Low dose dexamethasone as treatment for women with heavy menstrual bleeding: A response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM).

BACKGROUND: The symptom of heavy menstrual bleeding (HMB) diminishes quality-of-life for many mid-age women and imposes substantial societal burden. We investigated our hypothesis that HMB reflects impaired endometrial vasoconstriction due to endometrial glucocorticoid deficiency. Does reversing this deficiency, by short-term luteal-phase treatment with exogenous glucocorticoid (dexamethasone), ameliorate HMB? METHODS: In our Bayesian response-adaptive parallel-group placebo-controlled randomised trial, five pre-planned interim analyses used primary outcome data to adjust randomisation probabilities to favour doses providing most dose-response information. Participants with HMB, recruited from Lothian (Scotland) NHS clinics and via community invitations/advertisements, were aged over 18 years; reported regular 21-42 day menstrual cycles; and had measured menstrual blood loss (MBL) averaging ≥ 50 mL over two screening periods. Identically encapsulated placebo, or one of six Dexamethasone doses (0·2 mg, 0·4 mg, 0·5 mg, 0·6 mg, 0·75 mg, 0·9 mg), were taken orally twice-daily over five days in the mid-luteal phase of three menstrual cycles. Participants, investigators, and those measuring outcomes were masked to group assignment. Primary outcome, change in average MBL from screening to 'treatment', was analysed by allocated treatment, for all with data. TRIAL REGISTRATION: ClinicalTrials.gov NCT01769820; EudractCT 2012-003,405-98 FINDINGS: Recruitment lasted 29/01/2014 to 25/09/2017; 176 were screened, 107 randomised and 97 provided primary outcome data (n = 24,5,9,21,8,14,16 in the seven arms, placebo to 1·8 mg total daily active dose). In Bayesian normal dynamic linear modelling, 1·8 mg dexamethasone daily showed a 25 mL greater reduction in MBL from screening, than placebo (95% credible interval 1 to 49 mL), and probability 0·98 of benefit over placebo. Adverse events were reported by 75% (58/77) receiving dexamethasone, 58% (15/26) taking placebo. Three serious adverse events occurred, two during screening, one in a placebo participant. No woman withdrew due to adverse effects. INTERPRETATION: Our adaptive trial in HMB showed that dexamethasone 1·8 mg daily reduced menstrual blood loss. The role of dexamethasone in HMB management deserves further investigation. FUNDING: UK MRC DCS/DPFS grant MR/J003611/1.

Clinical investigation of fertility after uterine artery embolization.

BACKGROUND: Uterine artery embolization is an effective and safe technique for the treatment of uterine fibroids, but its use remains controversial for women who wish to procreate. OBJECTIVE: This study aimed to study the clinical, anatomic, and obstetrical results of uterine artery embolization in patients of childbearing age not eligible for myomectomy. STUDY DESIGN: This was a retrospective cohort study of 398 female patients under the age of 43 years who were treated by uterine artery embolization between 2003 and 2017 for symptomatic fibroids and/or adenomyosis. Uterine artery embolization was performed according to a standardized procedure (fertility-sparing uterine artery embolization technique), with ovarian protection in the event of dangerous utero-ovarian anastomosis. Magnetic resonance imaging and pelvic ultrasounds were performed before and after uterine artery embolization. RESULTS: The overall clinical success rate (ie, resolution of preembolization symptoms such as heavy menstrual bleeding, iron-deficiency anemia, pelvic pressure) was 91.2%, and there were no major complications. One year after uterine artery embolization, we observed a mean 73% reduction in myoma volume. A total of 108 patients (49.3%) presented with dangerous utero-ovarian anastomosis and 33 (14.5%) benefited from ovarian protection. In our group, there were 148 pregnancies and 109 live births; 74 children were born at term; 23 were born preterm, on average at 35.12±2.78 weeks. Including preterm births, the mean birthweight and birth length of the children were within normal limits. Restoration of uterine anatomy and ovarian protection were identified as the main predictive factors for obstetrical success. Restoration was also a major predictive factor for clinical success and was associated with a lower rate of miscarriage. CONCLUSION: This study provided detailed clinical and obstetrical outcomes for 398 female patients who underwent uterine artery embolization for fibroid treatment; it contributes to the identification of anatomic and technical factors that could have an impact on fertility after uterine artery embolization. Further controlled clinical trials are needed to confirm our findings and reevaluate this procedure's indications and limitations for women with a desire to procreate.

