Belimumabe para lúpus eritematoso sistêmico / Belimumab for systemic lupus erythematosus

CONTEXTO: O Lúpus Eritematoso Sistêmico (LES) é uma doença inflamatória crônica autoimune, multissistêmica, caracterizada pela produção de diversos autoanticorpos direcionados especialmente contra antígenos nucleares, geração de complexos imunes circulantes e ativação do sistema complemento, alguns dos quais causam lesão celular ou tecidual imunologicamente mediada. Atualmente, os tratamentos disponíveis no SUS são aqueles preconizados pelo Protocolo Clínico e Diretrizes Terapêuticas (PCDT) de LES. TECNOLOGIA: Belimumabe (Benlysta®). PERGUNTA: O uso do belimumabe associado à terapia padrão no tratamento de pacientes com LES é eficaz e seguro, quando comparado à terapia padrão (conforme preconizado no PCDT de LES)? EVIDÊNCIAS CIENTÍFICAS: Conforme seus resultados, o belimumabe é superior ao placebo como tratamento adjunto à terapia padrão no melhor controle da atividade de doença de pacientes com LES ativo (exceto nefrite ativa e grave e manifestações com envolvimento neurológico) nas avaliações realizadas na semana 52 de tratamento. Somente um estudo avaliou a eficácia na semana 76 de tratamento, não mostrando diferença estatisticamente significativa entre os grupos, demonstrando perda de efeito ao longo do tempo.Os principais eventos adversos foram artralgias, infecções do trato respiratório superior, cefaleia, fadiga e náuseas com perfil de segurança semelhante ao grupo placebo em todos os estudos. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Foi construído um modelo de impacto orçamentário com base na população tratada pelo Componente Especializado da Asistência Farmacêutica (CEAF) para LES. A estimativa foi de R$ 124.053.662,63 no primeiro ano e de R$ 697.183.992,46 ao longo dos 5 primeiros anos após a incorporação. DISCUSSÃO: O presente relatório foi elaborado como parte da conduta de revisão do PCDT de LES e tem por objetivo avaliar as evidências de eficácia e segurança do belimumabe no tratamento de LES, a fim de embasar a avaliação da CONITEC a respeito de sua incorporação na versão atualizada do PCDT. Há evidência fraca (em virtude da perda da eficácia em 76 semanas e segurança de longo prazo) para sugerir a incorporação do belimumabe como terapia adjunta no tratamento de pacientes com LES com mais de 18 anos que não responderam a terapia padrão conforme previsto no PCDT de LES excetuando-se os pacientes com nefrite lúpica ativa grave ou com lúpus ativo grave do sistema nervoso central. RECOMENDAÇÃO DA CONITEC: Os membros presentes deliberaram que o tema fosse submetido à consulta pública com recomendação preliminar desfavorável à incorporação do belimumabe para lúpus eritematoso sistêmico. CONSULTA PÚBLICA: Foram recebidas 93 contribuições técnico-científicas e 372 contribuições de experiência e opinião durante o período de consulta pública, entre 22/09/2017 e 11/10/2017. Dentre as contribuições técnico científicas, 90% foram contrárias à recomendação da CONITEC, algumas contribuições ressaltaram os resultados positivos do belimumabe em estudos clínicos, também foram anexados estudos que avaliaram a custo-efetividade do medicamento. Das contribuições de experiência e opinião, 63% declararam ser contrárias à recomendação da CONITEC, foram relatadas experiências de pacientes com o medicamento incluindo opiniões sobre sua eficácia e efeitos adversos. DELIBERAÇÃO FINAL: Aos 31 (trinta e um) dia do mês de janeiro de 2018, reuniu-se a Comissão Nacional de Incorporação de Tecnologias no SUS ­ CONITEC, regulamentada pelo Decreto nº 7.646, de 21 de dezembro de 2011, e os membros presentes deliberaram por unanimidade recomendar a não incorporação do belimumabe para lúpus eritematoso sistêmico. Foi assinado o registro de deliberação nº 326/2018. DECISÃO: Não incorporar o belimumabe para lúpus eritematoso sistêmico, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 19, de 10 julho de 2018, publicada no Diário Oficial da União nº 123, seção 1, página 97.

Patterns of care and burden of chronic idiopathic thrombocytopenic purpura in Brazil.

