Use Of GnRH Analogues Research Articles

Association between GnRH analogue use and atopic diseases in patients with prostate cancer: A population-based retrospective cohort study.

PurposeGonadotropin-releasing hormone (GnRH) analogues reduce testosterone levels to castration levels in patients with prostate cancer. However, the role of testosterone in atopic diseases has remained undefined. We aimed to investigate this role.Materials and methodsThis retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD). Patients with prostate cancer were categorized into two groups according to whether they received GnRH analogue treatment (study group I) or not (study group II), and men without prostate cancer and with no GnRH analogue use were defined to comprise the comparison group after their ages and index years were matched with group II. Cox proportional hazard models were used to assess the hazard ratio (HR) of atopic diseases.ResultsGroup I, group II, and the comparison group comprised 663, 2,172, and 8,688 individuals, respectively. Group I had a significantly lower risk of atopic diseases (adjusted HR: 0.66, 95% CI, 0.49–0.89, p < 0.01) than did group II. A reduced risk of atopic diseases was found when GnRH analogues were prescribed for 2 months (adjusted HR 0.53, 95% CI, 0.29–0.97, p = 0.04) and 2–14 months (adjusted HR 0.66, 95% CI, 0.49–0.89, p = 0.007). No significant difference in the risk of atopic diseases between group II and the comparison group was observed.ConclusionsA decreased risk of atopic diseases was observed in patients with prostate cancer treated with GnRH analogues. Further studies are warranted to verify the association between testosterone levels and atopic diseases.

Adult Height of Patients with SHOX Haploinsufficiency with or without GH Therapy: A Real-World Single-Center Study

Introduction: Isolated SHOX haploinsufficiency is a common monogenic cause of short stature. Few studies compare untreated and rhGH-treated patients up to adult height (AH). Our study highlights a growth pattern from childhood to AH in patients with SHOX haploinsufficiency and analyzes the real-world effectiveness of rhGH alone or plus GnRH analog (GnRHa). Methods: Forty-seven patients (18 untreated and 29 rhGH-treated) with SHOX haploinsufficiency were included in a longitudinal retrospective study. Adult height was attained in 13 untreated and 18 rhGH-treated (rhGH alone [n = 8] or plus GnRHa [n = 10]) patients. Results: The untreated group decreased height SDS from baseline to AH (−0.8 [−1.1; −0.4]), with an increase in the prevalence of short stature from 31% to 77%. Conversely, the rhGH-treated group had an improvement in height SDS from baseline to AH (0.6 [0.2; 0.6]; p < 0.001), with a reduction in the prevalence of short stature (from 61% to 28%). AH in the rhGH-treated patients was 1 SD (6.3 cm) taller than in untreated ones. Regarding the use of GnRHa, the subgroups (rhGH alone or plus GnRHa) attained similar AH, despite the higher prevalence of pubertal patients and worse AH prediction at the start of rhGH treatment in patients who used combined therapy. Conclusion: The use of rhGH treatment improves AH in patients with SHOX haploinsufficiency, preventing the loss of height potential during puberty. In peripubertal patients, the addition of GnRHa to rhGH allows AH attainment similar to the AH of patients who start rhGH alone in the prepubertal age.

18. Continuation of Gonadotropin-Releasing Hormone Analogue Use Among Transgender and Gender-Diverse Adolescents With Access to Low- or no-Cost Gender-Affirming Medical Care

The Endocrine Society Guideline for Transgender Care and the World Professional Association for Transgender Health Standards of Care recommend the use of gonadotropin-releasing hormone analogues (GnRHa) as a treatment option for adolescents with gender dysphoria who have not completed puberty. These medications attenuate sex hormone production and pause development of secondary sex characteristics. The effects of GnRHa are reversible, allowing adolescents time to explore their gender identity before determining if they would benefit from interventions with partially irreversible effects, such as gender-affirming hormones.

Treatment with gonadotropin-releasing hormone analogs (GnRHa) in childhood and adolescence

For several decades, gonadotropin releasing hormone analogs (GnRHa) are the medical treatment selected for central precocious puberty (CPP) in girls and boys. They generate an inhibition of the hypothalamus-pituitary-gonadal axis decreasing LH, FSH, estradiol and testosterone secretion and, in this way, they produce a regression of secondary sexual characters under treatment. In the last years, these analogs are also used in trans adolescents, in adolescents and young adults with oncological diseases, in some very particular situations in children with short stature and in patients with neurodevelopmental disorders. In Argentina the most commonly used formulations are triptorelin and leuprolide acetate depot forms. These analogs have proven both their efficacy and their safety. The aim of this paper is to review and update about the use of GnRHa in children and adolescents.

Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China

Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment. This randomized clinical trial, conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital and Zhejiang Cancer Hospital in China, was an open-label trial involving premenopausal women aged 18 to 49 years with operable stage I to III breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned in 2 parallel groups: treatment with chemotherapy with or without GnRHa. Enrollment occurred from September 2015 to August 2017, and follow-up ended December 2020. The data were analyzed in March 2021. A total of 405 patients were enrolled in the study, among whom 27 patients (6.7%) quit participation voluntarily, 33 (8.1%) did not meet the inclusion criteria and were excluded, and 15 (3.7%) were lost to follow-up. Ultimately 330 patients were included in the primary analysis, including 29 patients with baseline anti-Müllerian hormone levels less than 0.5ng/ mL. Eligible patients were randomly assigned (1:1) to receive chemotherapy with (n = 165) or without (n = 165) GnRHa. In patients randomized to receive GnRHa, 3.6 mg of goserelin or 3.75 mg of leuprorelin was injected subcutaneously once every 28 days from 1 to 2 weeks before the first cycle of chemotherapy to 4 weeks after the last cycle of chemotherapy. The primary end point was the rate of premature ovarian insufficiency (POI) at 12 months after chemotherapy. Premature ovarian insufficiency was defined as anti-Müllerian hormone levels of less than 0.5 ng/mL in this study. The secondary end point was overall survival (OS) and tumor-free survival (TFS). A total of 330 eligible patients could be evaluated with complete data, among whom 301 patients (91.2%; GnRHA group: mean [SD] age, 40.6 [6.7] years; control group: mean [SD] age, 40.2 [5.9] years) were eligible for primary end point analysis. At 12 months after the completion of chemotherapy, the POI rate was 10.3% (15 of 146) in the GnRHa group and 44.5% (69 of 155) in the control group (odds ratio, 0.23; 95% CI, 0.14-0.39; P < .001). Anti-Müllerian hormone resumption in the GnRHa group was significantly better than that in the control group (15 of 25 vs 6 of 44; odds ratio, 4.40; 95% CI, 1.96-9.89; P < .001). After a median follow-up of 49 months (range, 25-60 months), the differences in 4-year OS and TFS between the 2 groups were not significant. A post hoc analysis showed that in patients younger than 35 years, the TFS was higher in the GnRHa group than in the control group (93% vs 62%; P = .004; hazard ratio, 0.15; 95% CI, 0.03-0.82; P = .03). This randomized clinical trial found that administering GnRHa in treatment with chemotherapy for premenopausal patients with breast cancer reduces the risk of POI, which promotes the recovery of ovarian function. ClinicalTrials.gov Identifier: NCT02518191.

An Approach to the Evaluation and Management of the Obese Child With Early Puberty.

With the declining age at onset of puberty and increasing prevalence of childhood obesity, early breast development in young obese girls has become a more frequent occurrence. Here, we examine available literature to answer a series of questions regarding how obesity impacts the evaluation and management of precocious puberty. We focus on girls as the literature is more robust, but include boys where literature permits.Suggestions include: (1) Age cutoffs for evaluation of precocious puberty should not differ substantially from those used for nonobese children. Obese girls with confirmed thelarche should be evaluated for gonadotropin-dependent, central precocious puberty (CPP) to determine if further investigation or treatment is warranted. (2) Basal luteinizing hormone (LH) levels remain a recommended first-line test. However, if stimulation testing is utilized, there is a theoretical possibility that the lower peak LH responses seen in obesity could lead to a false negative result. (3) Advanced bone age (BA) is common among obese girls even without early puberty; hence its diagnostic utility is limited. (4) Obesity does not eliminate the need for magnetic resonance imaging in girls with true CPP. Age and clinical features should determine who warrants neuroimaging. (5) BA can be used to predict adult height in obese girls with CPP to inform counseling around treatment. (6) Use of gonadotropin-releasing hormone analogues (GnRHa) leads to increased adult height in obese girls. (7) Obesity should not limit GnRHa use as these agents do not worsen weight status in obese girls with CPP.

