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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Histrelin is a potent synthetic nonapeptide analog of GnRH marketed by Orion Pharma under the brand name VantasTM (Figure 8.29). Differing from the other GnRH analogues in containing an unusual N-benzylated-histidyl-residue, it was synthesized and then patented in 1981 by researchers at the Salk Institute (USA). Histrelin is used to treat hormone-sensitive advanced prostate cancer in men and uterine fibroids in women. It is also effective in treating central precocious puberty (CPP) in children.
Pubertal abnormalitiesPrecocious and delayed
Published in Joseph S. Sanfilippo, Eduardo Lara-Torre, Veronica Gomez-Lobo, Sanfilippo's Textbook of Pediatric and Adolescent GynecologySecond Edition, 2019
Treatment of precocity varies depending on etiology and degree of severity. For idiopathic central precocity, GnRH analog therapy can provide the benefit of delaying menses until a girl is psychologically ready for puberty and preventing rapid advancement of bone age that would compromise final height. The agonist may be given by injection daily (rarely prescribed), monthly, or every 12 weeks (leuprolide), by nasal spray (Nafarelin) or by intradermal implant (histrelin). The goal is to block GnRH to prevent pulsatile release of FSH and LH in response to GnRH until the provider and family believe the child should undergo pubertal maturation. Girls diagnosed over the age of 8 years will usually not require GnRH analog therapy.12 Patients undergoing GnRH suppression should have LH monitored 30–120 minutes after administration of a GnRH agonist. LH should be less than 4.5 IU/L during suppression. Patients with suppression by implant should have LH monitored 4 weeks after implantation and again every 6 months after suppression is achieved. Best height outcomes have been reported when GnRH therapy is discontinued by 12–12.5 years. Menarche occurs on average 16 months after leuprolide is discontinued. Because menarche occurring before age 11 years is associated with a higher risk for metabolic syndrome, cardiovascular disease, and cancer, GnRH agonists are generally continued to age 10–11 years.
The use of gonadotropin-releasing hormone agonists and the efficiency of in vitro fertilization
Published in David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham, Textbook of Assisted Reproductive Techniques, 2017
Pasquale Patrizio, Sanaz Ghazal, Judith A.F. Huirne, Roel Schats
Table 42.1 lists seven diff rent GnRH agonists, but only four are commonly used in IVF programs. An extensive search revealed only one article on the use of histrelin in IVF (48), while deslorelin has never been applied in human IVF. Except for its combination for the treatment of endometriosis, goserelin is not routinely used in ART, partly because it is only available as a depot preparation. Depot preparations also on the market for triptorelin and leuprolide, which are not to be used as first choices, as discussed earlier. Thirteen prospective randomized trials have compared diff rent agonists with each other (49–60). The problem with those studies is that the optimal dosage has not been determined for any of the applied individual agonists, and therefore the ability of these articles to answer the question of which compound should be used is limited. All the agonists seem eff ctive and the diff rences in the studies can be explained by dosage incompatibility. These studies make absolutely clear that proper dose-finding studies for the use of GnRH agonists in ART are still urgently needed. It is obvious that the dose required for the prevention of premature LH surges during controlled ovarian stimulation cycles in ART will be diff rent from that required to treat carcinoma of the prostate, which requires complete chemical castration (see below).
