Helping women to ovulate
David J Cahill in Practical Patient Management in Reproductive Medicine, 2019
A further development in the use of GnRH analogues is to use GnRH antagonists. GnRH antagonists act by receptor blockage, competitively inhibiting gonadotroph cells and immediately suppressing gonadotrophin secretion (27). They are rapidly reversible, which is advantageous. While GnRH antagonists have been around since GnRH agonists were introduced (28), their use in clinical practice was halted because the early forms provoked very strong histamine responses. Now that those problems have been overcome, the advantages of these drugs are evident. Fewer FSH injections are needed because the introduction of the antagonist in the latter part of the ovarian stimulation makes use of the body's own FSH drive as well as the exogenous injected drug. The combined benefits are a simple short protocol and a reduced incidence of ovarian hyperstimulation syndrome with the ability to start the next treatment cycle immediately (27).
Limits of reproductive technology
Elisabeth Hildt, Dietmar Mieth in In Vitro Fertilisation in the 1990s, 2018
At present a ‘long regime’ is used in the majority of centres. This consists of the administration of a gonadotrophin releasing hormone (GnRH) agonist or analogue. These drugs cause the release of natural FSH from the pituitary and if administered continuously will result in a state of pituitary FSH exhaustion (known as pituitary desensitisation or downregulation). It thus becomes possible for the clinician to have total control of the ovulatory process but in so doing large amounts of exogenous FSH are required to stimulate the ovaries. GnRH antagonists (rather than agonists) are currently undergoing clinical trials. These drugs have an advantage over the agonist in that it may be possible to inhibit the luteinising hormone (LH) surge (the signal from the pituitary to the ovary that the egg containing follicles are mature). It will thus become possible to avoid the use of the agonist with a consequent reduction in the amount of FSH necessary to induce ovarian stimulation.
Polycystic ovary syndrome and assisted reproduction
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
Women with PCOS undergoing IVF cycles respond differently to women with normal ovaries. For the obese, weight loss and lifestyle modification should remain pivotal in the management of infertility, improving success rates and reducing potentially serious outcomes both in the short and longer term. The GnRH antagonist protocol provides a safe alternative to the traditional GnRH agonist, culminating in similar live birth rates but much reduced OHSS severity. The GnRH antagonist protocol allows use of the GnRH agonist trigger and modified luteal-phase support to further reduce the incidence of OHSS. Metformin remains a useful adjunct in the potential reduction of OHSS. IVM is a promising treatment that may ameliorate many of these issues for the notoriously difficult to manage PCO.
Linzagolix: a new GnRH-antagonist under investigation for the treatment of endometriosis and uterine myomas
Published in Expert Opinion on Investigational Drugs, 2021
Susan Dababou, Simone Garzon, Antonio Simone Laganà, Simone Ferrero, Giulio Evangelisti, Marco Noventa, Maurizio Nicola D’Alterio, Stefano Palomba, Stefano Uccella, Massimo Franchi, Fabio Barra
GnRH antagonists have multiple advantages compared to GnRH-agonists, such as simple route of administration and immediate dose-dependent suppression of gonadotropins; this last characteristic is responsible for partial suppression at lower doses and almost complete suppression at higher doses; lastly, GnRH antagonists allow rapid resumption of ovarian function after treatment withdrawal. Since 1999, GnRH antagonists have been used to prevent premature luteinizing hormone (LH) surges in women undergoing controlled ovarian stimulation for IVF. New oral GnRH-antagonists, investigated in IVF stimulation protocols, may notably improve the experience of patients undergoing infertility treatment by reducing the need for daily subcutaneous injections, which are often a burden to patients. In the last years, third-generation oral GnRH antagonists have been investigated for treating women with benign gynecological diseases. Until now, elagolix and relugolix are the only GnRH antagonists reaching experimental clinical phase study and, subsequently, undergoing approval in some countries for the therapy of endometriosis or uterine myomas.
Relugolix: A new kid on the block among gonadotrophin-releasing hormone antagonists
Published in Arab Journal of Urology, 2021
Charalampos Fragkoulis, Ioannis Glykas, Athanasios Dellis, Iraklis Mitsogiannis, Athanasios Papatsoris
Clinical efficacy of GnRH antagonists is well established. Klotz et al. [11] evaluated degarelix in an open-label randomised phase III trial in terms of both efficacy and safety and compared with leuprolide, degarelix proved not to be inferior in achieving and maintaining testosterone suppression for a treatment period of 12 months. A major benefit of its use was the rapid testosterone suppression without a testosterone flare phenomenon plus a lower risk of PSA progression in patients with PSA level of >20 ng/dL. Patients participating in the aforementioned trial were offered the possibility of entering a 5-year extension period. Patients receiving degarelix continued their treatment in the same way and patients receiving leuprolide were switched to either degarelix 240/80 mg or degarelix 240/160 mg with all patients converting to degarelix 80 mg after regulatory approval. In terms of results, testosterone and PSA suppression were similar with the pivotal study. Patients who were constantly under degarelix presented a progression-free survival (PFS) hazard rate consistent with the extension phase of the trial [12]. Based on the results of a pooled analysis performed by Klotz et al [13] extracting data from five prospective phase III/IIIb trials, degarelix presented improved PSA reduction, longer PFS, as well as longer overall survival compared with GnRH agonists.
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.
Related Knowledge Centers
- Assisted Reproductive Technology
- Cetrorelix
- Receptor Antagonist
- Uterine Fibroid
- Endometriosis
- Prostate Cancer
- Gonadotropin-Releasing Hormone Receptor
- Gonadotropin-Releasing Hormone
- Female Infertility
- Hormone