AIMS: Although several therapeutic options are available for chronic immune thrombocytopenic purpura (cITP), little is known about the treatment of cITP in Brazil. MATERIALS AND METHODS: A multi-center, retrospective chart review, observational study was designed to describe the treatment patterns, clinical burden, resources use, and associated costs for adult patients diagnosed with cITP and treated in public and private institutions in Brazil. Patient charts were screened in reverse chronological order based on their last visit post January 1, 2012. (All costs were calculated using 1.00 USD = 3.9571 BRL, from February 2016.) Results: Of 340 patient charts screened, 50 patients were eligible for inclusion in the study. Single-drug therapy (prednisone, dexamethasone, or dapsone) was the most commonly used treatment, followed by combination therapies (azathioprine + prednisone, azathioprine + prednisone + danazol, and prednisone + dapsone). Splenectomy was performed in 22% of patients after at least first-line treatment. Platelet count and number of bleeding episodes at diagnosis were 31,561.1/mm3 (SD = ±26,396.1) and 40 episodes, respectively; in first-line, 92,631.1/mm3 (SD = ±79,955.3) and 19 episodes, respectively; in second-line, 96,950.0/mm3 (SD = ±76,476.4) and 17 episodes, respectively. Private system patients had a higher median cost compared to public system patients (USD 17.49/month, range = 0-2,020.77 vs USD 9.51/month, range = 0-192.64, respectively). LIMITATIONS: This study does not allow conclusions for causal explanations due to the cohort study design, and treatment patterns represent only the practices of physicians who have agreed to participate in the study. CONCLUSIONS: The data indicate that available therapeutic strategies for second- and third-line therapies appear to be limited.

Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long-term results.

The efficacy of danazol was assessed in 50 patients with myelofibrosis and anemia using the recently revised criteria of the International Working Group for Myelofibrosis Research and Treatment. According to them, anemia response (clinical improvement) is defined as transfusion cessation in transfusion-dependent patients or an Hb increase >2 g/dl in patients without transfusion requirements, both maintained for at least 12 weeks. Median follow-up from danazol start was 36 months (interquartile range [IQR] 19.2-58.8). Anemia response was achieved in 15 patients (30 %), including 5 of the 27 with transfusion dependency (18.5 %) and 10 of the 23 without transfusion requirements (43.5 %). Median time to response was 5 months (IQR 4-7) and median duration of the response 14 months (IQR 10-21). Among responder patients, 5 discontinued therapy due to toxicity or personal decision and 1 died from spleen rupture while being in response. A trend for worse response was seen in transfusion-dependent patients (p = 0.055). A platelet increase >50 × 10(9)/l was observed in 3 of 13 thrombocytopenic patients, all of whom had moderate thrombocytopenia. Toxicity was usually moderate, leading to treatment withdrawal in only 4 patients. Danazol is effective in 30 % of patients with anemia-associated myelofibrosis. The responses are less frequent in patients with transfusion dependency.

Sistema intrauterino liberador de levonorgestrel para o tratamento da menorragia idiopática / Levonorgestrel-releasing intrauterine system for the treatment of idiopathic menorrhagia