Severe primary hypothyroidism in an apparently asymptomatic 19-year-old woman: a case report.

BACKGROUND: Hypothyroidism is diagnosed on the basis of laboratory tests because of the lack of specificity of the typical clinical manifestations. There is conflicting evidence on screening for hypothyroidism. CASE PRESENTATION: We report a case of an apparently healthy 19-year-old Kuwaiti woman referred to our clinic with an incidental finding of extremely high thyroid-stimulating hormone (TSH), tested at the patient's insistence as she had a strong family history of hypothyroidism. Despite no stated complaints, the patient presented typical symptoms and signs of hypothyroidism on evaluation. Thyroid function testing was repeated by using different assays, with similar results; ultrasound imaging of the thyroid showed a typical picture of thyroiditis. Treatment with levothyroxine alleviated symptoms and the patient later became biochemically euthyroid on treatment. CONCLUSION: There is controversy regarding screening asymptomatic individuals for hypothyroidism; therefore, it is important to maintain a high index of suspicion when presented with mild signs and symptoms of hypothyroidism especially with certain ethnic groups, as they may be free of the classical symptoms of disease.

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding. OBJECTIVE: This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding. STUDY DESIGN: This multicenter, randomized controlled, noninferiority trial was performed in 26 hospitals and in a network of general practices in the Netherlands. Women with heavy menstrual bleeding, aged 34 years and older, without a pregnancy wish or intracavitary pathology were randomly allocated to treatment with either the levonorgestrel-releasing intrauterine system (Mirena) or endometrial ablation, performed with a bipolar radiofrequency device (NovaSure). The primary outcome was blood loss at 24 months, measured with a Pictorial Blood Loss Assessment Chart score. Secondary outcomes included reintervention rates, patient satisfaction, quality of life, and sexual function. RESULTS: We registered 645 women as eligible, of whom 270 women provided informed consent. Of these, 132 women were allocated to the levonorgestrel-releasing intrauterine system (baseline Pictorial Blood Loss Assessment Chart score, 616) and 138 women to endometrial ablation (baseline Pictorial Blood Loss Assessment Chart score, 630). At 24 months, mean Pictorial Blood Loss Assessment Chart scores were 64.8 in the levonorgestrel-releasing intrauterine system group and 14.2 in the endometrial ablation group (difference, 50.5 points; 95% confidence interval, 4.3-96.7; noninferiority, P=.87 [25 Pictorial Blood Loss Assessment Chart point margin]). Compared with 14 women (10%) in the endometrial ablation group, 34 women (27%) underwent a surgical reintervention in the levonorgestrel-releasing intrauterine system group (relative risk, 2.64; 95% confidence interval, 1.49-4.68). There was no significant difference in patient satisfaction and quality of life between the groups. CONCLUSION: Both the levonorgestrel-releasing intrauterine system and endometrial ablation strategies lead to a large decrease in menstrual blood loss in women with heavy menstrual bleeding, with comparable quality of life scores after treatment. Nevertheless, there was a significant difference in menstrual blood loss in favor of endometrial ablation, and we could not demonstrate noninferiority of starting with the levonorgestrel-releasing intrauterine system. Women who start with the levonorgestrel-releasing intrauterine system, a reversible and less invasive treatment, are at an increased risk of needing additional treatment compared with women who start with endometrial ablation. The results of this study will enable physicians to provide women with heavy menstrual bleeding with the evidence to make a well-informed decision between the 2 treatments.

Vascular effect of levonorgestrel intrauterine system on heavy menstrual bleeding: is it associated with hemodynamic changes in uterine, radial, and spiral arteries?

