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PubMed2002

Down-regulation of angiopoietin-1 expression in menorrhagia.

Angiogenesis is an essential component of endometrial repair and regeneration following menses. Perturbation of this process is associated with menorrhagia, a common gynecological disorder that results in excessive menstrual bleeding. Angiopoietin-1 (Ang-1) promotes vascular maturation via the Tie-2 receptor, while angiopoietin-2 (Ang-2) is its natural antagonist that destabilizes vessels and initiates neovascularization in the presence of vascular endothelial growth factor. To test the hypothesis that menorrhagia arises as a result of poor signal for vascular maturation, we have examined the expression of Ang-1, Ang-2, and Tie-2 in endometrium throughout the menstrual cycle from 30 normal women and 28 patients with menorrhagia. Ribonuclease protection assay and Western blot analysis showed Ang-2 expression was consistently higher than Ang-1 in normal endometrium throughout the cycle. However, with menorrhagia Ang-1 mRNA and protein were not detected or down-regulated, while Ang-2 was observed at similar levels in both normal and menorrhagic endometrium resulting in a greater than a 50% decrease in the ratio of Ang-1 to Ang-2 protein. In situ hybridization and immunohistochemical studies supported these findings and revealed cyclical changes in the expression of Ang-1 and Ang-2. These results suggest that the angiopoietin/Tie-2 system promotes vascular remodeling in endometrium and loss of normal Ang-1 expression may contribute to the excessive blood loss observed in menorrhagia.

Adult↗
PubMed1998

Frequency of inherited bleeding disorders in women with menorrhagia.

BACKGROUND: Although menorrhagia is a common gynaecological symptom, a specific cause is identified in less than 50% of affected women. We investigated the frequency of inherited bleeding disorders in women with menorrhagia. METHODS: Women referred for investigation of menorrhagia whose pelvis was normal on clinical examination and who had an estimated menstrual blood loss of more than 80 mL were studied. A detailed menstrual history and history about other bleeding symptoms was taken. The activated partial thromboplastin time, factor VIII activity, von-Willebrand-factor antigen and activity, and factor XI (FXI) were measured in all patients; further tests were done when results were at or outside the limits of the assays. FINDINGS: 150 women were screened. An inherited bleeding disorder was diagnosed in 26 (17%) patients: the disorders were von Willebrand's disease of mild (15) or moderate severity (three), mild FXI deficiency (four), mild von Willebrand's disease and FXI deficiency (one), combined von Willebrand's disease, FXI deficiency, and factor X deficiency (one), carriage of haemophilia-A gene (one), and platelet dysfunction (one). The frequency of von Willebrand's disease and FXI deficiency were 13% (95% CI 7.9-18.8%) and 4% (1.5-8.5%), respectively. Menorrhagia since menarche was noted in 11 (8.9%) of 123 women without a bleeding disorder compared with 13 (65%) of 20 women with von Willebrand's disease (p=0.001) and four (66.7%) of six women with FXI deficiency (p<0.001). INTERPRETATION: Inherited bleeding disorders are found in a substantial proportion of women with menorrhagia and a normal pelvis examination. We suggest that such patients should be investigated for these disorders-especially von Willebrand's disease-before invasive procedures are done.

Adult↗
PubMed2002

Quality of life instruments in studies of menorrhagia: a systematic review.

BACKGROUND: The use of quality of life (QoL) instruments in menorrhagia research is increasing but there is concern that not enough emphasis is placed on patient-focus in these measurements, i.e. on issues which are of importance to patients and reflect their experiences and concerns (clinical face validity). The objective was to assess the quality of QoL instruments in studies of menorrhagia. STUDY DESIGN: A systematic review of published research. Papers were identified through MEDLINE (1966-April 2000), EMBASE (1980-April 2000), Science Citation Index (1981-April 2000), Social Science Citation Index (1981-April 2000), CINAHL (1982-1999) and PsychLIT (1966-1999), and by manual searching of bibliographies of known primary and review articles. Studies were selected if they assessed women with menorrhagia for life quality, either developing QoL instruments or applying them as an outcome measure. Selected studies were assessed for quality of their QoL instruments, using a 17 items checklist including 10 items for clinical face validity (issues of relevance to patients' expectations and concerns) and 7 items for measurement properties (such as reliability, responsiveness, etc.). RESULTS: A total of 19 articles, 8 on instrument development and 11 on application, were included in the review. The generic Short Form 36 Health Survey Questionnaire (SF36) was used in 12/19 (63%) studies. Only two studies developed new specific QoL instruments for menorrhagia but they complied with 7/17 (41%) and 10/17 (59%) of the quality criteria. Quality assessment showed that only 7/19 (37%) studies complied with more than half the criteria for face validity whereas 17/19 (90%) studies complied with more than half of the criteria for measurement properties (P = 0.0001). CONCLUSION: Among existing QoL instruments, there is good compliance with the quality criteria for measurement properties but not with those for clinical face validity. There is a need to develop methodologically sound disease specific QoL instruments in menorrhagia focussing both on face validity and measurement properties.

