Tratamiento con análogos de la hormona liberadora de gonadotrofinas (aGnRH) en niñas, niños y adolescentes / Treatment with gonadotropin-releasing hormone analogs (GnRHa) in childhood and adolescence

Desde hace varias décadas, los análogos de la hormona liberadora de gonadotrofinas (aGnRH) son el tratamiento de elección en la pubertad precoz central (PPC) en niñas y en niños. Causan una inhibición del eje hipotálamo-hipófiso-gonadal, disminuyen la secreción de gonadotrofinas, estradiol y testosterona; como consecuencia, producen una regresión de los caracteres sexuales secundarios durante el tratamiento. En los últimos años, estos análogos también se utilizan en adolescentes transgénero, en adolescentes y adultas jóvenes con enfermedades oncológicas, en algunas situaciones muy particulares en niños y niñas con talla baja, y en pacientes con trastornos del neurodesarrollo. En Argentina, los más utilizados son el acetato de triptorelina y el acetato de leuprolide en sus formas de depósito. Estos medicamentos han demostrado eficacia y seguridad. El objetivo de esta publicación es realizar una revisión y actualización del uso de los aGnRH en niños, niñas y adolescentes.

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-pituitarygonadal 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.

Efficacy of Leuprorelide acetate (Eligard®) in daily practice in Brazil: a retrospective study with depot formulations in patients with prostate cancer

ABSTRACT Introduction: Androgen deprivation therapy (ADT) is the mainstay of therapy for advanced prostate cancer. Studies addressing the efficacy of different depot formulations of long acting luteinizing hormone releasing hormone agonists in the Brazilian population are lacking. We aimed to compare the efficacy of three schedules of leuprolide acetate in lowering PSA in a real world population. Materials and Methods: We reviewed the medical records of patients with prostate cancer seen at our institution between January 2007 and July 2018. We analyzed patients treated with long-acting leuprolide acetate and grouped these patients into three strata according to the administration of ADT every 1, 3 or 6 months. The primary outcome was the serum prostate specific antigen (PSA) levels at 6 and 12 months after treatment initiation. We used Friedman test to compare the distribution of PSA levels at baseline and at 6 and 12 months within each treatment stratum. We considered two-sided P values <0.05 as statistically significant. We analyzed toxicity descriptively. Results: We analyzed a total of 932 patients, with a median age of 72 years and a median time since diagnosis of prostate cancer of 8.5 months. ADT was administered monthly in 115 patients, quarterly in 637, and semiannually in 180. Nearly half of the patients had locally advanced disease. In comparison with baseline, median serum PSA levels were reduced at 12 months by at least 99.7% in the three strata (P <0.001 in all cases). Sexual impotence and hot flashes were the most frequently reported toxicities. Conclusion: To our knowledge, this is the largest assessment of real-world data on alternative schedules of leuprolide in a Brazilian population. Our study suggests that PSA levels can be effectively be reduced in most patients treated with monthly, quarterly, or semiannual injections of long-acting leuprolide acetate.

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

ABSTRACT Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Posterior reversible encephalopathy syndrome in a woman who used gonadotropin-releasing hormone agonists: a case report

Posterior reversible encephalopathy syndrome (PRES) is a newly described adverse effect possibly associated with gonadotropin-releasing hormone (GnRH) agonist therapy. We report a case of PRES after 2 doses of depot GnRH agonists in a 44-year-old woman with a huge myoma uteri and iron-deficiency anemia. Brain magnetic resonance imaging showed high signal lesions in both occipital lobes on fluid-attenuated inversion-recovery (FLAIR) images, compatible with PRES. After treatment with anticonvulsant, she recovered both radiographically and clinically. The association between PRES and GnRH agonist use is still enigmatic, and thus should be further clarified.

