CI 1.16 to 1.91). Progestin primed stimulation lasted significantly longer (mean difference 0.61 days, 95% CI 0.33 to 0.89) and required significantly more gonadotrophins (mean difference 433.2 IU, 95% CI 311.11 to 555.19) than the short GnRH agonist protocol, but the differences were clinically negligible. Safety parameters were similar between progestins and GnRH agonists. In conclusion, progestins can effectively prevent premature ovulation in assisted reproductive technology cycles. If larger and well-designed studies confirm these findings, progestins may be an effective and low-cost alternative to GnRH analogues when a fresh embryo transfer is not planned owing to a medical indication.

Ovarian 25OH-vitamin D production in young women affected by polycystic ovary syndrome.

INTRODUCTION: Vitamin D is involved in the regulatory mechanisms of ovarian function and is frequently low in PCOS patients. Since obesity and hyperinsulinemic state negatively influenced vitamin D levels, therefore, we evaluated the production of vitamin D at the ovarian level only in lean and normoinsulinemic PCOS subjects. Basal, GnRH analogue-induced ovarian production of 25OH-vitamin D (VitD) and a direct sampling at ovarian vein level were investigated. METHODS: Basal and GnRH analogue-induced hormone levels were evaluated at peripheral level in 45 subjects, aged 18-39 years, and in 22 healthy women with age- and BMI-matched as controls. In 12 PCOS patients, undergoing laparoscopy, a venous sampling at both peripheral and ovarian level was further done. All subjects presented low VitD levels, appropriate to the season and with no difference between PCOS and control subjects. RESULTS: GnRH analogue significantly stimulated plasma LH, FSH, 17-OHP and estradiol secretion (p from < 0.05 to < 0.001 vs basal levels), whereas no effect was observed on both serum AMH and VitD concentrations in all groups. A significant difference (p < 0.006), between peripheral and ovarian veins, was observed in both AMH and estradiol levels in PCOS subjects, while no gradient of VitD was detected. CONCLUSIONS: All patients presented with low VitD levels. The absence of any VitD variation, both at basal and after GnRH analogue administration, or at peripheral-ovarian vein gradient, suggests no pituitary-ovarian axis involvement in VitD production or its direct ovarian production in lean and normoinsulinemic PCOS subjects.

A case of hemorrhagic shock occurred during dienogest therapy for uterine adenomyosis.

We present a case of hemorrhagic shock occurred during dienogest therapy for uterine adenomyosis which necessitated an emergency hysterectomy. The patient was a 45-year-old woman with adenomyosis. Magnetic resonance imaging showed type I adenomyosis measuring 10 cm. She had a history of intimal thrombectomy of pulmonary embolism and had been receiving warfarin and aspirin until the onset of the hemorrhagic shock. Following 6-month of gonadotropin-releasing hormone analogue, dienogest was commenced. Nine months after switching to dienogest, the patient experienced a persistent abnormal uterine bleeding for 2 weeks, eventually causing a massive bleeding and was transferred to our emergency room. A diagnosis of hemorrhagic shock with a severe anemia (hemoglobin 3.6 g/dL) was made. Despite blood transfusion and warfarin antagonization, continuous bleeding ≥150 g/h was not controlled. Emergent hysterectomy was opted and enabled hemostasis. Although the number of patients with adenomyosis who can avoid surgery by dienogest is increasing, care must be taken during dienogest therapy, especially in patients with anticoagulants and after gonadotropin-releasing hormone analogue treatment. To prevent such a critical event, careful management including patient education should be carried out.

A CASE OF SOTOS SYNDROME CAUSED BY A NOVEL VARIANT IN THE NSD1 GENE: A PROPOSED RATIONALE TO TREAT ACCOMPANYING PRECOCIOUS PUBERTY.