Data Collection↗
PubMed1997

Menorrhagia--a search for epidemiological risk markers.

OBJECTIVE: To isolate epidemiological risk factors for menorrhagia. METHODS: Menstrual blood loss (MBL) of one bleeding episode of 182 healthy women was measured with the alkaline hematin method and the results were related to age, parity, body mass index and smoking habits. Multiple and logistic regression analysis was performed to isolate the variables that most influence MBL. Two consecutive menstrual episodes were measured in 117 women, to determine individual constancy. RESULTS: MBL increased significantly with age (Kruskal-Wallis, P < 0.03) and the percentage of women with menorrhagia was significantly higher above 40 years of age (Mann-Whitney's ranks sum test, P < 0.05). The odds ratio of parous:nulliparous women for menorrhagia was 2.27:1, but after adjustment for age this influence disappeared. Body mass index and smoking habits were not significantly related to menorrhagia. The mean difference between the MBL of two consecutive menstruations is 2.1 ml (S.E.: 1.7, 95% CI: -1.3 to 5.5 ml). CONCLUSIONS: Only age could be indicated as a risk marker for menorrhagia. Parity, body mass index and smoking habits appear to have no significant effect on MBL, when adjusted for age. The individual constancy in MBL between two consecutive cycles is very high and therefore one single measurement suffices in studies of MBL.

Adult↗
PubMed1998

Comparison of hysteroscopic endometrial resection and laparoscopic assisted vaginal hysterectomy for the treatment of menorrhagia.

BACKGROUND: To compare the advantages and disadvantages of the two endoscopic procedures, hysteroscopic endometrial resection and laparoscopic assisted vaginal hysterectomy (LAVH), in the treatment of menorrhagia. METHODS: Forty women requiring surgical treatment for menorrhagia underwent LAVH. These women were compared retrospectively with forty women having had endometrial resection for menorrhagia. The operations were performed between November 1991 and February 1995. RESULTS: Operating time, hospitalization and postoperative recovery were significantly shorter with endometrial resection than with LAVH. In the hysteroscopy group amenorrhea or hypomenorrhea was achieved in 80% of cases. Hysterectomy was performed in two cases (5%). In the hysteroscopy group all but three women (92%) were satisfied with the procedure, in the LAVH group all but one (97%). CONCLUSIONS: In the surgical treatment of menorrhagia both procedures are effective. LAVH is associated with a longer recovery period, but it offers a permanent relief of menorrhagia. Even though endometrial resection does not render all women treated amenorrhoic, the satisfaction rate during the follow-up period was high; it is a useful alternative with many short-term benefits.

Adult↗
PubMed2002

Menorrhagia from a haematologist's point of view. Part I: initial evaluation.

