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Erica A. Eugster - One of the best experts on this subject based on the ideXlab platform.
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© 2009 Lewis and Eugster, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Drug Design, Development and Therapy 2009:3 1–5 1
2016Co-Authors: Katherine A Lewis, Erica A. Eugster, Correspondence Katherine, A LewisAbstract:Experience with the once-yearly Histrelin (GnRHa) subcutaneous implant in the treatment of central precocious pubert
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experience with the Histrelin implant in pediatric patients
Author, 2016Co-Authors: Erica A. EugsterAbstract:The Histrelin implant has emerged as a therapeutic option for the treatment of central precocious puberty that has been favorably received by patients and providers. Inserted subcutaneously, the 50-mg implant provides continuous release of the potent gonadotropin-releasing hormone analog (GnRHa) Histrelin. Profound suppression of the hypothalamic-pituitary-gonadal (HPG) axis occurs within 1 month of its placement resulting in pubertal arrest, attenuation of skeletal advancement and a progressive increase in predicted adult height. Although marketed for annual use, suppression lasting 2 years from a single implant has been demonstrated. Placing and removing the device is a minor outpatient procedure easily accomplished by a pediatric surgeon using local anesthesia. The major downside to the implant is a ∼25% rate of breakage upon removal. Information about the recovery of the HPG axis following Histrelin explantation is limited but suggests an average time to menarche comparable with depot GnRHa formulations albeit with wide individual variation.
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long term continuous suppression with once yearly Histrelin subcutaneous implants for the treatment of central precocious puberty a final report of a phase 3 multicenter trial
PMC, 2015Co-Authors: Lawrence A Silverman, Gad B Kletter, Kirk E Neely, Katherine Lewis, Surya Chitra, Oksana Terleckyj, Erica A. EugsterAbstract:Context and Objective: The Histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy. Design: This was a phase 3, prospective, open-label study. Setting and Participants: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month Histrelin implant during a long-term extension phase. Outcome Measures: Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up. Results: Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from ...
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resumption of puberty in girls and boys following removal of the Histrelin implant
The Journal of Pediatrics, 2014Co-Authors: Marisa M Fisher, Deborah Lemay, Erica A. EugsterAbstract:Objectives To determine time to menarche in girls and testicular volume increase in boys after removal of a Histrelin implant, which causes profound hypothalamic-pituitary-gonadal axis suppression. Study design Medical records of patients treated with a Histrelin implant were reviewed. Seventy-one patients (56 girls) treated with the Histrelin implant were identified, of these patients, 37 explanted girls (68% naive) and 6 explanted boys (83% naive) were included in the analysis. Time to menarche after explantation in girls and time to testicular volume increase after explantation in boys were determined. Additional variables investigated included indication for and duration of treatment, history of menarche (girls), previous therapy, and age at beginning and end of Histrelin treatment. Results Of the girls, 30 were treated for central precocious puberty (CPP), 26 had menarche at an average of 12.75 months after explantation. Of the 30, 7 were treated for other indications, of whom 6 had reached menarche. In girls with CPP, older age at explantation correlated with sooner menarche ( P = .04). All boys achieved spontaneous testicular enlargement within 1 year of explantation. Conclusions This study documented resumption of puberty after Histrelin explantation in treatment naive and non-naive boys and girls with and without CPP. Menarche in girls with CPP occurs within a similar timeframe to that observed after other treatment approaches.
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a single Histrelin implant is effective for 2 years for treatment of central precocious puberty
The Journal of Pediatrics, 2013Co-Authors: Katherine A Lewis, Andrea K Goldyn, Karen W West, Erica A. EugsterAbstract:We investigated whether a "yearly" Histrelin implant would provide pubertal suppression when left in place for 2 years. Equivalent suppression was observed when comparing 12 and 24 months in 33 children with central precocious puberty. A single implant for 2 years reduces cost and number of implant procedures.
Irving M Spitz - One of the best experts on this subject based on the ideXlab platform.
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free α subunit is the most sensitive marker of gonadotropin recovery after treatment of central precocious puberty with the Histrelin implant
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Harry J Hirsch, Boris Chertin, Amicur Farkas, David Gillis, David Strich, Najiba Lahlou, Binyamina Rosenberghagen, Hadassa Hartman, Irving M SpitzAbstract:Background: Gonadotropin free α-subunit (FAS) levels paradoxically increase during GnRH agonist (GnRHa) treatment of central precocious puberty (CPP). The Histrelin implant suppresses gonadotropins and estradiol (E2) levels for 1 yr, but effects on FAS have not been described. Objectives: We aimed to determine whether FAS levels remain elevated during treatment with the implant, to assess the dynamics of FAS after removal, and to ascertain the reliability of FAS for monitoring gonadotropin secretion. Methods: Ten girls with CPP were studied. In eight, monthly im GnRHa preparations were given until implant insertion. Two naive girls did not receive prior GnRHa. Duration of implant treatment ranged from 18–63 months with repeated implant removals and insertions of new implants. LH, FSH, E2, and FAS were measured before implant insertion in the two naive patients and during treatment, and in all girls before and after implant removal. Results: FAS levels were 0.2 and 0.4 ng/ml (normal, <0.6 ng/ml) in the two...