The aim of this study was to evaluate the clinical and blood flow changes associated with the use of a levonorgestrel-releasing intrauterine device (LNG-IUD) in patients with idiopathic heavy menstrual bleeding (HMB). LNG-IUD was inserted into a total of 91 patients (39.5 ± 5.4 years) who were diagnosed with HMB. Uterine volume, ovarian volume, uterine, radial and spiral artery blood flow, Pictorial Blood Loss Assessment Chart (PBAC) scores, and other clinical and laboratory parameters were evaluated before and 12 months after insertion of LNG-IUD. Compared to pre-insertion values, LNG-IUD dramatically improved haemoglobin, PBAC scores, and endometrial thickness. Mean resistance indices of radial and spiral arteries significantly increased 12 months after insertion. Our study results suggest that a significant increase in the resistance indices of the intra-myometrial arteries in LNG-IUD users one year after insertion may be due to its local progestational effects, indicating a possible mechanism of LNG-IUD in reducing menstrual blood flow.Impact StatementsWhat is already known on this subject? The mechanisms of action of LNG-IUD on heavy menstrual bleeding include atrophy, decidualization and vascular changes of in the endometrium, resulting endometrial suppression. However, the exact mechanism to stop bleeding is not clear.What do the results of this study add? The present study suggests that one of the effects of the LNG-IUD on heavy menstrual bleeding is its ability to increase the resistance indexes of the intra-myometrial arteries.What are the implications of these findings for clinical practice and/or further research? These results will foster further studies on the effects of LNG-IUD on intra-myometrial arteries and will further assure clinicians on the vascular effect of LNG-IUD during management of heavy menstrual bleeding which includes hysterectomy as a final step.

Prevalence and knowledge of heavy menstrual bleeding among gynecology outpatients by scanning a WeChat QR Code.

The aim of this study was to assess menstrual blood loss (MBL) and knowledge of heavy menstrual bleeding (HMB) among the gynecology outpatients at Peking University People's Hospital, by scanning a WeChat (a social media application software developed by Tencent) QR Code using a mobile phone or tablet. This survey was conducted among outpatients who were treated at the Gynecology Department of Peking University People's Hospital between September 2016 and November 2016. All participants filled up the questionnaires and scales through WeChat: general information questionnaire, Pictorial Blood Loss Assessment Chart (PBAC), Menorrhagia Multi-Attribute Quality-of-Life Scale (MMAS), and HMB knowledge questionnaire. Menstrual blood volume was assessed by the PBAC and self-assessment. Among the 1152 patients who filled out the survey, 77.4% (892/1152) had normal menstrual cycle (assessed by the patients), 15.6% (180/1152) patients described themselves as HMB, whereas the results from PBAC showed that 58.0% (668/1152) had HMB (PBAC ≥100). Among patients with PBAC ≥100, only 26.8% (179/668) patients reported HMB through self-assessment. Regarding its impact on daily life, the MMAS scores of HMB patients (PBAC ≥100) were significantly lower compared to those with normal blood loss (P<0.001). Regarding the awareness to HMB, 63.2% (728/1152) of the patients were not familiar with HMB. HMB is a common abnormal uterine bleeding and is frequently found among Chinese gynecology outpatients. HMB has major impacts on a woman's quality of life, affecting both physical and emotional health domains. Since women generally have low levels of awareness and understanding of HMB, they could assess their blood loss using the PBAC, which they can forward to their health care provider using a mobile phone or tablet and the WeChat platform. This tool may be effortlessly used by the health care providers and patients to easily share HMB-related data.

Prolonged use of finasteride-induced gonadal sex steroids alterations, DNA damage and menstrual bleeding in women.

