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Therapeutic Options for Prostate Cancer: A Contemporary Update
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sakthivel Muniyan, Jawed A. Siddiqui, Surinder K. Batra
GnRH agonists are a decapeptide used to suppress the release of the gonadotropins and thus control the testosterone synthesis by testis [38–41]. GnRH agonists (leuprolide, Goserelin, triptorelin, and histrelin) is given either subcutaneous or intramuscularly as a long-term depot. The sustained release of these agents leads to a spike in gonadotropins release and gradually makes the receptors desensitization. In the long term, this leads to a decline in testosterone synthesis and secretion. The initial testosterone surge may lead to undesirable side effects such as spinal cord compression and urinary obstruction due to tumor growth. The initial surge (testosterone flare) is clinically managed by the addition of antiandrogens (combined androgen blockade (CAB)) up to a month [16, 42]. GnRH antagonists share the same pathway (gonadal axis) in controling the physiological testosterone level. Until recently, the GnRH antagonists were not successful in the clinic due to the instability of the peptides and repeated injection and associated injection-site reactions. Recently, one of the stable antagonists, degarelix, was shown effective in reducing the testosterone level and was made into the clinic by effectively reducing tumor growth which is equal to GnRH agonists [20, 43, 44]. The major advantage of GnRH targeting agents is its reversibility, and it also avoids the psychological belief on surgical castration.
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
GnRH antagonists can suppress release of luteinizing hormone and follicle-stimulating hormone from the pituitary by blocking the GnRH receptors and preventing their stimulation. Therefore, they can act very rapidly compared to the GnRH agonists which can take weeks to lower testosterone to castration levels. For example, clinical trials of the GnRH antagonist degarelix (FirmagonTM) have demonstrated complete ablation of testosterone within three days of treatment. The other significant advantage is that this mechanism of action avoids the tumor flare effect observed with GnRH agonists, thus avoiding the need for anti-androgen medication at the beginning of treatment, as is the case with GnRH agonists.
GnRH Antagonists in the Treatment of Uterine Fibroids
Published in John C. Petrozza, Uterine Fibroids, 2020
Tejumola Adegoke, Shruthi Mahalingaiah
Clinically significant fibroid disease occurs in up to 35% of Caucasian and 50% of African American women [11] and is the leading indication for hysterectomy. Gonadotropin-releasing hormone (GnRH) antagonists are currently under investigation as a nonsurgical option for the treatment of uterine fibroids, but have not become part of common practice.
Evaluating the role of endometrial colour Doppler dynamic tissue perfusion measurements in in vitro fertilisation success
Published in Journal of Obstetrics and Gynaecology, 2022
Seda Akgün Kavurmacı, Gülnaz Şahin, Ayşin Akdoğan, Ahmet Özgür Yeniel, Ferruh Acet, Erol Tavmergen, Ege Nazan Tavmergen Göker
Of these 30 patients, 70% (n = 21) had primary infertility and 30% (n = 9) had secondary infertility. Of all patients, 70% (n = 21) were undergoing their first IVT-ET procedure, whereas 30% (n = 9) were undergoing their second IVF-ET procedure. All patients were induced with the GnRH antagonist protocol for a mean duration of 7.2 ± 1.1 (6–10) days and a mean FSH dose of 1583.3 ± 725.7 (600–4500) IU. The embryos were transferred on day three in 80% (n = 24) and on day two in 20% (n = 6) of the cases. The mean endometrial thickness on TVUSG prior to embryo transfer was 10.9 ± 1.8 mm (7.8–15.6). Embryo transfer was performed on the mean 14.5 ± 1.2 d (13–17) of the cycle. A single embryo was transferred in 76.7% (n = 23) of the cases, and two embryos were transferred in 23.3% (n = 7) of the cases. Of the transferred embryos, 66.7% (n = 20) were grade 1 and 33.3% (n = 10) were grade 2 embryos (Table 2).
An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women
Published in Expert Opinion on Pharmacotherapy, 2022
Mohamed Ali, Hsin-Yuan Chen, Yi-Fen Chiang, Osama A Badary, Shih-Min Hsia, Ayman Al-Hendy
Although both uterine tissue and tumor will be unlikely to shrink due to the included ABT, with consequence of less alleviation of bulk symptoms, ABT is indispensable to avoid several side effects of using GnRH antagonist alone. Moreover, improved symptoms while treatment will probably resume shortly following relugolix treatment termination. Relugolix may shape up as an attractive nonsurgical alternative for patients who suffer from fibroids. As these trials show a safe and effective option to reduce HMB and pain, the treatment may be ideal for premenopausal patients who do not want to pursue surgery. Considering that similar BMD measures between the placebo and relugolix combination therapy groups, it may be considered for longer treatment duration beyond the two years limit. These effective oral GnRH antagonists can also be utilized as secondary prevention therapy to prevent tumor regrowth post myomectomy surgeries. However, more studies are need to compare clinical outcomes (i.e. decreased risk of fibroid recurrence, symptom recurrence, and need for reintervention) in patients with symptomatic UFs who are treated with relugolix combination therapy following surgery such as robotic, laparoscopic, or open abdominal myomectomy versus the standard of care treatment following myomectomy alone. Such studies might provide valuable insights into whether relugolix combination therapy is helpful in the postoperative management of women with symptomatic UFs.
The effects of luteinising hormone gene polymorphism on the outcomes of in vitro fertilisation and embryo transfer
Published in Journal of Obstetrics and Gynaecology, 2021
Yeonhee Ku, Min A. Hong, Soo Jin Chae, Kyung Sil Lim, Won-Don Lee, Jin Ho Lim, Young Min Choi
The clinical pregnancy rate was significantly lower in the carrier group than in the noncarrier group in GnRH antagonist cycles but not in IVF cycles with the long GnRH agonist protocol. There might be differences between the two protocols, which could explain the results of this study. Endogenous LH has been reported to be suppressed in IVF cycles with the GnRH antagonist protocol (Albano et al. 1997), and serum LH level has been found to be significantly lower in GnRH antagonist cycles than in long GnRH agonist cycles (Barmat et al. 2005). Pregnancy rates were similar in GnRH antagonist and long GnRH agonist cycles but in favour of long GnRH agonist cycles. Several studies have evaluated the effect of LH supplementation in GnRH antagonist cycles and found no additional benefit with LH supplementation in a general IVF population (Tarlatzis et al. 2006).