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The Cochrane Database of Systematic... Jul 2007Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an oestrogen dependent condition. This... (Review)
Review
BACKGROUND
Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an oestrogen dependent condition. This hormonal dependency has prompted the therapeutic use of ovulation suppression agents, in an effort to improve subsequent fertility.
OBJECTIVES
To assess the effectiveness of ovulation suppression agents, including danazol, progestins and oral contraceptives, in the treatment of endometriosis-associated subfertility in improving pregnancy outcomes including live birth.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Sub-fertility Group's specialised register of trials (searched October 5th, 2007) the Cochrane Register of Controlled Trials (The Cochrane Library, Issue 3, 2007), MEDLINE (1966-October 2007), EMBASE (1980 - October 2007) and reference lists of articles.
SELECTION CRITERIA
Randomised trials comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception in women with endometriosis. A total of twenty three RCTs comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception were identified.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed quality. We contacted study authors for additional information. Quality was assessed by of method of randomization,allocation concealment, blinding, completeness of follow-up, presence or absence of crossover and co-intervention. 2 x 2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using the I(2) test of heterogeneity. Subgroup analysis was conducted on those couples clearly identifiable as infertile or wanting to conceive.
MAIN RESULTS
Twenty four trials were included. The odds ratio for pregnancy following ovulation suppression versus placebo or no treatment for all women randomised was 0.79 (95% CI 0.54 to 1.14), P = 0.21 and 0.80 (95% CI 0.51 to 1.24), P = 0.32 respectively for subfertile couples only despite the use of a variety of suppression agents. There was no evidence of benefit from the treatment. The common odds ratio for pregnancy following all agents versus danazol for all women randomised was 1.38 (95% CI 1.05 to 1.82), P = 0.02 and OR 1.37 (95% CI 0.94 to 1.99), P = 0.10 for subfertile couples only. When GnRHa and danazol were directly compared, OR was 1.45 (95% CI 1.08 to 1.95) P = 0.01 for all women randomised and OR 1.63( 95% CI 1.12 to 2.37), P = 0.01 for subfertile couples only in favour of GnRH. No effect was observed for GnRH compared with oral contraception; OR 0.99 (95% CI 0.52 to 1.89), P = 0.98 for all women randomised and OR 0.79 ( 95% CI 0.37 to 1.69), P = 0.55. In all analyses the data were statistically homogeneous (I(2)=0%).
AUTHORS' CONCLUSIONS
There is no evidence of benefit in the use of ovulation suppression in subfertile women with endometriosis who wish to conceive.
Topics: Danazol; Endometriosis; Estrogen Antagonists; Female; Fertility Agents, Female; Humans; Infertility, Female; Ovulation; Randomized Controlled Trials as Topic
PubMed: 17636607
DOI: 10.1002/14651858.CD000155.pub2 -
Women's Health (London, England) Nov 2013Premenstrual dysphoric disorder (PMDD) is comprised of a cluster of affective, behavioral and somatic symptoms recurring monthly during the luteal phase of the menstrual... (Review)
Review
Premenstrual dysphoric disorder (PMDD) is comprised of a cluster of affective, behavioral and somatic symptoms recurring monthly during the luteal phase of the menstrual cycle. The disorder affects 3-8% of menstruating women and represents the more severe and disabling end of the spectrum of premenstrual disorders, which includes premenstrual syndrome and premenstrual aggravation of underlying affective disorder. Rigorous and specific diagnostic criteria for PMDD were specified in the Diagnostic and Statistical Manual of Mental Disorders IV (1994) and reaffirmed in the Diagnostic and Statistical Manual of Mental Disorders V (2013) and, consequently, there has been a marked increase in well-designed, placebo-controlled studies evaluating treatment modalities. Although the exact pathogenesis of PMDD is still elusive, treatment of PMDD and severe premenstrual syndrome has centered on neuromodulation via serotonin reuptake inhibitor antidepressants, and ovulation suppression utilizing various contraceptive and hormonal preparations. Unlike the approach to the treatment of depression, serotonergic antidepressants need not be given daily, but can be effective when used cyclically, only in the luteal phase or even limited to the duration of the monthly symptoms. Less, well-substantiated alternative treatments, such as calcium supplementation, agnus castus (chasteberry), Hypericum perforatum (St John's wort) and cognitive/behavioral/relaxation therapies, may be useful adjuncts in the treatment of PMDD. This review provides an overview of current information on the treatment of PMDD.