The aim of the present study was to examine the effect of prolonged use of finasteride on serum levels of dihydrotestosterone (DHT), estradiol (E2), progesterone, testosterone and androstenedione in women during the menstrual period. Further, to screen and compare the 5α-reductase activities through the expression of SRD5A1, SRD5A2 and AR gene and to determine the level of VEGF, VKOR and SAA gene expression and DNA damage. A total of 30 Saudi women aged between 25 and 35 years were enrolled in the study. The selected women were divided into two groups. The first group (n = 15) received 5 mg finasteride/day for prolonged period of one year and second group (n = 15) was taken as a healthy control. ELISA technique was used for measuring the serum levels of the targeted hormones, and Comet assay was used for checking the DNA integrity. Our findings revealed significant decrement of DHT, E2, progesterone and androstenedione levels and elevated levels of testosterone in group treated with daily oral doses of 5 mg finasteride/day compared with the control subjects. mRNA expression suggested that finasteride has concrete effects on the gene expression of the selected genes from the treated group in comparison with the control group. In addition, finasteride induced DNA damage, and heavy menstrual bleeding was noted in women treated with finasteride. In conclusion, the present findings revealed that finasteride has adverse health effects in women associated with gonadal sex steroids alterations, DNA damage and heavy menstrual bleeding with no consensus in the treatment of androgenetic alopecia in women.

Ulipristal acetate on quality of life and sexual function of women with uterine fibromatosis.

To evaluate quality of life and sexual function of childbearing-age women, affected by uterine fibromatosis undergoing medical treatment with ulipristal acetate. The data obtained by filling the questionnaires European Quality of Life Five-Dimension Scale and modified Female Sexual Function Index, were analyzed to assess UPA usefulness in improving QoL and sexual activity. A total of 139 patients affected by uterine fibromatosis undergoing conservative ulipristal acetate treatment were enrolled in this prospective observational cohort study. Seventy-one women (average age 46.5 years) answered the questionnaires: QoL and sexuality were evaluated before and after ulipristal acetate treatment. 59 patients (83.1%) had an improvement of QoL and general health state, with a reduction of VAS score after ulipristal acetate treatment. EQ-5D-5L showed a statistically significant improvement of usual act impairment, mobility, discomfort, anxiety/depression (p < .0005). There was no difference in personal care management after therapy. Modified FSFI showed a statistically significant improvement (p < .0001) of sexual satisfaction and sexual life. A not statistically significant improvement in dyspareunia was also highlighted. This study provides a clear picture about QoL impact on women and confirms the effectiveness of the ulipristal acetate in improving different aspects of daily and sexual life of patients undergoing medical treatment.

Bleeding changes after levonorgestrel 52-mg intrauterine system insertion for contraception in women with self-reported heavy menstrual bleeding.

BACKGROUND: The levonorgestrel 52-mg intrauterine system has proven efficacy for heavy menstrual bleeding treatment in clinical trials, but few data exist to demonstrate how rapidly the effects occur and the effects in women with self-reported heavy bleeding, as seen commonly in clinical practice. OBJECTIVE: Evaluate changes in bleeding patterns in women with self-reported heavy menstrual bleeding before levonorgestrel 52-mg intrauterine system insertion. STUDY DESIGN: A total of 1714 women aged 16-45 years old received a levonorgestrel 52-mg intrauterine system in a multicenter trial evaluating contraceptive efficacy and safety for up to 10 years. At screening, participants described their baseline menstrual bleeding patterns for the previous 3 months. Participants completed daily diaries with subjective evaluation of bleeding information for the first 2 years. For this analysis, we included women with at least 1 complete 28-day cycle of intrauterine system use and excluded women using a hormonal or copper intrauterine contraception in the month prior to study enrollment. We evaluated changes in menstrual bleeding and discontinuation for bleeding complaints per 28-day cycle over 26 cycles (2 years) in women who self-reported their baseline pattern as heavy. We also compared rates of amenorrhea, defined as no bleeding or spotting, within the entire study population in women with subjective heavy menstrual bleeding at baseline compared with those who did not complain of heavy menstrual bleeding. RESULTS: Of the 1513 women in this analysis, 150 (9.9%) reported baseline heavy menstrual bleeding. The majority of women reported no longer experiencing heavy menstrual bleeding by the end of cycle 1 (112/150, 74.7%) with even greater rates by cycle 2 (124/148, 83.8%). At the end of cycles 6, 13, and 26, 129 of 140 (92.1%; 95% confidence interval, 87.7%-96.6%), 114 of 123 (92.7%; 95% confidence interval, 88.1%-97.3%), and 100 of 103 (97.1%; 95% confidence interval, 93.8%-100%) women reported no heavy menstrual bleeding, respectively. After cycles 13 and 26, 63 of 123 (51.2%; 95% confidence interval, 42.4%-60.1%) and 66 of 103 (64.1%; 95% confidence interval, 54.8%-73.3%), respectively, reported their bleeding as amenorrhea or spotting only. A lower proportion of women with baseline self-reported heavy menstrual bleeding reported amenorrhea as compared with women in the overall study cohort without heavy menstrual bleeding at the end of 6 cycles (319 [25.5%] vs 21 [15.0%], P=.005) and 13 cycles (382 [34.4%] vs 26 [21.1%], P=.003); differences were not significant after 19 cycles (367 [37.2%] vs 36 [31.0%], P=.022) and 26 cycles (383 [43.5%] vs 38 [36.9%], P=.21). Only 4 (2.7%) women with baseline heavy menstrual bleeding discontinued for bleeding complaints (2 for heavy menstrual bleeding and 2 for irregular bleeding), all within the first year. CONCLUSION: Most women who self-report heavy menstrual bleeding experience significant improvement quickly after levonorgestrel 52-mg intrauterine system insertion. Discontinuation for bleeding complaints among women with baseline heavy menstrual bleeding is very low.