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relationships between fsh inhibin b anti mullerian hormone and testosterone during long term treatment with the gnrh agonist Histrelin in patients with prostate cancer
European Journal of Endocrinology, 2010Co-Authors: Talia Eldargeva, Boris Chertin, Amicur Farkas, Gad Liberty, Alon Fridmans, Ehud J Margalioth, Irving M SpitzAbstract:Objectives: Medical castration with long-acting GnRH-agonist (GnRHa) is a well-established treatment for metastatic prostate cancer. Our aim was to explore the relationships between FSH, inhibin B, antiMullerian hormone (AMH), and testosterone during treatment with an implant releasing GnRHa. Design: Analysis of hormone levels in frozen serum samples. Methods: Ten patients aged 77G7 (meansGS.E.M.) years with prostate cancer were treated with the GnRHa Histrelin for at least a year. Two weeks prior to insertion and for 3–4 months following removal the patients were treated with the antiandrogen flutamide. Serum inhibin B, FSH, testosterone, and AMH levels were measured retrospectively. Results: FSH, inhibin B, and testosterone increased during antiandrogen administration and levels fell after implant insertion. Four weeks post insertion, FSH gradually increased while inhibin B and testosterone remained fully suppressed. AMH levels did not change during antiandrogen treatment, but increased following implant insertion and remained elevated for the duration of implant use. Following removal, FSH and testosterone increased, inhibin B remained low, while AMH decreased. Conclusions: The secondary increase in FSH following initial suppression with the implant is probably related to impaired inhibin B secretion. The lack of inhibin B response to the secondary increase in FSH suggests that long-term exposure of Sertoli-cells to GnRHa impairs their function. This effect appears to be selective since unlike inhibin B, AMH increased. In the absence of testosterone, FSH has a role in AMH regulation.
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the Histrelin implant a novel treatment for central precocious puberty
Pediatrics, 2005Co-Authors: Harry J Hirsch, Boris Chertin, Tzina Lindenberg, Amicur Farkas, David Gillis, David Strich, Hadassa Gelber, Irving M SpitzAbstract:Objective. Standard treatment of central precocious puberty (CPP) consists of intramuscular or subcutaneous administration of a gonadotropin-releas- ing hormone (GnRH) agonist (GnRHa) at 3- to 4-week intervals. Although generally effective in suppressing clinical and laboratory parameters of puberty, GnRHa injections are painful, and the need for monthly clinic visits may contribute to poor compliance. Recently, a subcutaneous implant was developed that releases the GnRHa Histrelin at an average rate of 65 g/day. The aims of this study were to determine if a Histrelin im- plant would suppress gonadotropin and estradiol (E2 )i n girls with CPP for 1 year and to compare the suppression to standard treatment. Methods. We studied 11 girls with CPP to determine if the Histrelin implant can maintain long-term gonado- tropin suppression. Mean age at diagnosis was 6 1 ⁄2 years (range: 2-9 years). GnRH (100 g intravenously) stimu- lation tests (GnRH-STs) showed peak luteinizing hor- mone and follicle-stimulating hormone responses of 23 28 (mean SD) and 20 25 mIU/mL, respectively. All subjects were initially treated with depot intramuscular GnRHa triptorelin embonate. Implants were inserted subcutaneously under local anesthesia, and depot GnRHa treatment was discontinued. Six girls were fol- lowed for 15 months after insertion (group A). For the remaining 5 girls, the implant was removed after 9 months, and a new implant was inserted at the same incision site (group B). GnRH-STs were performed be- fore depot GnRHa treatment, immediately before im- plant insertion, at the 6- and 9-month visits for each patient and the 12- and 15-month visit for those girls followed for 15 months. Results. In all girls, breast development regressed, growth velocity decreased, and bone-age advancement was slowed. Basal gonadotropins and their responses to GnRH-STs and E2 levels were suppressed. Peak lutein- izing hormone and follicle-stimulating hormone re- sponses to GnRH-STs at preinsertion versus 9 months were 1.30 1.34 vs 0.25 0.08 and 1.68 1.08 vs 1.13 0.55 mIU/mL, respectively. Basal and stimulated gonad- otropin levels and E2 level remained suppressed in all 6 patients followed for 15 months after implant insertion. Patients and parents reported less pain and discomfort and less interference with school activity and work with the implant compared with standard monthly injections. Conclusions. The Histrelin implant consistently sup- presses clinical and laboratory parameters of puberty for 1 year and is a promising new technique for treating CPP without the pain and inconvenience of monthly injections. Pediatrics 2005;116:e798-e802. URL: www. pediatrics.org/cgi/doi/10.1542/peds.2005-0538; precocious puberty, gonadotropins, estradiol, GnRH agonists, histre- lin.
