Reduction In Menstrual Blood Loss Research Articles

Hysteroscopic diode laser myolysis: from a case series to literature review of incisionless myolysis techniques for managing heavy menstrual bleeding in premenopausal women.

This case series examined the safety and effectiveness of hysteroscopic myolysis using laser-induced interstitial thermo-therapy (LITT) for treating heavy menstrual bleeding (HMB) in premenopausal women with FIGO type 1 or 2 uterine fibroids, not planning for future fertility. Additionally, a comprehensive review of innovative, minimally invasive, incisionless myolysis techniques was conducted. Women with HMB, sonographically diagnosed with a single FIGO type 1 or 2 fibroid, underwent hysteroscopic myolysis using the Leonardo® diode laser. Effectiveness was assessed via transvaginal ultrasound measurement of myoma size, volume and vascularization pre and post-procedure. Moreover, we also evaluated any improvements in symptoms using the Pictorial Blood Loss Assessment Chart (PBAC score) scores. The procedure resulted in significant HMB reductions and noticeable fibroid size, volume, and vascularization decrease in all three patients, with no reported complications. The literature review revealed both advantages and limitations of the minimally invasive, incisionless myolysis techniques. Hysteroscopic laser myolysis is a safe and effective therapeutic intervention for patients experiencing HMB, diagnosed with FIGO type 1 or 2 fibroids, and not planning for future fertility. The procedure resulted in significant reductions in menstrual blood loss and fibroid size. Despite the promising results, it is essential to note the limitations of this report, including its case series design, a small number of patients, and a short follow-up period. Further research is necessary to confirm these results.

Low-Dose Elagolix for the Treatment of Heavy Menstrual Bleeding in Patients With Uterine Leiomyomas: A Randomized Controlled Trial.

To evaluate the safety and efficacy of elagolix 150 mg once-daily monotherapy in patients with heavy menstrual bleeding associated with uterine leiomyomas. A phase 4, randomized, double-blind, placebo-controlled, 6-month treatment study was conducted in premenopausal patients aged 18-51 years with heavy menstrual bleeding (defined as menstrual blood loss greater than 80 mL during one menstrual cycle) associated with uterine leiomyomas. Patients were randomized 2:1 to receive elagolix 150 mg once daily or placebo. The primary endpoint was reduction in menstrual blood loss volume to less than 80 mL at the final month and at least a 50% reduction in menstrual blood loss volume from baseline to the final month. Of 82 randomized patients, 54 received elagolix 150 mg and 28 received placebo. With elagolix, 49.4% (95% CI 35.1-63.8%) of patients met the primary endpoint, compared with 23.3% (95% CI 7.2-39.5%) of patients who received placebo ( P =.035). Statistically significant differences between elagolix and placebo in mean reduction of menstrual blood loss from baseline were seen as early as month 1 ( P <.05 for months 1-3 and 5). Significantly more patients receiving elagolix experienced suppression of bleeding compared with placebo ( P =.036). Greater improvements were observed in the elagolix group (vs placebo) in the proportion of patients with amenorrhea, in hemoglobin concentrations, and in health-related quality of life. No serious or severe adverse events were reported for elagolix, compared with 7.1% of participants in the placebo group having serious adverse events (coronavirus disease 2019 [COVID-19] n=1, enlarged uvula n=1). Three patients (5.6%) discontinued elagolix due to adverse events. Elagolix 150 mg once-daily monotherapy significantly improved heavy menstrual bleeding associated with uterine leiomyomas compared with placebo in premenopausal patients. Treatment with elagolix 150 mg once daily was generally well-tolerated in this study, with no new safety signals. AbbVie Inc. ClinicalTrials.gov , NCT03886220.

Comparison of menstruation recovery after ultrasound-guided suction curettage in patients with cesarean scar pregnancy pretreated using high-intensity focused ultrasound and uterine artery embolization

Objectives To investigate the menstruation recovery after two therapeutic regimens, high-intensity focused ultrasound (HIFU) or uterine artery embolization (UAE) combined with ultrasound-guided suction curettage, for premenopausal women with cesarean scar pregnancy (CSP). Materials and methods Seventy patients with CSP treated with HIFU followed by ultrasound-guided suction curettage and 63 patients with CSP treated with UAE followed by ultrasound-guided suction curettage in our hospital were retrospectively reviewed. The treatment parameters and the menstrual blood loss (MBL) volume at 6 months after the two therapeutic regimens were compared between the two groups. Results There was no significant difference in treatment results between the two groups. With regard to postoperative MBL volume, 5 out of 70 patients in the HIFU group and 22 out of 63 patients in UAE group exhibited a reduction in MBL, respectively. Multivariate logistic regression revealed that hypomenorrhea was more likely to occur in the UAE group than in the HIFU group (UAE group vs. HIFU group; OR 11.328, 95% CI 3.158–55.871; p < 0.001). Conclusion Compared to UAE, HIFU has less influence on postoperative MBL volume, which may be a fertility-sparing option for patients with CSP.