Sotos syndrome is characterized by overgrowth, macrocephaly, distinctive facial features, and learning disabilities and is associated with alterations in the nuclear receptor binding SET domain protein 1 (NSD1) gene. Due to the advanced bone age, the eventual adult height is usually at the upper limit of normal. In this case report, a 6-year and 10-month old boy who presented with Sotos syndrome was described. He also had increased testicular volumes with advanced bone age. The stimulated levels of gonadotropins revealed central precocious puberty and brain magnetic resonance imaging (MRI) showed a pineal cyst. A heterozygous duplication variant [NM_022455.4:c.4560dup; p.(His1521Thrfs*9)] in the NSD1 was identified. Triptorelin acetate treatment was started. The aim was to report the novel duplication variant in the NSD-1 in a patient with Sotos syndrome accompanied by a pineal cyst and central precocious puberty, and also to discuss the rationale for treating precocious puberty.

Intraoperative Effect of Preoperative Gonadotropin-Releasing Hormone Analogue Administration in Women Undergoing Cold Loop Hysteroscopic Myomectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To evaluate the intraoperative effects of gonadotropin-releasing hormone (GnRH) analogue pretreatment in patients undergoing cold loop hysteroscopic myomectomy. DESIGN: Randomized controlled trial (Canadian Task Force classification I). SETTING: Arbor Vitae Center for Endoscopic Gynecology, Rome, Italy. PATIENTS: A total of 99 patients were randomized and subsequently allocated to the GnRH analogue group or to the nonpharmacologic treatment control group. Fifteen patients were lost after allocation, and 42 patients per group underwent hysteroscopic myomectomy. INTERVENTIONS: Cold loop hysteroscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: The control group accomplished the treatment in a 1-step procedure more frequently than the GnRH analogue group (92.85% and 73.8% of cases, respectively; p = .040). The completion of the treatment was more unlikely in case of G2 myomas (p = .006), whereas no differences were recorded for G1 and G0 myomas. The multivariate analysis showed a significant correlation between the multiple-step treatment and the use of GnRH analogue (odds ratio, 5.365; 95% confidence interval [CI], 1.018-28.284; p = .048), grading (odds ratio, 4.503; 95% CI, 1.049-19.329; p = .043), and size of myomas (odds ratio, 1.128; 95% CI, 1.026-1.239; p = .013). CONCLUSIONS: Preoperative GnRH analogue administration did not facilitate the completion of cold loop hysteroscopic myomectomy in a single surgical procedure in G2 myomas and was correlated with a longer duration of the surgery. No significant benefits were found for G0 and G1 myomas. (ClinicalTrials.gov: NCT01873378.).

GnRH agonist pre-treatment for microwave endometrial ablation in women with less than 1 centimetre myometrial thickness.

We evaluated the efficacy of gonadotropin-releasing hormone agonist (GnRHa) therapy for improving the myometrial thickness in women with thin (less than 1 cm) uterine walls, a contraindication for microwave endometrial ablation (MEA). The normal myometrium thickness was 0.5 cm, 0.7 cm and 0.9 cm. After the third GnRHa dose, the myometrial thickness increased to over 1 cm in all the three patients, and all were able to undergo MEA. The VAS score for menorrhagia improved in all the cases. The patient satisfaction levels were 10 in 2 of the 3 patients, and 5 in the other. There was no symptom recurrence, and no adjuvant therapy was administered. GnRHa therapy in women with submucous leiomyomata and a myometrial thickness of less than 1 cm could effectively thicken the myometrium, allowing for the use of MEA.

GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial.

BACKGROUND: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI. PATIENTS AND METHODS: This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI. RESULTS: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups. CONCLUSION: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.

Short versus long gonadotropin-releasing hormone analogue suppression protocols in advanced age women undergoing IVF/ICSI.

OBJECTIVE: To compare the effective of two GnRH-a protocols for ovarian stimulation in advanced age women undergoing IVF/ICSI cycles. STUDY DESIGN: A total of 1149 IVF-ET/ICSI cycles were retrospectively identified. The cycles were divided two groups, namely a long-protocol group and a short-protocol group. RESULTS: The numbers of oocytes retrieved, and high-quality embryos in the long-protocol group were significantly greater than those in the short-protocol group. In the long-protocol group, the implantation and pregnancy rates were 17.22% and 33.67%, respectively, and these values were significantly higher than those in the short-protocol group (8.24% and 15.96%, p < 0.05). CONCLUSIONS: Our study demonstrated that the long protocol was superior to the short protocol for advanced age women.