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effective long term androgen suppression in men with prostate cancer using a hydrogel implant with the gnrh agonist Histrelin
Urology, 2001Co-Authors: Peter N. Schlegel, Irving M Spitz, Boris Chertin, Amicur Farkas, Petr Kužma, J Frick, Andreas Gomahr, Doris MackAbstract:Abstract Objectives. To evaluate the effectiveness of a hydrogel implant containing the gonadotropin-releasing hormone (GnRH) agonist Histrelin in suppressing testosterone production in men with prostate cancer and to determine the effective dose (one, two, or four implants). Methods. Forty-two men with prostate cancer and indications for androgen ablation were treated with one, two, or four implants. In two of the clinics, comprising 27 subjects, the treatment period was 12 months, with replacement with the same number of implants at 12-month intervals. In a third clinic, which treated 15 subjects, the implants were left in place for up to 30 months. The total experience was 605 treatment months. Results. The Histrelin levels were detected in serum proportional to the number of implants placed. The response, however, was similar among all three dose levels, with testosterone and luteinizing hormone essentially completely suppressed. Serum testosterone levels decreased from 21.9 ± 17.6 nmol/L to 0.93 ± 1.57 nmol/L within 1 month and were maintained at 0.55 ± 0.24 nmol/L at 6 months and 0.60 ± 0.28 nmol/L after 12 months of treatment. Of the 38 assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks of the initial implant placement. All patients followed for up for 12 months after placement of the initial set of implants maintained suppression of testosterone production while the implant was in place. Conclusions. The Histrelin hydrogel implant provided adequate and reliable delivery of the potent GnRH agonist Histrelin during at least 1 year using a single implant in men with prostate cancer. No apparent advantages were found in using more than one implant, and the question of the possible effectiveness of even lower doses remains open. This treatment modality appears to be both safe and effective.
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an implant releasing the gonadotropin hormone releasing hormone agonist Histrelin maintains medical castration for up to 30 months in metastatic prostate cancer
The Journal of Urology, 2000Co-Authors: Boris Chertin, Irving M Spitz, Tzina Lindenberg, Petr Kužma, Nurit Algur, Tami Zer, Alfred Moo J Young, Raphael Catane, Amicur FarkasAbstract:Purpose: The administration of gonadotropin hormone-releasing hormone agonists is well established for treating metastatic prostate cancer. In an ongoing study we evaluated the effect of a long acting implant that releases the gonadotropin hormone-releasing hormone agonist Histrelin ([ImBzl]D-His6, Pro9-Net) in 15 patients with disseminated prostate cancer. Materials and Methods: The 2.6 cm. implant releasing 60 μg. Histrelin daily is inserted subcutaneously into the upper arm using local anesthesia. Of the patients 8 received 1 and the remainder received 2 implants. Treatment with the antiandrogen flutamide or cyproterone acetate began 2 weeks before implant insertion and continued for up to 12 weeks. Testosterone, luteinizing hormone (LH) and prostate specific antigen were determined monthly, and a metastatic evaluation was performed every 6 months. Results: LH and testosterone increased after flutamide administration and decreased after implant insertion. By day 28 LH and testosterone were completely suppressed. LH and testosterone decreased immediately after cyproterone acetate administration. Prostate specific antigen began to decrease during antiandrogen therapy and decreased further after implant insertion. One patient requested implant removal after 1 year for personal reasons and 1 died of an unrelated cause 18 months after insertion. Escape was demonstrated in 4 cases at 5, 10, 12 and 19 months, although LH and testosterone remained suppressed. Duration of treatment in the remaining 9 patients was between 21 and 30 months. LH and testosterone remained completely suppressed and prostate specific antigen levels were in the normal range. The clinical and biochemical response was identical in those who received 1 or 2 implants. At 12 months 8 patients were challenged at intermittent intervals for up to 24 months with a bolus of 100 μg. gonadotropin hormone-releasing hormone followed by 2 weeks of flutamide. The response was compared with that in untreated controls recently diagnosed with prostate cancer. Unlike controls there was complete LH suppression in the 8 challenged patients. Conclusions: A Histrelin implant suppresses LH and testosterone in prostate cancer for up to 30 months. This finding represents a significant improvement over existing preparations, which must be administered at 1 to 3-month intervals.
Amicur Farkas - One of the best experts on this subject based on the ideXlab platform.