126P Effects of GnRHa on ovarian function against chemotherapy-induced gonadotoxicity in premenopausal women with breast cancer in China: A prospective randomized controlled trial (EGOFACT)

Premature ovarian insufficiency (POI) is a common toxic effect of chemotherapy in premenopausal female patients. Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. There has never been any randomized controlled study data on Chinese patients.

Induction of ovulation after artificial insemination in rabbits: Intramuscular injection of gonadotropin-releasing hormone (GnRH) agonist vs. intravenous administration of mated doe serum

BACKGROUND: Rabbits are reflex ovulators with the ovulatory process triggered by neuro-hormonal impulses generated during natural mating. When applying artificial insemination (AI), an array of biostimulation techniques and/or exogenous hormones (e.g., gonadotropin-releasing hormone (GnRH) or its analogues) must be used to induce ovulations in female rabbits. However, the effectiveness of various biostimulation techniques and exogenous hormones is not always satisfactory and the use of GnRH analogues is additionally associated with high production costs. Therefore, developing an alternative inexpensive, efficient and safe treatment for the induction of ovulation in artificially inseminated does is urgently needed. OBJECTIVES: In the present study, we examined and compared the effects of mated doe serum (MDS) and GnRH analogue (Gonadorelin) administered immediately after artificial insemination on circulating concentrations of luteinizing hormone (LH) and fertility in New Zealand does. METHODS: Forty artificially inseminated does were allocated to four equinumerous groups that received: 0.2 ml of saline i.m. (Control G), 0.8 µg of Gonadorelin dissolved in 0.2 ml of saline i.m. (Treatment G), 2.5 ml of mixed sex normal rabbit serum i.v. (Control M) or 2.5 ml of mated doe serum (MDS)/doe i.v. (Treatment M). RESULTS: A peak in systemic LH concentrations occurred earlier in Treatment M compared with Treatment G does (71 vs. 107 min post-AI, respectively; P≤ 0.05); mean LH concentrations did not vary (P≤ 0.05) from the pre-AI values in both control groups. Serum LH concentrations remained higher (P≤ 0.05) in Treatment M compared with Treatment G does from 30 to 90 min post-AI but they were greater (P≤ 0.05) in Treatment G than in Treatment M group at 120 and 160 min after AI. Gonadorelin and MDS injections both resulted in the same kindling rate (80%) at each of the four consecutive AI’s (initiated 30 days post-partum) and they were significantly greater than those recorded in control animals (20%). CONCLUSION: It can be concluded that MDS administration is an effective treatment to induce ovulations in rabbits, with the repeatability like that achieved with a GnRH analogue.

Use of gonadotropin-releasing hormone analogs in children.

In this review, we outline the usage and formulations of gonadotropin-releasing hormone analogs (GnRHas) in central precocious puberty (CPP), short stature, and gender diverse individuals, as well as adverse effects, long-term outcomes, and monitoring of therapy. There is a particular focus on citing references published within the last 24 months. Long-acting formulations of GnRHa now include Federal Drug Administration approval for subcutaneous injections. Significant adverse events continue to be rarely reported; extremely rare events include arterial hypertension and pseudotumor cerebri. There continue to be no significant long-term consequences including the impact upon body mass index and bone mineral density, which appear to be transient. GnRHas have been used in differences of sexual development (DSD) and increasingly in the treatment of adolescent transgender individuals. GnRHas remain as the only fully efficacious therapy for CPP and effectively suppress pubertal hormones in other situations. The use of GnRHa therapy in gender incongruent individuals has proven beneficial and has become a standard of care, whereas use in those with DSDs should still be considered experimental. http://links.lww.com/MOP/A62.

Exogenous progesterone for LH surge prevention is redundant in ovarian stimulation protocols

During ovarian stimulation for IVF–embryo transfer treatment, a premature LH surge may lead to progesterone elevation that disrupts endometrial maturation and affects the probability of pregnancy following fresh embryo transfer. Preventing this LH surge and progesterone elevation using gonadotrophin-releasing hormone (GnRH) analogues is considered a standard practice. The same policy applies to cycles in which the ‘freeze-all’ protocol has been selected from the outset (e.g. donors), but the need for this has not been discussed. Moreover, in ‘freeze-all’ cycles, exogenous progesterone administration tends to replace GnRH antagonists, without reducing efficacy after embryo transfer in frozen-thawed cycles. Nevertheless, as exogenous progesterone is expected to have the same impact on the endometrium as endogenous progesterone, it is clear that, unlike in fresh cycles, in ‘freeze-all’ cycles an endogenous LH surge prevention does not seem necessary. Therefore, both GnRH antagonists and exogenous progesterone appear to be redundant in ‘freeze-all’ cycles, and in this context the indications for the use of GnRH analogues in ovarian stimulation protocols need to be revisited.

