Outcome of uterine functional structures protection by fertility preservative PUSH surgery in diffuse adenomyosis.

This study reports the outcomes of an innovative fertility-preserving surgery for the treatment of diffuse adenomyosis that is known as a surgery for protection of uterine structure for healing (PUSH Surgery). Developed at Peking University Shenzhen Hospital, PUSH Surgery aims to achieve radical excision of adenomyotic lesions by reconstructing the uterus with overlapping muscle flaps to promote optimal healing of the uterine wall and reduce the risk of scar rupture in subsequent pregnancies. PUSH Surgery was performed on 146 patients with diffuse adenomyosis, with uteri measuring from 8 to 16 gestational weeks and an average volume of 230 ± 150cm³. Regular follow-up was conducted for up to 156 months, revealing a significant reduction in VAS pain scores from 9.4 ± 1.2 before the surgery to 0.3 ± 0.8 and 0.6 ± 1.0 at 1 and 2 years post-surgery, respectively, with a continuous alleviation rate of 96.4% after the operations. Notably, 100% of patients with severe menorrhagia reported normal menstruation volumes within 2 years. Additionally, 31 patients attempted to conceive, resulting in a 58% postoperative pregnancy rate and a 60.0% intrauterine live embryo rate. Operation-related complications occurred in 2.7% of patients, with a 3.6% recurrence rate after more than 2 years of follow-up. Importantly, no cases of uterine rupture or severe complications were observed in the pregnant patients. In conclusion, PUSH Surgery offers a promising approach for the radical excision of adenomyotic lesions, promoting improved tissue healing and significant symptom relief.

Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use.