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free α subunit is the most sensitive marker of gonadotropin recovery after treatment of central precocious puberty with the Histrelin implant
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Harry J Hirsch, Boris Chertin, Amicur Farkas, David Gillis, David Strich, Najiba Lahlou, Binyamina Rosenberghagen, Hadassa Hartman, Irving M SpitzAbstract:Background: Gonadotropin free α-subunit (FAS) levels paradoxically increase during GnRH agonist (GnRHa) treatment of central precocious puberty (CPP). The Histrelin implant suppresses gonadotropins and estradiol (E2) levels for 1 yr, but effects on FAS have not been described. Objectives: We aimed to determine whether FAS levels remain elevated during treatment with the implant, to assess the dynamics of FAS after removal, and to ascertain the reliability of FAS for monitoring gonadotropin secretion. Methods: Ten girls with CPP were studied. In eight, monthly im GnRHa preparations were given until implant insertion. Two naive girls did not receive prior GnRHa. Duration of implant treatment ranged from 18–63 months with repeated implant removals and insertions of new implants. LH, FSH, E2, and FAS were measured before implant insertion in the two naive patients and during treatment, and in all girls before and after implant removal. Results: FAS levels were 0.2 and 0.4 ng/ml (normal, <0.6 ng/ml) in the two...
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relationships between fsh inhibin b anti mullerian hormone and testosterone during long term treatment with the gnrh agonist Histrelin in patients with prostate cancer
European Journal of Endocrinology, 2010Co-Authors: Talia Eldargeva, Boris Chertin, Amicur Farkas, Gad Liberty, Alon Fridmans, Ehud J Margalioth, Irving M SpitzAbstract:Objectives: Medical castration with long-acting GnRH-agonist (GnRHa) is a well-established treatment for metastatic prostate cancer. Our aim was to explore the relationships between FSH, inhibin B, antiMullerian hormone (AMH), and testosterone during treatment with an implant releasing GnRHa. Design: Analysis of hormone levels in frozen serum samples. Methods: Ten patients aged 77G7 (meansGS.E.M.) years with prostate cancer were treated with the GnRHa Histrelin for at least a year. Two weeks prior to insertion and for 3–4 months following removal the patients were treated with the antiandrogen flutamide. Serum inhibin B, FSH, testosterone, and AMH levels were measured retrospectively. Results: FSH, inhibin B, and testosterone increased during antiandrogen administration and levels fell after implant insertion. Four weeks post insertion, FSH gradually increased while inhibin B and testosterone remained fully suppressed. AMH levels did not change during antiandrogen treatment, but increased following implant insertion and remained elevated for the duration of implant use. Following removal, FSH and testosterone increased, inhibin B remained low, while AMH decreased. Conclusions: The secondary increase in FSH following initial suppression with the implant is probably related to impaired inhibin B secretion. The lack of inhibin B response to the secondary increase in FSH suggests that long-term exposure of Sertoli-cells to GnRHa impairs their function. This effect appears to be selective since unlike inhibin B, AMH increased. In the absence of testosterone, FSH has a role in AMH regulation.
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the Histrelin implant a novel treatment for central precocious puberty
Pediatrics, 2005Co-Authors: Harry J Hirsch, Boris Chertin, Tzina Lindenberg, Amicur Farkas, David Gillis, David Strich, Hadassa Gelber, Irving M SpitzAbstract:Objective. Standard treatment of central precocious puberty (CPP) consists of intramuscular or subcutaneous administration of a gonadotropin-releas- ing hormone (GnRH) agonist (GnRHa) at 3- to 4-week intervals. Although generally effective in suppressing clinical and laboratory parameters of puberty, GnRHa injections are painful, and the need for monthly clinic visits may contribute to poor compliance. Recently, a subcutaneous implant was developed that releases the GnRHa Histrelin at an average rate of 65 g/day. The aims of this study were to determine if a Histrelin im- plant would suppress gonadotropin and estradiol (E2 )i n girls with CPP for 1 year and to compare the suppression to standard treatment. Methods. We studied 11 girls with CPP to determine if the Histrelin implant can maintain long-term gonado- tropin suppression. Mean age at diagnosis was 6 1 ⁄2 years (range: 2-9 years). GnRH (100 g intravenously) stimu- lation tests (GnRH-STs) showed peak luteinizing hor- mone and follicle-stimulating hormone responses of 23 28 (mean SD) and 20 25 mIU/mL, respectively. All subjects were initially treated with depot intramuscular GnRHa triptorelin embonate. Implants were inserted subcutaneously under local anesthesia, and depot GnRHa treatment was discontinued. Six girls were fol- lowed for 15 months after insertion (group A). For the remaining 5 girls, the implant was removed after 9 months, and a new implant was inserted at the same incision site (group B). GnRH-STs were performed be- fore depot GnRHa treatment, immediately before im- plant insertion, at the 6- and 9-month visits for each patient and the 12- and 15-month visit for those girls followed for 15 months. Results. In all girls, breast development regressed, growth velocity decreased, and bone-age advancement was slowed. Basal gonadotropins and their responses to GnRH-STs and E2 levels were suppressed. Peak lutein- izing hormone and follicle-stimulating hormone re- sponses to GnRH-STs at preinsertion versus 9 months were 1.30 1.34 vs 0.25 0.08 and 1.68 1.08 vs 1.13 0.55 mIU/mL, respectively. Basal and stimulated gonad- otropin levels and E2 level remained suppressed in all 6 patients followed for 15 months after implant insertion. Patients and parents reported less pain and discomfort and less interference with school activity and work with the implant compared with standard monthly injections. Conclusions. The Histrelin implant consistently sup- presses clinical and laboratory parameters of puberty for 1 year and is a promising new technique for treating CPP without the pain and inconvenience of monthly injections. Pediatrics 2005;116:e798-e802. URL: www. pediatrics.org/cgi/doi/10.1542/peds.2005-0538; precocious puberty, gonadotropins, estradiol, GnRH agonists, histre- lin.