Guideline No. 389-Medical Management of Symptomatic Uterine Leiomyomas - An Addendum.

OBJECTIVES: The aim of this guideline is to provide clinicians with an update to the 2015 Clinical Practice Guideline on the Management of Uterine Fibroids. As new information and evidence has become available since 2015, the Gynaecology Clinical Practice Committee of the Society for Obstetricians and Gynaecologists of Canada has determined that an addendum to that document was necessary to inform members about treatment modalities for uterine fibroids. OUTCOMES: Implementation of this guideline update should optimize the decision-making process of women and their health care providers in proceeding with further investigation or therapy for uterine leiomyomas, having considered the disease process and available treatment options and reviewed the risks and anticipated benefits. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, and Cochrane Systematic Reviews in February 2015 to April 2018, using appropriate controlled vocabulary (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy, uterine artery embolization, hysterectomy, heavy menstrual bleeding, menorrhagia). The reference lists of articles identified were also searched for other relevant publications. Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to April 2018. Most of the unpublished data have not been evaluated scientifically. The product monograph was also reviewed up to December 31st, 2018. BENEFITS, HARMS, AND COSTS: The majority of fibroids are asymptomatic and require no intervention or further investigations. For symptomatic fibroids such as those causing menstrual abnormalities (e.g., heavy, irregular, and prolonged uterine bleeding), iron deficiency anemia, or bulk symptoms (e.g., pelvic pressure/pain, obstructive symptoms), hysterectomy is a definitive solution. However, it is not the preferred solution for women who wish to preserve fertility and/or their uterus. The selected treatment should be directed towards an improvement in symptomatology and quality of life. The cost of the therapy to the health care system and to women with fibroids must be interpreted in the context of the cost of untreated disease conditions and the cost of ongoing or repeat investigative or treatment modalities. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.

The impact of menstrual symptoms on everyday life: a survey among 42,879 women.

BACKGROUND: Menstrual symptoms such as dysmenorrhea, heavy menstrual bleeding, and perimenstrual mood disorders are known to be widespread among the general population. From studies in patients with endometriosis and premenstrual disorder, it has been shown that these symptoms can have a large impact on women's quality of life and account for substantial health care use. Furthermore, it is estimated that many women initially do not consult a doctor while facing menstrual symptoms. Consequently, the impact of menstrual symptoms on daily activities in the general population is unknown. OBJECTIVE: To obtain a nationwide overview of menstrual symptoms and their impact on everyday activities. STUDY DESIGN: Nationwide, cross-sectional, internet-based survey among 42,879 women aged 15-45 years, conducted from July to October 2017. OUTCOME MEASURES: presence of menstrual symptoms, pain or intensity score, impact on daily activities. RESULTS: Dysmenorrhea was the most common symptom, with a prevalence of 85%, followed by psychological complaints (77%), and tiredness (71%). During their menstrual period, 38% of all women reported not to be able to perform all their regular daily activities. From the women that had to skip tasks because of their symptoms, only 48.6% told their family that menstrual symptoms were the reason for the transfer of tasks. CONCLUSION: Menstrual symptoms are widespread among the general population. One in 3 women quit daily activities owing to menstrual symptoms. Half of all women did not mention menstrual complaints being the reason for transferring tasks in a family setting. These results must be interpreted with caution owing to the potential for selection bias. However, considering the impact of menstrual symptoms on daily activities in a large group of women, it is time to open the societal dialogue and improve education for both patients and doctors.