BACKGROUND: Heavy menstrual bleeding and pain are common reasons women discontinue intrauterine device (IUD) use. Copper IUD (Cu IUD) users tend to experience increased menstrual bleeding, whereas levonorgestrel IUD (LNG IUD) users tend to have irregular menstruation. Medical therapies used to reduce heavy menstrual bleeding or pain associated with Cu and LNG IUD use include non-steroidal anti-inflammatory drugs (NSAIDs), anti-fibrinolytics and paracetamol. We analysed treatment and prevention interventions separately because the expected outcomes for treatment and prevention interventions differ. We did not combine different drug classes in the analysis as they have different mechanisms of action. This is an update of a review originally on NSAIDs. The review scope has been widened to include all interventions for treatment or prevention of heavy menstrual bleeding or pain associated with IUD use. OBJECTIVES: To evaluate all randomized controlled trials (RCTs) that have assessed strategies for treatment and prevention of heavy menstrual bleeding or pain associated with IUD use, for example, pharmacotherapy and alternative therapies. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to January 2021. SELECTION CRITERIA: We included RCTs in any language that tested strategies for treatment or prevention of heavy menstrual bleeding or pain associated with IUD (Cu IUD, LNG IUD or other IUD) use. The comparison could be no intervention, placebo or another active intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. Primary outcomes were volume of menstrual blood loss, duration of menstruation and painful menstruation. We used a random-effects model in all meta-analyses. Review authors assessed the certainty of evidence using GRADE. MAIN RESULTS: This review includes 21 trials involving 3689 participants from middle- and high-income countries. Women were 18 to 45 years old and either already using an IUD or had just had one placed for contraception. The included trials examined NSAIDs and other interventions. Eleven were treatment trials, of these seven were on users of the Cu IUD, one on LNG IUD and three on an unknown type. Ten were prevention trials, six focused on Cu IUD users, and four on LNG IUD users. Sixteen trials had high risk of detection bias due to subjective assessment of pain and bleeding. Treatment of heavy menstrual bleeding Cu IUD Vitamin B1 resulted in fewer pads used per day (mean difference (MD) -7.00, 95% confidence interval (CI) -8.50 to -5.50) and fewer bleeding days (MD -2.00, 95% CI -2.38 to -1.62; 1 trial; 110 women; low-certainty evidence) compared to placebo. The evidence is very uncertain about the effect of naproxen on the volume of menstruation compared to placebo (odds ratio (OR) 0.09, 95% CI 0.00 to 1.78; 1 trial, 40 women; very low-certainty evidence). Treatment with mefenamic acid resulted in less volume of blood loss compared to tranexamic acid (MD -64.26, 95% CI -105.65 to -22.87; 1 trial, 94 women; low-certainty evidence). However, there was no difference in duration of bleeding with treatment of mefenamic acid or tranexamic acid (MD 0.08 days, 95% CI -0.27 to 0.42, 2 trials, 152 women; low-certainty evidence). LNG IUD The use of ulipristal acetate in LNG IUD may not reduce the number of bleeding days in 90 days in comparison to placebo (MD -9.30 days, 95% CI -26.76 to 8.16; 1 trial, 24 women; low-certainty evidence). Unknown IUD type Mefenamic acid may not reduce volume of bleeding compared to Vitex agnus measured by pictorial blood assessment chart (MD -2.40, 95% CI -13.77 to 8.97; 1 trial; 84 women; low-certainty evidence). Treatment of pain Cu IUD Treatment with tranexamic acid and sodium diclofenac may result in little or no difference in the occurrence of pain (OR 1.00, 95% CI 0.06 to 17.25; 1 trial, 38 women; very low-certainty evidence). Unknown IUD type Naproxen may reduce pain (MD 4.10, 95% CI 0.91 to 7.29; 1 trial, 33 women; low-certainty evidence). Prevention of heavy menstrual bleeding Cu IUD We found very low-certainty evidence that tolfenamic acid may prevent heavy bleeding compared to placebo (OR 0.54, 95% CI 0.34 to 0.85; 1 trial, 310 women). There was no difference between ibuprofen and placebo in blood volume reduction (MD -14.11, 95% CI -36.04 to 7.82) and duration of bleeding (MD -0.2 days, 95% CI -1.40 to 1.0; 1 trial, 28 women, low-certainty evidence). Aspirin may not prevent heavy bleeding in comparison to paracetamol (MD -0.30, 95% CI -26.16 to 25.56; 1 trial, 20 women; very low-certainty evidence). LNG IUD Ulipristal acetate may increase the percentage of bleeding days compared to placebo (MD 9.50, 95% CI 1.48 to 17.52; 1 trial, 118 women; low-certainty evidence). There were insufficient data for analysis in a single trial comparing mifepristone and vitamin B. There were insufficient data for analysis in the single trial comparing tranexamic acid and mefenamic acid and in another trial comparing naproxen with estradiol. Prevention of pain Cu IUD There was low-certainty evidence that tolfenamic acid may not be effective to prevent painful menstruation compared to placebo (OR 0.71, 95% CI 0.44 to 1.14; 1 trial, 310 women). Ibuprofen may not reduce menstrual cramps compared to placebo (OR 1.00, 95% CI 0.11 to 8.95; 1 trial, 20 women, low-certainty evidence). AUTHORS' CONCLUSIONS: Findings from this review should be interpreted with caution due to low- and very low-certainty evidence. Included trials were limited; the majority of the evidence was derived from single trials with few participants. Further research requires larger trials and improved trial reporting. The use of vitamin B1 and mefenamic acid to treat heavy menstruation and tolfenamic acid to prevent heavy menstruation associated with Cu IUD should be investigated. More trials are needed to generate evidence for the treatment and prevention of heavy and painful menstruation associated with LNG IUD.

Heavy menstrual bleeding: assessment and management: Last updated 24 May 2021

This guideline covers assessing and managing heavy menstrual bleeding (menorrhagia). It aims to help healthcare professionals investigate the cause of heavy periods that are affecting a woman's quality of life and to offer the right treatments, taking into account the woman's priorities and preferences.

Vilaprisan in women with uterine fibroids: the randomized phase 2b ASTEROID 1 study.

OBJECTIVES: To assess the safety and efficacy of four vilaprisan doses (0.5-4.0 mg) in women with uterine fibroids. DESIGN: Randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Ninety-eight centers in 12 countries. PATIENT(S): Women aged 18-50 years with uterine fibroids and heavy menstrual bleeding were randomized equally to oral vilaprisan at 0.5, 1.0, 2.0, or 4.0 mg or placebo once daily. INTERVENTION(S): Treatment for 12 weeks, 24-week follow-up. MAIN OUTCOME MEASURE(S): Primary end point was absence of scheduled or unscheduled bleeding/spotting. Key secondary efficacy end points included volume of menstrual blood loss and change in fibroid volume. RESULT(S): A total of 309 patients were randomized, and 300 received treatment. Complete absence of bleeding/spotting was observed in 30%, 56%, 54%, and 60% of patients in the vilaprisan 0.5, 1.0, 2.0, and 4.0 mg groups, respectively, versus 1.7% with placebo. After 12 weeks, >83% of women achieved amenorrhea (<2 mL/28 days) with ≥1.0 mg vilaprisan versus 9% with placebo. Heavy menstrual bleeding stopped (but returned at a lower volume after treatment cessation) with ≥1.0 mg vilaprisan treatment. Reductions in fibroid volume of up to 41% were observed. Most patients receiving vilaprisan reported improvements in symptom severity. No safety concerns were identified in general safety, endometrial safety (by biopsy), laboratory values, and ultrasound examinations. CONCLUSION(S): ASTEROID 1 supports the efficacy of vilaprisan for the treatment of heavy menstrual bleeding associated with uterine fibroids. Daily oral treatment with vilaprisan 0.5-4.0 mg was well tolerated, and vilaprisan 2.0 mg once daily has been selected for further investigation. CLINICAL TRIAL REGISTRATION NUMBER: NCT02131662.