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effective long term androgen suppression in men with prostate cancer using a hydrogel implant with the gnrh agonist Histrelin
Urology, 2001Co-Authors: Peter N. Schlegel, Irving M Spitz, Boris Chertin, Amicur Farkas, Petr Kužma, J Frick, Andreas Gomahr, Doris MackAbstract:Abstract Objectives. To evaluate the effectiveness of a hydrogel implant containing the gonadotropin-releasing hormone (GnRH) agonist Histrelin in suppressing testosterone production in men with prostate cancer and to determine the effective dose (one, two, or four implants). Methods. Forty-two men with prostate cancer and indications for androgen ablation were treated with one, two, or four implants. In two of the clinics, comprising 27 subjects, the treatment period was 12 months, with replacement with the same number of implants at 12-month intervals. In a third clinic, which treated 15 subjects, the implants were left in place for up to 30 months. The total experience was 605 treatment months. Results. The Histrelin levels were detected in serum proportional to the number of implants placed. The response, however, was similar among all three dose levels, with testosterone and luteinizing hormone essentially completely suppressed. Serum testosterone levels decreased from 21.9 ± 17.6 nmol/L to 0.93 ± 1.57 nmol/L within 1 month and were maintained at 0.55 ± 0.24 nmol/L at 6 months and 0.60 ± 0.28 nmol/L after 12 months of treatment. Of the 38 assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks of the initial implant placement. All patients followed for up for 12 months after placement of the initial set of implants maintained suppression of testosterone production while the implant was in place. Conclusions. The Histrelin hydrogel implant provided adequate and reliable delivery of the potent GnRH agonist Histrelin during at least 1 year using a single implant in men with prostate cancer. No apparent advantages were found in using more than one implant, and the question of the possible effectiveness of even lower doses remains open. This treatment modality appears to be both safe and effective.
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an implant releasing the gonadotropin hormone releasing hormone agonist Histrelin maintains medical castration for up to 30 months in metastatic prostate cancer
The Journal of Urology, 2000Co-Authors: Boris Chertin, Irving M Spitz, Tzina Lindenberg, Petr Kužma, Nurit Algur, Tami Zer, Alfred Moo J Young, Raphael Catane, Amicur FarkasAbstract:Purpose: The administration of gonadotropin hormone-releasing hormone agonists is well established for treating metastatic prostate cancer. In an ongoing study we evaluated the effect of a long acting implant that releases the gonadotropin hormone-releasing hormone agonist Histrelin ([ImBzl]D-His6, Pro9-Net) in 15 patients with disseminated prostate cancer. Materials and Methods: The 2.6 cm. implant releasing 60 μg. Histrelin daily is inserted subcutaneously into the upper arm using local anesthesia. Of the patients 8 received 1 and the remainder received 2 implants. Treatment with the antiandrogen flutamide or cyproterone acetate began 2 weeks before implant insertion and continued for up to 12 weeks. Testosterone, luteinizing hormone (LH) and prostate specific antigen were determined monthly, and a metastatic evaluation was performed every 6 months. Results: LH and testosterone increased after flutamide administration and decreased after implant insertion. By day 28 LH and testosterone were completely suppressed. LH and testosterone decreased immediately after cyproterone acetate administration. Prostate specific antigen began to decrease during antiandrogen therapy and decreased further after implant insertion. One patient requested implant removal after 1 year for personal reasons and 1 died of an unrelated cause 18 months after insertion. Escape was demonstrated in 4 cases at 5, 10, 12 and 19 months, although LH and testosterone remained suppressed. Duration of treatment in the remaining 9 patients was between 21 and 30 months. LH and testosterone remained completely suppressed and prostate specific antigen levels were in the normal range. The clinical and biochemical response was identical in those who received 1 or 2 implants. At 12 months 8 patients were challenged at intermittent intervals for up to 24 months with a bolus of 100 μg. gonadotropin hormone-releasing hormone followed by 2 weeks of flutamide. The response was compared with that in untreated controls recently diagnosed with prostate cancer. Unlike controls there was complete LH suppression in the 8 challenged patients. Conclusions: A Histrelin implant suppresses LH and testosterone in prostate cancer for up to 30 months. This finding represents a significant improvement over existing preparations, which must be administered at 1 to 3-month intervals.
Katherine A Lewis - One of the best experts on this subject based on the ideXlab platform.