Topics: Contraceptives, Oral, Hormonal; Danazol; Estrogen Antagonists; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Mood Disorders; Premenstrual Syndrome; Selective Serotonin Reuptake Inhibitors
PubMed: 24161307
DOI: 10.2217/whe.13.62 -
Annals of Hepatology 2011
Topics: Adult; Biopsy; Cholecystectomy, Laparoscopic; Danazol; Endometriosis; Estrogen Antagonists; Female; Gallstones; Humans; Incidental Findings; Liver Diseases; Peritoneum; Treatment Outcome
PubMed: 21677338
DOI: No ID Found -
Pharmaceuticals (Basel, Switzerland) Nov 2022Danazol is a treatment option for autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Three patients with AIHA and eight patients with ITP between 2008...
Danazol is a treatment option for autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Three patients with AIHA and eight patients with ITP between 2008 and 2022 were enrolled in the Rheumatology Outpatient Clinic of Chang Gung Memorial Hospital, Kaohsiung. Those patients were refractory or intolerant to conventional therapy and were treated with danazol. All the patients received an initial dose of danazol (200-400 mg). The observation period was 6 months. Three patients (100%) with AIHA and six (75%) with ITP achieved treatment response after 6 months of danazol therapy. The dose of glucocorticoid for responders could be reduced to ≤5 mg/day of prednisolone, and the immunosuppressants, except hydroxychloroquine and azathioprine for systemic lupus erythematosus, could be discontinued. Adverse events were acne in two (18.2%) patients and transient dose-related liver function impairment in one (9.1%) patient in the current series. Danazol therapy appears to be a favorable alternative for refractory AIHA and ITP by altering the erythrocyte membrane to resist osmotic lysis and protecting platelets against complement-mediated lysis. In this report, we also performed a literature review and searched the PubMed/Cochrane Library for articles published from 1984 to January 2022 on danazol therapy for patients with AIHA and ITP.
PubMed: 36355549
DOI: 10.3390/ph15111377 -
The Journal of Allergy and Clinical... Aug 2023Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better...
BACKGROUND
Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care.
OBJECTIVE
To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients.
METHODS
A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data.
RESULTS
The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home.
CONCLUSIONS
Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients.
Topics: Humans; Female; Male; Angioedemas, Hereditary; Complement C1 Inhibitor Protein; Danazol; United Kingdom; Surveys and Questionnaires
PubMed: 37146882
DOI: 10.1016/j.jaip.2023.04.035 -
The Cochrane Database of Systematic... Jul 2007Heavy 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... (Meta-Analysis)
Meta-Analysis Review
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
We searched the Menstrual Disorders and Subfertility Group's Specialised Register (April 2007). We also searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2007), MEDLINE (1966 to April 2007), EMBASE (1980 to April 2007, CINAHL (1982 to April 2007). Attempts were also made to identify trials from citation lists of included trials and relevant review articles.
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. 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 to 28.2) and progestogens (OR 4.05, 95% CI 1.6 to10.2). Danazol was shown to significantly lower the duration of menses when compared with NSAIDs (WMD -1.0; 95% CI -1.8 to -0.3) and a progesterone releasing IUD (WMD -6.0; 95% CI -7.3 to -4.8). There were no randomised trials comparing Danazol with tranexamic acid or the levonorgestrel-releasing intrauterine system.
AUTHORS' CONCLUSIONS
Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments. The use of Danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. The small number of trials, and the small sample sizes of the included trials limit the recommendations for clinical care. Further studies are unlikely in the future and this review will not be updated unless further studies are identified.
Topics: Danazol; Estrogen Antagonists; Female; Humans; Menorrhagia; Randomized Controlled Trials as Topic
PubMed: 17636649
DOI: 10.1002/14651858.CD001017.pub2 -
Frontiers in Medicine 2021Stanozolol and danazol are widely used in the treatment of aplastic anemia; however, their mechanisms of action are unclear. Bone marrow mononuclear cells from 10...