[Additional non-contraceptive effects of contraception: CNGOF Contraception Guidelines]. / Bénéfices non contraceptifs des contraceptions. RPC Contraception CNGOF.

Hormonal and intrauterine contraceptive methods provide women with highly efficient protection against undesired pregnancy. Additional non-contraceptive effects are now well documented. Combined hormonal contraceptives use, either through the oral transdermal and vaginal route, allow a reduction in menorrhagia, dysmenorrhea, functional ovarian cysts, benign breast and uterine disease, endometriosis-related pain and recurrence. A reduction in ovarian cancer risks, including in women with BRCA syndrome, endometrial and colon cancer is documented. This effect is prolonged for years after contraception discontinuation. Non-contraceptive benefits of progestin-only contraceptives are less documented. Use of the levonorgestrel IUD is associated with a reduction in menorrhagia, dysmenorrhea including in case of endometriosis. Copper IUD use is associated with a decrease in cervix and endometrial cancer risk.

Heavy menstrual bleeding: a global survey of health care practitioners' perceptions.

OBJECTIVES: This study sought to assess the perceptions of health care practitioners (HCPs) regarding heavy menstrual bleeding (HMB). METHODS: We developed an online survey for HCPs administered in 10 countries (Brazil, Canada, China, France, Germany, Korea, Russia, Spain, UK and USA), in order to assess their perceptions regarding HMB. RESULTS: We received 1032 responses. Most HCPs considered more than 7 days of bleeding abnormal. There was a significant difference in the definition of HMB between countries (p < .001). Most HCPs measured menstrual blood loss by the number of sanitary pads or tampons needed, followed by the impact on patients' daily activities. The majority of HMB patients (61%) were diagnosed as having a non-structural disorder with no causative identifiable coagulopathy. Patient acceptance and compliance were each relevant for the treatment decisions of half of the HCPs. Treatment options for idiopathic HMB featured mainly oral contraceptives and the levonorgestrel-releasing intrauterine system. Surgery was mentioned as a treatment option for idiopathic HMB by 44% of HCPs. CONCLUSION: The definition of HMB and HCP perceptions of HMB regarding diagnostic and therapeutic issues varied between countries. Surgery was mentioned as a treatment for idiopathic HMB by nearly half of HCPs. Clinician education is greatly needed to improve the management of women with HMB.

Outcome of patients with uterine fibroids after 3-month ulipristal acetate therapy.

OBJECTIVES: To determine the proportion and the characteristics of patients who did or did not respond after 3 months of ulipristal acetate (UPA) therapy. STUDY DESIGN: In this retrospective cohort study conducted in the University Hospital of Bordeaux (France) and University Medical Center Ljubljana (Slovenia), symptomatic non-menopausal patients with fibroids that qualified for surgery were pretreated by 3 months of oral UPA 5 mg/day. Clinical success was defined by normalization of the bleeding score, and/or regression of pelvic pain, and/or abdominal distension. Imaging success was defined by reduction in fibroid volume ≥ 25%. RESULTS: The clinical and imaging success rates were 54/66 (82%) and 39/66 (59%) respectively. The absence of previous pregnancy (p = 0.004) and the size of the dominant fibroid ≥ 80 mm (p = 0.004) were independent factors associated with clinical failure. Age <35 years (p = 0.02) was the only independent factor associated with imaging failure. CONCLUSION: Young women developing fibroids and/or women with large fibroids may be resistant to ulipristal acetate therapy.

Specifying the effects of physician's communication on patients' outcomes: A randomised controlled trial.

