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Principles of Pathophysiology of Infertility Assessment and Treatment*
Published in Asim Kurjak, Ultrasound and Infertility, 2020
Joseph G. Schenker, Aby Lewin, Menashe Ben-David
The use of gonadotropin-releasing hormone (Gn-RH) agonists is a new therapeutic approach. The antigonadotrophic action of luteinizing hormone-releasing hormone (LH-RH) agonists can induce regulation of fibroids by reducing follicle-stimulating hormone (FSH)-induced estrogen secretion and depriving the myoma of its growth stimulus.
The Pineal Gland and Melatonin
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
Jerry Vriend, Nancy A.M. Alexiuk
The site(s) and mechanism(s) of action of melatonin continue to elude researchers. Using the assumption that melatonin is the active pineal hormone, we may restate the question of the site(s) of action of pineal products in terms of the site(s) of action of melatonin. It should be noted, however, that a considerable amount of research, during the 1970s and 1980s, dealt with attempts to identify, isolate, purify, and synthesize a pineal peptide hormone. Unlike the research resulting in the isolation and synthesis of hypothalamic hormones, attempts at identifying a specific pineal peptide hormone were remarkably unsuccessful. Many of these studies were attempts to isolate a specific pineal antigonadotropic hormone.161,177,445–447
Chronic pelvic pain and endometriosis
Published in Joseph S. Sanfilippo, Eduardo Lara-Torre, Veronica Gomez-Lobo, Sanfilippo's Textbook of Pediatric and Adolescent GynecologySecond Edition, 2019
Joseph S. Sanfilippo, Jessica Papillon Smith, M. Jonathon Solnik
Dienogest is an oral progestin now used as a monotherapy at a dose of 2 mg daily in patients with endometriosis. This medication is highly selective for the progesterone receptor, leading to strong progestational effects, moderate antigonadotrophic effects, and minimal androgenic, glucocorticoid, or mineralocorticoid effects.61 Multiple studies have shown dienogest to be both safe and effective in the treatment of adults with endometriosis.62–64 However, studies in the pediatric adolescent population were lacking until recently. In 2017, Ebert et al. published the results of the VISanne Study to Assess Safety in ADOlescents (VISADO study). This prospective observational study evaluated the safety and efficacy of dienogest 2 mg daily in adolescents aged 12–18 with clinically suspected or laparoscopically confirmed endometriosis. Results demonstrated that endometriosis-associated pain was substantially reduced and that the drug was very well tolerated during the 52-week trial. However, there was an associated decrease in lumbar bone mineral density with only a partial recovery after 6 months of treatment discontinuation.65 In light of these findings, it is necessary to adopt an individualized approach when prescribing dienogest, as with DMPA. One must balance the benefits of decreased pain with the potential risks to bone health in each patient, and provide counseling in this regard. Patients should also be informed that dienogest has not been tested or approved as a contraceptive, so the concomitant use of barrier contraception is necessary in sexually active teenagers.
Current approaches to overcome the side effects of GnRH analogs in the treatment of patients with uterine fibroids
Published in Expert Opinion on Drug Safety, 2022
Mohamed Ali, Mohamed Raslan, Michał Ciebiera, Kornelia Zaręba, Ayman Al-Hendy
Gonadotropin-releasing hormone (GnRH) analogs have been one of the main pharmacological modalities in the treatment of UFs [8,32]. These analogs have been extensively used in clinical medicine since they were identified and synthesized in 1971 [33]. These drugs are used in gynecology and oncology for the modulation of the pulsatile release of GnRH. They bind to the receptor of the frontal lobe of the pituitary gland inhibiting the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH are peptide hormones that regulate ovarian and testicular function and are essential for normal growth, sexual development, and reproduction. These pituitary gonadotropins are under the control of the above mentioned GnRH, which is produced in the hypothalamus and released in response to the circulating levels of estrogens and progesterone [34]. GnRH analogs are made of different peptides and are structurally related to GnRH. Very recently researchers have also obtained new small molecules (e.g. elagolix), which are structurally distinct (non-peptide) from and unrelated to GnRH analogs [35]. The majority of the above-mentioned substances present antigonadotropic properties. However, some may present pro-gonadotropic properties (e.g. gonadorelin), depending on whether they act to increase or decrease gonadotropin release [34].
Pharmacodynamics of combined estrogen-progestin oral contraceptives 3. Inhibition of ovulation
Published in Expert Review of Clinical Pharmacology, 2018
Carlo Bastianelli, Manuela Farris, Elena Rosato, Ivo Brosens, Giuseppe Benagiano
The action of this new progestin has been investigated in 13 healthy subjects to whom daily doses of 1.25, 2.5, or 5 mg were administered [44]. Nomegestrol acetate (NOMAC) inhibited ovulation in all women, with LH and P levels being constantly depressed. With 2.5 and 5 mg doses, plasma E2 remained low with high FSH values. With 1.25 mg, circulating levels of E2 were similar to those observed during the control follicular phase, with a concomitant decrease in FSH secretion. When the antigonadotropic activity of NOMAC was tested [45,46], it was found that it is not antagonized by flutamide and is not mediated via the androgen receptor. The exact mode of action of NOMAC was then investigated in 10 normally cycling women, 3 with McCune-Albright syndrome (MCA, characterized by gonadotropin-independent ovarian function), and 5 with functional hypothalamic amenorrhea. Ovulation was suppressed in all subjects when treated with 5 mg/daily NOMAC. In normal subjects, mean plasma LH levels, LH pulse frequency, and the LH response to exogenous GnRH were significantly decreased. A direct effect of NOMAC on the ovaries was ruled out, since in subjects with MCA syndrome, ovaries were unmodified. In subjects with functional hypothalamic amenorrhea, pulsatile GnRH administration recreated a normal ovulatory menstrual cycle, but administration of NOMAC prevented ovulation, as well as any increase in plasma E2, and decreased the amplitude of LH pulses. In a 6-month long trial at the daily dose of 5 mg, NOMAC significantly decreased E2 and P levels (p < 0.001) [47].
Complete remission of cerebral endometriosis with dienogest: a case report
Published in Gynecological Endocrinology, 2018
Paolo Maniglio, Enzo Ricciardi, Federica Meli, Federica Tomao, Michele Peiretti, Donatella Caserta
In the last decade, the anti-estrogenic effect of progesterone has been mimicked in an effort to create medical therapies for endometriosis [19]. Particularly, dienogest, a synthetic steroid, is currently being studied for its possible clinical use for the treatment of this medical condition. It exhibits highly selective binding to the progesterone receptor and has high progestational and significant antiandrogenic activity, but only moderate antigonadotrophic activity. Scientific evidences showed that this medication at a dose of 2 mg daily for 12 weeks was significantly more effective than placebo for reducing endometriosis associated pain [20]. However, none of both these therapies proved to be effective for complete regression of symptoms [21]. Furthermore, few studies are available about the long-term therapy of extra-pelvic endometriosis, that is, often treated with surgical strategies (when it is possible) with frequent recurrences [1].