Relugolix Combination Therapy in Women With Uterine Fibroids and Adenomyosis: LIBERTY 1 and 2 Trials [ID: 1345355

INTRODUCTION: Adenomyosis and uterine fibroids (UFs) may coexist in women with heavy menstrual bleeding (HMB). Relugolix combination therapy (Relugolix-CT: relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) is approved in the United States to treat HMB associated with UFs and moderate-to-severe pain associated with endometriosis. A post-hoc analysis of the pivotal, 24-week LIBERTY 1 and 2 studies evaluated the efficacy of Relugolix-CT versus placebo in the subgroup with ultrasound evidence of adenomyosis. METHODS: Baseline ultrasound images from women enrolled in the replicate, IRB-approved LIBERTY studies were evaluated for adenomyosis using predefined criteria. Primary endpoint: proportion of study completers with baseline adenomyosis who were HMB responders, defined as 50% or higher reduction in menstrual blood loss (MBL) volume from baseline and less than 80-mL MBL over the last 35 days. Pooled LIBERTY 1 and 2 results are presented. RESULTS: Of women who completed the LIBERTY studies, 111/610 (18.2%) had ultrasound evidence of adenomyosis at study entry. The prevalence of adenomyosis was similar between treatment groups (18.3% and 14.0% for Relugolix-CT and placebo, respectively). In this subgroup, 83.8% of women treated with Relugolix-CT were HMB responders versus 27.6% of women who received placebo; responders in the overall population were 72.3% and 16.8%, respectively. Additionally, 64.9% of women in this subgroup who received Relugolix-CT were amenorrheic over the last 35 days of treatment, versus 6.9% of women treated with placebo. CONCLUSION: Relugolix-CT effectively reduced HMB in women with UFs and adenomyosis through 24 weeks. Efficacy in this subgroup of women was generally similar to the overall study population.

The Minitouch Office Endometrial Ablation Procedure: Results from a Prospective, Multicenter, Pivotal Clinical Trial

<h3>Study Objective</h3> To evaluate safety and effectiveness of the Minitouch Office Procedure for treatment of heavy menstrual bleeding. <h3>Design</h3> Prospective, multicenter, single-arm, open label, pivotal clinical trial. Follow-up assessments were conducted at 24 hours, 2 weeks, 3-, 6-, and 12-months post-procedure. <h3>Setting</h3> Physician's Office - 5 US sites. <h3>Patients or Participants</h3> 114 premenopausal women with a history of heavy menstrual bleeding and a Pictorial Blood Loss Assessment (PBLAC) score >150. The demographics were as follows - mean ± SD (range): age 41.6 ± 4.6 (30-50) years, parity 2.3 ± 1.1 (0-5), sounding depth 8.6 ± 1.1 (7.0-11.0) cm, uterine cavity length 5.2 ± 0.8 (4.0-7.0) cm, and endometrium thickness 9.5 ± 4.2 (3.0-23.4) mm. <h3>Interventions</h3> All 114 Minitouch Office Procedures were performed without endometrial pretreatment or period timing. Cervical dilation was not required in 93% of the procedures since the device diameteris slim at 3.8mm. The procedure does not require a cavity integrity test or cavity sealing. <h3>Measurements and Main Results</h3> The primary effectiveness endpoint was reduction of menstrual blood loss to a PBLAC score ≤75 which was met by 90% (102/114) of the subjects, with 52% (59/114) of the subjects reporting amenorrhea. Pre-procedure, 47% of the subjects reported their bleeding limiting work either ‘quite a bit' or ‘extremely', and an additional 30% reported ‘moderately'. Post-procedure, the percentages reduced to 0% and 3% respectively. 81% (92/114) of the subjects were discharged within 30 minutes post-procedure, with an average pain score of 2.6 (scale 0 to 10) at discharge. There were no device or procedure-related serious adverse events. <h3>Conclusion</h3> The Minitouch Office Endometrial Ablation procedure is safe and effective. It can be performed in a physician's office, does not require endometrial pretreatment or period timing, and has a short recovery period.

Interventions for heavy menstrual bleeding; overview of Cochrane reviews and network meta-analysis.

Interventions for heavy menstrual bleeding; overview of Cochrane reviews and network meta-analysis.

Effectiveness of Levonorgestrel Releasing Intrauterine System in Perimenopausal Women with Heavy Menstrual Bleeding: A Prospective Study at a Teaching Hospital in India.