OBJECTIVE: To experimentally test the effects of physician's affect-oriented communication and inducing expectations on outcomes in patients with menstrual pain. METHODS: Using a 2×2 RCT design, four videotaped simulated medical consultations were used, depicting a physician and a patient with menstrual pain. In the videos, two elements of physician's communication were manipulated: (1) affect-oriented communication (positive: warm, emphatic; versus negative: cold, formal), and (2) outcome expectation induction (positive versus uncertain). Participants (293 women with menstrual pain), acting as analogue patients, viewed one of the four videos. Pre- and post video participants' outcomes (anxiety, mood, self-efficacy, outcome expectations, and satisfaction) were assessed. RESULTS: Positive affect-oriented communication reduced anxiety (p<0.001), negative mood (p=0.001), and increased satisfaction (p<0.001) compared to negative affect-oriented communication. Positive expectations increased feelings of self-efficacy (p<0.001) and outcome expectancies (p<0.001), compared to uncertain expectations, but did not reduce anxiety. The combination of positive affect-oriented communication and a positive expectation reduced anxiety (p=0.02), increased outcome expectancies (p=0.01) and satisfaction (p=0.001). CONCLUSION: Being empathic and inducing positive expectations have distinct and combined effects, demonstrating that both are needed to influence patients' outcomes for the best. PRACTICE IMPLICATIONS: Continued medical training is needed to harness placebo-effects of medical communication into practice.

Manifestation of tranexamic acid toxicity in chronic kidney disease and kidney transplant patients: A report of four cases and review of literature.

AIM: Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent commonly used for the prevention and treatment of bleeding disorders. The aim of this study is to describe the clinical manifestation of TXA toxicity in chronic kidney disease (CKD) patients. METHODS: From 2005 to 2014, we encountered four CKD patients who experienced severe complications related to TXA. Clinical manifestations and outcome of these patients were recorded. We then performed a qualitative literature review of published cases of TXA toxicity in CKD patients in the PubMed database from 1 January 1972 to 31 December 2015. RESULTS: In our centre, two peritoneal dialysis (PD) patients developed neurotoxicity after intravenous TXA use for surgical bleeding and one PD patient developed neurotoxicity after oral TXA use for post-polypectomy colonic bleeding. One kidney transplant recipient developed acute obstructive uropathy due to retention of blood clot at the pelvi-ureteric junction of graft kidney after taking oral TXA for menorrhagia. Dosage of TXA was not adjusted according to renal function in all cases. All of them recovered without permanent disability after TXA was stopped. From our literature search, we identified two cases of neurotoxicity (one PD, one stage 4 CKD patient), one case of retinal toxicity in a haemolysis (HD) patient, one case of ligneous conjunctivitis in a CKD patient, and one case of toxic epidermal necrolysis in a CKD patient. CONCLUSION: Neurotoxicity is a very common clinical manifestation of TXA toxicity in CKD patients. Thrombotic complication is rare. Dosage adjustment of TXA is essential in CKD patients.

Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency.

INTRODUCTION: Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available. AIM: The aim of this study was to assess safety and efficacy of a new, high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary FX deficiency. METHODS: Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL(-1) ) received 25 IU kg(-1) pdFX as on-demand treatment or short-term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end-of-study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters. RESULTS: Sixteen enrolled subjects (six aged 12-17 years; 10 aged 18-58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half-life were 2.00 (2.12; 1.79-2.37) IU dL(-1) per IU kg(-1) and 29.4 (28.6; 25.8-33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters. CONCLUSION: These results demonstrate that a dose of 25 IU kg(-1) pdFX is safe and efficacious for on-demand treatment and short-term prophylaxis in subjects with moderate or severe hereditary FX deficiency.