Stanozolol and danazol are widely used in the treatment of aplastic anemia; however, their mechanisms of action are unclear. Bone marrow mononuclear cells from 10 patients newly diagnosed with aplastic anemia and 10 healthy volunteers were collected and cultured together with stanozolol, danazol, or blank control separately for marrow colony assays. K562 cell lines that had been incubated with stanozolol, danazol, or blank control were tested for erythroid or megakaryocytic differentiation. Meanwhile, CB6F1/Crl mice were injected with 1 × 10 C57BL/6 donor-originated lymphocytes after irradiation with 5 Gy total body irradiation to establish a model for immune-mediated bone marrow failure (aplastic anemia mouse model). Mice with aplastic anemia were treated with cyclosporin A monotherapy, cyclosporin A in combination with stanozolol, and cyclosporin A in combination with danazol for 30 days. Peripheral blood cell counts once a week and bone marrow colony assays at the end of 1 month were performed. The proportion of T cell subsets, level of inflammatory factors, erythropoietin, and thrombopoietin were detected before and after treatment. The levels of erythropoietin receptors on bone marrow mononuclear cells after treatment were tested using western blotting. In the experiments, the number of burst-forming units-erythroid; colony-forming units-granulocyte and macrophage; and colony-forming units-granulocyte, erythrocyte, monocyte, and megakaryocyte in the patients with aplastic anemia were significantly lower than that in the normal controls ( < 0.05). However, the number of colonies and mean fluorescence intensity of CD235a or CD41 expression in the harvested cultured cells were not significantly different among the different treatment groups in the patients with aplastic anemia, normal controls, and K562 cell lines. These results show that stanozolol and danazol produce no direct hematopoiesis-stimulating effects on progenitor cells. In the experiment, the mice with aplastic anemia treated with cyclosporin A and danazol exhibited the most rapid recovery of platelet; the platelet count returned to normal levels after 3 weeks of treatment, which was at least 1 week earlier than in the other groups. In contrast, mice treated with cyclosporin A and stanozolol exhibited the highest hemoglobin level at the end of treatment ( < 0.05). Bone marrow colony assays at 30 days showed that the number of burst-forming units-erythroid was the highest in mice treated with cyclosporin A and stanozolol, while the number of colony-forming units-granulocyte and macrophage was the highest in those treated with cyclosporin A and danazol. Compared to cyclosporin A monotherapy, additional stanozolol and danazol can both increase the level of regulatory T cells and upregulate interleukin-10, inhibiting the expression of tumor necrosis factor-α ( < 0.05). However, IL-2 was more effectively reduced by danazol than by stanozolol ( < 0.05). The cyclosporin A- and stanozolol-treated mice showed higher serum erythropoietin (corrected by hemoglobin level) and higher erythropoietin receptor levels in bone marrow mononuclear cells than the other groups ( < 0.05). Neither stanozolol nor danazol directly stimulated hematopoiesis . However, , stanozolol may exhibit an advantage in improving erythropoiesis, while danazol may induce stronger effects on platelets. Both danazol and stanozolol exhibited immunosuppressive roles. Stanozolol could enhance the secretion of erythropoietin and expression of erythropoietin receptor in bone marrow mononuclear cells.
PubMed: 34124083
DOI: 10.3389/fmed.2021.615195 -
The Cochrane Database of Systematic... Mar 2012Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of reproductive age and may present as pain or infertility. The pelvic pain may be in the form of dysmenorrhoea, dyspareunia or pelvic pain. Initially a combination of estrogens and progestagens was used to create a pseudopregnancy and alleviate the symptoms associated with endometriosis. Progestagens alone or anti-progestagens have been considered as alternatives because they are inexpensive and may have a better side effect profile than other choices.
OBJECTIVES
To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis.
SEARCH METHODS
We used the search strategy of the Menstrual Disorders and Subfertility Group to identify all publications which described or might have described randomised controlled trials (RCTs) of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis. We updated the review in 2011.
SELECTION CRITERIA
We considered only RCTs which compared the use of progestagens and anti-progestagens with other interventions, placebo or no treatment for the alleviation of symptomatic endometriosis.