The current status of hormone treatment for prostate cancer patients in Korean real-world practice: a multi-institutional observational study / 亚洲男科学杂志(英文版)

We aimed to evaluate the current nationwide trend, efficacy, safety, and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea. A total of 292 men with any biopsy-proven PCa (TanyNanyMany) from 12 institutions in Korea were included in this multi-institutional, observational study of prospectively collected data. All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs. Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl-1) at 4-week visit and (2) breakthrough (serum testosterone >50 ng dl-1 after castration). Safety assessments included routine examinations for potential adverse events, laboratory tests, blood pressure, body weight, and bone mineral density (BMD, at baseline and at the last follow-up visit). QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26). The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0%), and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0% for combination and 58.0% for monotherapy). The castration and breakthrough rates were 78.4% and 6.6%, respectively. The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment. In addition, the mean BMD T-score was significantly lower at the last follow-up (mean: -1.950) compared to baseline (mean: -0.195). The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]: 12.2) to 78.3 (s.d.: 8.1), with significant deterioration only in the urinary domain (mean: 23.5 at baseline and 21.9 at the 4-week visit). These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.

Clinical and laboratory parameters of gonadotropin-releasing hormone analog treatment effectiveness in children with precocious puberty

OBJECTIVE: There are no doubts about the clinical benefits of treatment with GnRH analogs for patients diagnosed with central precocious puberty (CPP). However, laboratory monitoring of CPP is still a matter of considerable controversy in the literature. Therefore, the main objective of this study was to evaluate the cut-off values of stimulated LH that determine gonadotrophic suppression. METHODS: Twenty-four girls, on treatment with leuprorelin acetate (LA) at 3.75 mg IM every 28 days, were studied. The clinical parameters used to indicate clinical effectiveness were regression or maintenance of sexual characteristics according to the Tanner stage, growth velocity reduction, reduction or maintenance of the difference between bone age and chronological age and maintenance or improvement of the final height prediction. For the laboratory effectiveness test, basal estradiol, LH, and FSH levels were collected before and 1 and 2 h after the administration of 3.75 mg LA. RESULTS: Eleven girls showed improvement in all clinical parameters, and their effectiveness tests were compared to those of the other patients to calculate the cut-off values, which were ≤3.64 IU/L (p=0.004*) for LH after 1 h and ≤6.10 IU/L (p<0.001*) for LH after 2 h. CONCLUSION: The LH response after the LA stimulation test, associated with clinical data and within a context of CPP, constitutes a reliable and feasible resource and can assist in monitoring the effectiveness of treatment.

Therapeutic Effects of Leuprorelin (Leuprolide Acetate) in Sexual Offenders with Paraphilia

BACKGROUND: This study examined the clinical effects of leuprolide acetate in sexual offenders with paraphilic disorders evaluated by means of objective psychiatric assessment. METHODS: The subjects of this study were seven sexual offenders who were being treated by means of an injection for sexual impulse control by a court order. They had been diagnosed with paraphilia by a psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and had been put on probation by the Ministry of Justice between January 2016 and December 2016. RESULTS: After twelve months, we observed significant improvement in symptoms, as decrease of abnormal sexual interest and activity, sexual fantasy, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Impulsivity (GCI-I). There were a mild feminization of the body shape, feelings of fatigue, and mild hot flushes. No other adverse effect was reported. CONCLUSION: These results suggested that the clinical effects of leuprolide acetate in sexual offenders might be an effective treatment and safety strategy.

Uterine fibroid shrinkage after short-term use of selective progesterone receptor modulator or gonadotropin-releasing hormone agonist

OBJECTIVE: The aim of this study was to evaluate the effect of short-term use of selective progesterone receptor modulator (SPRM) or gonadotropin-releasing hormone (GnRH) agonist on uterine fibroid shrinkage among Korean women. METHODS: This retrospective study involved 101 women with symptomatic uterine fibroids who received ulipristal acetate (SPRM, n=51) and leuprolide acetate (GnRH agonist, n=50) for 3 months between November 2013 and February 2015. The fibroid volume was measured both before and after treatment using ultrasonography, computed tomography, and magnetic resonance imaging. The outcomes were compared between the SPRM and GnRH agonist groups. RESULTS: The median rate of fibroid volume reduction after SPRM treatment was 12.4% (IQR −14.5% to 40.5%) which was significantly lower than the reduction rate observed after GnRH agonist treatment (median 34.9%, IQR 14.7% to 48.6%, P=0.004). 19 of 51 (37.3%) patients with SPRM treatment did not show any response of volume shrinkage, while 7 of 50 (14.0%) women with GnRH agonist showed no response (P=0.007). CONCLUSION: Short-term SPRM treatment yields lower volume reduction than GnRH agonist treatment in Korean women with symptomatic fibroids. Further large-scale randomized trials are needed to confirm our findings.