To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on heavy menstrual bleeding in perimenopausal women. This was a prospective, observational clinical study conducted on 42 perimenopausal women with heavy menstrual bleeding who met the study eligibility criteria. LNG-IUS was inserted in the postmenstrual phase following baseline evaluation. The patients were followed up at the 4, 12, and 24 weeks. Pictorial blood assessment chart (PBAC) score, hemoglobin and serum ferritin levels, and endometrial thickness were assessed before insertion and during the follow-up visits. Two patients (4.8%) were lost to follow-up, three patients (7.1%) opted for hysterectomy, two women (4.8%) experienced spontaneous expulsion and 35 (83.3%) women continued the usage. Menstrual blood loss assessed using the median PBAC score (interquartile range) significantly reduced (P < 0.001) from the pre-insertion level of 280 (246-306) to 124 (60-200) at 4 weeks to 45 (34-76) at 12 weeks and further to 32 (20-50) at the end of 24 weeks. Simultaneously, a significant (P < 0.001) improvement in the mean hemoglobin and serum ferritin levels and a significant (P < 0.001) decrease in endometrial thickness were observed. The most common side effect was spotting (50.0%) and vaginal discharge (38.1%). LNG-IUS causes a remarkable reduction in menstrual blood loss and marked improvement in dysmenorrhea. It also reduces anemia by improving the hemoglobin and ferritin levels. Thus, it can serve as an effective treatment option for heavy menstrual bleeding in perimenopausal women and prevent the need for a hysterectomy.

Efficacy of Oral Tranexamic Acid Versus Combined Oral Contraceptives for Heavy Menstrual Bleeding.

IntroductionHeavy menstrual bleeding (HMB) is characterized by high blood loss (>80 mL per cycle) at regular menstrual intervals. It can have an impact on a woman's bodily, mental, and/or material well-being. The etiology is varied and can be local, systemic, or iatrogenic. The occurrence of HMB is between 4% and 27%, depending on objective menstrual bleeding measurements and on high estimates based on subjective bleeding measures. This study was conducted to assess the efficacy of oral tranexamic acid versus combined oral contraceptive (COC) pills in the management of excessive menstrual bleeding.MethodologyA comparative study was conducted at the Obstetrics and Gynecology Department of Combined Military Hospital Peshawar, Pakistan, from October 2020 to March 2021. Women aged above 18 years who presented with heavy menstrual bleeding (HMB) were included in the study. The exclusion criteria included all women with contraindications to the use of tranexamic acid, such as lactating mothers, pregnancy, use of oral contraceptives or steroids, history of renal malfunction or stroke, family history of thromboembolic disease, and ovarian or endometrial carcinoma. Patients with diagnosed leiomyomas with a size between >1 and 10 cm were included in the study. Women were allocated randomly into group A who received oral tranexamic acid 3.9-4 g per day or group B who received oral COC pills containing a combination of ethinyl estradiol 30 μg and norgestrel 0.3 mg. The efficacy of treatment was considered successful if there was a mean reduction in menstrual blood loss that was significantly greater than the baseline values.ResultsThere were 178 patients in total, with 89 patients in each group. It was found that both oral tranexamic acid and combined oral contraceptives were equally effective in reducing the mean blood loss among patients and there was no statistical difference observed between the two groups. Upon stratification, it was found that both treatment groups were highly effective in younger age groups. Similarly, there was no significant difference in efficacy with respect to diabetes mellitus or hypertension. However, in individuals with leiomyomas, efficacy was significantly higher in patients who were in group B (combined oral contraceptives) (p = 0.004), and 46.1% of women in group A and 60.6% of women in group B did not experience any discomfort.ConclusionThe current study revealed that both oral tranexamic acid and COC pills were equally effective in reducing the mean blood loss among patients with HMB. It was further found that the efficacy of both therapies was significantly higher in younger age groups. The efficacy of therapy was significantly reduced with the increasing age of the patient. Moreover, it was found that patients with leiomyomas benefitted more significantly from COC pills. There were no severe adverse effects reported in the study. However, future researches can explore the long-term side effects of both therapies.In short, both therapies were comparable in terms of efficacy and safety. Heavy menstrual bleeding can negatively impact a woman, emotionally and physically. Therefore, it is encouraged that physicians use their expert judgment while prescribing either oral tranexamic acid or COC pills to patients with HMB.

A Comparative Study of Tranexamic Acid and Ethamsylate in Dysfunctional Uterine Bleeding

