Relugolix 120mg tablets

Background: Uterine fibroids (UFs) and endometriosis are gynecological conditions that significantly increase morbidity among women of reproductive age. Relugolix, a novel gonadotropin-releasing hormone receptor antagonist, is approved in combined therapy for the management of symptoms related to these disorders. However, its potential impact on bone mineral density (BMD) and osteoporosis risk should be considered when using a gonadotropin-releasing hormone (GnRH) antagonist. This systematic review aims to evaluate the effects of daily relugolix intake in monotherapy and combination therapy on BMD, ensuring safe long-term management. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed, Medline, and the Cochrane Library. Relevant clinical guidelines from international societies were also reviewed. Studies assessing the impact of relugolix on BMD were selected, and data on treatment efficacy, adverse effects, and bone health outcomes were synthesized. Results: Relugolix monotherapy has been associated with significant BMD loss due to its potent estrogen-suppressing effect. To mitigate this, combination therapy with estradiol and norethisterone acetate has been developed. Although initial monotherapy before transitioning to combination therapy results in transient BMD reduction, clinical trials have demonstrated that relugolix combination therapy maintains BMD over two years while effectively reducing endometriosis- and UF-related symptoms. Conclusions: Relugolix combination therapy is an effective and well-tolerated treatment for UFs and endometriosis, minimizing the risk of hypoestrogenism-related bone loss while maintaining clinical benefits. Although monotherapy may lead to transient BMD reduction, combination therapy appears to stabilize bone health.

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Background: Relugolix offers a promising alternative for endometriosis-associated pain, yet its comprehensive impact on health-related quality of life (HRQoL), particularly as measured by the disease-specific EHP-30 questionnaire, remains underexplored. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating relugolix for endometriosis-associated pain, with a primary focus on HRQoL assessed by the Endometriosis Health Profile-30 (EHP-30). Data extracted included EHP-30 domain scores changes and proportion of EHP-30 Pain Domain Responders, along with intervention details, control type, and follow-up duration. Results: Five RCTs were included. Overall, relugolix significantly improved EHP-30 Pain domain scores (MD = 6.77, 95% CI: 3.15 to 10.39, p=0.0002) but showed substantial heterogeneity (I²=90.7%). Subgroup analysis by control type showed significant differences (p<0.0001): Relugolix was highly effective against placebo (MD = 15.31, 95% CI: 12.18 to 18.45) and placebo-matching combination therapy (MD = 8.86, 95% CI: 5.03 to 12.69), but numerically less effective than leuprorelin (MD = -3.79, 95% CI: -6.27 to -1.31). Relugolix significantly increased EHP-30 Pain Domain Responders (OR = 3.245, 95% CI: 2.496; 4.219, p < 0.0001). For other EHP-30 domains, relugolix demonstrated significant improvements in Emotional Well-being (MD = 5.71, 95% CI: 1.87; 9.55, p=0.0036), Social Support (MD = 6.40, 95% CI: 0.88; 11.93, p=0.0231), and Self-image (MD = 6.00, 95% CI: 1.03; 10.96, p=0.0179) compared to placebo. Conclusion: Oral relugolix significantly improves EHP-30 pain domain scores and patient response rates in endometriosis, particularly when compared to placebo. It also positively impacts emotional well-being, social support, and self-image.

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Endometriosis is a chronic gynecological condition commonly associated with pelvic pain, dysmenorrhea, dyspareunia, and infertility. Owing to the limitations and adverse effects of traditional hormonal therapies, this study aimed to evaluate the efficacy and safety of elagolix and relugolix for the management of endometriosis-related pain, in comparison with other therapeutic alternatives. A systematic search was conducted in PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane, SciELO, ScienceDirect, and Google Scholar, including randomized clinical trials (RCTs) published between 2014 and 2025. Methodological quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, together with the GRADE and Jadad tools. Nine clinical trials met the inclusion criteria. The findings suggest that both relugolix and elagolix, whether administered as monotherapy or in combination with estrogens and progestins, effectively reduce endometriosis-associated pain, improve the quality of life, and decrease the need for opioid use. Reported adverse events were generally mild, with minimal loss of bone mineral density (BMD). Importantly, the strongest and most consistent evidence supports the use of relugolix in combination with add-back therapy, which appears to provide sustained efficacy and a more favorable long-term safety profile than monotherapy. Thus, relugolix with hormonal add-back therapy emerges as a safe and effective long-term treatment option for endometriosis-related symptoms, offering significant clinical benefits while mitigating hypoestrogenic side effects.