Does Depot Analog Suppression Have Positive Effects on All Other Frozen-thawed Embryo Transfer Cycles in Addition to Endometriosis?

Introduction: The study investigated whether Gonadotropin-releasing hormone analog (GnRH-a) suppression before elective frozen-thawed embryo transfer (FET) allows better ongoing pregnancy rates (OPR) in women without endometriosis. Material and methods: Retrospective cohort study including FET cycles performed in one academic fertility center from 2014 October to 2019 December. In the analog suppression group (ASG), depot analog was given on day 2 or 3, and estradiol (E2) treatment was started on the 21st day of analog usage. Intramuscular progesterone (100 mg/d) was added to E2 till the fetal heartbeat was seen. Then vaginal progesterone (600 mg/d) was continued until the 12th week of gestation. Results: Among 523 FET, 22.4% underwent analog suppression, 77.6% had not undergone analog suppression before FET. There was no difference between groups concerning endometrial thickness, the number of embryos transferred, development of embryo stage at FET cycle, and cryopreservation technique. Implantation rate and ongoing pregnancy rates were significantly higher in the ASG than in the non-analog suppression group (NASG). Conclusion: The use of GnRH-a before FET increases implantation rate and ongoing pregnancy rate not only in endometriosis cases but also in other patients with different infertility causes.

Studies on fixed-time ovulation induction in the pig

A technology that allows for manipulating of oestrus and ovulation, and would then also allow for fixed-time insemination, can be of great benefit for swine farms that operate using sow batch management due, at least in part, to savings in labour and the production of large batches of evenly developed pigs. Thanks to the current knowledge on endocrine regulation of follicle development and ovulation, and the availability of numerous reproductively active substances such a technology is now available. It covers procedures for synchronising oestrus based on the use of altrenogest in gilts and of batch-wise weaning in sows, for stimulating follicle development using eCG and for inducing of ovulation using hCG or LH as well as GnRH analogues. While the procedures for oestrus synchronisation stand alone, other procedures require additional treatments. If fixed-time insemination is the goal, oestrus needs to be synchronised and follicular development and ovulation induced by the use of GnRH analogues and hCG with ovulation occurring within 36-42 hrs. It is a general recommendation to inseminate those animals twice, i.e. 24 and 40 hrs after ovulation induction. However, the aforementioned technology requires healthy animals and a solid management and cannot be used to compensate for poor management.

RECOMBINANT LUTEINIZING HORMONE ASSOCIATED WITH RECOMBINANT FOLLICLE STIMULATING HORMONE FOR OVARIAN STIMULATION: DECREASED INCIDENCE OF IMMATURE OOCYTES AND BETTER CLINICAL OUTCOMES

It has been demonstrated that the use of GnRH analogues decreases the concentration of LH available to developing follicles, nevertheless, both gonadotrophins, LH and FSH, are crucial to normal follicular development. Luteinizing hormone also plays an important role in oocyte maturation during natural cycles. However, whether patients undergoing COS may benefit from co-administration of r-LH and r-FSH, when either a GnRH-antagonist or a GnRH-agonist protocol is used is to be elucidated. The goal for the present study was to evaluate the effect of the combination of recombinant LH (rLH) with recombinant FSH (rFSH) on ICSI clinical outcomes.

Use of GnRH analogue in the endometriosis recurrence after surgery

: Endometriosis recurrence after surgery is still an issue that afflicts the gynecologist. Adjuvant hormonal treatments have been suggested and approved in order to delay recurrence in symptoms and endometriotic lesions. The current review analyzes the impact of postoperative gonadotropin-releasing hormone agonists administration on the recurrence rate of endometriosis. We selected randomized controlled trials on this topic. The reported findings are controversial and the definition of recurrence varies among the sources. The emerging results report that the postoperative administration of gonadotropin-releasing hormone agonists seems beneficial on symptoms control and it delays the subjective recurrence (although it is related to the known side effects), but the duration of the post-operative treatment plays an important role.