The evaluation of menorrhagia should no longer be solely the task of the gynaecologist. In women with ovulatory bleeding (regular cycles), the prevalence of von Willebrand disease (vWD) in about 15% of these, as well as disorders of platelet function and fibrinolysis causing menorrhagia, warrants an active role by the haematologist. Initial intake should include documentation of menorrhagia by the pictorial chart assessment of menstrual flow. Baseline characteristics of menstrual flow should also be documented, including the frequency of changing the sanitary pad on the heaviest day, use of more than one sanitary pad at a time, number of days lost from school/work and the impact of menses on various quality-of-life parameters. Menorrhagia since menarche, a past history of surgical- and/or dental-related bleeding and a past history of postpartum haemorrhage are items of the bleeding symptom audit that appear in part to predict vWD in women with menorrhagia. Epistaxis and easy bruising do not appear to be clearly discriminatory symptoms. Initial testing should include the complete blood cell count, prothrombin time, activated partial thromboplastin time, iron profile, serum creatinine, thyroid stimulating hormone level, factor VIII level, vWF antigen, ristocetin cofactor and platelet aggregation studies. Additional haemostatic studies may also include a factor XI level and euglobulin clot lysis time. This extensive medical evaluation should assure both the patient and the gynaecologist that the possibility of an underlying haemostatic disorder has been thoroughly investigated, to avoid the patient undergoing further costly procedures and surgical interventions if an underlying haemostatic disorder remains unrecognized.

Clinical Laboratory Techniques↗
PubMed2001

Bleeding disorders: A common cause of menorrhagia in adolescents.

OBJECTIVE: To determine the frequency of underlying bleeding disorders in adolescents with menorrhagia. STUDY DESIGN: We retrospectively reviewed the charts of all girls, aged 10 to 19 years, who presented to our children's hospital for inpatient or outpatient evaluation of menorrhagia between January 1990 and November 1998. RESULTS: At presentation, 9 of the 71 girls (13%) had thrombocytopenia (platelet count <150,000/microL; range, 5000-106,000/microL). The most common causes for thrombocytopenia were immune thrombocytopenic purpura (n = 5) and myelosuppression caused by chemotherapy (n = 2). Of 14 girls who underwent a more detailed hemostatic evaluation, 8 were given a diagnosis of a hereditary coagulation disorder: 6 had platelet function defects and 2 had type 1 von Willebrand disease. Excessive menstrual bleeding commonly results in anemia. One half of the total group had anemia (hemoglobin <12.0 g/dL). Seven girls (10%) had potentially life-threatening anemia (hemoglobin <5.0 g/dL). CONCLUSIONS: Acquired and congenital bleeding disorders are common causes of menorrhagia in adolescent girls. Severe anemia is a frequent complication of menorrhagia. We recommend that adolescents without thrombocytopenia who present with menorrhagia receive a comprehensive hemostatic evaluation, including testing for von Willebrand disease and platelet function defects.

Adolescent↗
PubMed2005

Temporary uterine artery occlusion for treatment of menorrhagia and uterine fibroids using an incisionless Doppler-guided transvaginal clamp: case report.

We report the successful treatment of a 43-year-old woman with menorrhagia and multiple uterine fibroids by temporary uterine artery occlusion. Using a Doppler-guided transvaginal clamp, her uterine arteries were non-invasively identified and occluded by mechanical compression against the cervix for 6 h. Following removal of the clamp, blood flow in the uterine arteries returned immediately. Menorrhagia symptoms were tracked with the Ruta Menorrhagia Severity Scale. Uterine and fibroid volumes were measured by analysis of magnetic resonance images. The patient's self-reported menorrhagia symptoms were significantly reduced at 6 months (70% reduction in Ruta score) and both uterine volume and fibroid volume had decreased by more than 44% at 6 months. This case report illustrates the potential applicability of a simple-to-use, non-surgical device for the treatment of menorrhagia and uterine fibroids by temporary uterine artery occlusion.

Adult↗
PubMed2005

Age and the prevalence of bleeding disorders in women with menorrhagia.

OBJECTIVE: A study was conducted to evaluate the frequency and types of hemostatic defects occurring in adolescent and perimenopausal-age women diagnosed with menorrhagia. METHODS: A total of 115 women with a physician diagnosis of menorrhagia, including 25 adolescent women, 25 perimenopausal-age women, and 65 women between the ages of 20 and 44, underwent comprehensive hemostatic testing for possible bleeding disorders. Frequencies of bleeding disorders were calculated and compared. RESULTS: Forty-seven percent of women were found to have hemostatic abnormalities, including platelet dysfunction, von Willebrand's disease, and coagulation factor deficiencies. Adolescents and perimenopausal-age women with menorrhagia were just as likely to have hemostatic abnormalities as were women aged 20 to 44. CONCLUSION: These results demonstrate that underlying bleeding disorders are frequently found in adolescent, postadolescent reproductive age, and perimenopausal-age women presenting with menorrhagia and suggest that women with menorrhagia should be considered for further hemostatic evaluation.