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Relugolix is a novel orally administered gonadotropin-releasing hormone (GnRH) antagonist approved for androgen deprivation therapy (ADT) in advanced prostate cancer. Its oral formulation, rapid onset of action, and potentially improved cardiovascular safety profile distinguish it from traditional injectable GnRH antagonists. This review evaluates current primary research on the clinical effectiveness and safety of Relugolix compared to established ADT agents. A structured literature search was conducted using PubMed, targeting primary research articles that assessed the efficacy and safety of oral Relugolix. Inclusion criteria comprised original studies with clinical endpoints such as testosterone suppression, prostate-specific antigen (PSA) response, and castration resistance-free survival (CRFS). Exclusion criteria included reviews, meta-analyses, and studies not investigating Relugolix. Searches were completed by two independent reviewers compared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Nine primary studies met the inclusion criteria, including randomized controlled trials (RCTs), subgroup analyses, pharmacokinetic modelling, and observational studies. In the HERO trial, Relugolix achieved castration-level testosterone (<50 ng/dL) in 96.7% of patients, outperforming Leuprolide (88.3%) in both speed (median = 4 days vs. 29 days) and magnitude of suppression. Subgroup analyses demonstrated consistent efficacy across patients receiving concomitant therapies with a lower incidence of major cardiovascular events in the Relugolix group. Additional studies confirmed its effectiveness when combined with radiotherapy in comparison with Degarelix. Pharmacokinetic modelling supported rapid and sustained testosterone suppression even during short treatment interruptions. Relugolix is an effective and well-tolerated oral GnRH antagonist for patients with advanced prostate cancer. It offers rapid testosterone suppression, high rates of CRFS, and a potentially favorable cardiovascular safety profile compared to injectable ADT agents. These advantages, along with oral administration, support its use as a viable alternative in clinical practice. Further long-term studies are warranted to confirm sustained outcomes and optimize treatment regimes.

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Background: Relugolix, an oral GnRH receptor antagonist, is effective in treating uterine myomas and endometriosis. However, concerns persist regarding the venous thromboembolism (VTE) risk associated with its combination with oral estradiol (E2) and norethisterone acetate (NETA). Objective: This expert opinion evaluates the thrombotic risk of relugolix combined therapy (relugolix-CT) based on pharmacological data, clinical trials, and regulatory assessments. Methods: A review of pivotal trials (LIBERTY 1, LIBERTY 2, SPIRIT 1, SPIRIT 2), regulatory reports (European Medicines Agency, Food and Drug Administration), and real-world safety data was conducted, focusing on hemostatic effects and VTE risk. Results: Relugolix monotherapy reduces estrogen levels, leading to minor decreases in coagulation factors. While E2 and NETA mitigate hypoestrogenic effects, concerns about their prothrombotic potential remain. However, clinical trials and postmarketing surveillance have not shown a significant increase in VTE risk. A meta-analysis suggests that E2-based regimens have a lower thrombotic risk than ethinylestradiol-based therapies. Conclusion: The VTE risk of relugolix-CT appears lower than that of traditional combined oral contraceptives. Nonetheless, patient selection is essential, particularly for those with thrombotic risk factors. Continued real-world surveillance is crucial to refining its safety profile in clinical practice.