A Case of Foreign Body Granuloma Caused by Subcutaneous Injection of Leuprorelin Acetate / 대한피부과학회지

Leuprorelin acetate is a synthetic analog of luteinizing hormone-releasing hormone (LHRH). Recently, hormone-dependent tumors (prostate cancer and breast cancer) have been treated without surgery using this LHRH agonist. A 74-year-old man presented with a subcutaneous tumor in the abdomen. He had received a subcutaneous injection of depot leuprorelin acetate 2 months previously and radiotherapy for prostate cancer. The subcutaneous tumor was totally excised. Histopathologic findings revealed necrosis of fat tissue, many granulomatous nodules composed of giant cells with vacuoles in the dermis and subcutis, and inflammatory cell infiltrates, including mainly lymphohistiocytes. A diagnosis of foreign body granuloma due to depot injection of leuprorelin acetate was made. He revisited our hospital after 1 month with a subcutaneous tumor on his Lt. upper arm. He had received a subcutaneous injection of leuprorelin acetate 1 week ago on that site. We treated it with intralesional triamcinolone injection. Here, we report a case of granulomatous reaction due to leuprorelin acetate injection, which produced subcutaneous nodules.

Raloxifene Administration in Women Treated with Long Term Gonadotropin-releasing Hormone Agonist for Severe Endometriosis: Effects on Bone Mineral Density

OBJECTIVES: To evaluate the efficacy of raloxifene in preventing bone loss associated with long term gonadotropin-releasing hormone agonist (GnRH-a) administration. METHODS: Twenty-two premenopausal women with severe endometriosis were treated with leuprolide acetate depot at a dosage of 3.75 mg/4 weeks, for 48 weeks. Bone mineral density (BMD) was evaluated at admission, and after 12 treatment cycles. RESULTS: At cycle 12 of GnRH-a plus raloxifene treatment, lumbar spine, trochanter femoral neck, and Ward's BMD differed from before the treatment. A year after treatment, the lumbar spine and trochanter decreased slightly, but were not significantly different. CONCLUSIONS: Our study shows that the administration of GnRH-a plus raloxifene in pre-menopausal women with severe endometriosis, is an effective long-term treatment to prevent bone loss.

Good Response of a Salivary Duct Carcinoma to Androgen Deprivation Therapy / 대한내과학회지

Salivary duct carcinoma (SDC) is a rare, aggressive tumor. Androgen deprivation therapy (ADT) has been shown to have beneficial effects on SDC-expressing androgen receptors (ARs). A 69-year-old male with a right neck mass presented to our clinic. Computed tomography (CT) of the neck revealed a mass (6 cm diameter) on the right parotid gland, and enlarged lymph nodes. Examination of a needle biopsy sample identified SDC-expressing ARs. We performed total parotidectomy with bilateral neck dissection and concurrent postoperative chemoradiotherapy (total 66 Gy) with cisplatin (35 mg/m2), followed by another two cycles of chemotherapy (cisplatin 60 mg/m2, 5 FU 750 mg/m2). Post-treatment neck CT indicated that no residual tumor tissue remained; however, chest CT indicated recurrence in the right axilla. We initiated ADT with bicalutamide and leuprolide. Five months later, the axillar tumor tissue had almost disappeared. Our case demonstrates that ADT is effective for SDC of ARs. Therefore, clinicians should consider ADT in recurrent or metastatic SDC of ARs.