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© 2009 Lewis and Eugster, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Drug Design, Development and Therapy 2009:3 1–5 1
2016Co-Authors: Katherine A Lewis, Erica A. Eugster, Correspondence Katherine, A LewisAbstract:Experience with the once-yearly Histrelin (GnRHa) subcutaneous implant in the treatment of central precocious pubert
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a single Histrelin implant is effective for 2 years for treatment of central precocious puberty
The Journal of Pediatrics, 2013Co-Authors: Katherine A Lewis, Andrea K Goldyn, Karen W West, Erica A. EugsterAbstract:We investigated whether a "yearly" Histrelin implant would provide pubertal suppression when left in place for 2 years. Equivalent suppression was observed when comparing 12 and 24 months in 33 children with central precocious puberty. A single implant for 2 years reduces cost and number of implant procedures.
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random luteinizing hormone often remains pubertal in children treated with the Histrelin implant for central precocious puberty
The Journal of Pediatrics, 2013Co-Authors: Katherine A Lewis, Erica A. EugsterAbstract:Objective To investigate the use of random ultrasensitive (US) luteinizing hormone (LH) levels to monitor children being treated with a Histrelin implant for central precocious puberty (CPP). Study design This was a prospective, uncontrolled, observational study at a pediatric endocrinology tertiary center. Thirty-three children (26 girls; mean age 7.2 ± 2.5 years) treated with a Histrelin implant for CPP were enrolled. A random US LH measurement was obtained at 6 months, and a gonadotropin-releasing hormone analog stimulation test was performed at 12 months. Clinic visits occurred at baseline and at 6-month intervals. Results In 59% of the patients (17 of 29), the 6-month random US LH exceeded the prepubertal range of ≤0.3 IU/L. In contrast, gonadotropin-releasing hormone analog stimulation tests revealed complete hypothalamic-pituitary-gonadal axis suppression (peak LH Conclusion The random US LH level does not revert to a prepubertal range in more than one-half of patients with a Histrelin implant and documented hypothalamic-pituitary-gonadal axis suppression. Long-term studies are needed to elucidate the optimal strategy for monitoring treatment in children with CPP.
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experience with the once yearly Histrelin gnrha subcutaneous implant in the treatment of central precocious puberty
Drug Design Development and Therapy, 2008Co-Authors: Katherine A Lewis, Erica A. EugsterAbstract:In 2007, a hydrogel Histrelin implant was approved for the treatment of children with central precocious puberty (CPP). Children with CPP commonly have reduced height potential due to premature closure of the epiphyseal growth plates from exposure to sex steroids. Gonadotropin-releasing hormone analog (GnRHa) treatment halts puberty and allows for improvement of adult height. A hydrogel implant delivery system utilizing the potent GnRHa, Histrelin, was first developed for use in men with prostate cancer. A once yearly Histrelin subcutaneous implant was subsequently developed for the treatment of children with CPP. Studies to date have demonstrated safety, tolerability, and effectiveness of this treatment option in patients treated up to 2 years. The most common adverse effects of the implant relate to implant site pain or bruising. Cost of this treatment seems comparable to somewhat higher than the commonly used GnRHa treatment option, depot leuprolide. While long term studies are needed to establish continued efficacy and safety beyond 2 years of treatment, the Histrelin implant appears to be an attractive option for GnRHa treatment in patients with CPP.
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Experience with the once-yearly Histrelin (GnRHa) subcutaneous implant in the treatment of central precocious puberty
Dove Medical Press, 2008Co-Authors: Katherine A Lewis, Erica A. EugsterAbstract:Katherine A Lewis, Erica A EugsterDepartment of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, USAAbstract: In 2007, a hydrogel Histrelin implant was approved for the treatment of children with central precocious puberty (CPP). Children with CPP commonly have reduced height potential due to premature closure of the epiphyseal growth plates from exposure to sex steroids. Gonadotropin-releasing hormone analog (GnRHa) treatment halts puberty and allows for improvement of adult height. A hydrogel implant delivery system utilizing the potent GnRHa, Histrelin, was first developed for use in men with prostate cancer. A once yearly Histrelin subcutaneous implant was subsequently developed for the treatment of children with CPP. Studies to date have demonstrated safety, tolerability, and effectiveness of this treatment option in patients treated up to 2 years. The most common adverse effects of the implant relate to implant site pain or bruising. Cost of this treatment seems comparable to somewhat higher than the commonly used GnRHa treatment option, depot leuprolide. While long term studies are needed to establish continued efficacy and safety beyond 2 years of treatment, the Histrelin implant appears to be an attractive option for GnRHa treatment in patients with CPP.Keywords: central precocious puberty, Histrelin, implant, gonadotropin-releasing-hormone analog
Boris Chertin - One of the best experts on this subject based on the ideXlab platform.