Effect of goserelin and leuprolide added to the semen on reproductive performance in rabbits - Short communication.

The aim of this study was to evaluate the ability of two synthetic GnRH analogues, goserelin and leuprolide, to induce ovulation in rabbit does using intravaginal administration. A total of 252 primiparous lactating does were randomly divided into five groups that, at the time of insemination, received the following treatments for ovulation induction: 1 µg of buserelin administered intramuscularly (control group), 5 µg of goserelin added to the semen dose (Group G5), 10 µg of goserelin added to the semen dose (Group G10), 5 µg of leuprolide added to the semen dose (Group L5), and 10 µg of leuprolide added to the semen dose (Group L10). The kindling rate was 80.5% in Group G10 and 75.0% in Group L10; these values are comparable to the kindling rate obtained in the control group (85.9%). The kindling rates in Groups G5 and L5 were significantly lower than in the control group (60.0%, 54.2% and 85.9%, respectively). The number of live-born rabbits was not significantly affected by the ovulation induction treatment. As regards the total number of rabbits born the only significant difference was observed between Groups G5 and L5. This study shows the possibility of inducing ovulation in rabbits by adding goserelin and leuprolide directly to the semen dose.

Gonadotrophin-releasing hormone analogue or dienogest plus estradiol valerate to prevent pain recurrence after laparoscopic surgery for endometriosis: a multi-center randomized trial.

OBJECTIVES: To evaluate the efficacy of dienogest + estradiol valerate (E2V) and gonadotrophin-releasing hormone analogue (GnRH-a) in reducing recurrence of pain in patients with chronic pelvic pain due to laparoscopically diagnosed and treated endometriosis. DESIGN: Multi-center, prospective, randomized study. SETTING: Three university departments of obstetrics and gynecology in Italy. POPULATION: Seventy-eight women who underwent laparoscopic surgery for endometriosis combined with chronic pelvic pain. METHODS: Post-operative administration of dienogest + E2V for 9 months (group 1) or GnRH-a monthly for 6 months (group 2). MAIN OUTCOME MEASURES: A visual analogue scale was used to test intensity of pain before laparoscopic surgery at 3, 6 and 9 months of follow up. A questionnaire to investigate quality of life was administered before surgery and at 9 months of follow up. RESULTS: The visual analogue scale score did not show any significant differences between the two groups (p = 0.417). The questionnaire showed an increase of scores for all women compared with pre-surgery values, demonstrating a marked improvement in quality of life and health-related satisfaction with both treatments. No significant differences were found between the groups. The rate of apparent endometriosis recurrence was 10.8% in group 1 and 13.7% in group 2 (p = 0.962). CONCLUSION: Both therapies seemed equally efficacious in preventing endometriosis-related chronic pelvic pain recurrence in the first 9 months of follow-up.

Sertoli-Leydig cell tumors: hormonal profile after dynamic test with GnRH analogue: triptorelin represents a useful tool to evaluate tumoral hyperandrogenism.

We report the case of a 15-year-old woman with signs of hyperandrogenism affected by a Sertoli-Leydig cell tumor (SLCT). In our patient, blood analysis showed a high testosterone (T) level (T: 8.53 nmol/L; nv < 1.87 nmol/L) while the GnRH-analogue test demonstrated an exaggerated secretion of 17-hydroxyprogesterone (OHP), T, and androstenedione (A) by the ovary after stimulation. We compared the GnRH-analogue test of our patient with that obtained in a group of normal and healthy women (no. 8 subjects, 16-26 years old), men (no. 4 subjects, 18-28 years old), and in a group of PCOS patients with age and body weight compared. We found in our patient a value of OHP, 17-beta estradiol (E2) and T, from 2 to 18 times higher than healthy women. When we compared our patient with healthy men, we differently observed a comparable response of T. The response of our patient was also comparable with that observed in the PCOS group for E2. During the post-surgical follow up, the GnRH-analogue test of our patient showed a response of OHP, T, and E2 comparable with that of the PCOS group. The GnRH-analogue test is a useful tool to characterize steroidogenesis in SLCT.

