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Reducing Intraoperative Blood Loss in Myomectomy
Published in Rooma Sinha, Arnold P. Advincula, Kurian Joseph, FIBROID UTERUS Surgical Challenges in Minimal Access Surgery, 2020
Sunita R. Tandulwadkar, Manish Y. Machave, Abhishek Chandavarkar
These can broadly be divided into preoperative and intraoperative approaches. Preoperatively, patients can be administered gonadotropin-releasing hormone (GnRH) analogues or aromatase inhibitors in an attempt to shrink the myoma(s) and potentially decrease blood loss. The effectiveness of this has been questioned secondary to the potential loss of the surgical plane and consequently increased difficulty in completing the surgery. Newer agents under current investigation include selective progesterone receptor modulators.
Hormonal Regulation in the Treatment of Fibroids
Published in John C. Petrozza, Uterine Fibroids, 2020
Victoria Fitz, Steven L. Young
Given the limitations (vide supra) of progestin receptor agonists and GnRH agonists, investigators have recently turned their attention to selective progesterone receptor modulators (SPRMs), including ligands such as mifepristone, ulipristal and asoprisnil, which have agonist, antagonist or mixed effects on progesterone receptors, depending on the target tissue and its physiological state. The SPRM ligand binds to PR-A or PR-B (both found in higher concentrations in leiomyoma tissue compared with surrounding myometrium), and initiates interactions with co-repressors or co-activators that dictate whether the SPRM is an agonist or antagonist in that cellular environment.
Medical Options for Uterine Fibroids in the Context of Reproduction
Published in Botros R.M.B. Rizk, Yakoub Khalaf, Mostafa A. Borahay, Fibroids and Reproduction, 2020
Hoda Elkafas, Mona Al Helou, Qiwei Yang, Ayman Al-Hendy
So far, therapies for fibroids are limited, and no pharmacological agent is accepted and approved for long-term treatment of fibroids [27]. The primary treatments of uterine fibroids—myomectomy and hysterectomy—have been recognized and announced as solutions for all cases. However, these options are only for women who are not planning for future pregnancies. For women who refuse surgical operation and prepare for future fertility, the best treatment choice is to control and stabilize hormone levels at uterine fibroid cells. Drug-based strategies have been traditionally accepted as a presurgical adjuvant to diminish fibroid volume, but not for long-term treatment plans. Current pharmaceuticals either fail to fix symptoms entirely or are correlated with unacceptable side effects that restrict their long-term use [27]. Ongoing studies in the field predict fibroid drug treatment options for a significant role beyond short-term preoperative adjuvant therapy. Unfortunately, traditional hormonal therapy carries an intrinsic side effect for a long-term treatment option. Here, we cover the main pharmacological agents that were considered or are currently being investigated for their role in uterine fibroid management, with particular stress on selective progesterone receptor modulators (SPRMs) and GnRH agonists and antagonists. The mechanism of action, side effects, and trials of modern, emerging medical options for treating and controlling the symptoms of uterine fibroids and their approval status by the U.S. Food and Drug Administration (FDA) are reviewed and summarized in Table 6.1.
Dual agonist–antagonist effect of ulipristal acetate in human endometrium and myometrium
Published in Expert Review of Molecular Diagnostics, 2021
Ana Salas, Paula Vázquez, Aixa R. Bello, Delia Báez, Teresa A. Almeida
Uterine leiomyoma (UL), also called fibroid or myoma, is the most commonly diagnosed tumor of the female genital tract with an incidence of 40% at the age of 35 and nearly 70–80% around the age of 50 [1]. Severe symptoms develop in 15–30% of patients with menorrhagia or excessively heavy menses being the most common. Although the direct cause of development of these tumors is unknown, accumulating evidence suggests that genetic and epigenetic mechanisms are involved in fibroids initiation and growth [2,3]. Alteration of these (epi)genetic mechanisms could be triggered by intrinsic abnormalities of the myometrium, abnormal expression of estrogen receptors, hormonal changes, or altered responses to ischemic damage during the menstrual cycle [2]. In addition, dependency of sexual steroid hormones, especially progesterone (P4), is accepted as determinant for tumor initiation and growth [4]. For this reason, selective progesterone receptor modulators (SPRMs) have been developed as a promising pharmacological therapy for uterine fibroids.
Relugolix for the treatment of uterine fibroids
Published in Expert Opinion on Pharmacotherapy, 2020
ML Rocca, AR Palumbo, D Lico, A Fiorenza, G Bitonti, S D’Agostino, C Gallo, C Di Carlo, F Zullo, R Venturella
Selective progesterone receptor modulators (SPRMs) have been introduced for treatment of several gynecological conditions developed to target the progesterone receptor with a mix of agonist and antagonist properties. In patients with uterine fibroids, ulipristal acetate (UPA) (Esmya) has demonstrated efficacy. It is used both as pre-surgical [34,35] and long-term [36,37] treatment of symptomatic fibroids. UPA induces amenorrhea, reduces uterine volume and decreases volume dimension with a sustained effect until 6 months after the end of treatment, without adverse effect on endometrial tissue [34–36]. Following reports of serious liver injury, including four cases of serious liver injury leading to hepatic transplantation, the review of Esmya was carried out by European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC). On 31 May 2018, EMA recommended that several measures be put in place to minimize the risk of rare but serious liver injury with UPA. In its latest update (13 March 2020), the uterine fibroid drug was recalled [38].
The role of pharmacotherapy in the treatment of endometriosis across the lifespan
Published in Expert Opinion on Pharmacotherapy, 2020
Kaia Schwartz, Natalia C. Llarena, Jenna M. Rehmer, Elliott G. Richards, Tommaso Falcone
Progesterone resistance is a key part of the pathogenesis of endometriosis. Progesterone has an anti-estrogenic effect on the endometrium; however, in endometriosis, stromal cells fail to respond appropriately to progesterone and therefore do not inactivate estrogen. The combination of this failure to inactivate estrogen and this dysregulated aromatase activity results in high levels of estrogen in tissues affected by endometriosis [11]. Selective progesterone receptor modulators (SPRM) may address this aspect of the disease. SPRMs have differential effects on progesterone receptors of different tissues. They can act as pure agonists, pure antagonists, or partial agonist/antagonists depending on progesterone receptor expression in different tissue [58]. The most commonly studied SPRM is mifepristone. A Cochrane review summarizing the evidence for selective progesterone receptor modulators in the treatment of endometriosis concluded that there is moderate evidence that mifepristone is effective in reducing the dysmenorrhea symptoms [84]. There may be a negative side effect of endometrial hyperplasia in patients taking SPRMs that needs to be further investigated.