Dataset Information

Moving Toward Individualized Medicine for Uterine Leiomyomas.

ABSTRACT: Uterine leiomyomas are common and life-altering for many women. Despite a wide range of symptoms, varying characteristics of the uterus and the leiomyomas themselves, and many alternatives, hysterectomy accounts for almost three fourths of all surgical therapy, yet there is increasing evidence for a variety of procedural therapies for symptomatic leiomyomas and a new generation of medical therapies under development. With increasing evidence of long-term risk from hysterectomy and new data regarding leiomyoma biology, individualized medical approaches to leiomyomas are likely in the near future. Key biological attributes that influence this disease process are common driver mutations and the new appreciation of the interaction of smooth muscle cells and fibroblasts. Additionally, the interaction between cell types and steroid hormone responsiveness likely plays a role in pathogenesis that can be leveraged in individualized therapy. However, given the independent clonal nature of leiomyomas within the same uterus, moving in the direction of biopsies for individual leiomyomas to understand the biology is unlikely to be fruitful. Use of advanced imaging will likely continue to evolve not only to accurately predict malignant disease, including sarcomas, but to predict leiomyoma subtypes, response to therapy, or both. We predict the continued evolution of therapy from excisional or interventional therapies to medical therapies and ultimately prediction of at-risk individuals. Ideally, individualized therapies will offer primary prevention for women at high risk of leiomyomas and secondary prevention after initial treatment.

SUBMITTER: Laughlin-Tommaso SK

PROVIDER: S-EPMC6153058 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Moving Toward Individualized Medicine for Uterine Leiomyomas.

Laughlin-Tommaso Shannon K SK Stewart Elizabeth A EA

Obstetrics and gynecology 20181001 4

Uterine leiomyomas are common and life-altering for many women. Despite a wide range of symptoms, varying characteristics of the uterus and the leiomyomas themselves, and many alternatives, hysterectomy accounts for almost three fourths of all surgical therapy, yet there is increasing evidence for a variety of procedural therapies for symptomatic leiomyomas and a new generation of medical therapies under development. With increasing evidence of long-term risk from hysterectomy and new data regar ...[more]

PMID: 30130343

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Project description:BackgroundUterine leiomyomas and adenomyosis are both common and often associated with abnormal uterine bleeding (AUB), including the symptom of heavy menstrual bleeding (HMB). Understanding the prevalence of adenomyosis in women with uterine leiomyomas could inform clinicians and patients in a way that may improve therapeutic approaches.ObjectiveTo explore the prevalence of adenomyosis in a group of women who underwent hysterectomy for AUB-L, to determine the prevalence of submucous leiomyomas, and to examine the utility of preoperative ultrasound to detect the presence of adenomyosis.MethodsThe Kaiser Permanente Hysterectomy Database (KPHD) was searched for women aged 18-52 undergoing hysterectomy for leiomyoma-associated chronic AUB (AUB-L) in 2018 and 2019. A target sample of 400 comprised those with at least 3 years in the Health System. Radiologists evaluated preoperative pelvic ultrasound images to determine leiomyoma size and level 2 FIGO type (submucous or other), and the linked electronic medical record abstracted for clinical features, including histopathological evidence of adenomyosis.ResultsOf the 370 subjects that met the study criteria, adenomyosis was identified via histopathology in 170 (45.9%). There was no difference in the adenomyosis prevalence with (47.1%) and without (43.0%) at least one submucous leiomyoma. Subgroup analysis of ultrasound images by an expert radiologist for the presence of adenomyosis demonstrated a positive predictive value of 54.0% and a negative predictive value of 43.4%.ConclusionsAdenomyosis was present in almost half of this AUB-L cohort undergoing hysterectomy and was equally prevalent in those with and without submucous leiomyomas as determined by sonographic evaluation. The imaging findings are in accord with prior investigators and demonstrate that 2-D ultrasound is insensitive to the presence of adenomyosis when the uterus is affected by leiomyomas. Further research is necessary to determine the impact of various adenomyosis phenotypes on the presence and severity of the symptom of HMB.

Project description:ObjectiveIn the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.MethodsWomen with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in the extension study. The primary efficacy endpoint was the proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction in menstrual blood loss volume from LIBERTY study baseline to the last 35 days of treatment (defined as responders ). Analyses were conducted for all three randomized treatment groups from pivotal studies.ResultsOverall, 477 women enrolled, 476 were treated, and 363 (76.1%) completed 52 weeks. Among patients treated with relugolix combination therapy through 52 weeks (n=163), sustained improvement in heavy menstrual bleeding was observed in 87.7% (responders). The least squares mean menstrual blood loss volume reduction was 89.9%, with 70.6% of patients achieving amenorrhea. At week 52, 59.0% of patients with anemia at baseline had improvements in hemoglobin concentration of greater than 2 g/dL. Distress due to uterine leiomyoma-associated symptoms measured by the BPD (Bleeding and Pelvic Discomfort) scale score was reduced by 51.3 points. Sustained reductions in uterine and uterine leiomyoma volume were observed. Bone mineral density was preserved through week 52.ConclusionImprovements in heavy menstrual bleeding and anemia and reduction of uterine leiomyoma-associated symptom burden were sustained through up to 52 weeks of treatment with relugolix combination therapy in women with uterine leiomyomas. No new safety concerns were identified, and BMD was maintained.Clinical trial registrationClinicalTrials.gov , NCT03049735; NCT03103087; NCT03412890.Funding sourceMyovant Sciences GmbH.

Dataset Information

Moving Toward Individualized Medicine for Uterine Leiomyomas.

Publications

Moving Toward Individualized Medicine for Uterine Leiomyomas.

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