Choice of primary outcomes evaluating treatment for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem with a variety of treatment options and many studies have been performed evaluating treatment effects. Consistency in the choice and definition of primary and secondary outcomes is important for the interpretation of data and for the synthesis of data in systematic reviews or individual patient data meta-analysis (IPDMA). OBJECTIVE: To give insight into the primary endpoints and outcome measures chosen in randomised controlled trials (RCTs) and systematic reviews regarding the treatment of HMB. SEARCH STRATEGY: Published systematic reviews and RCTs. SELECTION CRITERIA: Full reports of RCTs or systematic reviews. DATA COLLECTION AND ANALYSIS: For RCTs, we used the primary outcomes, as they were used for the sample size calculation. For systematic reviews, all outcomes listed as primary were included. Four authors selected the studies. RESULTS: Twelve different primary outcomes were reported by 66 RCTs, most blood loss- related (44/66 studies). Amenorrhoea was the most common blood loss primary outcome (16/44 studies) and the Pictorial Blood Loss Assessment Chart (PBAC) was the most used measurement tool (27/44 studies). Satisfaction was the second most prevalent primary outcome measure (13/66 studies). In all, 14/26 (54%) systematic reviews prespecified a single primary outcome, whereas all other reviews used composite primary outcomes. Blood loss was the most studied outcome (12/26 reviews). CONCLUSIONS: The most used primary outcomes in HMB studies relate to blood loss but there is no consistency regarding the endpoints chosen or measurement tools used to describe blood loss. Standardising outcomes will aid valid comparison and interpretation of data pertaining to the treatment of HMB. TWEETABLE ABSTRACT: A standardised collection of outcomes in heavy menstrual bleeding research is urgently needed.

Long-Term Efficacy of Laparoscopic or Robotic Adenomyomectomy with or without Medical Treatment for Severely Symptomatic Adenomyosis.

BACKGROUND/AIMS: To determine the long-term efficacy of laparoscopic or robotic adenomyomectomy with or without gonadotropin-releasing hormone (GnRH) for the treatment of severely symptomatic adenomyosis. METHODS: Between August 2008 and May 2011, we prospectively observed 33 patients who underwent laparoscopic or robotic adenomyomectomy with uterine artery ligation for the treatment of symptomatic adenomyosis. Seventeen patients (52%) received 3-course GnRH agonist treatment after the adenomyomectomy. RESULTS: The mean operating time was 147.4 ± 52.0 min, and the mean blood loss was 36.1 ± 37.4 ml. Postoperative complications occurred in 5 patients, including 4 cases of febrile morbidity, 1 case of ileus and 1 case of pelvic abscess. Patients had statistically significant symptom relief during the 3-year follow-up period. Four of the 33 patients (12%) showed symptom relapse; 3 patients showed a relapse with dysmenorrhea and 1 patient showed a relapse with menorrhagia. There were no significant differences in terms of therapeutic outcomes between surgical-only and surgical-medical treatment. CONCLUSION: Laparoscopic or robotic adenomyomectomy was feasible and safe for women with severely symptomatic adenomyosis who requested uterine preservation. Moreover, this procedure provided long-term symptom control, regardless of postoperative GnRH agonist administration.

Outcome measures for heavy menstrual bleeding.

Heavy menstrual bleeding is one of the most commonly encountered gynecological problems. While accurate objective quantification of menstrual blood loss is of value in the research setting, it is the subjective assessment of blood loss that is of greater importance when assessing the severity of heavy menstrual bleeding and any subsequent response to treatment. In this review the various approaches to objective, subjective and semi-subjective assessment of menstrual blood loss will be discussed.

Intermediate and long-term outcomes following uterine artery fibroid embolization.

OBJECTIVE: To assess patients' satisfaction and the intermediate and long-term patterns of symptom progression following uterine artery fibroid embolization (UAE). STUDY DESIGN: Intermediate (2-6 years) and long-term (9-14 years) follow-up questionnaire survey to women who underwent UAE during the period 1996-2000, at a tertiary referral centre. RESULTS: The mean (SD) age of women at the time of embolization was 43 (5.58) years. A total of 142/197 (72.1%) women had the embolization in view of heavy menstrual periods, while 87/197 (44%) indicated a desire to retain fertility. 160/197 (81.7%) women who completed Q1 reported an improvement in menstrual symptoms compared to 41/80 (51.2%) for Q2 [p<0.01]. The majority indicated they would recommend the procedure to a friend (Q1: 165 (83.8%), Q2: 62/80 (77.5%)) [p=0.75]. 23/80 (28.8%) required further surgical treatment following UAE, and within the latter group, only 7/23 (30.4%) were satisfied with the embolization. 22/80 (27.5%) tried for a pregnancy following the procedure, and of these 3/22 (13.6%) had a live birth. The mean (SD) age at the menopause for women who returned Q2 was 49.1 (4.91) years. CONCLUSIONS: The majority of women were satisfied with the embolization and noted an improvement in menstrual symptoms. However, this improvement diminished over time following the embolization, and over a quarter of women required further surgical intervention. Findings from this study may provide useful information in counselling women undergoing UAE and help guide clinicians in their patient selection criteria when discussing the procedure.

Prophylaxis escalation in severe von Willebrand disease: a prospective study from the von Willebrand Disease Prophylaxis Network.