A DOENÇA: Aspectos clínicos e epidemiológicos da doença: A menorragia é clinicamente definida como a perda sanguínea, durante o período menstrual, excessiva em quantidade ou número de dias (definidos como habituais naquela mulher). O sangramento excessivo é considerado na maioria dos casos, aquele que envolvem uma perda de sangue menstrual maior que 80 ml. Em um sentido mais amplo, a menorragia também é definida como a perda excessiva de sangue menstrual que interfere com a qualidade física, social, emocional e /ou material de uma mulher. Isso pode ocorrer por si só ou em combinação com outros sintomas. Esta condição não está associada com uma mortalidade significativa, no entanto, trata-se de causa comum de procura ao ginecologista. Deve-se distinguir a menorragia de outros diagnósticos ginecológicos comuns. Isso inclui a metrorragia (perda sanguínea, de origem corporal, fora do período menstrual), menometrorragia (perda sanguínea irregular e prolongada) e polimenorréia (sangramento com intervalos menores do que 21 dias). Muitas vezes estes termos recebem descrições e definições conflitantes. Em boa parte das mulheres que sofrem de menorragia, as patologias ou causas que levam à perda excessiva de sangue não podem ser identificadas, justificando dessa forma a denominação menorragia idiopática. . Esse diagnóstico é firmado após a realização de exames diagnósticos, como a ultrassonografia, e o descarte de outras condições que poderiam levar à desregulação ou sangramento em excesso, como endometriose, terapia de reposição hormonal, dentre outros. Outras causas como complicações da gestação (ectópica, aborto), doenças pélvicas (mioma, pólipo endometrial ou cervical, adenomiose, cervicite, grave infecção vaginal, carcinoma do trato reprodutivo, hiperplasia endometrial), doenças sistêmicas (distúrbios hemostáticos, distúrbios da tireóide, lúpus eritematoso sistêmico, insuficiência renal crônica, insuficiência hepática) e causas iatrogênicas (hormonioterapia, contraceptivos injetáveis, medicamentos como tranquilizantes, antidepressivos, anticoagulantes e corticoides) também devem ser afastadas. Os dados epidemiológicos da menorragia idiopática são bastante imprecisos, pela própria subjetividade ou dificuldade em se determinar um sangramento menstrual excessivo. Assim, os estudos trazem acometimentos entre 8,0-51,6% de mulheres com uma maior prevalência em mulheres com idade mais avançada. No Brasil, não há uma estatística nacional sobre a doença, mas um estudo realizado em 2011 na cidade de Pelotas-RS mostrou que a prevalêcia de mulheres com menorragia atendidas pelo SUS de 2006 a 2011 foi de 35,3%, com maior prevalência entre as mulheres mais velhas e com elevado número de gravidezes. TRATAMENTO RECOMENDADO: O tratamento médico da menorragia pode envolver tratamentos farmacológicos ou cirúrgicos, e a escolha do tratamento adequado deve levar em conta algumas condições individuais das mulheres, como idade, doença concomitantes, tratamentos anteriores, opção pela fertilidade e o próprio custo do tratamento, que estará relacionado à sua adesão ao tratamento. Como alternativas de tratamento para a menorragia temos: Antiinflamatórios não esteróides, Contraceptivos orais, Terapia com prostagênio, Agonistas do hormônio liberador de gonadotrofina, Danazol, Estrogênios conjugados, Ácido tranexâmico, Sistema intra-uterino liberador de levonorgestrel (SIU-LNG), Curetagem, Ablação endometrial, Histerectomia. A TECNOLOGIA: Levonorgestrel - O levonorgestrel é um progestógeno com atividade anti-estrogênica utilizado em ginecologia de diversas formas: como componente progestogênico em contraceptivos orais e na terapia de reposição hormonal ou isoladamente para contracepção em pílulas contendo somente progestógeno e implantes subdérmicos. O lenorgestrel também pode ser administrado na cavidade uterina por meio de um endoceptivo (SIU) possibilitando o uso de doses menores, com liberação diretamente no órgão-alvo. EVIDÊNCIAS CIENTÍFICAS: Além da análise dos estudos apresentados pelo demandante, a Secretaria-Executiva da CONITEC realizou busca na literatura por artigos científicos, com o objetivo de localizar a melhor evidência científica disponível sobre o tema. Para isso, foi considerada a estratégia de busca descrita no Quadro 3, tendo como principal critério de inclusão o tipo de estudo considerado a melhor evidência para avaliar a eficácia de uma tecnologia para tratamento, isto é, revisões sistemáticas e ensaios clínicos randomizados (ECR). Outro critério de inclusão foi estudos que avaliassem a eficácia e/ou segurança do dispositivo intrauterino liberador de levonorgestrel no tratamento de Menorragia Idiopática. Alguns critérios de exclusão foram estabelecidos: registros de ensaios controlados em andamento, revisões narrativas, estudos sobre outros medicamentos que não o de interesse, estudos que incluam outras indicações do medicamento, estudos de biologia molecular ou ensaios pré-clínicos (com modelos animais), estudos fase I/II, estudos sem grupo comparador, relatos ou séries de casos, e estudos escritos em outro idioma que não inglês, português ou espanhol. Não houve restrições com relação à data de publicação, sendo resgatados artigos até a data de 29/01/2013. CONSIDERAÇÕES FINAIS: As evidências atualmente disponíveis sobre eficácia e segurança do sistema intrauterino liberador de levonorgestrel 52mg mostram que o produto apresentou-se como alternativa possível a mulheres com menorragia idiopática, com resultados de redução do sangramento menstrual superior ao das terapias farmacológicas existentes e, em termos de melhora na qualidade de vida, similares ao da histerectomia, alternativa cirúrgica padrão-ouro com 100% de eficácia. No entanto, a evidência comparando diretamente os desfechos entre o uso do SIU-LNG e a histerectomia ainda é escassa, e não demonstrou superioridade em relação à histerectomia sob qualquer aspecto, sugerindo-se que estudos de longo prazo sejam realizados para avaliar as taxas de permanência e satisfação com o dispositivo, e se o tratamento cirúrgico está sendo de fato evitado ou apenas postergado. Mesmo considerando o fato de que a opção pelo SIU-LNG é menos invasiva e com menor potencial para complicações do que o procedimento cirúrgico da histerectomia, observou-se nos estudos uma alta taxa de descontinuação do uso do SIU-LNG pelas mulheres e posterior opção pela cirurgia. Considerando todas as limitações metodológicas e de impacto orçamentário, os resultados sugerem que a tecnologia demandada, no contexto do Sistema Único de Saúde, não apresentou superioridade clínica e pode não ser mais custo-efetiva que a histerectomia, procedimento padrão já incorporado ao SUS, com similaridade em relação aos aspectos de qualidade de vida, além de maior eficácia. Assim, o conjunto de argumentos à disposição configura-se como insuficiente para assegurar que a incorporação do produto, dentro da indicação e escopo oferecidos, apresenta reais e inequívocas vantagens para o sistema de saúde público brasileiro. DELIBERAÇÃO FINAL: Na 15º reunião ordinária, os membros do plenário da CONITEC discutiram todas as contribuições da consulta pública, no entanto nenhuma delas trouxe informações ou dados relevantes para a mudança da decisão. Houve consenso que o SIU-LNG não se aplica a toda a população-alvo apresentada pelo demandante, e que o SUS dispõe de outras opções terapêuticas farmacológicas para o tratamento desta condição, nos casos em que não é necessária a histerectomia. Assim, os membros da CONITEC presentes na 15º reunião ordinária, ratificaram, por unanimidade, a deliberação de não recomendar a incorporação do sistema intrauterino liberador de levonorgestrel 52mg para o tratamento da menorragia idiopática. DECISÃO: PORTARIA Nº 31, de 3 de julho de 2013 - Torna pública a decisão de não incorporar o sistema intrauterino liberador de levonorgestrel para o tratamento da menorragia idiopática no Sistema Único de Saúde (SUS).