Precocious Puberty and GnRH Analogs: Current Treatment Practices and Perspectives among US Pediatric Endocrinologists.

INTRODUCTION: Gonadotropin releasing hormone analogs (GnRHas) are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. METHODS: The Drugs and Therapeutics Subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the USA. The survey consisted of four main subsections: (1) description of clinical practice; (2) self-assessment of knowledge base of pediatric and adult GnRHa formulations; (3) current practice for treating central precocious puberty (CPP); and (4) utilization of healthcare resources. RESULTS: There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the 3-month preparation, and the histrelin implant (Supprelin®) (88%, 96%, and 91%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) (65%) and 6-month subcutaneous leuprolide (Fensolvi®) (45%). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44%), but in practice, respondents reported a higher percentage of patients treated with the 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (64%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. CONCLUSIONS: The survey indicated there is more familiarity with older, shorter acting GnRHas, which are prescribed in greater numbers than newer, longer acting formulations. There is lack of consensus on the need for central nervous system (CNS) imaging in girls presenting with CPP between 6 and 8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability, there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Longitudinal assessment of auxological parameters, adult height outcome and its determinants in leuprolide-treated Indian girls with idiopathic central precocious puberty.

OBJECTIVES: To assess auxological parameters, adult height outcome and its determinants in Indian girls with idiopathic central precocious puberty (iCPP) treated with gonadotropin-releasing hormone analogues (GnRHa). METHODS: Retrospective study. Inclusion: data on girls with iCPP from initiation to stopping GnRHa (n=179). Exclusion: boys, peripheral, organic central precocity. RESULTS: Mean age of starting GnRHa: 8.2± 1.1 years, duration: 2.8± 1.2 years. 11.7 % had attained menarche at first presentation. The difference between bone (BA) and chronological (CA) ages reduced significantly from 2.6± 0.9 years (onset) to 1.6± 0.8 years (cessation). Weight, BMI Z-scores increased (p<0.01), height Z-scores decreased (0.8 vs. 0.6; p<0.01), predicted adult height (PAH) and Z-scores improved by 3.5 cm, 0.5 SDS following treatment (p<0.01). Overweight/obese girls (vs. normal BMI) were taller, with more advanced BA at starting (height Z-score: 0.7 vs. 1.0, BA-CA: 2.2 vs. 2.9 years), stopping (height Z-score: 0.5 vs. 0.9, BA-CA: 1.4 vs. 1.9 years) treatment, but showed no difference in PAH at starting, stopping treatment. Adult height data (n=58) revealed 1.9 cm gain above target height. Adult height Z-scores significantly exceeded target height Z-scores (p<0.01). Mean adult height (157.1± 5.8 cm) crossed PAH at starting treatment (155.9± 6.4 cm) but remained 1.6 cm lesser than PAH at cessation. Adult weight, BMI Z-scores (-0.2± 1.3, -0.1± 1.2) were significantly lower (p<0.01) than those at stopping GnRHa. Height gain adjusted for age at starting GnRHa correlated negatively with height, weight, BMI, Tanner-staging, BA, FSH, Estradiol at treatment onset, BA at cessation, and correlated positively with treatment duration. CONCLUSIONS: GnRHa treatment in Indian girls with iCPP resulted in improved PAH, decelerated bone age advancement and growth velocity. Most girls achieved adult height within target range, surpassing PAH at treatment initiation. Lesser anthropometric, sexual, skeletal maturity, lower baseline FSH, estradiol, longer treatment duration, less advanced BA at stopping GnRHa may translate into better adult height outcomes.