BACKGROUND: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may require von Willebrand factor (VWF) replacement therapy. There are little data on the use of prophylaxis in VWD, and none have been applied in a prospective, treatment escalation design. OBJECTIVE: Evaluate the effect of escalating dose prophylaxis in severe VWD. METHODS: Patients eligible for enrollment in this prospective study included those with type 1 VWD with VW factor activity-ristocetin cofactor ratio ≤ 20% and unresponsive to desmopressin, patients with type 2 VWD not responsive to desmopressin and all subjects with type 2B and type 3 VWD. Entry criteria were strictly defined, as were therapy escalation parameters and clinical data collection. RESULTS: Eleven subjects completed the study. Six had type 2A, and five had type 3 VWD. Six patients presented with epistaxis, three with GI bleeding, and two with joint bleeding. Seven had dose escalation above the first level. Among the 10 subjects with evaluable bleeding log data, use of prophylaxis decreased the median annualized bleeding rate from 25 to 6.1 (95% confidence interval of the rate difference: -51.6 to -1.7), and the median annualized bleeding rate was even lower (4.0; 95% confidence interval: -57.5 to -5.3) when the subjects reached their final dosing level. CONCLUSION: This is the first prospective study to demonstrate that prophylaxis with VW factor concentrates is highly effective in reducing mucosal and joint bleeding rates in clinically severe VWD.

Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy: results from the von Willebrand Disease Prophylaxis Network.

Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed in severe haemophilia A, may also be observed. The bleeding patterns of VWD can affect quality of life, and may be life-threatening. The von Willebrand Disease Prophylaxis Network is an international study group formed with the goal of investigating the role of prophylaxis in clinically severe VWD. The objective of the present study is to investigate the response to prophylaxis focusing primarily on epistaxis, joint bleeding, gastrointestinal bleeding, and heavy bleeding associated with menses. Data from 105 subjects, 10 enrolled in a prospective study and 95 in a retrospective study between 2008 and 2013, were available for analysis. The median annualized rate reductions in bleeding were significant for epistaxis (P < 0.0001), gastrointestinal bleeding (P = 0.0003), joint bleeding (P < 0.0001), and menorrhagia (P = 0.008). Doses on a group level were approximately the same prior to and during prophylaxis, but more patients with gastrointestinal bleeding had prophylaxis three or more times per week as well as higher dosages. Our study, which primarily used retrospective data, indicates that prospective studies are needed to better delineate the doses and dose intervals that should be used for prophylactic treatment of VWD.

Randomized comparison of bleeding patterns in women using a combined contraceptive vaginal ring or a low-dose combined oral contraceptive on a menstrually signaled regimen.

OBJECTIVES: To compare bleeding patterns for 12 months continuous use of a contraceptive ring [contraceptive vaginal ring (CVR)] and pill [combined oral contraceptive (COC)] on a menstrually signaled regimen and the effectiveness of 4 days "treatment withdrawal" to stop bleeding. STUDY DESIGN: Women, 66 to each group, were randomized to continuous use of a CVR (15 mcg ethinyl estradiol/150 mcg etonogestrel) or a low-dose pill (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for 360 days on a menstrually signaled regimen. Bleeding/spotting days, daily use of ring or pill, was recorded. Endpoint was the total number of bleeding/spotting days for each method over four 90-day reference periods (RP) plus the analysis of bleeding patterns using modified World Health Organization criteria. RESULTS: There was a reduction in the mean (±S.D.) number of bleeding/spotting days from RP1 (CVR 14.2±10; pill 16.6±10.9) to RP4 (CVR 8.8±9.6; pill 8.8±9.1). Fifteen percent of CVR and 4% COC users experienced amenorrhea or infrequent bleeding throughout the study. Amenorrhea increased over time (RP1 vs. RP4: CVR 10% vs. 21% and COC 2% vs. 30%). Compliance with the menstrually signaled regimen was poor. Ceasing hormones for 4 days stopped a bleeding episode within 5 days in the majority of episodes and many stopped spontaneously. CONCLUSION: Bleeding patterns with continuous use of the CVR and COC are similar and improve over 1 year of use. The unpredictability, but short duration, of bleeding episodes should be stressed during counseling. IMPLICATION: This information for clinicians and women about breakthrough bleeding patterns with use of a CVR or combined pill over 12 months using a menstrually signaled regimen will give women an indication of what to expect with continuous use.