Association of celiac disease and hereditary angioedema due to C1-inhibitor deficiency. Screening patients with hereditary angioedema for celiac disease: is it worth the effort?

OBJECTIVE: Hereditary angioedema due to C1-inhibitor deficiency is a life-threatening condition, which manifests as edematous attacks involving subcutaneous tissues and/or the upper airway/gastrointestinal mucosa. Celiac disease is a gluten-sensitive small intestinal disorder that can lead to severe villous atrophy, malabsorption, and malignancy. Both hereditary angioedema and celiac disease may present with abdominal symptoms. Our aim was to study the occurrence of celiac disease in the hereditary angioedema population, as well as to analyze the clinical course of cases with both diseases. METHODS: One hundred and twenty-eight patients with hereditary angioedema were screened for celiac disease, using serological methods [antiendomysial antibodies-immunoglobulin A (IgA), antiendomysial antibodies-IgG and tissue transglutaminase-IgA, tissue transglutaminase-IgG]. Clinical data of a child with hereditary angioedema and celiac disease diagnosed earlier were added to the dataset to be analyzed. Thus, the total number of patients was 129, comprising 107 adults and 22 pediatric patients. In patients with celiac disease, molecular genetics analysis (human leukocyte antigen-DQA1, human leukocyte antigen-DQB1) was carried out along with the introduction of a gluten-free diet and regular follow-up. RESULTS: Four out of the 22 children were diagnosed with celiac disease in our hereditary angioedema population. The prevalence of celiac disease among our pediatric patients with hereditary angioedema (22 children) was higher than in the general population (18.1 vs. 1.2%). Switching from the wheat starch-containing tranexamic acid product to danazol and introducing a gluten-free diet mitigated abdominal symptoms of hereditary angioedema. CONCLUSION: Similarities between the symptoms of hereditary angioedema and celiac disease may cause difficulties in differential diagnosis, as well as in choosing the appropriate therapy. In our opinion, screening hereditary angioedema patients for celiac disease is warranted if abdominal attacks or neurological symptoms persist despite adequate management. Complement testing is recommended whenever abdominal symptoms persist despite the histological and serological remission of gluten-sensitive enteropathy after the introduction of a gluten-free diet.