Abstract: Background: Dysfunctional Uterine Bleeding is irregular uterine bleeding that occurs in the absence of recognizable pelvic pathology, general medical disease or pregnancy. Bleeding may be excessively heavy or light and may be prolonged, frequent or random. About 1-2% of women with improperly managed an ovulatory bleeding eventually may develop endometrium cancer. There is less evidence which states the effectiveness of both the drugs because of which this study has been performed. Aim and Objectives: The objective of the study was to compare the efficacy of tranexamic acid and ethamsylate and to study the reduction in heavy menstrual bleeding. Materials and Methods: This study is a prospective comparative study which was conducted at Employee State Insurance Hospital, Ayanavaram, and Chennai. Of 56 patients recruited for the study with randomisation, 28 patients were in group A (tranexamic acid) and 28 patients were in group B (ethamsylate). Four patients were lost for follow up and two patients discontinued the given drugs. Hence 50 patients were included in the study. Group A received Tranexamic acid 500mg, BD, from 1 to 5 days of the menstruation for three consecutive cycles. Similarly Group B received Ethamsylate 500mg, BD from 1 to 5 days of the menstruation for three consecutive cycles. Results: Female patients between the age group of 39-45 years are mostly affected with dysfunctional uterine bleeding (DUB). PBAC mean score showed a significant reduction in menstrual blood loss both with tranexamic acid (293.84± 137.50) and ethamsylate (326.24±83.89), but tranexamic acid proved to be more efficacious. Hb level in tranexamic acid (12.96± 0.99) group was seen to be increased slightly when compared with ethamsylate group (12.024±1.07). The Endometrium thickness of the patients receiving tranexamic acid (3.404± 0.99) was between the normal ranges. Use of tranexamic acid and ethamsylate improved health-related quality of life. Conclusion: This study suggests that both tranexamic acid and ethamsylate are effective in management of dysfunctional uterine bleeding. Tranexamic acid was superior to ethamsylate in terms of effectiveness, reduction in blood loss and improvement in quality of life. Key words: Dysfunctional uterine bleeding, Endometrium thickness, Tranexamic acid, Ethamsylate, Menstruation.

O-136 Once-daily relugolix combination therapy results in sustained reduction in symptoms and improved quality of life in women with uterine fibroids treated over 52 weeks

Abstract Study question What is the effect of relugolix combination therapy (Relugolix-CT) on symptom burden and health-related quality-of-life (HR-QoL) in patients with uterine fibroids (UF) over 52 weeks? Summary answer Relugolix-CT demonstrated sustained, clinically meaningful improvement in patient-reported symptom severity and HR-QoL over 52 weeks in women with UF. What is known already In LIBERTY 1 and 2 randomized clinical trials, once-daily Relugolix-CT (40 mg relugolix, an oral gonadotropin-releasing hormone receptor antagonist, estradiol 1 mg, norethindrone acetate 0.5 mg) significantly reduced menstrual blood loss (MBL) and UF-associated pain versus placebo in women with UF and heavy menstrual bleeding (HMB), and was well tolerated, with bone mineral density (BMD) preservation through 24 weeks. In the LIBERTY long-term extension study, a sustained reduction in MBL was observed along with no new safety signals and BMD maintenance through 52 weeks. Relugolix-CT was previously shown to significantly improve patient-reported symptom severity and HR-QoL through 24 weeks. Study design, size, duration In the LIBERTY 1 and 2 studies, 770 premenopausal women with ultrasound-documented clinically significant UF and alkaline-hematin documented HMB were randomized 1:1:1 to Relugolix-CT for 24 weeks, relugolix 40 mg for 12 weeks followed by Relugolix-CT for 12 weeks, or placebo for 24 weeks. Women who completed the pivotal studies were eligible to enroll in the 28-week extension study (N = 477 enrolled). Patients included in the extension study received open-label once-daily Relugolix-CT. Participants/materials, setting, methods Changes from baseline to Weeks 24 and 52 in the Uterine Fibroid Symptom (UFS)-QoL symptom severity scale, Bleeding and Pelvic Discomfort scale (BPD; assessing distress due to HMB, passing blood clots, pelvic pressure/tightness); and HR-QoL (sub)scales were assessed. Higher symptom severity and BPD scores reflect higher severity and distress, respectively; higher HR-QoL scores indicate better outcomes. Least-squares mean changes were provided for the original pivotal-study randomized treatment groups Relugolix-CT and placebo. Main results and the role of chance A sustained improvement in symptom severity was observed for the Relugolix-CT group from baseline to Weeks 24 and 52, with LS mean changes of –36.9 and –37.3 points, respectively. In patients initially treated with placebo, small changes were observed at Week 24 (–10.8 points), whereas a greater reduction from baseline was demonstrated at Week 52 (–35.0 points) after transitioning to Relugolix-CT. Considering the BPD, measuring distress from key UF symptoms, LS mean changes of –50.9 and –51.3 points were observed in the Relugolix-CT group from baseline to Week 24 and 52, respectively. In patients initially treated with placebo, small changes were observed at Week 24 (–15.9 points), whereas a greater reduction from baseline was demonstrated at Week 52 (–48.6 points) after transitioning to Relugolix-CT. Treatment with Relugolix-CT also resulted in a sustained improvement in different aspects of HR-QoL. LS mean total HR-QoL score increased from baseline to Weeks 24 and 52 by 40.8 and 40.4 points, respectively. In patients initially treated with placebo, small changes were observed at Week 24 (11.4 points), whereas a greater increase from baseline was demonstrated at Week 52 (39.0 points) after transitioning to Relugolix-CT at Week 24. Limitations, reasons for caution The 28-week LIBERTY long-term extension study was non-comparative. Analyses were performed in a subset of patients who completed the LIBERTY pivotal studies and were eligible for the extension study. However, it is important to note that the demographic and baseline disease characteristics were similar between pivotal and long-term extension populations. Wider implications of the findings Relugolix-CT resulted in a sustained reduction in UF symptom burden, particularly in terms of distress from key UF symptoms, and a sustained improvement of HR-QoL over 52 weeks. Improvements observed after transitioning from placebo to Relugolix-CT at 24 weeks confirmed the positive effect of Relugolix-CT on UF-associated symptoms and HR-QoL. Trial registration number NCT03412890

Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis

ObjectiveTo determine if coexisting adenomyosis limits the efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy in reducing heavy menstrual bleeding in women with uterine fibroids.DesignPooled analysis of two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids [UF]-1 and UF-2).SettingA total of 153 gynecological clinical care settings in the United States and Canada.Patient(s)Premenopausal women (18–51 years) with >80 mL of menstrual blood loss (MBL)/cycle and uterine fibroids with and without coexisting adenomyosis diagnosed by ultrasound and/or magnetic resonance imaging at baseline.Intervention(s)Participants were randomized 1:1:2 to placebo, elagolix 300 mg twice daily alone, or elagolix 300 mg twice daily with estradiol 1 mg/norethindrone acetate 0.5 mg once daily.Main Outcome Measure(s)The primary endpoint was the proportion of women who had <80 mL of MBL during the final month and ≥50% reduction in MBL from baseline to the final month. Adverse events were monitored.Result(s)Of 786 women treated across the two trials, 16% (126 women) had coexisting adenomyosis. Among this subset, a significantly greater proportion of women who received elagolix with add-back therapy (77.1% [95% confidence interval, 66.2, 88.0]) met both primary endpoint criteria compared with women who received placebo (12.2% [95% confidence interval, 1.0, 23.4]). Adverse events most frequently reported in the elagolix with add-back adenomyosis subset were hot flushes (18.3%), nausea (11.7%), and night sweats (8.3%).Conclusion(s)Elagolix with add-back therapy significantly reduced heavy menstrual bleeding in women with uterine fibroids and coexisting adenomyosis, suggesting that elagolix efficacy was not adversely affected by the presence of adenomyosis (Elaris UF-1 and UF-2 Clinical-Trials.gov numbers, NCT02654054 and NCT02691494).

Oriahnn: New Drug Approved for Treating Heavy Menstrual Bleeding in Women With Uterine Fibroids.

To review data of elagolix plus estradiol and norethindrone acetate as add-back therapy for the treatment of heavy menstrual bleeding (HMB) in premenopausal women with uterine fibroids. Literature search of PubMed/MEDLINE and SCOPUS was performed using the search terms Oriahnn; elagolix, estradiol, norethindrone AND heavy menstrual bleeding; elagolix AND heavy menstrual bleeding; and gonadotropin-releasing hormone receptor antagonist AND heavy menstrual bleeding between January 1, 1996, to March 2, 2021. Additional data were obtained from prescribing information, references of identified articles, and abstracts from scientific meetings. Clinical trials and articles discussing elagolix plus add-back therapy for the management of HMB in women with leiomyomas were included. Phase 3 trials met the primary end point of menstrual blood loss (MBL) less than 80 mL at month 6 and at least a 50% reduction in MBL from baseline to the final month in 68.5% of women taking elagolix plus add-back therapy enrolled in UF-1 (8.7% placebo) and 76.5% of women in UF-2 (10% placebo). The most common adverse effects include hot flushes, nausea, headache, and night sweats. Women with symptomatic uterine fibroids can experience significant HMB resulting in distress, depression, and anxiety. Surgical intervention remains the most commonly recommended and chosen treatment. Elagolix plus add-back therapy is a nonsurgical, oral option. Elagolix plus add-back therapy is effective in reducing menstrual bleeding associated with uterine fibroids. However, there are several warnings and precautions that must be considered.

