A plain language summary of the perspectives of women who were interviewed about their experiences with uterine fibroids.

WHAT IS THIS SUMMARY ABOUT?: This summary describes what researchers learned during interviews of women with uterine fibroids and heavy menstrual bleeding (or period bleeding). At this time, little is known about how women perceive the impact of uterine fibroids on their lives and more information is needed. The goal of this study was to provide new information about the symptoms women have and how these symptoms affect their everyday lives. These interviews were done to better understand how uterine fibroid symptoms affect the lives of women in their own words. WHAT WERE THE RESULTS?: Thirty women from the United States, who had completed a clinical trial for a new treatment for heavy menstrual bleeding and uterine fibroids, agreed to be interviewed. The women described what their experiences with uterine fibroids were and the impact these experiences with uterine fibroids had on their lives before participating in the clinical trial. The most common symptoms of uterine fibroids the women described were heavy bleeding with their menstrual periods, pain in the pelvis or groin area, the passing of blood clots, and anemia (or low hemoglobin in red blood cells). Women said their symptoms affected them physically, emotionally, socially, and financially. They also said their symptoms made it hard to do daily activities, sleep, have a sex life, and go to work or school. WHAT DO THE RESULTS MEAN?: Women who have heavy menstrual bleeding and uterine fibroids experience various uterine fibroid symptoms, and these symptoms affect most parts of the their lives.

Quality of life improvements in women with uterine fibroids treated with relugolix combination therapy during the LIBERTY long-term extension study: A descriptive subgroup analysis in women with anemia at baseline.

OBJECTIVE: To investigate the effects of 52 weeks of treatment with relugolix combination therapy (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) on symptoms of uterine fibroids (UF) and quality of life (QoL) in women with heavy menstrual bleeding associated with UF and anemia (hemoglobin ≤10.5 g/dL) at baseline. METHODS: This post hoc analysis included women from the LIBERTY long-term extension study with anemia (hemoglobin concentration ≤10.5 g/dL) at pivotal study baseline and documented hemoglobin values at week 52 (anemia-evaluable population). Treatment responders: women achieving a menstrual blood loss volume of <80 mL and a ≥50% reduction over the last 35 days of treatment. Anemia responders were women achieving a hemoglobin increase of >2 g/dL from baseline to week 52. Least squares (LS) mean changes from baseline in uterine fibroid symptom (UFS)-QoL symptom severity, fatigue, and health-related QoL total (HR-QoL) and (sub)scale scores were calculated. RESULTS: In total, 115 women were included in the anemia-evaluable population. Of 39 anemia-evaluable women who received continuous treatment with relugolix combination therapy for 52 weeks, 34 (87.2%) met treatment responder criteria and 23 (59.0%) were anemia responders. LS mean hemoglobin concentration increased by 29.4% at week 52. LS mean UFS-QoL symptom severity and fatigue scores decreased by 38.5 and 31.9 points, respectively, and HR-QoL total score increased by 41.6 points. CONCLUSION: In women with UF and a high disease burden due to anemia, relugolix combination therapy substantially improved hemoglobin levels, decreased distress due to symptoms, especially fatigue, over 52 weeks.

Relugolix combination therapy in European women with symptomatic uterine fibroids: a subgroup analysis from the randomized phase 3 LIBERTY pivotal trials.

OBJECTIVE: In the 24-week, phase 3 LIBERTY 1 (L1) and LIBERTY 2 (L2) trials, relugolix combination therapy (relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg)) reduced uterine fibroid (UF)-associated symptoms. This post hoc analysis assessed safety and efficacy of relugolix-CT in European women from L1/L2. METHODS: Premenopausal women (aged 18-50 years) with UF-associated heavy menstrual bleeding (HMB) were randomized 1:1:1 in L1 (N = 388) and L2 (N = 382) to relugolix-CT or placebo for 24 weeks, or delayed relugolix-CT (relugolix 40 mg then relugolix-CT; 12 weeks each). Primary endpoint: proportion of responders (menstrual blood loss (MBL) <80 mL and reduction of ≥50% from baseline MBL volume) over the last 35 days of treatment. Secondary endpoints: MBL volume, amenorrhea, UF-associated pain, symptom severity, distress related to bleeding and pelvic discomfort, health-related quality of life (HRQoL). Safety endpoints included adverse event (AE) reporting and bone mineral density (BMD) assessment. RESULTS: In European women from L1/L2 (N = 124, 16%), a significantly greater proportion of treatment responders was observed with relugolix-CT vs. placebo (85.4% vs. 19.1%, respectively; nominal p < .0001). There were statistically significant improvements with relugolix-CT vs. placebo for several secondary endpoints: reduction in MBL volume, amenorrhea rate, proportion achieving mild-to-no pain, reduction in symptom severity and distress from bleeding and pelvic discomfort, and improvement in HRQoL. Incidence of AEs and percentage changes in BMD from baseline to week 24 were similar for relugolix-CT and placebo. CONCLUSIONS: In European women with UF and HMB, once-daily relugolix-CT vs. placebo improved UF-associated symptoms and preserved BMD.