Premenstrual dysphoric disorder: burden of illness and treatment update.

Five percent of menstruating women have severe premenstrual symptoms and impairment of functioning defined as premenstrual dysphoric disorder (PMDD). Clinically significant premenstrual symptoms occur in at least an additional 20% of menstruating women. The diagnosis of PMDD should be confirmed by prospective symptom charting over 2 menstrual cycles to confirm the timing of the symptoms and to rule out other diagnoses. The burden of illness of PMDD includes disruption of parenting and partner relationships and decreased productivity in work roles. In addition, women with PMDD have increased use of health care services such as clinician visits and increased use of prescription medications and over-the-counter preparations. The etiology of PMDD is multifactorial. In particular, dysregulation of the serotonin and allopregnanolone systems is implicated. Several effective treatment options exist, including serotonergic antidepressant medications and an oral contraceptive that contains ethinyl estradiol and drosperinone. In addition, other hormones that suppress ovulation, anxiolytics, cognitive therapy, chasteberry and calcium may be helpful.

An open and randomized study comparing the efficacy of standard danazol and modified triptorelin regimens for postoperative disease management of moderate to severe endometriosis.

OBJECTIVE: To compare the efficacy of danazol and triptorelin (Decapeptyl CR, Ferring, Kiel, Germany) in the management of moderate and severe endometriosis in terms of symptom control and revised American Fertility Society (AFS) score reduction, and to evaluate the hormonal profile of patients treated with triptorelin every 6 weeks. DESIGN: Open and randomized trial. SETTING: Kwong Wah Hospital, a large public hospital in an urban location (Hong Kong). PATIENT(S): Forty patients after their first conservative operation for endometriosis, with surgical confirmation of revised AFS stage III or IV endometriosis. INTERVENTION(S): Postoperative 6 months' therapy of danazol or triptorelin every 6 weeks, postmedical therapy second-look laparoscopy. MAIN OUTCOME MEASURE(S): Symptom control and patients' tolerance during medical therapy, posttherapy revised AFS score, hormonal profile during triptorelin therapy. RESULT(S): Pain control was similar between danazol and triptorelin therapy. There was less breakthrough bleeding with triptorelin. More patients failed to complete the whole course of danazol because of its side effects. The revised AFS score at second-look laparoscopy did not show a significant difference between the two medications. Adequate pituitary suppression was observed with injection of triptorelin every 6 weeks. CONCLUSION(S): Lengthening of triptorelin administration intervals from 4 weeks to 6 weeks is effective in maintaining a hypoestrogenic state. Patients were more compliant with triptorelin than danazol. Thus, triptorelin injection every 6 weeks is more cost-effective than conventional regimens.

A cost effectiveness analysis of goserelin compared with danazol as endometrial thinning agents.