Use of GnRH Analogues in the Reduction of Submucous Fibroid for Surgical Hysteroscopy: A Systematic Review and Meta-Analysis.

Gonadotropin-releasing hormone analogues (GnRH-a) have been used preoperatively before hysteroscopic myomectomy to decrease the size and vascularization of the myomas, but evidence to support this practice is weak. Our objective was to analyze the use of GnRH-a in the reduction of submucous fibroid as a facilitator for surgical hysteroscopy from published clinical trials. Studies from electronic databases (Pubmed, Scielo, EMBASE, Scopus, PROSPERO), published between 1980 and December 2018. The keywords used were fibroid, GnRH analogue, submucous, histeroscopy, histeroscopic resection and their correspondents in Portuguese. The inclusion criteria were controlled trials that evaluated the GnRH-a treatment before hysteroscopic resection of submucous myomas. Four clinical trials were included in the meta-analysis. Two review authors extracted the data without modification of the original data, using the agreed form. We resolved discrepancies through discussion or, if required, we consulted a third person. The present meta-analysis included a total of 213 women and showed no statistically significant differences in the use of GnRH-a compared with the control group for complete resection of submucous myoma (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.80-1.11); operative time (mean difference [MD]: - 3.81; 95%CI : - 3.81-2.13); fluid absorption (MD: - 65.90; 95%CI: - 9.75-2.13); or complications (RR 0.92; 95%CI: 0.18-4.82). The present review did not support the routine preoperative use of GnRH-a prior to hysteroscopic myomectomy. However, it is not possible to determine its inferiority when compared with the other methods due to the heterogeneity of existing studies and the small sample size.

GnRHa treatments of Atlantic Salmon broodstock suppresses effects of endocrine disruptors, benefitting offspring quality

The use of synthetic hormones to regulate sexual maturity in captive fish is a common practice. With aquaculture practices, fish production is desired throughout the year, necessitating the maintenance of quality standards, mainly regarding the characteristics of the fish produced. Embryonic development may be affected by toxins in the environment and by a variety of pathologies. The aim of this study was to determine the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on captive male and female Atlantic Salmon (Salmo salar) broodstock, observing the effects on the hormonal milieu and impacts on breeding outcomes. Sexually mature fish were fertilized with and without imposing a GnRHa treatment to evaluate the development of offspring up to the fry stage. The concentrations of 17β-estradiol (E2) and testosterone (T) were determined using commercially available ELISA kits. The results indicate the administration of GnRHa had marked effects on reductions of morphological deformities in the offspring and promoted development during the larval stage by inducing sexual maturity in both treated parents. The E2/T ratio results indicate the presence of endocrine disruptors. It is concluded that the use of GnRHa at a dose of 10 ug/kg in captive male and female Atlantic salmon broodstock has an inhibitory effect on the impacts of endocrine disruptors, does not affect fertilization rate, and has positive effects on development of offspring by reducing the number of morphological deformities during the larval stage of development.

Trajectories of Adolescents Treated with Gonadotropin-Releasing Hormone Analogues for Gender Dysphoria

Gonadotropin-releasing hormone analogues (GnRHa) are recommended as initial treatment for adolescents diagnosed with gender dysphoria, providing time to follow gender identity development and consider further treatment wishes without distress caused by unwanted pubertal changes. This has been described as an extended diagnostic phase. However, there are also concerns about the physical, neurocognitive, and psychosocial effects of this treatment. In this retrospective study, we document trajectories after the initiation of GnRHa and explore reasons for extended use and discontinuation of GnRHa. Treatment was considered appropriate in 143 (67%) of the 214 adolescents eligible for GnRHa treatment by virtue of their age/pubertal status, and all started GnRHa (38 transgirls, 105 transboys; median age, 15.0 years [range, 11.1–18.6] and 16.1 years [range, 10.1–17.9]). After a median duration of 0.8 years (0.3–3.8) on GnRHa, 125 (87%) started gender-affirming hormones (GAH). Nine (6%) discontinued GnRHa, five of whom no longer wished gender-affirming treatment. Thirteen had used GnRHa for longer than required by protocol for reasons other than logistics and regularly met with a mental health professional during this time, supporting the use of GnRHa treatment as an extended diagnostic phase. In conclusion, the vast majority who started GnRHa proceeded to GAH, possibly due to eligibility criteria that select those highly likely to pursue further gender-affirming treatment. Due to the observational character of the study, it is not possible to say if GnRHa treatment itself influenced the outcome. Few individuals discontinued GnRHa, and only 3.5% no longer wished gender-affirming treatment.