Characterizing adolescents with heavy menstrual bleeding and generalized joint hypermobility.

Patients with generalized joint hypermobility (JHM) may experience excessive bruising/bleeding, with heavy menstrual bleeding (HMB) commonly reported. We performed a retrospective review of 30 adolescents seen in a Young Women's Hematology Clinic with both HMB and JHM. We found that (1) a significant delay (mean 36 months, range 5-72) occurred between menarche and referral to specialty care, (2) HMB had moderate to severe impact on school and physical activities in 60% of patients, and (3) most patients (68%) required escalation of their initial therapy. We suggest providers consider JHM as a risk factor for a more complex clinical course.

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.

Inter-rater agreement in the diagnosis of adenomyosis by 2- and 3-dimensional transvaginal ultrasonography.

OBJECTIVES: To assess the inter-rater agreement of 2-dimensional (2D) and 3-dimensional (3D) transvaginal ultrasonography (TVUS) in the diagnosis of adenomyosis. METHODS: This prospective study included premenopausal women (n = 96) with heavy menstrual bleeding, menstrual pain, or both who were scheduled for hysterectomy or transcervical resection of the endometrium. All women underwent real-time 2D TVUS and subsequently offline 3D TVUS, which was blinded to 2D TVUS, by a single expert rater and a single nonexpert rater for the diagnosis of adenomyosis based on standardized pattern recognition and junctional zone measurements. Three-dimensional TVUS was done on a computer with 3D volumes recorded during 2D TVUS by both raters. The expert rater reported the image quality of all 3D volumes (n = 192). Inter-rater agreement (Cohen's κ) was assessed for both techniques, and the improvement over time was assessed for 2D TVUS. RESULTS: Diagnosis of adenomyosis showed good (κ = 0.69) and poor (κ = 0.21) inter-rater agreement with 2D and 3D TVUS, respectively (P < .05). The agreement with 2D TVUS improved over time. The agreement with 3D TVUS was slightly better for expert-recorded 3D volumes (κ = 0.40), which also had better image quality (P < .05). The most reproducible 2D and 3D features were anechoic lacunae (κ = 0.52) and junctional zone irregularity (κ = 0.27), respectively. CONCLUSIONS: Standardized pattern recognition during real-time 2D TVUS may result in good agreement between expert and nonexpert raters for the diagnosis of adenomyosis. Offline 3D TVUS is less reproducible, and junctional zone measurements do not improve the inter-rater agreement. The low inter-rater agreement may be related to a lack of experience and low image quality of nonexpert-recorded 3D volumes.

Thrombin generation during a regular menstrual cycle in women with von Willebrand disease.

Fluctuations of the sex steroids during the menstrual cycle might significantly influence hemostasis. This association, derived from a number of the observations on healthy women, is yet to be described in females affected by bleeding disorders. The aim of the current study was to assess the changes in hemostatic variables in women with vWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with healthy controls. The study group included 12 vWD-affected females with regular menstrual cycle, with none of them being prescribed any hormonal treatment. The control group consisted of 102 healthy females, matched for age and BMI. Within the vWD group FVIII and FX were both significantly higher during follicular phase than in luteal phase (p = 0.013 and p = 0.033 respectively). AT, FII, FVII and FX were higher in women with vWD, compared with controls during both phases of the menstrual cycle (p < 0.0005, p < 0.0005, p = 0.001 and p < 0.0005). In women with vWD, lag time and time to peak were prolonged during both phases of the menstrual cycle(p < 0.0005), while peak thrombin concentration was reduced (p = 0.003 and p = 0.002 during follicular and luteal phase respectively) compared to healthy peers. Lower levels of FVIII and FX during luteal phase may predispose women to the development of the menorrhagia - common complication of vWD. Women with vWD need more time to reach the peak thrombin concentration, while the latter still remains less than in healthy women. Higher levels of AT in vWD-affected females, compared to controls, may also contribute to the existing bleeding tendency in this cohort.