Leuprolide Acetate-induced Foreign Body Granuloma in a Patient with Prostate Cancer / 대한피부과학회지

Leuprolide acetate is an established luteinizing hormone-releasing hormone (LHRH) agonist used as a first-line treatment in advanced prostate cancer. An 80-year-old man presented with a localized erythematous patch with an indurated plaque and nodule and pustules on the left upper arm. The patient had been treated for metastatic prostate cancer with subcutaneous injections of leuprolide acetate 18 months previously. Histopathologic findings revealed granulomas with multinucleated giant cells from the dermis to the subcutaneous fat layer. The granuloma contained numerous round vacuoles. Cultures from the tissue for bacteria, fungi, and mycobacteria were all negative. The diagnosis of leuprolide acetate-induced foreign body granuloma was made by clinicopathologic findings. Various theories on the mechanism of local reactions to leuprolide have been suggested. The formation of granulomas may be related to the poly (lactic-co-glycolic acid) polymers or leuprolide itself. The depth of injection could have also contributed; therefore, intramuscular injection is recommended to minimize granuloma formation. To the best of our knowledge, there has been no reported case of leuprolide-induced foreign body granuloma in a patient with prostate cancer in the Korean literature. Dermatologists need to know that leuprolide acetate depot injection may cause a granulomatous reaction.

Leuprolide Acetate-induced Foreign Body Granuloma in a Patient with Prostate Cancer / 대한피부과학회지

Leuprolide acetate is an established luteinizing hormone-releasing hormone (LHRH) agonist used as a first-line treatment in advanced prostate cancer. An 80-year-old man presented with a localized erythematous patch with an indurated plaque and nodule and pustules on the left upper arm. The patient had been treated for metastatic prostate cancer with subcutaneous injections of leuprolide acetate 18 months previously. Histopathologic findings revealed granulomas with multinucleated giant cells from the dermis to the subcutaneous fat layer. The granuloma contained numerous round vacuoles. Cultures from the tissue for bacteria, fungi, and mycobacteria were all negative. The diagnosis of leuprolide acetate-induced foreign body granuloma was made by clinicopathologic findings. Various theories on the mechanism of local reactions to leuprolide have been suggested. The formation of granulomas may be related to the poly (lactic-co-glycolic acid) polymers or leuprolide itself. The depth of injection could have also contributed; therefore, intramuscular injection is recommended to minimize granuloma formation. To the best of our knowledge, there has been no reported case of leuprolide-induced foreign body granuloma in a patient with prostate cancer in the Korean literature. Dermatologists need to know that leuprolide acetate depot injection may cause a granulomatous reaction.

Evaluation of central precocious puberty treatment with GnRH analogue at the Triangulo Mineiro Federal University (UFTM)

Objective To report our experience of treating central precocious puberty (CPP) with a GnRH analogue with respect to the final heights (FH) attained in patients who completed treatment. Subjects and methods Among 105 records of children diagnosed with precocious puberty, 62 cases (54 girls and 8 boys), who were treated with leuprolide acetate/3.75 mg/monthly, were selected, and divided into 4 groups: group 1 (G1), 25 girls who attained FH; group 2 (G2), 18 girls who completed treatment but did not reach FH; group 3 (G3), 11 girls still under treatment; and group 4 (G4), 8 boys, 5 of which attained FH. Treatment was concluded at a bone age of 12 years, and follow-up continued until FH was achieved. Results In both G1 and G2 groups, height standard deviation score (SDS), weight-SDS and percentile of body mass index (PBMI) did not show intra/intergroup differences at the beginning and at interruption of treatment, but when added, G1+G2, height-SDS and weight-SDS differed significantly (p = 0.002 and 0.0001, respectively). In G1, 19 of 25 cases attained TH, and average height gain was 16.7 cm (7.7- 27.1); there was significant difference between FH and prediction of FH at the start (PFH at start) (p = 0.0001), as well as between PFH at interruption vs TH and vs FH (p = 0.007) with FH higher than TH (p = 0.004). Significant correlation was identified between FH and height gain after treatment. Conclusion As shown by some studies, GnRH analogue treatment was effective in children with CPP reaching FH near the genetic target.

Apoplejía tumoral pituitaria / Pituitary tumor apoplexy

La apoplejía tumoral pituitaria es un síndrome infrecuente que resulta del infarto y/o hemorragia espontánea de un adenoma pituitario preexistente. Ya que el evento primario involucra el adenoma, este síndrome debe ser nombrado como apoplejía tumoral pituitaria y no como apoplejía pituitaria. El aumento súbito en la presión de los contenidos de la silla turca da como resultado una cefalea de inicio agudo (puede ser incluso una "cefalea en trueno") de intensidad severa, alteraciones visuales y compromiso en la función pituitaria. El diagnóstico se basa en una alta sospecha clínica, imagen por resonancia magnética y medición de hormonas hipofisiarias en sangre. El tratamiento se basa en medidas de soporte (líquidos intravenosos y corticoides) y en casos sin buena respuesta o con deterioro neurológico, descompresión de silla turca. A continuación presentamos el caso de un adenoma previamente no diagnosticado que debutó como apolejía tumoral pituitaria. (Acta Med Colomb 2015; 40: 249-253).

