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Uterine fibroids, benign tumors originating from uterine smooth muscle cells, vary in prevalence depending on patient ethnicity, hormonal exposure, and genetics. Due to their high incidence, these neoplasms pose a significant burden on healthcare systems. Current treatment strategies range from routine monitoring in asymptomatic cases to surgical procedures such as myomectomy or hysterectomy in symptomatic patients, with an increasing trend toward uterus-preserving or non-surgical alternatives. This review examines the existing medical treatments for uterine fibroids and delves into the potential of emerging therapies. A scoping review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Medical therapies are divided into hormonal and non-hormonal treatments; however, long-term, safe, and effective treatments in the treatment of uterine fibroids are limited. In addition to established therapies, there is an increasing number of studies investigating the effect of substances such as vitamin D or green tea extract on uterine fibroids. Some studies investigate acupuncture as a possible alternative therapy. While existing treatments offer symptomatic relief and preparation for surgery, our findings point to a significant need for further research into long-term solutions, especially owing to recent limitations in the use of ulipristal acetate due to risk of liver damage. Initial studies involving vitamin D and epigallocatechin gallate are encouraging; however, additional research is required to establish definitive therapeutic roles.

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BackgroundEndometriosis, PCOS, adenomyosis, and dysmenorrhea are major illnesses. Hormonal as well as non-hormonal treatments were evaluated for COCs, progestins, GnRH analogues, LNG-IUS, relugolix, and adjunctive therapies. These treatments resulted in the categorization of the benefits in varying degrees.Methods149 clinical trials have been included. Evaluating the methodological quality was done through the Jadad scale, while the GRADE criteria were used to assess the reliability of the evidence. When these data were available, effect sizes, standardized mean differences (SMD), 95% confidence intervals (CI), and p-values were extracted.ResultsIt was observed that COCs and progestins considerably lowered pelvic pain and menstrual irregularities (SMD -0.35 to -0.58, 95% CI -0.90 to -0.08, pConclusionsEndometriosis disorder have been treated well with hormonal therapies. Different endocrine therapies based on the patient's specific characteristics and the degree of tolerability should be used to achieve the maximum effect of clinical outcomes.

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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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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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PurposeUterine fibroids are the most common pelvic tumors in women, representing the primary indication of hysterectomy. Gonadotropin-releasing hormone (GnRH) antagonists represent a new therapeutic option for premenopausal women. The aim of this review is to evaluate the efficacy and safety of GnRH antagonists in the treatment of uterine fibroids (size reduction and symptom control).MethodsA review of studies from electronic databases (PubMed and Cochrane Central) published up to December 2023 was performed. Eleven randomized clinical trials with a total of 4164 patients were included in the review, which evaluated GnRH antagonists (Relugolix, Elagolix, Linzagolix and Cetrorelix) against placebo or GnRH agonists in premenopausal women with uterine fibroids and heavy menstrual bleeding.ResultsThe results of the measures evaluated to determine the efficacy and safety of GnRH antagonists versus placebo are favorable for the variables of control of uterine bleeding (Relative risk (RR) = 5.09; 95% CI 3.19 to 8.14), percentage reduction of fibroid volume (Mean difference (MD) = -27.36; 95% CI -38.89 to -15.83) and lower reduction of bone density (MD -0.35; 95% CI -0.47 to -0.24). The results do not allow us to conclude whether there are differences between the alternatives compared in the control of vasomotor symptoms.ConclusionsGnRH antagonists represent an effective alternative for uterine fibroids treatment as they allow a superior reduction in menstrual bleeding and uterine fibroid volume compared to the placebo group.

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Purpose of reviewWhile laparoscopic surgery plays a key role in the management of endometriosis, symptoms commonly recur, and repeat surgery comes with increased risk. Medical management, including hormonal and nonhormonal treatment, is vital in managing painful symptoms. This review summarizes recent evidence regarding various medical management options available to treat pelvic pain associated with endometriosis.Recent findingsEfficacy of dienogest vs. combined oral contraceptive on pain associated with endometriosis: randomized clinical trial.Once daily oral relugolix combination therapy vs. placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2).A randomized, double-blind, placebo-controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis.Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study.SummaryAll symptomatic women with suspected endometriosis who are not desiring immediate fertility can be offered suppressive treatment to control symptoms and slow the progression of disease. First-line treatments include the combined oral contraceptive pill and progestogens. Second-line treatments include gonadotropin-releasing hormone agonists and antagonists but current guidelines recommend that these should be reserved for people whose symptoms fail to be controlled by first-line agents. The use of complementary and alternative medicines is also increasing in both volume and number of agents used.

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BackgroundSymptomatic uterine fibroids are burdensome to live with; they are associated with symptom-related distress, affect daily activities, and reduce health-related quality of life. The LIBERTY randomized clinical trials showed that oral relugolix combination therapy (40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate once daily) markedly improved fibroid-associated symptoms and conditions, including heavy menstrual bleeding, pain, and anemia, and was well-tolerated.ObjectiveThis study aimed to evaluate the effect of relugolix combination therapy on the symptom burden and health-related quality of life among women with uterine fibroids.Study designTwo replicate, multinational, double-blind, 24-week, randomized, placebo-controlled, phase 3 studies, LIBERTY 1 and LIBERTY 2, were conducted in premenopausal women with uterine fibroid-associated heavy menstrual bleeding (≥80 mL per cycle for 2 cycles or ≥160 mL during 1 cycle). The symptom burden and health-related quality of life were secondary endpoints and were assessed using the validated Uterine Fibroid Symptom and Quality of Life questionnaire, which the participants completed at baseline and at week 12 and 24 of treatment. For this secondary analysis, the pooled LIBERTY 1 and LIBERTY 2 data set was used. The Uterine Fibroid Symptom and Quality of Life questionnaire is made up of a Symptom Severity scale and a Health-Related Quality of Life scale, the latter of which includes 6 subscales focusing on the following aspects of daily life: concern, activities, energy or mood, control, self-consciousness, and sexual function. The Revised Activities subscale of the Health-Related Quality of Life scale addresses the impact of uterine fibroids on physical and social activities. Symptom burden was also assessed via the Bleeding and Pelvic Discomfort subscale, a patient-reported outcome measure derived from the Uterine Fibroid Symptom Severity scale that focuses on distress from key uterine fibroid symptoms, which was a key secondary endpoint. Least squares mean changes from baseline to week 24 in the Symptom Severity scale, Bleeding and Pelvic Discomfort subscale, overall Health-Related Quality of Life scale, and the respective subscales were compared between the relugolix combination therapy and placebo groups. Responder analyses of the proportion of women who experienced a clinically meaningful change from baseline to week 24 were conducted for the Bleeding and Pelvic Discomfort and the activity subscales. A stratified Cochran-Mantel-Haenszel test, adjusted for stratification factors (region [North America vs rest of world] and baseline menstrual blood loss volume), was used for treatment comparisons.ResultsAcross both trials, 509 women were randomized to the relugolix combination therapy or placebo groups (April 2017-December 2018). Participants on relugolix combination therapy showed a statistically significant reduction in symptom severity (-33.5 vs -12.1; nominal PConclusionAfter 24 weeks of treatment with relugolix combination therapy, women with symptomatic uterine fibroids experienced substantial improvements in health-related quality of life with all subscales showing improvement, including emotional well-being, physical and social activities, and sexual function. In addition, women reported substantial reductions in the overall symptom burden and distress caused by key fibroid-associated symptoms.

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