Evaluation and management of heavy menstrual bleeding in adolescents: the role of the hematologist.

Heavy menstrual bleeding (HMB) is frequently reported by adolescents. The role of the hematologist is threefold in evaluating such patients: (1) perform a clinical and laboratory evaluation for an underlying bleeding disorder on the basis of the degree of clinical suspicion, (2) identify and manage any concomitant iron deficiency, and (3) provide input to the referring provider regarding the management of HMB, particularly for patients with identified hemostatic defects. Several clues in the menstrual history should raise suspicion for an underlying bleeding disorder, such as menses lasting >7 days, menstrual flow which soaks >5 sanitary products per day or requires product change during the night, passage of large blood clots, or failure to respond to conventional therapies. A detailed personal and family history of other bleeding symptoms should also be obtained. Iron deficiency with and without anemia is commonly found in young women with HMB. Therefore, it is important to obtain measures of hemoglobin and ferritin levels when evaluating these patients. Iron supplementation is often a key component of management in the adolescent with heavy menses and is still needed in those who have received packed red cell transfusions as a result of severe anemia. Strategies for decreasing menstrual blood flow are similar for adults and adolescents with heavy menses, with combined hormonal contraceptives recommended as first-line therapy. However, there are adolescent-specific considerations for many of these agents, and they must be incorporated into shared decision-making when selecting the most appropriate treatment.

Effect of baseline menstrual bleeding pattern on copper intrauterine device continuation.

BACKGROUND: Heavy menstrual bleeding is a leading cause of copper intrauterine device discontinuation. Thus, girls and women with heavy baseline menstrual bleeding may be at increased risk for early copper intrauterine device discontinuation. OBJECTIVE: Our objective was to assess if there was an association between baseline menstrual bleeding pattern prior to intrauterine device insertion and discontinuation rate at 12 months among study participants who chose copper intrauterine device at baseline. STUDY DESIGN: We performed a secondary analysis of the Contraceptive CHOICE Project, a prospective observational cohort study of 9256 girls and women offered no-cost contraception for 2-3 years. Included in our study were participants who chose copper intrauterine device for contraception and for whom method continuation data at 12 months were available. Prior to contraception initiation, participants were asked to qualify their menstrual bleeding over the past year as: light, moderate, moderately heavy, or heavy. Light bleeding corresponded to using ≤10 pads/tampons per period. Moderate, moderately heavy, and heavy bleeding corresponded to 11-20 pads/tampons, 21-30 pads/tampons, and >30 pads/tampons per period, respectively. Subjects were then categorized into either a "heavy" baseline group (those reporting moderately heavy or heavy bleeding at baseline), or a "not heavy" group (those reporting light or moderate bleeding). The 12-month continuation rate for each group was then calculated using Kaplan-Meier survival function, and hazard ratio for risk of discontinuation was evaluated using a Cox proportional hazard model to determine if moderately heavy or heavy bleeding at baseline was associated with early discontinuation. RESULTS: Of the 918 girls and women meeting the inclusion criteria for this analysis, 165 were in the heavy baseline bleeding group, while 753 were in the not heavy bleeding group. The 12-month continuation rates for groups were similar: 80.2% (heavy) and 85.0% (not heavy; P = .24). Patients reporting either moderately heavy or heavy baseline bleeding were not at increased risk for early discontinuation of copper intrauterine device (hazard ratio, 1.21; 95% confidence interval, 0.88-1.66). Our sample size provided >90% power to detect a clinically important difference of 15% (assuming 20% discontinuation rate in not heavy bleeding group and a 35% discontinuation rate in the heavy bleeding group). CONCLUSION: We did not find that girls and women who reported baseline moderately heavy or heavy menstrual bleeding were at increased risk for early discontinuation. Thus, we do not believe that girls and women with heavy menstrual bleeding should be discouraged from using this safe and highly effective form of contraception.