OBJECTIVE: To analyse the cost, effectiveness and cost effectiveness of two endometrial thinning agents prior to laser ablation for dysfunctional uterine bleeding: danazol and goserelin. SETTING: A district general hospital. DESIGN: A retrospective cost effectiveness analysis, from the perspective of the health service, based on data from an open, randomised, parallel group comparative study of 160 pre-menopausal women with dysfunctional uterine bleeding. METHODS: Within the trial, length of operation and duration of hospital stay was recorded for each woman. Resource use due to complications of surgery and adverse drug events was evaluated by one of the authors (R.G.). Additional surgery after completion of the study was collected using a postal questionnaire which was distributed to every woman who had undergone surgery. Resource use was costed using detailed unit costs from a specific NHS trust and from published sources. A cost effectiveness analysis was undertaken relating differential cost to differential rates of amenorrhoea at women's last point of follow up. RESULTS: Information on amenorrhoea was available from 138 women, of whom 111 had completed the questionnaire to indicate longer term follow up. Women who did not complete the clinical trial were not included in this economic evaluation. On average, women randomised to goserelin spent less time in theatre and on the ward. Based on longer term follow up, rates of retreatment were similar in the two groups. The mean (SD) health service cost of women in the goserelin group was pound sterling 323.84 (pound sterling 309.94), compared with pound sterling 243.45 (pound sterling 265.23) in the danazol group; median (range) costs were pound sterling 220.29 (pound sterling 191-pound sterling 2127) and pound sterling 159.76 (pound sterling 140-pound sterling 1426) in the two groups, respectively. These costs were significantly higher for goserelin (P = 0.0001). The goserelin group also had a higher rate of amenorrhoea (38.8% vs 28.6%, P = 0.23). Based on mean differences in cost, the incremental cost of goserelin per additional woman with amenorrhoea was pound sterling 788; based on median differences in cost the ratio was pound sterling 590. CONCLUSIONS: The shorter duration in theatre and stay in hospital provided a modest offset of the higher acquisition cost of goserelin, but the overall cost of management remained significantly higher than managing women with danazol. The rates of amenorrhoea indicated that goserelin was more effective at 24 weeks and approximately two years after surgery, although statistical significance was only achieved at 24 weeks. The economic impact of women withdrawn from treatment was not considered, but sensitivity analysis indicates that these women may have had a large effect on the overall result of this study. Purchasers will need to decide whether the additional cost of management with goserelin is justified by the increased rates of amenorrhoea and the reduced withdrawals from treatment.

[Medical treatment of endometriosis]. / Traitements médicaux de l'endométriose.

Medical treatment of endometriosis has been applied since 40 years. Its rational is based upon the hormone-dependency of the endometriotic lesions inducing a resting status. Adhesions, endometriomas or fibrous sequellae do not respond to medical treatment. Its use in case of associated infertility is very limited. Numerous agents are available for clinical use. Progestins are efficient on pelvic pain, contra-indications, clinical and metabolic tolerance are linked to the hormonal activity of the molecules. They have a low cost. Newer pills deserve to be evaluated. Danazol has now few indications in regards to its clinical and metabolic side-effects. Gn-RH analogs bear a potent efficacy and a very low intrinsic toxicity. They are preferentially used in severe cases, in association with surgery and before an IVF. Add back therapy improves the clinical tolerance and reduces bone mass loss. Many parameters should be taken into account when selecting a specific modality.

Voice changes in women treated for endometriosis and related conditions: the need for comprehensive vocal assessment.

Hormonal treatments which have an androgenic effect have the potential to cause vocal changes. The changes in vocal fold structure and voice quality are considered to be irreversible. To date, studies have documented subjective vocal changes or documented single cases without detailed, baseline voice assessments. The impact on laryngeal function of women taking these androgenic treatments requires further detailed, objective assessment. The need for increased awareness of the actions of androgenic hormones on womens' voices, and the benefits of a thorough voice assessment are discussed.

Hysterectomy vs. resectoscopic endometrial ablation for the control of abnormal uterine bleeding. A cost-comparative study.

This study compared the costs of endometrial ablation using the uterine resectoscope to those of hysterectomy in a group of patients treated for abnormal uterine bleeding who were enrolled in a national managed health care organization. The cost of endometrial ablation during the periprocedural period was significantly lower than that of hysterectomy, with much of the difference coming from the hospitalization required for the latter procedure. The postprocedural cost for ablation was higher than for hysterectomy owing to the need for second ablations or hysterectomy in 13 of the 85 ablation patients. Preprocedure costs were not different between ablation and hysterectomy. A reanalysis of the data, however, that excluded patients who required a second ablation or hysterectomy suggested that these additional procedures were responsible for the higher postprocedural costs in the ablation group. Resectoscopic endometrial ablation for the treatment of abnormal uterine bleeding resulted in lower periprocedure costs and lower overall treatment costs to the health plan in the groups studied as compared with hysterectomy. Greater familiarity with the technique of resectoscopic endometrial ablation, improved patient selection for the procedure and the use of appropriate pharmacotherapy for suppressing endometrial growth prior to ablation probably substantially improve the rate of success, reduce postprocedural costs and further enhance the cost advantage of this procedure.