The Burden of Uterine Fibroids from the Perspective of US Women Participating in Open-Ended Interviews.

Background: Research on women's perspective of uterine fibroids (UF) experiences using their own words is limited. This study aimed to provide new insights on the symptoms experienced and their impacts on daily life. Methods: Interview substudy in 30 US women with heavy menstrual bleeding (HMB) associated with UF who completed one of two phase 3, randomized, double-blind, placebo-controlled trials (LIBERTY 1 and 2; ClinicalTrials.gov identifiers: NCT03049735, NCT03103087). Women who consented to participate in this substudy were interviewed after their last clinical trial study visit. Concepts (i.e., symptoms and impacts) of importance to women were determined via open-ended questions, and the frequency of symptoms and their impacts, including the relationship between pain and menstruation, were assessed. Data were analyzed using established qualitative research methods, including grounded theory and constant comparative methods, and concept saturation was assessed. Results: Fifteen unique symptoms of UF emerged: the most commonly reported were HMB (n = 30, 100.0%), pelvic pain (n = 28, 93.3%), and passing of blood clots (n = 24, 80.0%). In total, 25 unique impacts were identified across eight concepts: physical impacts, activities of daily living, sleep, emotional impacts, sex life, social impacts, work and school, and financial impacts. Concept saturation was achieved for both symptoms and impacts. Conclusion: This study provides data on the symptoms experienced by women with HMB associated with UF, as well as the negative impacts of these symptoms as reported using their own words. The study findings confirm the significant burden associated with symptomatic UF.

One-year efficacy and safety of the iron-based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis.

BACKGROUND: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with sevelamer carbonate (sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and sevelamer in the peritoneal dialysis (PD) patient population. METHODS: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. RESULTS: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with sevelamer. CONCLUSIONS: Sucroferric oxyhydroxide is noninferior to sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.

Iron-related parameters in dialysis patients treated with sucroferric oxyhydroxide.

BACKGROUND: Sucroferric oxyhydroxide is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphataemia in adult dialysis patients. This post hoc analysis of a randomized, 24-week Phase 3 study and its 28-week extension was performed to evaluate the long-term effect of sucroferric oxyhydroxide on iron parameters. METHODS: A total of 1059 patients were randomized to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or sevelamer carbonate ('sevelamer') 2.4-14.4 g/day (n = 349) for up to 52 weeks. The current analysis only included patients who completed 52 weeks of continuous treatment (n = 549). Changes in iron-related parameters and anti-anaemic product use during the study were measured. RESULTS: Some changes in iron-related parameters across both treatment groups were observed during the first 24 weeks of the study, and to a lesser extent with longer-term treatment. There were small, but significantly greater increases in mean transferrin saturation (TSAT) and haemoglobin levels with sucroferric oxyhydroxide versus sevelamer during the first 24 weeks (change in TSAT: +4.6% versus +0.6%, P = 0.003; change in haemoglobin: +1.6 g/L versus -1.1 g/L, P = 0.037). Mean serum ferritin concentrations also increased from Weeks 0 to 24 with sucroferric oxyhydroxide and sevelamer (+119 ng/mL and +56.2 ng/mL respectively; no statistically significant difference between groups). In both treatment groups, ferritin concentrations increased to a greater extent in the overall study population [>70% of whom received concomitant intravenous (IV) iron], compared with the subset of patients who did not receive IV iron therapy during the study. The pattern of anti-anaemic product use was similar in both treatment groups, with a trend towards higher use of IV iron and erythropoiesis-stimulating agents with sevelamer. CONCLUSIONS: Initial increases in some iron-related parameters were observed in both treatment groups but were more pronounced with sucroferric oxyhydroxide. These differences between treatment groups with respect to changes in iron parameters are likely due to minimal iron absorption from sucroferric oxyhydroxide.

The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro.