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free α subunit is the most sensitive marker of gonadotropin recovery after treatment of central precocious puberty with the Histrelin implant
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Harry J Hirsch, Boris Chertin, Amicur Farkas, David Gillis, David Strich, Najiba Lahlou, Binyamina Rosenberghagen, Hadassa Hartman, Irving M SpitzAbstract:Background: Gonadotropin free α-subunit (FAS) levels paradoxically increase during GnRH agonist (GnRHa) treatment of central precocious puberty (CPP). The Histrelin implant suppresses gonadotropins and estradiol (E2) levels for 1 yr, but effects on FAS have not been described. Objectives: We aimed to determine whether FAS levels remain elevated during treatment with the implant, to assess the dynamics of FAS after removal, and to ascertain the reliability of FAS for monitoring gonadotropin secretion. Methods: Ten girls with CPP were studied. In eight, monthly im GnRHa preparations were given until implant insertion. Two naive girls did not receive prior GnRHa. Duration of implant treatment ranged from 18–63 months with repeated implant removals and insertions of new implants. LH, FSH, E2, and FAS were measured before implant insertion in the two naive patients and during treatment, and in all girls before and after implant removal. Results: FAS levels were 0.2 and 0.4 ng/ml (normal, <0.6 ng/ml) in the two...
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relationships between fsh inhibin b anti mullerian hormone and testosterone during long term treatment with the gnrh agonist Histrelin in patients with prostate cancer
European Journal of Endocrinology, 2010Co-Authors: Talia Eldargeva, Boris Chertin, Amicur Farkas, Gad Liberty, Alon Fridmans, Ehud J Margalioth, Irving M SpitzAbstract:Objectives: Medical castration with long-acting GnRH-agonist (GnRHa) is a well-established treatment for metastatic prostate cancer. Our aim was to explore the relationships between FSH, inhibin B, antiMullerian hormone (AMH), and testosterone during treatment with an implant releasing GnRHa. Design: Analysis of hormone levels in frozen serum samples. Methods: Ten patients aged 77G7 (meansGS.E.M.) years with prostate cancer were treated with the GnRHa Histrelin for at least a year. Two weeks prior to insertion and for 3–4 months following removal the patients were treated with the antiandrogen flutamide. Serum inhibin B, FSH, testosterone, and AMH levels were measured retrospectively. Results: FSH, inhibin B, and testosterone increased during antiandrogen administration and levels fell after implant insertion. Four weeks post insertion, FSH gradually increased while inhibin B and testosterone remained fully suppressed. AMH levels did not change during antiandrogen treatment, but increased following implant insertion and remained elevated for the duration of implant use. Following removal, FSH and testosterone increased, inhibin B remained low, while AMH decreased. Conclusions: The secondary increase in FSH following initial suppression with the implant is probably related to impaired inhibin B secretion. The lack of inhibin B response to the secondary increase in FSH suggests that long-term exposure of Sertoli-cells to GnRHa impairs their function. This effect appears to be selective since unlike inhibin B, AMH increased. In the absence of testosterone, FSH has a role in AMH regulation.
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the Histrelin implant a novel treatment for central precocious puberty
Pediatrics, 2005Co-Authors: Harry J Hirsch, Boris Chertin, Tzina Lindenberg, Amicur Farkas, David Gillis, David Strich, Hadassa Gelber, Irving M SpitzAbstract:Objective. Standard treatment of central precocious puberty (CPP) consists of intramuscular or subcutaneous administration of a gonadotropin-releas- ing hormone (GnRH) agonist (GnRHa) at 3- to 4-week intervals. Although generally effective in suppressing clinical and laboratory parameters of puberty, GnRHa injections are painful, and the need for monthly clinic visits may contribute to poor compliance. Recently, a subcutaneous implant was developed that releases the GnRHa Histrelin at an average rate of 65 g/day. The aims of this study were to determine if a Histrelin im- plant would suppress gonadotropin and estradiol (E2 )i n girls with CPP for 1 year and to compare the suppression to standard treatment. Methods. We studied 11 girls with CPP to determine if the Histrelin implant can maintain long-term gonado- tropin suppression. Mean age at diagnosis was 6 1 ⁄2 years (range: 2-9 years). GnRH (100 g intravenously) stimu- lation tests (GnRH-STs) showed peak luteinizing hor- mone and follicle-stimulating hormone responses of 23 28 (mean SD) and 20 25 mIU/mL, respectively. All subjects were initially treated with depot intramuscular GnRHa triptorelin embonate. Implants were inserted subcutaneously under local anesthesia, and depot GnRHa treatment was discontinued. Six girls were fol- lowed for 15 months after insertion (group A). For the remaining 5 girls, the implant was removed after 9 months, and a new implant was inserted at the same incision site (group B). GnRH-STs were performed be- fore depot GnRHa treatment, immediately before im- plant insertion, at the 6- and 9-month visits for each patient and the 12- and 15-month visit for those girls followed for 15 months. Results. In all girls, breast development regressed, growth velocity decreased, and bone-age advancement was slowed. Basal gonadotropins and their responses to GnRH-STs and E2 levels were suppressed. Peak lutein- izing hormone and follicle-stimulating hormone re- sponses to GnRH-STs at preinsertion versus 9 months were 1.30 1.34 vs 0.25 0.08 and 1.68 1.08 vs 1.13 0.55 mIU/mL, respectively. Basal and stimulated gonad- otropin levels and E2 level remained suppressed in all 6 patients followed for 15 months after implant insertion. Patients and parents reported less pain and discomfort and less interference with school activity and work with the implant compared with standard monthly injections. Conclusions. The Histrelin implant consistently sup- presses clinical and laboratory parameters of puberty for 1 year and is a promising new technique for treating CPP without the pain and inconvenience of monthly injections. Pediatrics 2005;116:e798-e802. URL: www. pediatrics.org/cgi/doi/10.1542/peds.2005-0538; precocious puberty, gonadotropins, estradiol, GnRH agonists, histre- lin.