Assessment of medical treatments for menorrhagia.

Although usually not life-threatening, dysfunctional uterine bleeding (DUB) can cause discomfort and disruption to life for many women. It has been poorly researched in the past, primarily because of difficulties in trying to accurately measure blood loss and response to treatment. There are several different therapies currently available but, for many, actual evidence of their efficacy is lacking from scientific data. Progestogens are the most frequently prescribed drugs for the treatment of DUB. Data support their use in anovulatory women but a number of comparative trials have shown that an overall reduction in blood loss of only 20% is achieved in ovulatory women. Their use, therefore, must be questioned as the first line of treatment. Combined oral contraceptives were at one time popular but whether the low-dose, current generation pills are equally effective awaits appropriate trials. Prostaglandin synthetase inhibitors can be useful, with up to a third of women with menorrhagia benefiting from a reduction of between 25% and 35% in blood loss. A proportionally greater reduction is seen in women with more excessive bleeding. Antifibrinolytic drugs have been shown to reduce menstrual blood loss in DUB by 50% and would be useful in women in whom oestrogens are contraindicated. Gonadotrophin-releasing hormone analogues are highly effective because of their ability to induce amenorrhoea, but long-term use is contraindicated because of their hypo-oestrogenic effects. One other effective therapy for menorrhagia has been danazol.(ABSTRACT TRUNCATED AT 250 WORDS)

Depot leuprolide acetate versus danazol in the treatment of women with symptomatic endometriosis: a multicenter, double-blind randomized clinical trial. II. Assessment of safety. The Lupron Endometriosis Study Group.

OBJECTIVES: This is the first multicenter, double-blind randomized clinical trial that compares a depot gonadotropin-releasing hormone agonist with danazol in the treatment of endometriosis. Efficacy results have been previously reported; this report focuses on safety data. STUDY DESIGN: A total of 270 patients from 22 centers were randomly selected to receive either leuprolide acetate depot (3.75 mg injected monthly) or danazol (800 mg administered orally daily). Safety outcomes included adverse effects, clinical laboratory changes, and bone mineral density changes. RESULTS: Most patients receiving either drug reported side effects, most of which were related to the hypoestrogenism of leuprolide (e.g., vasodilatation) and relative hyperandrogenism of danazol (e.g., weight gain). Similarly small numbers of patients dropped out of the two treatment groups because of the side effects encountered. Leuprolide depot caused a greater decrease in bone density; preliminary data suggest a return to baseline on cessation of the drug. Danazol was associated with alteration of serum lipids, specifically a significant decrease in high-density lipoprotein. CONCLUSIONS: Although side effects were commonly reported in both groups, the drugs were similarly safe in terms of the absence of serious complications and the results of cessation of therapy. Side effects were largely reversible on discontinuation of medication. More longitudinal data are necessary before the possibility of long-term risks can be excluded, especially as they pertain to bone mineral density and lipids.

Nafarelin in the management of endometriosis: quality of life assessment.

Quality of life is important when comparing the relative advantages of nafarelin versus danazol for the treatment of endometriosis. Recent studies have investigated the potential differences between the safety profiles of nafarelin and danazol and the impact of these profiles on the patient's quality of life. Results show that although these drugs have similar efficacy, they are associated with very different safety profiles. Most notable are the androgenic effects such as weight gain associated with danazol. With nafarelin, hypoestrogenic side effects, such as hot flashes, are more common. More important, these differences in safety profiles may prove to be relevant to patient satisfaction and compliance with therapy.

Danazol: objective assessment in the treatment of endometriosis.

The objective assessment of Danocrine (Danazol, Winthrop) in the treatment of endometriosis was hampered in the 1970s by the absence of a universally accepted classification. The American Fertility Society (AFS) classification, proposed in 1979, has now become widely accepted. However, there is a lack of recorded objective data utilizing the AFS score before and after Danazol therapy. In a series of 51 patients with endometriosis, who underwent laparoscopy, then received Danazol, 800 mg daily for 6 months, and had a repeat laparoscopy, there was a statistically significant improvement in the AFS score in Stage I and II disease.