74. Use of the Levonorgestrel Intrauterine System in Adolescents and Young Adults with Heavy Menstrual Bleeding Due to a Bleeding Diathesis

<h3>Background</h3> Heavy menstrual bleeding (HMB) is a common problem among adolescent girls, exacerbated by Inherited Bleeding Disorders (IBD) and Joint Hypermobility (JH), including Ehlers-Danlos Syndrome (EDS). Studies have examined use of the levonorgestrel intrauterine system (LNG-IUS) in adult women with IBDs, showing reduction in menstrual blood loss and high continuation rates, but questions remain regarding rates of IUS expulsion and need for hemostatic agents with insertion. A few studies have addressed teens with IBDs or JH and LNG-IUS, reinforcing positive outcomes. However, study sizes were small, limiting conclusions regarding bleeding profiles, IUS expulsion, and long-term continuation. The objective of this study was to report on our patients with HMB and a bleeding diathesis using the LNG-IUS, including post-IUS bleeding profiles, rates of IUS expulsion and long-term continuation. <h3>Methods</h3> After IRB approval, we conducted a retrospective review of females, ages 12-25, who presented to our multidisciplinary bleeding clinic with HMB. Charts were selected using ICD-10 codes for HMB and diagnosis of an IBD or JH Disorder, treated with the LNG-IUS. Data was extracted from the chart by a single provider, including demographics, bleeding diagnosis, bleeding profiles before and after insertion, medications prescribed, continuation rate, and complications. Primary outcome was bleeding pattern after insertion. Secondary outcomes included rates of IUD expulsion and continuation. Descriptive statistics were reported as means, ranges and frequencies. LNG-IUS continuation rates were recorded and used to construct a survival graph. <h3>Results</h3> 35 patients met inclusion criteria. Mean age at menarche was 11.6. Mean age at insertion was 16.9 (range 11-23); majority were Caucasian (73.3%). Von Willebrand Disease was present in 16 patients (45.7%) and JH Disorders in 12 (34.3%, Table 1). Majority (91.4%) had tried at least one hormonal regimen prior to LNG-IUS. Follow up bleeding data was available on 33 patients (Table 1); one patient was excluded for same-day removal and one for removal at 2 weeks for cramping. Majority (81.8%) reported improvement in bleeding, with 60.6% reporting spotting or amenorrhea. IUS expulsion occurred in 3 patients (9.1%) despite hemostatic agents administered at insertion. Mean continuation was 5.08 years (95% CI 4.24-5.92), with 79% likelihood that patients kept their IUD in place for at least 2.5 years, and some up to 6 years (Figure 1). <h3>Conclusions</h3> The LNG-IUS is an effective treatment for adolescents and young adults with HMB and a bleeding diathesis, with high rates of amenorrhea. Rates of IUD expulsion appear higher than the general population during first 30 days, but long-term continuation rates remain high.

Effect of Vitamin D3 supplementation on symptomatic uterine leiomyoma in women with Hypovitaminosis D

Objective:The objective of this study is to evaluate the effect of Vitamin D3 on symptoms, uterine and leiomyoma volume in women with symptomatic leiomyoma and hypovitaminosis D.Materials and Methods:In this pilot, interventional, prospective study, 30 premenopausal women with uterine leiomyoma and concomitant hypovitaminosis D (<30 ng/ml) received Vitamin D3 in doses of 60,000 IU weekly for 8 weeks followed by 60,000 IU every 2 weeks for another 8 weeks. Change in symptoms, uterine, and leiomyoma volume was evaluated at 8 weeks and 16 weeks. Serum Vitamin D3 levels were repeated at 16 weeks of therapy.Results:A significant negative correlation was observed between the baseline 25-hydroxy Vitamin D (25(OH) Vitamin D3) and leiomyoma volume (r = –0.434, P < 0.001). There was significant reduction of menstrual blood loss by 29.89% (P = 0.003) and severity of dysmenorrhea, pelvic pain, and backache by 44.12%, 35%, and 50% (P < 0.001, 0.019, and 0.002), respectively, at 16 weeks. At end of therapy, there was 6% reduction in mean uterine volume and 11% in leiomyoma volume which was not significant. Serum 25(OH) Vitamin D3 was significantly higher than baseline level (17.44 ± 5.82 vs. 39.38 ± 8.22, P < 0.001) at end of therapy.Conclusion:Vitamin D3 supplementation is effective in reducing leiomyoma-related symptoms and stabilizing uterine and leiomyoma volume.