DATA COLLECTION AND ANALYSIS
We have added six new studies, bringing the total of included studies to 13 in the update of this review. The six newly included studies evaluated progestagens (comparisons with placebo, danazol, oral or subdermal contraceptive, oral contraceptive pill and danazol, gonadotrophin-releasing hormone (GnRH) analogue and other drugs). The remaining studies compared the anti-progestagen gestrinone with danazol, GnRH analogues or itself.
MAIN RESULTS
The progestagen medroxyprogesterone acetate (100 mg daily) appeared to be more effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI -8.61 to -5.39; P < 0.00001) compared with placebo. There was evidence of significantly more cases of acne (six versus one) and oedema (11 versus one) in the medroxyprogesterone acetate group compared with placebo. There was no evidence of a difference in objective efficacy between dydrogesterone and placebo.There was no evidence of a benefit with depot administration of progestagens versus other treatments (low dose oral contraceptive or leuprolide acetate) for reduced symptoms. The depot progestagen group experienced significantly more adverse effects.There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups.There was no evidence of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006).
AUTHORS' CONCLUSIONS
There is only limited evidence to support the use of progestagens and anti-progestagens for pain associated with endometriosis.
Topics: Danazol; Dydrogesterone; Endometriosis; Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Medroxyprogesterone Acetate; Pelvic Pain; Progesterone Congeners; Progestins
PubMed: 22419284
DOI: 10.1002/14651858.CD002122.pub2 -
The World Allergy Organization Journal Aug 2023I have read the article titled "" by Wang et al (2022) with great interest. This study examined the change in throat microbiota and its association with laryngeal edema...
I have read the article titled "" by Wang et al (2022) with great interest. This study examined the change in throat microbiota and its association with laryngeal edema (LE) attacks and attack severity in hereditary angioedema (HAE) patients. This study demonstrated the comparative richness of Bacteroidetes and Prevotellaceae in recent LE attacks and detected positive association between the attack severity scores and Bacteroidetes richness. Nevertheless, I have some questions and concerns about the methodological design of their study. For instance, in the article, the description of HAE and HAE patients is not exactly correct. I do not also agree with the authors on the effect of long-term prophylactic danazol use in HAE patients of this study. It is very important when or how the swab was obtained after the LE attack. The last, not the least, point now is what the authors suggest to improve this dysbiosis in these HAE patients. The discussion to elaborate these points in the study could be helpful and enlightening for readers and future research in this area.
PubMed: 37577027
DOI: 10.1016/j.waojou.2023.100806 -
Annals of Hematology Feb 2016Recently, great progress has been achieved in the treatment of chronic lymphocytic leukemia (CLL). However, some patients, particularly older patients with comorbidities...
Recently, great progress has been achieved in the treatment of chronic lymphocytic leukemia (CLL). However, some patients, particularly older patients with comorbidities or with relapsed/refractory leukemia, still have limited therapeutic options. There is an urgent need to discover less toxic and more effective drugs for CLL patients. Applying new modalities or substances that are widely used for the treatment of other diseases has been reported to improve results in CLL treatment. This study aimed to assess the non-chemotherapeutic drug danazol for its potential to destroy leukemic cells. Leukemic cells, obtained from the peripheral blood and bone marrow of 23 CLL patients, were cultured in the presence of danazol and its combination with the purine nucleoside analogs fludarabine and cladribine and bendamustine. After 24 h of incubation, the rate of apoptosis indicated by active caspase-3 expression, and cytotoxicity indicated by forward light scatter and light scatter analysis, was assessed by flow cytometry. We also measured expression of apoptosis-regulating proteins of BCL family and active caspase 9 and active caspase 8 expressions in leukemic cells. Danazol had a caspase-dependent pro-apoptotic and cytotoxic effect on leukemic cells in a tumor-specific manner. The mechanisms of its action appear to be complex and should be precisely established; however, induction of apoptosis involving both mitochondrial and receptor cascades appears to be most probable. Danazol showed a synergic effect with cladribine, an additive effect with fludarabine, and an infra-additive effect with bendamustine. The rate of danazol-induced apoptosis and cytotoxicity did not differ between patients with better and worse prognostic markers. Our results indicate that danazol may be a potential therapeutic agent for CLL patients alone and in combination with purine analogs.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cytotoxins; Danazol; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Purine Nucleosides; Tumor Cells, Cultured
PubMed: 26692089
DOI: 10.1007/s00277-015-2579-5