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GnRH Antagonists in the Treatment of Uterine Fibroids
Published in John C. Petrozza, Uterine Fibroids, 2020
Tejumola Adegoke, Shruthi Mahalingaiah
Conversely, the literature indicates that GnRH antagonists induce near-immediate pituitary inhibition without initial stimulation. They thus avoid the associated vasomotor symptoms and exacerbation of hormone-sensitive disease. Furthermore, it appears that fibroid shrinkage can occur in the absence of gonadotropin suppression, suggesting that GnRH antagonists function through alternative mechanisms. The change in fibroid echogenicity observed by Flierman et al. [34] implies that these agents affect fibroid tissue composition as well as size. Their dose-dependent effect can be exploited to obtain the desired degree of suppression while avoiding the adverse effects of hypoestrogenism [34]. Lastly, significant decrease in uterine and fibroid size can be achieved with short courses of treatment and may be a superior alternative for short-term preoperative fibroid suppression.
Fibroids and Assisted Reproduction Technology
Published in Botros R.M.B. Rizk, Yakoub Khalaf, Mostafa A. Borahay, Fibroids and Reproduction, 2020
Medical management of fibroids exploits the progesterone and estrogen responsiveness of uterine fibroids. Medical treatment, however, is not curative for fibroids. It has been considered as an option for symptom control and fibroid volume reduction. GnRH analogs have been commonly used. Other therapies including aromatase inhibitors, selective estrogen receptor modulators, and selective progesterone receptor modulators (SPRMs) have also been tried without the hypoestrogenic effects of the GnRH analogs. Currently, the two most studied and promising medical treatments are the GnRH agonist and SPRMs [2].
Mechanisms of action for estrogen in cardioprotection
Published in Barry G. Wren, Progress in the Management of the Menopause, 2020
Data from experimental studies suggest that estrogens are important regulators of cardiac tissues in females in vivo. Hypoestrogenism invariably leads to changes which may be considered non-advantageous to women. These effects can be reversed, to a degree, by estrogen replacement therapy. From a clinical point of view, two types of conclus,ons can be drawn from these studies: first, that estrogen replacement therapy reduces the occurrence and impact of risk factors of cardiac ischemia in women; second, that estrogens can protect the ischemic heart in women. Understanding the cellular and molecular mechanisms by which estrogens regulate cardiovascular functions in females is important for instituting appropriate treatment modalities to postmenopausal women.
The latest advances in the pharmacological management of endometriosis
Published in Expert Opinion on Pharmacotherapy, 2023
Gabriel Hartner, Heinrich Husslein, Lorenz Kuessel, Manuela Gstoettner, Denise Tiringer, René Wenzl, Alexandra Perricos
Elagolix is the first GnRH antagonist commercially available that can be administered orally because of its non-peptide structure. It has been approved for the treatment of heavy to moderate symptoms caused by endometriosis in premenopausal women with a dose of 150 mg once daily or 200 mg twice daily, depending on the patient’s symptoms. This approval was based on studies on women with surgically documented endometriosis. While the best efficacy in pain management was observed with a dose of 200 mg twice daily, the high dose went hand in hand with a higher occurrence of adverse events. These side effects, associated with the hypoestrogenic state, include nausea, hot flashes, a decrease in bone mineral density (BMD), mood swings, and an increase in serum lipid levels. Similar to GnRH-agonists, the treatment duration of elagolix is limited to 6 months with doses of 200 mg twice daily (for the treatment of dyspareunia) or 24 months with doses of 150 mg once daily, in patients without hepatic impairment. Contraception during intake of elagolix is advised, as clinical trials on 3500 women reported pregnancies in 49 study participants who received this GnRH antagonist. Furthermore, congenital malformations were observed in two pregnancies after treatment with a daily dose of 150 mg [18]. Further research is directed toward examining the pain-relieving effect of elagolix in combination with add-back therapy (usually in the form of a progestin or estrogen/progestin combination), hoping to prolong the approved treatment duration of the GnRH antagonist by counteracting its hypoestrogenic side-effects [12,13,19,20].
Menopausal hormonal therapy in surgically menopausal women with underlying endometriosis
Published in Climacteric, 2022
P. Tanmahasamut, M. Rattanachaiyanont, K. Techatraisak, S. Indhavivadhana, T. Wongwananuruk, P. Chantrapanichkul
Surgically induced menopause is the menopausal state following surgical removal of both ovaries (i.e. bilateral salpingo-oophorectomy [BSO]). BSO is associated with a sudden decrease in estrogen level, and a hypoestrogenic state can significantly impair quality of life due to menopause-related symptoms that include vasomotor symptoms, sleep deprivation, mood change and dyspareunia. These symptoms are more prevalent and severe in women with surgical menopause than those who naturally transition into menopause [1]. Furthermore, hypoestrogenism is a risk factor for cardiovascular disease and osteoporosis [2,3]. The Global Consensus Statement on menopausal hormone therapy (MHT) recommends that MHT for surgically menopausal women be initiated soon after surgery and continued until at least the average age at natural menopause to prevent long-term health consequences from early menopause [4,5].
Premature ovarian insufficiency: a toolkit for the primary care physician
Published in Climacteric, 2021
I. Lambrinoudaki, S. A. Paschou, M. A. Lumsden, S. Faubion, E. Makrakis, S. Kalantaridou, N. Panay
Estrogen-only therapy is the most appropriate treatment of hypoestrogenism for women after hysterectomy. In women with an intact uterus, a progestogen should be added to prevent endometrial hyperplasia. Natural progesterone 200 mg, dihydrogesterone 10–20 mg, oral norethisterone 1–5 mg or transdermal norethisterone 0.25 mg are recommended7,24–27 (Table 3). Oral progestogens are administered once or twice daily sequentially for 10–14 days per month, leading to regular monthly menstrual bleeding. Transdermal norethisterone is administered twice weekly for 14 days per month, resulting in regular monthly bleeding24,25. Some women prefer to take a daily progestogen as part of a ‘continuous combined’ regimen without menstrual bleeding, in which case lower doses can be given. Cyclic regimens are preferable for those who wish to maximize their chances of achieving a spontaneous pregnancy (albeit unlikely) and those planning oocyte donation or in vitro fertilization in the near future.