Adolescent↗
PubMed2004

Endometrial ablation for von Willebrand disease-related menorrhagia--experience with seven cases.

BACKGROUND: Endometrial ablation has recently gained popularity as a treatment of menorrhagia in the general population. In the von Willebrand disease (VWD) patient, intuitively, it would appear that the failure rate would be higher because of the underlying hypocoaguability increasing the likelihood for re-bleeding. In a consecutive series of seven patients, we assessed the efficacy and safety of endometrial ablation in VWD-related menorrhagia. PATIENTS AND METHODS: We performed a retrospective analysis using chart review and a 21-item questionnaire administered to seven (six type 1, one type 2A) women who underwent endometrial ablation between the years 1997 and 2001. Parameters assessed included operative complications, the development of abdominal pains, recurrence of menstrual bleeding post-ablation and the change in the pre-/post-ablation quality of life (QOL). Three patients underwent endomyometrial resection and one each underwent rollerball, thermal, electrocautery and balloon ablation. All patients were pre-treated with i.v. desmopressin (DDAVP) except the 2A patient who received Humate P. Mean age of the patient was 41 +/- 6 years and follow-up was for 45 months (range 31-73) post-ablation. RESULTS: No significant perioperative bleeding complications were observed in any of the patients. All patients initially responded (two amenorrhoea, four hypomenorrhoea, one moderate improvement). In all patients, QOL assessed by 10 parameters improved significantly following the ablation procedure, regardless of the specific technique used. However, at the end of follow-up, only one patient remained amenorrheic, one was hypomenorrheic, one had moderate improvement and four patients experienced recurrence of menorrhagia, three eventually requiring a hysterectomy at a median of 11 months post-ablation. CONCLUSION: Endometrial ablation appears to be a safe procedure that improves the QOL in patients with VWD-related menorrhagia. However, its long-term efficacy appears to be lower in VWD patients when compared with women with menorrhagia without VWD.

Adult↗
PubMed1998

Perceptions of women on the impact of menorrhagia on their health using multi-attribute utility assessment.

OBJECTIVE: To assess patient preferences regarding the treatment of menorrhagia using the multi-attribute utility methodologies, to produce a clinically applicable scale, and to assess health outcomes following treatment of menorrhagia. METHODS: Women referred to the gynaecology department for the treatment of menorrhagia were interviewed regarding the effects of menorrhagia on different aspects of their life. Their concerns were categorised into main components of health (domains). The relative importance of each domain was rated by the women using importance points which were distributed to represent the perceived importance of each domain. A series of statements (intra-domain statements) was developed for each domain, which described various possible conditions of that component of health. These were also rated using a one metre visual analogue scale with numerical anchor points at zero (worst) and 100 (best). RESULTS: The components of health considered most important were, in order of impact, family life, followed by physical health, work life, psychological health, practical difficulties and social life. The scores for the intra-domain statements were combined into a scale to allow the calculation of a final health state utility for a particular outcome based upon the statements the patient chooses within each domain. DISCUSSION: In planning treatment for menorrhagia clinicians can assess a woman's current perception of their health, using a simple to administer clinical scale.

Adult↗
PubMed2004

Benefits and risks of pharmacological agents used for the treatment of menorrhagia.

Menorrhagia affects the lives of many women. The assessment of menstrual flow is highly subjective and gauging the severity of the condition by objective assessment of menstrual blood loss is impractical. In treating menorrhagia, the primary aim should be to improve quality of life. Women are willing to undergo quite invasive treatment in order to achieve this. Drug therapy is the initial treatment of choice and the only option for those who wish to preserve their reproductive function. Despite the availability of a number of drugs, there is a general lack of an evidence-based approach, marked variation in practice and continuing uncertainty regarding the most appropriate therapy. Adverse effects and problems with compliance also undermine the success of medical treatment. This article reviews the available literature to compare the efficacy and tolerability of different medical treatments for menorrhagia. Tranexamic acid and mefenamic acid are among the most effective first-line drugs used to treat menorrhagia. Despite being used extensively in the past, oral luteal phase norethisterone is probably one of the least effective agents. Women requiring contraception have a choice of the combined oral contraceptive pill, levonorgestrel-releasing intrauterine system (LNG-IUS) or long-acting progestogens. Danazol, gestrinone and gonadotropin-releasing hormone analogues are all effective in terms of reducing menstrual blood loss but adverse effects and costs limit their long-term use. They have a role as second-line drugs for a short period of time in women awaiting surgery. While current evidence suggests that the LNG-IUS is an effective treatment, further evaluation, including long-term follow up, is awaited. Meanwhile, the quest continues for the ideal form of medical treatment for menorrhagia--one that is effective, affordable and acceptable.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Tranexamic acid: a review of its use in the management of menorrhagia.