Pituitary tumor apoplexy is an infrequent condition resulting from infarction and/or spontaneous bleeding from a pre-existing pituitary adenoma. This entity requires the prior existence of an adenoma in order to be named as pituitary tumor apoplexy, otherwise, it should be named pituitary apoplexy. The sudden increase in pressure of the sella turcica's contents results in a clinical syndrome characterized by headache (which can be "thunderclap headache"), visual disturbances and hypopituitarism. Diagnosis is not always straight forward and requires high clinical suspicion in addition to magnetic resonance imaging and measurement of serum pituitary hormones. Treatment is mainly based on supportive measures (intravenous fluids and steroids) and surgical decompression in those cases with no response to medical treatment and progressive neurological impairment. We report the case of a patient with a previously unknown pituitary adenoma presenting as a tumor apoplexy. (Acta Med Colomb 2015; 40: 249-253).

Protective Effects of KH-204 in the Bladder of Androgen-Deprived Rats

PURPOSE: We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats. MATERIALS AND METHODS: Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment. RESULTS: Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis. CONCLUSIONS: Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity.

Comments to "A Case of Pityriasis Rosea Associated with Leuprolide Acetate" / 대한피부과학회지

No abstract available.

Efficacy and safety of domestic leuprorelin in girls with idiopathic central precocious puberty: a multicenter, randomized, parallel, controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In central precocious puberty (CPP), the pulse secretion and release of gonadotropin-releasing hormone (GnRH) are increased due to early activation of the hypothalamic-pituitary-gonadal axis, resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics. The CPP without organic disease is known as idiopathic CPP (ICPP). The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin (GnRH analog) in girls with ICPP.</p><p><b>METHODS</b>A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups. One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate, 79 girls in the control group were treated with imported leuprorelin acetate. They all were treated and observed for 6 months. After 6-month treatment, the percentage of children with peak luteinizing hormone (LH) ≤3.3 U/L, the percentage of children with peak LH/peak follicle stimulating hormone (FSH) ratio <0.6, the improvements of secondary sexual characteristics, gonadal development and sex hormone levels, the change of growth rate of bone age (BA) and growth velocity, and drug adverse effects between two groups were compared.</p><p><b>RESULTS</b>After the treatment, the percentage of children with a suppressed LH response to GnRH, defined as a peak LH ≤3.3 U/L, at 6 months in test and control groups were 96.80% and 96.20%, respectively, and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%, respectively. The sizes of breast, uterus and ovary of children and the levels of estradiol (E 2 ) were significantly reduced, and the growth rate of BA was also reduced. All the differences between pre- and post-treatment in each group were statistically significant (P < 0. 05), but the differences of the parameters between two groups were not significant (P > 0.05).</p><p><b>CONCLUSIONS</b>Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP. Its effectiveness and safety are comparable with imported leuprorelin.</p>

A Case of Mental Retardation with Paraphilia Treated with Depot Leuprorelin

Paraphilia is a psychiatric disease that has been difficult to cure. However, recently developed therapeutic methods hold promise. The patient was a 20-yr-old male with chief complaints of continuous masturbation, genital exposure, and aggressive behavior that started 2 yr ago. We administered leuprorelin 3.6 mg intramuscular injection per month, a depot gonadotrophin-releasing hormone analogue, to this patient who a severe mentally retardation with paraphilia. The clinical global impression (CGI)-severity, CGI-improvement and aberrant behavior checklist were performed. After one month, we observed significant improvement in symptoms, such as decreases of abnormal sexual behavior and sexual desire. The GnRH analogues are suggested to be used as an alternative or supplementary therapeutic method for sexual offenders after clinical studies.

Foreign Body Granuloma Secondary to Leuprorelin Acetate

No abstract available.