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effective long term androgen suppression in men with prostate cancer using a hydrogel implant with the gnrh agonist Histrelin
Urology, 2001Co-Authors: Peter N. Schlegel, Irving M Spitz, Boris Chertin, Amicur Farkas, Petr Kužma, J Frick, Andreas Gomahr, Doris MackAbstract:Abstract Objectives. To evaluate the effectiveness of a hydrogel implant containing the gonadotropin-releasing hormone (GnRH) agonist Histrelin in suppressing testosterone production in men with prostate cancer and to determine the effective dose (one, two, or four implants). Methods. Forty-two men with prostate cancer and indications for androgen ablation were treated with one, two, or four implants. In two of the clinics, comprising 27 subjects, the treatment period was 12 months, with replacement with the same number of implants at 12-month intervals. In a third clinic, which treated 15 subjects, the implants were left in place for up to 30 months. The total experience was 605 treatment months. Results. The Histrelin levels were detected in serum proportional to the number of implants placed. The response, however, was similar among all three dose levels, with testosterone and luteinizing hormone essentially completely suppressed. Serum testosterone levels decreased from 21.9 ± 17.6 nmol/L to 0.93 ± 1.57 nmol/L within 1 month and were maintained at 0.55 ± 0.24 nmol/L at 6 months and 0.60 ± 0.28 nmol/L after 12 months of treatment. Of the 38 assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks of the initial implant placement. All patients followed for up for 12 months after placement of the initial set of implants maintained suppression of testosterone production while the implant was in place. Conclusions. The Histrelin hydrogel implant provided adequate and reliable delivery of the potent GnRH agonist Histrelin during at least 1 year using a single implant in men with prostate cancer. No apparent advantages were found in using more than one implant, and the question of the possible effectiveness of even lower doses remains open. This treatment modality appears to be both safe and effective.
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an implant releasing the gonadotropin hormone releasing hormone agonist Histrelin maintains medical castration for up to 30 months in metastatic prostate cancer
The Journal of Urology, 2000Co-Authors: Boris Chertin, Irving M Spitz, Tzina Lindenberg, Petr Kužma, Nurit Algur, Tami Zer, Alfred Moo J Young, Raphael Catane, Amicur FarkasAbstract:Purpose: The administration of gonadotropin hormone-releasing hormone agonists is well established for treating metastatic prostate cancer. In an ongoing study we evaluated the effect of a long acting implant that releases the gonadotropin hormone-releasing hormone agonist Histrelin ([ImBzl]D-His6, Pro9-Net) in 15 patients with disseminated prostate cancer. Materials and Methods: The 2.6 cm. implant releasing 60 μg. Histrelin daily is inserted subcutaneously into the upper arm using local anesthesia. Of the patients 8 received 1 and the remainder received 2 implants. Treatment with the antiandrogen flutamide or cyproterone acetate began 2 weeks before implant insertion and continued for up to 12 weeks. Testosterone, luteinizing hormone (LH) and prostate specific antigen were determined monthly, and a metastatic evaluation was performed every 6 months. Results: LH and testosterone increased after flutamide administration and decreased after implant insertion. By day 28 LH and testosterone were completely suppressed. LH and testosterone decreased immediately after cyproterone acetate administration. Prostate specific antigen began to decrease during antiandrogen therapy and decreased further after implant insertion. One patient requested implant removal after 1 year for personal reasons and 1 died of an unrelated cause 18 months after insertion. Escape was demonstrated in 4 cases at 5, 10, 12 and 19 months, although LH and testosterone remained suppressed. Duration of treatment in the remaining 9 patients was between 21 and 30 months. LH and testosterone remained completely suppressed and prostate specific antigen levels were in the normal range. The clinical and biochemical response was identical in those who received 1 or 2 implants. At 12 months 8 patients were challenged at intermittent intervals for up to 24 months with a bolus of 100 μg. gonadotropin hormone-releasing hormone followed by 2 weeks of flutamide. The response was compared with that in untreated controls recently diagnosed with prostate cancer. Unlike controls there was complete LH suppression in the 8 challenged patients. Conclusions: A Histrelin implant suppresses LH and testosterone in prostate cancer for up to 30 months. This finding represents a significant improvement over existing preparations, which must be administered at 1 to 3-month intervals.