A single blood sample for stimulated LH assayed by ICMA is useful for monitoring the treatment efficacy of triptorelin depot in girls
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2022
Yuan Zhou, Ruofan Jia, Fan-Sheng Kong, Min Chen, Feng Ren, Zhuangjian Xu, Yaping Ma
GnRHa is an ideal substitute. Several studies have shown the value of GnRHa stimulation test for evaluating the treatment efficacy in CPP, but there are differences in the cut-off values by different dosage forms [21–25]. For leuprolide (20 μg/kg) stimulation test to evaluate the treatment efficacy of histrelin (50 mg), PLH within 60 min decreased from (28.2 ± 19.97) IU/L to (0.8 ± 0.39) IU/L (ICMA) [21]. In another study, all patients had PLH concentrations below 2.5 IU/L (ICMA) during leuprolide (20 μg/kg) stimulation test one month after treatment [22]. For leuprolide (20 μg/kg) stimulation test to evaluate the treatment efficacy of leuprolide (45 mg), LH concentrations at 30 min decreased from (23.5 ± 3.1) IU/L initially to (3.0 ± 0.8) IU/L at week 24 and to (2.3 ± 0.2) IU/L at week 48 (electro-chemiluminescence immunoassay, ECLIA) [23]. PLH < 2.2 IU/L (ICMA) during leuprolide (20 μg/kg) stimulation test was found to be the cut-off value for evaluating the treatment efficacy of leuprolide (30 mg) [24]. A study demonstrated that LH and FSH responses to triptorelin (100 μg/dose) stimulation test correlated with clinical inhibition of pubertal development during GnRHa treatment (enzyme immunoassay; immunoradiometric assay, IRMA) [25]. In the present study, PLH ≤ 2.25 IU/L (ICMA) during triptorelin (100 μg/dose) stimulation test could be used as a cut-off value to confirm the suppression of HPGA after triptorelin depot (3.75 mg) treatment. Therefore, PLH concentrations within 60 min after triptorelin stimulation can effectively evaluate the treatment efficacy of triptorelin depot in girls with puberty disorders.
Advanced delivery of leuprorelin acetate for the treatment of prostatic cancer
Published in Expert Review of Anticancer Therapy, 2022
Axel S Merseburger, Marie Christine Roesch
In Europe, the main available LHRH agonists are leuprorelin, goserelin, buserelin and triptorelin acetate, all based on biodegradable microspheres or implants containing the active drug, which are injected subcutaneously or intramuscularly [23,25]. Histrelin acetate is also available in some European countries; nevertheless, it represents a minor option since it requires a surgical procedure for the insertion. Among these different options, leuprorelin acetate (leuprolide acetate) is well established as the leading LHRH analog due to its favorable tolerability and, today, it represents the LHRH analog most prescribed worldwide [12,26]. Leuprorelin acetate is available as a 1-, 3-, 6- and 12-month preparation, marketed under different brand names worldwide [23,25]. Among them, the development of second-generation leuprorelin acetate (LA) depot formulation (Eligard®, Recordati S.p.A) allowed a consistent and controlled release of leuprorelin between injections and a more efficient reduction of testosterone levels with respect to conventional LHRH agonists [27].
Emerging hormonal agents for the treatment of prostate cancer
Published in Expert Opinion on Emerging Drugs, 2022
Emily Bochner, Sam Gold, Ganesh V. Raj
Androgen deprivation is most commonly achieved in contemporary practice via LHRH agonism. Available therapies include leuprolide, goserelin, triptorelin, and histrelin; their depot or slow-release formulations allow for dosing schedules ranging from monthly to yearly. The decreased frequency of administration can be convenient for patients who often require this medication for the remainder of their lives. LHRH agonist monotherapy has been studied extensively in comparison to orchiectomy with results showing equivocal survival outcomes [23]. Time to castration with LHRH agonist is ~1 month, but initially, a dramatic increase in both LH and testosterone levels – up to a 10-fold increase in these hormone levels – may be seen, that can cause rapid progression of spinal or weight-bearing skeletal metastases resulting in potentially life-threatening spinal cord compression or pathologic fractures [24,25]. Concurrent use of AR antagonists (i.e. bicalutamide) has been shown to effectively prevent the downstream activity of testosterone surge via AR blockade. LHRH agonism is also associated with injection site pain, osteoporosis, vasomotor dysfunction, metabolic syndrome with increased risk of myocardial infarction, fatigue, anemia, and sexual dysfunction [26]. Moreover, after cessation of LHRH agonist treatment, recovery of testosterone levels is often slow, highly variable, and hypogonadism may persist.