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British Medical Journal Jun 1979
Topics: Angioedema; Complement Inactivator Proteins; Danazol; Humans
PubMed: 466137
DOI: No ID Found -
Fertility and Sterility Nov 2006Women with endometriosis typically present with pelvic pain, infertility or an adnexal mass. Surgery for persistent adnexal masses may be indicated to remove an... (Review)
Review
Women with endometriosis typically present with pelvic pain, infertility or an adnexal mass. Surgery for persistent adnexal masses may be indicated to remove an endometrioma or other pelvic pathology. Surgical or medical therapy is efficacious for pelvic pain due to endometriosis, but treatment of endometriosis in the female partner of an infertile couple raises a number of complex clinical questions that do not have simple answers.
Topics: Danazol; Endometriosis; Estrogen Antagonists; Female; Fertility; Gynecologic Surgical Procedures; Humans; Infertility, Female; Insemination, Artificial; Progestins; Reproductive Techniques, Assisted; Superovulation
PubMed: 17055813
DOI: 10.1016/j.fertnstert.2006.08.014 -
Acta Obstetricia Et Gynecologica... Jun 2012Rectovaginal endometriosis can be a cause of severe pain, dyspareunia and intestinal problems. A thorough examination is needed and should include diagnostic imaging,... (Review)
Review
Rectovaginal endometriosis can be a cause of severe pain, dyspareunia and intestinal problems. A thorough examination is needed and should include diagnostic imaging, such as transvaginal or transrectal ultrasound or magnetic resonance imaging. Medical therapies, such as oral contraceptives, progestins and levonorgestrel-releasing intrauterine devices, all seem to reduce pain and should always be considered. Surgical treatment is challenging and implies a risk of severe complications. It is preferable to treat endometriotic lesions with superficial infiltration into the rectal wall by local laparoscopic excision, while segmental rectal resection is needed in the case of severe intestinal infiltration. This review describes available diagnostic tools, the possibilities for medical treatment and the alternative surgical approaches.
Topics: Administration, Intravaginal; Aromatase Inhibitors; Barium Sulfate; Colon; Constipation; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Contrast Media; Danazol; Diagnostic Imaging; Dysmenorrhea; Dyspareunia; Endometriosis; Endoscopy, Digestive System; Enema; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Humans; Intrauterine Devices; Laparoscopy; Levonorgestrel; Pelvic Pain; Postoperative Complications; Progesterone Congeners; Rectal Diseases; Rectum; Vagina; Vaginal Diseases
PubMed: 22268648
DOI: 10.1111/j.1600-0412.2012.01367.x -
The Cochrane Database of Systematic... Aug 2019Heavy menstrual bleeding (HMB) is a menstrual blood loss perceived by women as excessive that affects the health of women of reproductive age, interfering with their...
BACKGROUND
Heavy menstrual bleeding (HMB) is a menstrual blood loss perceived by women as excessive that affects the health of women of reproductive age, interfering with their physical, emotional, social and material quality of life. Whilst abnormal menstrual bleeding may be associated with underlying pathology, in the present context, HMB is defined as excessive menstrual bleeding in the absence of other systemic or gynaecological disease. The first-line therapy is usually medical, avoiding possibly unnecessary surgery. Of the wide variety of medications used to reduce HMB, oral progestogens were originally the most commonly prescribed agents. This review assesses the effectiveness of two different types and regimens of oral progestogens in reducing ovulatory HMB.This is the update of a Cochrane review last updated in 2007, and originally named "Effectiveness of cyclical progestagen therapy in reducing heavy menstrual bleeding" (1998).
OBJECTIVES
To determine the effectiveness, safety and tolerability of oral progestogen therapy taken either during the luteal phase (short cycle) or for a longer course of 21 days per cycle (long cycle), in achieving a reduction in menstrual blood loss in women of reproductive age with HMB.
SEARCH METHODS
In January 2019 we searched Cochrane Gynaecology and Fertility's specialized register, CENTRAL, MEDLINE, Embase, CINAHL and PsycInfo. We also searched trials registers, other sources of unpublished or grey literature and reference lists of retrieved trials. We also checked citation lists of review articles to identify trials.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing different treatments for HMB that included cyclical oral progestogens were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trials for risk of bias and extracted data. We contacted trial authors for clarification of methods or additional data when necessary. We only assessed adverse events if they were separately measured in the included trials. We compared cyclical oral progestogen in different regimens and placebo or other treatments. Our primary outcomes were menstrual blood loss and satisfaction with treatment; the secondary outcomes were number of days of bleeding, quality of life, compliance and acceptability of treatment, adverse events and costs.
