PubMed · 59031
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T Lind, D B Cook. 1976-06-26. Letter: How does danazol work?. https://doi.org/10.1016/s0140-6736(76)93044-0
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BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an attractive treatment option, but there is considerable variation in practice and uncertainty about the most effective therapy. Danazol is a synthetic steroid with anti-oestrogenic and anti progestogenic activity, and weak androgenic properties. Danazol suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss and to amenorrhoea in some women. OBJECTIVES: To determine the effectiveness and tolerability of danazol when used for heavy menstrual bleeding in women of reproductive years. SEARCH STRATEGY: All studies which might describe randomised controlled trials of danazol for the treatment of heavy menstrual bleeding were obtained by electronic searches of MEDLINE, EMBASE, Current Contents, CINAHL, National Research Register and the Menstrual Disorders and Subfertility Group's Specialist Register of controlled trials (on 6 November 2001). Attempts were also made to identify trials from citation lists of included trials and relevant review articles. In most cases the first author of each included trial was contacted for unpublished additional information. SELECTION CRITERIA: Randomised controlled trials of danazol versus placebo, any other medical (non-surgical) therapy or danazol in different dosages for heavy menstrual bleeding in women of reproductive age with regular HMB measured either subjectively or objectively. Trials that included women with post menopausal bleeding, intermenstrual bleeding and pathological causes of heavy menstrual bleeding were excluded. DATA COLLECTION AND ANALYSIS: Nine RCTs, with 353 women, were identified that fulfilled the inclusion criteria for this review. Quality assessment and data extraction were performed independently by two reviewers. The main outcomes were menstrual blood loss, the number of women experiencing adverse effects, weight gain, withdrawals due to adverse effects and dysmenorrhoea. If data could not be extracted in a form suitable for meta-analysis, they were presented in a descriptive format. MAIN RESULTS: Most data were not in a form suitable for meta analysis, and the results are based on a small number of trials, all of which are under-powered. Danazol appears to be more effective than placebo, progestogens, NSAIDs and the OCP at reducing MBL, but confidence intervals were wide. Treatment with danazol caused more adverse events than NSAIDs (OR 7.0; 95% CI 1.7, 28.2) and progestogens (OR 4.05, 95% CI 1.6, 10.2), but this did not appear to affect adherence to treatment. Danazol was shown to significantly lower the duration of menses when compared with NSAIDs (WMD -1.0; 95% CI -1.8, -0.3) and a progesterone releasing IUD (WMD -6.0; 95% CI -7.3, -4.8). There were no randomised trials comparing danazol with tranexamic acid or the levonorgestrel-releasing intrauterine system. REVIEWER'S CONCLUSIONS: Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments, though it is uncertain whether it is acceptable to women. The use of danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. Overall no strong recommendations can be made due to the small number of trials, and the small sample sizes of the included trials.
Our understanding of the pathophysiology of ITP owes to pioneering work of W J Harrington in 1951, delineating the immunologic nature of platelet destruction. In ITP, antibody-coated platelets are destroyed by macrophages of RES. However, other mechanisms are also implicated: C-mediated platelet lysis and newly described C-independent peroxide injury. Both induce platelet fragmentation and lysis, generating procoagulant platelet microparticles (PMP). A third mechanism of platelet consumption in the microvasculature is proposed, based on overlapping syndromes of ITP and TTP in some patients. In assessing hemostasis in ITP, platelet counts alone is not sufficient. Evaluation of platelet clumping, giant platelets, and platelet activation, marked by increased PMP is useful. Patients with platelet activation or giant platelets bleed less and detection of clumping prevents unwarranted therapy. Thrombotic complications may develop in ITP. A syndrome, characterized by recurrent TIA-like symptoms, progressive memory loss due to ischemic small vessel disease is described. The management of ITP should include the search for and elimination of underlying causes and careful evaluation of hemostasis. Therapy is divided into definitive vs symptomatic measures. The former including splenectomy, danazol, chemotherapy offers lasting remission after therapy was stopped, while the later including glucocorticoids, gammaglobuin, antiD antibodies and others increases platelet counts but seldom sustains remission upon withdrawal. Danazol therapy is up-dated since it is an effective and safe definite measure in ITP.
Endometriosis is a common gynecologic disorder that affects approximately 14% of all women and 30% to 50% of infertile women. Since the most common symptoms of endometriosis--progressive dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility--are also symptoms of multiple disorders, a diagnosis of endometriosis can be elusive and confirmed only by visualization, that is, laparoscopy. Endometriosis is often treated surgically upon diagnosis; however, the rate of recurrence is high, suggesting that a combination of therapeutic approaches might provide better outcomes than any one option alone. The most widely utilized hormonal treatments for endometriosis are GnRH agonists and oral contraceptives; agents indicated by the Food and Drug Administration include GnRH agonists and the androgen, danazol. The majority of evidence in support of medical therapy for endometriosis is largely observational, with the exception of studies of GnRH agonists, danazol, and a few progestins. Conventional treatment approaches for the medical management of endometriosis focus on suspected endometriosis, following a diagnosis of endometriosis, following surgical treatment of endometriosis, long-term management, and retreatment. Although major advances have been made in the treatment of endometriosis in recent decades, lack of randomized clinical trials evaluating the use of agents such as oral contraceptives alone or as add-back therapy for GnRH agonists, or those that examine combined medical and surgical treatments, has hampered the ability of physicians to provide the broadest range of medical therapies for this disorder. Future trials addressing these issues are warranted.