Endocrine Disorders, Contraception, and Hormone Therapy during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Gonadotropin-releasing hormone (GnRH) agonists are widely used in clinical gynecologic practice for the treatment of endometriosis and uterine leiomyomas. Leuprolide acetate (Lupron) is an agent that is frequently used for these conditions. Although no epidemiological studies are published of infants born following Lupron therapy, it is unlikely that the risk of congenital anomalies is high following exposure to this drug during pregnancy (Friedman and Polifka, 2006). Chronic administration of agonists downregulates the pituitary gonadotropin receptors, thereby suppressing release of LH and FSH, leading to a hypoestrogenic state. The likelihood of pregnancy occurring while a woman is given GnRH agonists is extremely low. However, GnRH agonists may also be used prior to HMG therapy in infertile women undergoing in vitro fertilization cycles. Typically, administration is begun in the luteal phase of the cycle, when a patient may be in the early stage of a pregnancy. No epidemiologic studies are published on the risk malformations in the offspring of women treated with this drug during pregnancy.
Prostate Cancer
Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple in Basic Urological Sciences, 2021
ADT aims to lower/block androgen activity:Lowering testosteroneBilateral orchidectomy to remove testosterone-producing Leydig cells.GHRH agonist: downregulates GnRH receptors.GHRH antagonist: blocks GnRH receptors.CYP17A1 inhibitor (Abiraterone): inhibits androgen synthesis.Blocking androgen effectNon-steroidal anti-androgens (Bicalutamide): block androgen receptors.
Therapeutic Options for Prostate Cancer: A Contemporary Update
Surinder K. Batra, Moorthy P. Ponnusamy in Gene Regulation and Therapeutics for Cancer, 2021
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.
Superior mesenteric ganglion via ovarian plexus nerve involved in the cross-talk between noradrenaline and GnRH in rat ovaries
Published in Systems Biology in Reproductive Medicine, 2023
María Belén Delsouc, Sandra Vallcaneras, Cristina Daneri Becerra, Fabián Heber Mohamed, Marina Fernández, Adriana Soledad Vega Orozco, Marilina Casais
During estrus, the stage related to the ovulatory process that begins the luteal phase (Ajayi and Akhigbe 2020), noradrenergic stimulation of SMG reduced the levels of GnRH in the ovary medium. This could be due to the influence of different neurotransmitters released in the ovary through OPN, such as neuropeptide Y (NPY), substance P, and even NA (Dees et al. 1986; Aguado 2002; Daneri et al. 2013). Indeed, the results obtained in the denervated ovary seem to support our assumption, because the inhibitory effect of NA on GnRH was significant at 60 min but could not be sustained, possibly due to the absence of other factors that reach the ovaries through the OPN. Thus, our ex vivo model highlights the importance of the sympathetic innervation of the ovary that involves OPN in the modulation of endogenous GnRH levels. GnRH can perform stimulatory or inhibitory effects on ovary, so its regulation is essential to favor the continuity of reproductive cycle.
Effectiveness of gonadotrophin-releasing hormone agonist therapy to improve the outcomes of intrauterine insemination in patients suffering from stage I-II endometriosis
Published in Annals of Medicine, 2022
Kemei Zhang, Shisi Huang, Haiyan Xu, Jiaou Zhang, Ensheng Wang, Yang Li, Changling Zhu, Jing Shu
The most common side effects of GnRH-a therapy included hot flash (7.32%), sexual hypoactivity (2.44%) and vaginal dryness (9.77%), which were mild and temporal. No other severe side effects were observed in all subjects. As shown in Table 1, more patients with stage II endometriosis were given GnRH-a therapy (75.86% vs 24.14%), while fewer patients with stage I were treated with GnRH-a (27.94% vs 72.06%). The r-AFS score of patients with or without GnRH-a therapy were 7.56 ± 3.81 and 2.88 ± 1.95, respectively. The differences were both significant (p = .000). There were no statistical differences in terms of female age, body mass index (BMI), Antimullerian hormone (AMH), basal hormones before laparoscopy surgery, duration of infertility, female education, unhealthy lifestyle and medical history between the two groups.
Current status and challenges of drug development for hormonal treatment of endometriosis: a systematic review of randomized control trials
Published in Gynecological Endocrinology, 2022
Vendy Zajec, Mislav Mikuš, Salvatore Giovanni Vitale, Maurizio Nicola D’alterio, Marija Gregov, Marko Jakov Šarić, Jose Carugno, Stefano Angioni, Mario Ćorić
An alternative pharmacological approach to GnRH receptor agonists is the use of GnRH receptor antagonists, which competitively binds to the GnRH receptor resulting in downregulation of the hypothalamic-pituitary-gonadal axis, producing a hypoestrogenic state similar to the one obtained with GnRH agonists. GnRH antagonists do not cause a transient increase in gonadotropin secretion and therefore do not cause an initial transient exacerbation of symptoms [25]. The injectable GnRH antagonist cetrorelix demonstrated optimal efficacy in the treatment of EAPP with an acceptable safety profile. Recently, oral nonpeptide forms of GnRH antagonists have become available. They can be administered orally at different doses, providing dose-dependent estrogen suppression with more tolerable side effects at lower doses [9]. We found four new GnRH antagonists that have been studied in phase 2 or phase 3 RCTs for the treatment of EAPP during the last decade.
Related Knowledge Centers
- Anterior Pituitary
- Luteinizing Hormone
- Peptide Hormone
- Tropic Hormone
- Releasing & Inhibiting Hormones
- Follicle-Stimulating Hormone
- Gnrh Neuron
- Hypothalamus
- Gonadotropin-Releasing Hormone Family
- Hypothalamic–Pituitary–Gonadal Axis