MAIN RESULTS
This review identified 15 randomized controlled trials (RCTs) with 1071 women in total. Most of the women knew which treatment they were receiving, which may have influenced their judgements about menstrual blood loss and satisfaction. Other aspects of trial quality varied among trials.We did not identify any RCTs comparing progestogen treatment with placebo. We assessed comparisons between oral progestogens and other medical therapies separately according to different regimens.Short-cycle progestogen therapy during the luteal phase (medroxyprogesterone acetate or norethisterone for 7 to 10 days, from day 15 to 19) was inferior to other medical therapy, including tranexamic acid, danazol and the progestogen-releasing intrauterine system (Pg-IUS (off of the market since 2001)), releasing 60 mcg of progesterone daily, with respect to reduction of menstrual blood loss (mean difference (MD) 37.29, 95% confidence interval (CI) 17.67 to 56.91; I = 50%; 6 trials, 145 women). The rate of satisfaction and the quality of life with treatment was similar in both groups. The number of bleeding days was greater on the short cycle progestogen group compared to other medical treatments. Adverse events (such as gastrointestinal symptoms and weight gain) were more likely with danazol when compared with progestogen treatment. We note that danazol is no longer in general use for treating HMB.Long-cycle progestogen therapy (medroxyprogesterone acetate or norethisterone), from day 5 to day 26 of the menstrual cycle, is also inferior to the levonorgestrel-releasing intrauterine system (LNG-IUS), releasing tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss (MD 16.88, 95% CI 10.93 to 22.84; I = 87%; 4 trials, 355 women). A higher proportion of women taking norethisterone found their treatment unacceptable compared to women having Pg-IUS (Peto odds ratio (OR) 0.12, 95% CI 0.03 to 0.40; 1 trial, 40 women). However, the adverse effects of breast tenderness and intermenstrual bleeding were more likely in women with the LNG-IUS. No trials reported on days of bleeding or quality of life for this comparison.The evidence supporting these findings was limited by low or very low gradings of quality; thus, we are uncertain about the findings and there is a potential that they may change if we identify other trials.
AUTHORS' CONCLUSIONS
Low- or very low-quality evidence suggests that short-course progestogen was inferior to other medical therapy, including tranexamic acid, danazol and the Pg-IUS with respect to reduction of menstrual blood loss. Long cycle progestogen therapy (medroxyprogesterone acetate or norethisterone) was also inferior to the LNG-IUS, tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss.
Topics: Danazol; Female; Humans; Intrauterine Devices, Medicated; Medroxyprogesterone Acetate; Menorrhagia; Progesterone; Progestins; Quality of Life; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 31425626
DOI: 10.1002/14651858.CD001016.pub3 -
The Journal of Endocrinology Sep 2019Selective androgen receptor modulators (SARMs) have been proposed as therapeutics for women suffering from breast cancer, muscle wasting or urinary incontinence. The...
Selective androgen receptor modulators (SARMs) have been proposed as therapeutics for women suffering from breast cancer, muscle wasting or urinary incontinence. The androgen receptor (AR) is expressed in the uterus but the impact of SARMs on the function of this organ is unknown. We used a mouse model to compare the impact of SARMs (GTx-007/Andarine®, GTx-024/Enobosarm®), Danazol (a synthetic androstane steroid) and dihydrotestosterone (DHT) on tissue architecture, cell proliferation and gene expression. Ovariectomised mice were treated daily for 7 days with compound or vehicle control (VC). Uterine morphometric characteristics were quantified using high-throughput image analysis (StrataQuest; TissueGnostics), protein and gene expression were evaluated by immunohistochemistry and RT-qPCR, respectively. Treatment with GTx-024, Danazol or DHT induced significant increases in body weight, uterine weight and the surface area of the endometrial stromal and epithelial compartments compared to VC. Treatment with GTx-007 had no impact on these parameters. GTx-024, Danazol and DHT all significantly increased the percentage of Ki67-positive cells in the stroma, but only GTx-024 had an impact on epithelial cell proliferation. GTx-007 significantly increased uterine expression of Wnt4 and Wnt7a, whereas GTx-024 and Danazol decreased their expression. In summary, the impact of GTx-024 and Danazol on uterine cells mirrored that of DHT, whereas GTx-007 had minimal impact on the tested parameters. This study has identified endpoints that have revealed differences in the effects of SARMs on uterine tissue and provides a template for preclinical studies comparing the impact of compounds targeting the AR on endometrial function.