Toward more targeted and cost-effective gonadotropin-releasing hormone analog treatment in girls with central precocious puberty

The use of gonadotropin-releasing hormone analogs (GnRHa) for the treatment of central precocious puberty (CPP), especially in girls, has increased rapidly in recent years. In the context of a secular trend towards earlier puberty onset, many girls now treated for CPP are healthy children experiencing puberty onset within the early end of the normal range. Justifications for GnRHa treatment include the preservation of adult height (AH) potential and the alleviation of presumed distress of early maturation and menarche. With a case of a family requesting treatment for an 8-year-old girl in early puberty as a background, studies of the effect of untreated CPP and of GnRHa treatment of CPP on AH are reviewed. In addition, the limited evidence relating CPP to significant psychological distress - in part due to early menses, and for the amelioration of such distress by GnRHa treatment - is discussed. Taken together, current information suggests that for girls with mildly early onset of puberty (ages 7-9 years), an informed assent discussion with the family should include the consideration of reassurance and observation for many girls who might otherwise receive 2-4 years of GnRHa treatment for a poorly defined benefit and at a cost of at least $20-30,000 per year.

Transition memories: experiences of transadult women with hormone therapy and their beliefs on the usage of hormone blockers to suppress puberty.

In recent years, an increasing number of specialized gender clinics have been prescribing gonadotropin-releasing hormone (GnRH) analogs to adolescents diagnosed with gender dysphoria (GD) to suppress puberty. This paper presents qualitative research on the hormone therapy (HT) experiences of older trans-people and their views on puberty suppression. The main aim of this research was to explore the psychological aspects of hormonal treatments for gender non-conforming adults, including the controversial use of puberty suppression treatments. Using a semi-structured interview format, ten adult trans-women were interviewed (mean age: 37.4) to explore their personal histories regarding GD onset and development, their HT experiences, and their views on the use of GnRH analogs to suppress puberty in trans-children and adolescents. the interview transcripts were analyzed using the consensual qualitative research method from which several themes emerged: the onset of GD, childhood experiences, experiences with puberty and HT, views on the puberty suspension procedure, and the effects of this suspension on gender identity and sexuality. The interviews showed that overall, the participants valued the new treatment protocol due to the opportunity to prevent the severe body dysphoria and social phobia trans-people experience with puberty. It seems that the risk of social isolation and psychological suffering is increased by the general lack of acceptance and stigma toward trans-identities in the Italian society. However, during gender transitions, they highlight the need to focus more on internal and psychological aspects, rather than over-emphasize physical appearance. This study gives a voice to an under-represented group regarding the use of GnRH analogs to suppress puberty in trans-individuals, and collected firsthand insights on this controversial treatment and its recommendations in professional international guidelines.

Long-term effects and significant Adverse Drug Reactions (ADRs) associated with the use of Gonadotropin-Releasing Hormone analogs (GnRHa) for central precocious puberty: a brief review of literature.

Central precocious puberty (CPP) is defined as an early pubertal development that occurs before the age of 9 years in boys and 8 years in girls. It results from premature activation of the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone agonists (GnRHa) have been the gold standard therapy for CPP for more than 30 years. These compounds have a high affinity for the pituitary LHRH receptor and are resistant to enzymatic degradation. Through continuous stimulation, GnRHa inhibit the pulsatile secretion of gonadotropin, resulting in hormonal suppression, cessation of pubertal development, and normalization of growth and skeletal maturation rates. The goal of therapy is to halt pubertal progression and delay epiphyseal maturation that leads to improvement of final adult height. There are no widely accepted guidelines for how long to continue treatment with a GnRHa for CPP, and individual practice varies widely. Furthermore, conflicting results have been published on the long-term effects of GnRHa therapy in patients with CPP. Therefore, we reviewed the current literature focusing our attention on the long-term effects and the significant adverse drug reactions (ADRs) observed during treatment with GnRHa in patients with CPP. Our review may provide the necessary data to enable clinicians to administer GnRHa in the safest and most appropriate way. Further studies are necessary to identify the mechanisms of development of potential adverse drug reactions related to GnRHa therapy in CPP. (www.actabiomedica.it)