Treatment approved for heavy menstrual bleeding associated with fibroids

Oriahnn (AbbVie) is the first and only FDA-approved oral treatment for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. The treatment is a combination capsule containing elagolix 300 mg, estradiol 1 mg, and norethindrone 0.5 mg for the morning dose copackaged with a capsule of elagolix 300 mg for the evening dose. Uterine fibroids, common benign tumors in premenopausal women, can have a significant impact on quality of life, with symptoms such as heavy menstrual bleeding, pain, and bowel and bladder issues. Treatment options have included various surgical procedures such as hysterectomy and myomectomy, and medical therapies to reduce heavy menstrual bleeding (e.g., hormonal contraceptives, tranexamic acid, and NSAIDs). “Although surgical treatments, such as hysterectomy, are available, patients may not qualify for surgery or want the procedure,” said Christine P. Nguyen, MD, acting director, division of Urology, Obstetrics and Gynecology in FDA’s Center for Drug Evaluation and Research in an FDA news release. She noted that “various non-surgical therapies are used to treat fibroid-related heavy menstrual bleeding, but none have been FDA-approved specifically for this use.” The approval of Oriahnn now offers patients a nonsurgical option to help manage their condition. Uterine fibroids can be detected in up to 80% of women by the age of 50. Their growth is dependent on estrogen and progesterone, with the prevalence of fibroids increasing during a woman’s reproductive years. Race has also been identified as a risk factor for uterine fibroids, with Black women having a higher lifetime prevalence of fibroids and more severe symptoms compared with white women. Although some women may be asymptomatic, it is estimated that 20% to 50% of women seek either surgical or nonsurgical treatment to manage their symptoms. Oriahnn contains a gonadotropin-releasing hormone receptor antagonist (elagolix 300 mg), an estrogen (estradiol 1 mg), and a progestin (norethindrone acetate 0.5 mg). The elagolix results in a dose-dependent suppression of luteinizing hormone and follicle-stimulating hormone, leading to decreased concentrations of estradiol and progesterone and reduced bleeding associated with the uterine fibroids. The inclusion of estradiol and norethindrone in the morning dose helps achieve a balance between the reduction of heavy menstrual bleeding and associated hypoestrogenic adverse effects. The labeling states that the estradiol may reduce the bone loss that may occur with the reduction in estrogen levels from the elagolix, and the norethindrone may work to protect the uterus from the potential adverse endometrial effects from unopposed estrogen. The treatment may be given for up to 24 months. Approval was based on data from two randomized Phase III trials that evaluated data from 591 premenopausal women with heavy menstrual bleeding who were treated with elagolix 300 mg, estradiol 1 mg, and norethindrone 0.5 mg in the morning and elagolix 300 mg in the evening or placebo for 6 months. In both trials, more women who received the active treatment had reductions in menstrual blood loss compared with placebo from baseline to the final month of treatment. The most common adverse effects with Oriahnn from the clinical trials were hot flushes, headache, fatigue, and irregular vaginal bleeding. Numerous warnings and precautions are also listed in the label, with bone loss being one of them because of duration-dependent decreases in bone mineral density that may occur due to low estrogen levels. This effect may not be reversible and is the reason for limiting treatment to 24 months. Other warnings and precautions include thromboembolic disorders and vascular events, mood disorders, elevated blood pressure, and changes in menstrual bleeding patterns and the reduced ability to recognize pregnancy. Women should be counseled to use nonhormonal contraception while receiving treatment and for one week after discontinuing the drug.

Predictors of response for elagolix with add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids

BACKGROUND:Uterine fibroids are one of the most common neoplasms found among women globally, with a prevalence of approximately 11 million women in the United States alone. The morbidity of this common disease is significant because it is the leading cause of hysterectomy and causes significant functional impairment for women of reproductive age. Factors including age, body mass index, race, ethnicity, menstrual blood loss, fibroid location, and uterine and fibroid volume influence the incidence of fibroids and severity of symptoms. Elagolix is an oral gonadotropin-releasing hormone receptor antagonist that competitively inhibits pituitary gonadotropin-releasing hormone receptor activity and suppresses the release of gonadotropins from the pituitary gland, resulting in dose-dependent suppression of ovarian sex hormones, follicular growth, and ovulation. In Elaris Uterine Fibroids 1 and Uterine Fibroids 2, 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, treatment of premenopausal women with elagolix with hormonal add-back therapy demonstrated reduction in heavy menstrual bleeding associated with uterine fibroids.OBJECTIVE:This analysis aimed to evaluate the safety and efficacy of elagolix (300 mg twice a day) with add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate once a day) in reducing heavy menstrual bleeding associated with uterine fibroids in various subgroups of women over 6 months of treatment.STUDY DESIGN:Data were pooled from Elaris Uterine Fibroid-1 and Uterine Fibroid-2 studies, which evaluated premenopausal women (18–51 years) with heavy menstrual bleeding (>80 mL menstrual blood loss per cycle, alkaline hematin methodology) and ultrasound-confirmed uterine fibroid diagnosis. Subgroups analyzed included age, body mass index, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume (largest fibroid identified by ultrasound). The primary endpoint was the proportion of women with <80 mL menstrual blood loss during the final month and ≥50% menstrual blood loss reduction from baseline to final month. Secondary and other efficacy endpoints included mean change in menstrual blood loss from baseline to final month, amenorrhea, symptom severity, and health-related quality of life. Adverse events and other safety endpoints were monitored.RESULTS:The overall pooled Elaris Uterine Fibroid-1 and Uterine Fibroid-2 population was typical of women with fibroids, with a mean age of 42.4 (standard deviation, 5.4) years and a mean body mass index of 33.6 (standard deviation, 7.3) kg/m2 and 67.6% of participants being black or African American women. A wide range of baseline uterine and fibroid volumes and menstrual blood loss were also represented in the overall pooled study population. In all subgroups, the proportion of responders to the primary endpoint, mean change in menstrual blood loss, amenorrhea, reduction in symptom severity, and improvement in health-related quality of life were clinically meaningfully greater for women who received elagolix with add-back therapy than those who received placebo and consistent with the overall pooled study population for the primary endpoint (72.2% vs 9.3%), mean change in menstrual blood loss (−172.5 mL vs −0.8 mL), amenorrhea (50.4% vs 4.5%), symptom severity (−37.1 vs −9.2), and health-related quality of life score (39.9 vs 8.9). Adverse events by subgroup were consistent with the overall pooled study population.CONCLUSION:Elagolix with hormonal add-back therapy was effective in reducing heavy menstrual bleeding associated with uterine fibroids independent of age, body mass index, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume.

Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

Effect of Elagolix on Menstrual Blood Loss in Women With Uterine Fibroids and Adenomyosis [15B

INTRODUCTION: Evaluate the efficacy of elagolix with add-back therapy on menstrual blood loss (MBL) and safety in women with uterine fibroids (UF), heavy menstrual bleeding (HMB) and adenomyosis. METHODS: Pooled data from two investigational, IRB approved, 6-month, randomized, double-blind, placebo-controlled phase 3 studies, Elaris UF-1 and UF-2, was used to conduct a subset analysis in premenopausal women (18–51 years) with HMB (&gt;80mL MBL/cycle) associated with UF and baseline adenomyosis diagnosed by ultrasound and/or MRI. Primary endpoint was the proportion of women with &lt;80mL MBL during the final month and ≥50% reduction in MBL from baseline to final month. Secondary and other efficacy endpoints included proportion of women who achieved amenorrhea or suppression of bleeding during the final month. MBL was assessed with alkaline hematin method. Adverse events (AEs) and bone mineral density (BMD) were monitored. RESULTS: Of 790 women treated, 126 (16%) had adenomyosis at baseline. Proportion of responders for the primary endpoint was significantly greater (P&lt;.001) for elagolix+E2/NETA [76.8% (95% CI 65.84, 87.82)] compared to placebo [12.1% (95% CI 0.97, 23.15)]. Responder rate was significantly greater (P&lt;.001) for elagolix+E2/NETA versus placebo for amenorrhea and suppression of bleeding. These results, along with AEs and mean change in lumbar BMD from baseline to month 6, were consistent with the all-subject group. CONCLUSION: In women with HMB associated with UF and co-existing adenomyosis at baseline, elagolix +E2/NETA significantly reduced MBL versus placebo similar to the all-subject group suggesting that elagolix is effective in reducing HMB in women with UF despite the presence of adenomyosis.

Up to 12 Months of Elagolix Sustained Menstrual Blood Loss Reduction in Women With Uterine Fibroids [OP04-5D

INTRODUCTION: An investigational, IRB-approved, phase 3 extension study (Elaris UF-EXTEND) of two 6-month, phase 3 studies evaluated the efficacy and safety of an additional 6-months (up to 12-months) of elagolix (oral gonadotropin-releasing hormone antagonist) with hormonal add-back therapy in women with heavy menstrual bleeding (HMB) and uterine fibroids (UF). METHODS: Women who received elagolix 300 mg twice-daily with add-back (estradiol 1 mg/norethindrone acetate 0.5 mg once-daily [E2/NETA]) or elagolix alone in the preceding studies continued the same treatment for an additional 6-months in the extension study. Primary endpoint was the percentage of women with menstrual blood loss (MBL) &lt;80 mL during final month of treatment and ≥50% MBL reduction from baseline to final month of treatment; MBL measured by alkaline hematin method. Safety assessments included bone mineral density (BMD) changes. RESULTS: 433 women who completed the 6-month treatment period in either of the two preceding studies were enrolled in the extension study. In women who received up to 12-months of elagolix+E2/NETA, 87.9% met the primary endpoint; 74.8% had suppression of bleeding (no bleeding, spotting allowed) at final month; 72.5% with baseline hemoglobin ≤10.5g/dL had an hemoglobin increase &gt;2 g/dL at extension month 6. Mean baseline MBL (mean±SD=224.7±147.9 mL) was reduced with elagolix+E2/NETA as early as extension month 1 (mean [95% CI]=-186.5 [-209.2, -163.9] mL) and sustained through extension month 6 (mean [95% CI]=-221.4 [-239.11, -183.68] mL). Mean BMD decreases from baseline to extension month 6 were significantly less with elagolix+E2/NETA than elagolix alone. CONCLUSION: Up to 12-months of elagolix+E2/NETA provided sustained MBL reduction in women with UF. Inclusion of add-back attenuated BMD decreases associated with elagolix alone.

Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids

BackgroundUterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding.MethodsWe conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal “add-back” therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation.ResultsA total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.ConclusionsElagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.)