Tranexamic acid (Transamin), Cyklokapron, Exacyl, Cyklo-f) is a synthetic lysine derivative that exerts its antifibrinolytic effect by reversibly blocking lysine binding sites on plasminogen and thus preventing fibrin degradation. In a number of small clinical studies in women with idiopathic menorrhagia, tranexamic acid 2-4.5 g/day for 4-7 days reduced menstrual blood loss by 34-59% over 2-3 cycles, significantly more so than placebo, mefenamic acid, flurbiprofen, etamsylate and oral luteal phase norethisterone at clinically relevant dosages. Intrauterine administration of levonorgestrel 20 microg/day, however, produced the greatest reduction (96% after 12 months) in blood loss; 44% of patients treated with levonorgestrel developed amenorrhoea. Tranexamic acid 1.5 g three times daily for 5 days also significantly reduced menstrual blood loss in women with intrauterine contraceptive device-associated menorrhagia compared with diclofenac sodium (150 mg in three divided doses on day 1 followed by 25 mg three times daily on days 2-5) or placebo. Tranexamic acid, mefenamic acid, etamsylate, flurbiprofen or diclofenac sodium had no effect on the duration of menses in the studies that reported such data. In a large noncomparative, nonblind, quality-of-life study, 81% of women were satisfied with tranexamic acid 3-6 g/day for 3-4 days/cycle for three cycles, and 94% judged their menstrual blood loss to be 'decreased' or 'strongly decreased' compared with untreated menstruations. The most commonly reported drug-related adverse events are gastrointestinal in nature. The total incidence of nausea, vomiting, diarrhoea and dyspepsia in a double-blind study was 12% in patients who received tranexamic acid 1g four times daily for 4 days for two cycles (not significantly different to the incidence in placebo recipients). In conclusion, the oral antifibrinolytic drug tranexamic acid is an effective and well tolerated treatment for idiopathic menorrhagia. In clinical trials, tranexamic acid was more effective at reducing menstrual blood loss than mefenamic acid, flurbiprofen, etamsylate and oral luteal phase norethisterone. Although it was not as effective as intrauterine administration of levonorgestrel, the high incidence of amenorrhoea and adverse events such as intermenstrual bleeding resulting from such treatment may be unacceptable to some patients. Comparative studies of tranexamic acid with epsilon - aminocaproic acid, danazol and combined oral contraceptives, as well as long-term tolerability studies, would help to further define the place of the drug in the treatment of menorrhagia. Nevertheless, tranexamic acid may be considered as a first-line treatment for the initial management of idiopathic menorrhagia, especially for patients in whom hormonal treatment is either not recommended or not wanted.

Antifibrinolytic Agents↗
PubMed2002

[Menorrhagia and inherited disorders of coagulation].

Menorrhagia, a common complaint among women, may be a manifestation of an underlying inherited disorder of coagulation. In this review, the most frequent hereditary bleeding disorders associated with menorrhagia are briefly analyzed. Particularly, the epidemiological, clinical and diagnostic characteristics of von Willebrand disease, factor VIII, factor IX and factor XI deficiencies are examined. The influence of external factors (age, phase of menstrual cycle and hormonal therapy) on coagulation factor levels is also analyzed. Finally, the main therapeutic options (such as hormonal therapy, tranexamic acid and desmopressin), for the treatment of menorrhagia in women with hereditary bleeding disorders are reviewed. Since inherited bleeding disorders are frequently associated with menorrhagia, the conclusion is drawn that an underlying congenital bleeding disorder should be ruled out in any woman with menorrhagia.