Abstract licence: CC BY-NC-ND

Background: Elagolix, Linzagolix, and Relugolix, as oral gonadotropin-releasing hormone antagonists, have emerged as promising treatments for endometriosis-associated pain. Objective: To evaluate pain intensity reduction as the primary outcome and assess side effects and quality of life as secondary outcomes through an updated meta-analysis. Materials and Methods: A systematic search was conducted in Cochrane, Scopus, and PubMed/Medline. Study quality was assessed using the Cochrane risk of bias in non-randomized studies of interventions tool. The pooled standard mean difference and p-value were calculated using a random-effects model (DerSimonian-Laird method), and the inconsistency index was applied to evaluate heterogeneity. Results: 7 randomized controlled trials were included. Gonadotropin-releasing hormone antagonists significantly reduced dysmenorrhea, dyspareunia, and non-menstrual chronic pelvic pain when measured with the verbal and numeric rating scales, but not with the modified Biberoglu and Behrman score. Secondary outcomes showed significant improvements in health status (endometriosis health profile and patient global impression of change). However, treatment was associated with increased hot flushes (3.61-fold higher), an 8.96% increase in low-density lipoprotein after 6 months, and a rise in high-density lipoprotein compared with placebo. Bone mineral density in the spine was significantly lower in the treatment group (p &lt; 0.001). Conclusion: This meta-analysis provides updated evidence on Elagolix, Linzagolix, and Relugolix, confirming their effectiveness in managing endometriosis-associated pain, while highlighting important considerations regarding metabolic and bone health.

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An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate [Myfembree® (USA); Ryeqo® (EU)] (hereafter referred to as relugolix combination therapy) has been approved in the USA for the management of moderate to severe pain associated with endometriosis in premenopausal women and in the EU for the symptomatic treatment of endometriosis in adult women of reproductive age with a history of previous medical or surgical treatment for their endometriosis. The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix decreases estradiol and progesterone levels, while the addition of estradiol/norethisterone acetate mitigates hypoestrogenic effects including bone mineral density (BMD) loss and vasomotor symptoms. In two pivotal phase III trials, relugolix combination therapy significantly improved dysmenorrhoea and non-menstrual pelvic pain in premenopausal women with moderate to severe endometriosis. The combination also reduced overall pelvic pain and dyspareunia, reduced analgesic and opioid use, and improved health-related quality of life. The efficacy of relugolix combination therapy was sustained over the longer term (up to 2 years). Relugolix combination therapy was generally well tolerated and BMD loss over time was minimal. With the convenience of a once daily oral dosing regimen, relugolix combination therapy is a valuable addition to the options currently available for the management of endometriosis-associated pain. Endometriosis is a disease where tissue similar to the lining of the uterus grows outside the uterus and may reach other organs. This causes chronic pain as a result of increased inflammation and scar tissue. Women with endometriosis may experience painful menstrual periods, pelvic pain between periods, pain during sex, painful bowel movements and painful urination. Recently, a fixed-dose tablet comprising relugolix, estradiol and norethisterone (also known as norethindrone) acetate [Myfembree® (USA); Ryeqo® (EU)] (hereafter referred to as relugolix combination therapy) has been approved to treat endometriosis-associated pain. The treatment works by decreasing levels of ovarian hormones (estrogen and progesterone). In clinical trials, relugolix combination therapy improved period pain and pain between periods in women with moderate to severe pain associated with endometriosis. The treatment also improved other symptoms (overall pelvic pain and pain during sex), reduced the need for pain medications and improved health-related quality of life. Relugolix combination therapy was generally well tolerated and caused minimal bone loss, which is known to occur with some hormone therapies. With the convenience of a once daily oral pill, relugolix combination therapy is a valuable addition to the options currently available for women with endometriosis-associated pain.

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Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, has been established as an effective androgen deprivation therapy (ADT) for advanced prostate cancer, offering advantages over traditional GnRH agonists. The combination of relugolix with androgen receptor pathway inhibitors (ARPIs) is increasingly utilized in clinical practice, necessitating an understanding of its pharmacokinetics, efficacy, safety, and drug-drug interactions. This review explores the real-world data and clinical studies evaluating relugolix coadministration with ARPIs, including enzalutamide, abiraterone, apalutamide, and darolutamide. Pharmacokinetic interactions, particularly via the CYP3A4 enzyme system and P-glycoprotein (P-gp) transporter, influence drug exposure and, in theory, necessitate dose adjustments in certain combinations. However, clinical studies and real-world studies suggest that relugolix maintains testosterone suppression when combined with ARPIs even if administered in a standard dose. While these findings support the efficacy and safety of relugolix-based combination therapy, further large-scale prospective trials are needed to refine treatment recommendations and provide information on long-term outcomes.

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