AIMS: Hyperphosphatemia in advanced chronic kidney disease (CKD) necessitates the use of phosphate binders. This in vitro study assessed phosphate binding and Fe release properties of the novel iron-based phosphate binder PA21. MATERIALS AND METHODS: Phosphate adsorption and Fe release were assessed under conditions simulating administration of PA21 on an empty stomach and full stomach across a pH range to which PA21 would be exposed during passage through the gastrointestinal (GI) tract. RESULTS: PA21 showed a robust phosphate binding capacity over the entire physiologically relevant pH range. The high binding capacity at low pH indicates that phosphate binding could begin in the stomach. Under the current experimental setting, the maximal bound phosphate to Fe ratio was 0.47 mmol P/mmol Fe. The largest amount of Fe release was observed at the lowest pH without phosphate and was much lower in the presence of phosphate. These results are in line with the formation of iron phosphate at low pH, as indicated by X-ray photoelectron spectroscopy and thermodynamic calculations. Fe release was minimal (≤ 0.35%) across pH 2.5 - 8.5. CONCLUSIONS: These studies demonstrate that PA21 has potent phosphate binding capacity and low iron release over a physiologically relevant pH range in the GI tract. These features indicate PA21 could be an effective alternative phosphate binder for CKD patients.

Oral hormone therapy with 17beta-estradiol and 17beta-estradiol in combination with norethindrone acetate in the prevention of bone loss in early postmenopausal women: dose-dependent effects.

OBJECTIVE: A 2-year multicenter, double-blind, randomized, placebo-controlled study examined the efficacy and safety of different doses of 17beta-estradiol (E(2)) alone and continuous-combined oral formulations of E(2) and norethindrone acetate (NETA) versus placebo in the prevention of bone loss in newly menopausal women. DESIGN: Patients were randomized to one of seven groups: placebo, E(2) 0.25 mg, E2 0.5 mg, E(2) 1 mg, E(2) 1 mg/NETA 0.25 mg, E(2) 1 mg/NETA 0.5 mg, or E(2) 2 mg/NETA 1 mg. Treatment was a once-daily tablet taken for 26 months. The primary efficacy endpoint was the change in bone mineral density (BMD) at the lumbar spine, measured by dual-energy x-ray absorptiometry, at screening and at 13, 19, and 26 months. BMD changes at the femoral neck and trochanter were also assessed. Biochemical markers of bone metabolism were measured at baseline, and at 3, 6, 13, 19, and 26 months. Histological diagnoses of endometrial samples were tabulated for each treatment group. RESULTS: A total of 327 women were randomized and 189 women completed the 2-year trial. BMD at the lumbar spine decreased 2.3% in the placebo group. The lowest dose of unopposed E(2) prevented bone loss at the spine and hip. Significant increases in spine BMD compared with placebo occurred in all groups of treatment with E(2) and were more pronounced in the combination groups. Compared with placebo, women receiving active treatment experienced greater reductions in bone resorption markers. The effects were evident by 6 months and generally remained stable thereafter. Adverse events, primarily associated with the endometrium, were the most common reasons for discontinuation. CONCLUSIONS: There is a dose-dependent effect of E(2) on BMD. The addition of NETA seems to enhance the response in BMD observed with E(2). Low doses of E(2) (1 mg and lower) can be considered for the prevention of osteoporosis, while titrating the hormone dose to individual patient's needs.

Influence of different HRT regimens on mammographic density.

OBJECTIVES: A prospective, randomized, open-label study was conducted to evaluate effects on mammographic density in postmenopausal and late perimenopausal women receiving continuous combined or sequential combined hormone replacement therapy (HRT). METHODS: The subjects were randomized to treatment with low-dose continuous combined HRT containing 1 mg 17beta-estradiol plus 0.5 mg norethisterone acetate (Activelle) or a sequential combined HRT regimen consisting of 0.625 mg conjugated equine estrogens for 28 days plus 5 mg medrogestone for 14 days (Presomen). Mammograms were obtained at baseline and after 9 cycles (each 28 days) of treatment. RESULTS: The majority of women (approximately two-thirds in each treatment group) had no changes in mammographic breast density between baseline and the final study visit. There were no marked differences between treatment groups. Approximately 20% of women in both groups had a slight increase in mammographic density. Only 10-14% of women in both groups had a pronounced increase in mammographic density. The analyses of the degree of change showed no remarkable differences between treatments. CONCLUSION: These results indicate that the increase in mammographic density with a low-dose continuous combined HRT regimen is no greater than that with a sequential combined HRT regimen. The type of progestogen does not have an impact on the extent of mammographic density changes.