Blood Coagulation Disorders, Inherited↗
PubMed1986

Naproxen reduces idiopathic but not fibromyoma-induced menorrhagia.

To compare the effect of naproxen on idiopathic and myoma-induced menorrhagia, 11 women with myomatosus uterus and 14 women with idiopathic menorrhagia (menstrual blood loss greater than 80 mL) were treated in a double-blind trial with placebo or naproxen during four consecutive menstruations. Placebo had no effect on menstrual blood loss. Naproxen (500 to 1000 mg daily for five days) reduced menstrual blood loss by 35.7% in women with idiopathic menorrhagia, but it had no consistent effect on myoma-induced menorrhagia. No side effects occurred during naproxen use. Thus, naproxen may prove a suitable treatment for idiopathic but not for myoma-induced menorrhagia.

Adult↗
PubMed2004

Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year follow-up.

CONTEXT: Because menorrhagia is often a reason for seeking medical attention, it is important to consider outcomes and costs associated with alternative treatment modalities. Both the levonorgestrel-releasing intrauterine system (LNG-IUS) and hysterectomy have proven effective for treatment of menorrhagia but there are no long-term comparative studies measuring cost and quality of life. OBJECTIVE: To compare outcomes, quality-of-life issues, and costs of the LNG-IUS vs hysterectomy in the treatment of menorrhagia. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted between October 1, 1994, and October 6, 2002, and enrolling 236 women (mean [SD] age, 43 [3.4] years) referred to 5 university hospitals in Finland for complaints of menorrhagia. INTERVENTIONS: Participants were randomly assigned to treatment with the LNG-IUS (n = 119) or hysterectomy (n = 117) and were monitored for 5 years. MAIN OUTCOME MEASURES: Health-related quality of life (HRQL) as measured by the 5-Dimensional EuroQol and the RAND 36-Item Short-Form Health Survey, other measures of psychosocial well-being (anxiety, depression, and sexual function), and costs. RESULTS: After 5 years of follow-up, 232 women (99%) were analyzed for the primary outcomes. The 2 groups did not differ substantially in terms of HRQL or psychosocial well-being. Although 50 (42%) of the women assigned to the LNG-IUS group eventually underwent hysterectomy, the discounted direct and indirect costs in the LNG-IUS group (2817 dollars [95% confidence interval, 2222 dollars-3530 dollars] per participant) remained substantially lower than in the hysterectomy group (4660 dollars [95% confidence interval, 4014 dollars-5180 dollars]). Satisfaction with treatment was similar in both groups. CONCLUSIONS: By providing improvement in HRQL at relatively low cost, the LNG-IUS may offer a wider availability of choices for the patient and may decrease costs due to interventions involving surgery.

Adult↗
PubMed1996

On the value of menorrhagia as a predictor for coagulation disorders.

The value of menorrhagia as a predictor for mild bleeding disorders has been very little studied and the results are divergent. In the present study on 30 women with objectively verified menorrhagia, we found a significantly increased prevalence of von Willebrand's disease (20%). By keeping a strict sampling and laboratory routine, and by restricting sampling to cycle days 5-7, we also obtained a very low interindividual variation of von Willebrand factor and coagulation factor VIII. We conclude that menorrhagia is a valuable predictor for coagulation and platelet disorders, and that time of sampling is of importance. This should be considered in the investigation of menorrhagia, and can be a guideline in looking for mild bleeding disorders.

Adult↗
PubMed1981

Acute adolescent menorrhagia.

Acute menorrhagia in adolescence is a much underestimated clinical problem, often requiring urgent medical intervention. In a 9-year case review between January, 1971, and January, 1980, we looked at all admissions to a children's hospital for acute menorrhagia, where genital tract pathology had been excluded. A primary coagulation disorder was found in almost 20% of these 59 patients. One quarter of those with severe menorrhagia (hemoglobin less than 10 gm/100 ml), one third of those requiring transfusion, and one half of those presenting at menarche had such an underlying disorder. Therefore, proper screening and therapy are essential in all girls with menorrhagia. Conventional methods of hormonal control are only partially effective in these special cases.

Adolescent↗