Topics: Acetamides; Aminophenols; Anilides; Cell Proliferation; Danazol; Dihydrotestosterone; Epithelial Cells; Female; Gene Expression; Humans; Receptors, Androgen; Uterus
PubMed: 31319382
DOI: 10.1530/JOE-19-0153 -
Fertility and Sterility Jul 1982The mechanism of action of danazol is poorly understood, but this testosterone (T) derivate is frequently used in the clinical treatment of endometriosis, and its... (Comparative Study)
Comparative Study
The mechanism of action of danazol is poorly understood, but this testosterone (T) derivate is frequently used in the clinical treatment of endometriosis, and its tendency to androgenic/anabolic side effects is well known. The interaction of danazol with T binding to sex-hormone-binding globulin (SHBG) was studied with the use of an aqueous two-phase system with polyethylene glycol (PEG) and dextran for equilibrium partition. Competitive binding studies were also performed with norethisterone (NET), d-norgestrel (d-Ng), medroxyprogesterone acetate (MPA), and tamoxifen (TMX). Danazol, d-Ng, and NET were found to exert a marked T displacing activity, while MPA and TMX had no significant effect. The low values for SHBG binding capacity that were found during danazol therapy mainly reflect occupation of binding sites by danazol and to a lesser degree a real decrease in protein concentration. It was calculated that during treatment the total SHBG capacity in serum is approximately 20 times exceeded. Therapeutic danazol serum levels are 1000 times those of normal female total T levels; and since the affinity to SHBG for danazol was found to be 1/20 that to T one should conclude an almost total occupation of binding sites. The endocrine effects of danazol might be interpreted in terms of T displacement and as a consequence of increased levels of free T during therapy.
Topics: Binding, Competitive; Danazol; Dose-Response Relationship, Drug; Endometriosis; Female; Humans; Norethindrone; Norgestrel; Pregnadienes; Progesterone; Sex Hormone-Binding Globulin; Testosterone
PubMed: 7201414
DOI: 10.1016/s0015-0282(16)46395-8 -
Blood Jan 2013A mild thrombocytopenia is relatively frequent during pregnancy and has generally no consequences for either the mother or the fetus. Although representing no threat in... (Review)
Review
A mild thrombocytopenia is relatively frequent during pregnancy and has generally no consequences for either the mother or the fetus. Although representing no threat in the majority of patients, thrombocytopenia may result from a range of pathologic conditions requiring closer monitoring and possible therapy. Two clinical scenarios are particularly relevant for their prevalence and the issues relating to their management. The first is the presence of isolated thrombocytopenia and the differential diagnosis between primary immune thrombocytopenia and gestational thrombocytopenia. The second is thrombocytopenia associated with preeclampsia and its look-alikes and their distinction from thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. In this review, we describe a systematic approach to the diagnosis and treatment of these disease entities using a case presentation format. Our discussion includes the antenatal and perinatal management of both the mother and fetus.
Topics: Adult; Algorithms; Antibodies, Monoclonal, Murine-Derived; Anticoagulants; Combined Modality Therapy; Contraindications; Danazol; Diagnosis, Differential; Disease Management; Female; Fetal Monitoring; HELLP Syndrome; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Infant, Newborn; Plasma Exchange; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Purpura, Thrombocytopenic, Idiopathic; Purpura, Thrombotic Thrombocytopenic; Recurrence; Rituximab; Thrombocytopenia; Young Adult
PubMed: 23149846
DOI: 10.1182/blood-2012-08-448944 -
Annals of Hepatology 2011Thrombocytopenia is a common hematologic disorder observed in patients with chronic hepatitis C virus (HCV) infection. Combined peginterferon (PEG-INF) and ribavirin... (Clinical Trial)
Clinical Trial
BACKGROUND
Thrombocytopenia is a common hematologic disorder observed in patients with chronic hepatitis C virus (HCV) infection. Combined peginterferon (PEG-INF) and ribavirin treatment may exacerbate thrombocytopenia in patients with HCV.
OBJECTIVE
The aim of this pilot clinical trial was to assess the efficacy, tolerability and safety of Danazol in thrombocytopenia associated with PEG-INF and ribavirin treatment in patients with HCV.
MATERIAL AND METHODS
We included patients whose platelets were < 90,000/mm³ and who were undergoing antiviral treatment. Danazol (300-600 mg/day) was administered during and until the end of antiviral therapy [7.6 months (2 to 11 months)]. The monitoring was performed through platelet analysis and liver function tests. A viral load test was done at the beginning and end of treatment. Fortynine patients receiving a combined therapy of PEG-INF, ribavirin and Danazol increased their platelet levels to 121,081/mm³ (46,000-216,000/mm³); 10.6% of patients gained > 100,000 platelets/mm³, and 71% of patients maintained their initial platelet levels. Sustained viral response (SVR) was achieved in 63% of patients. SVR rates were high in patients with genotype non 1 (78.7%) and decreased in patients with genotype 1 (60.1%). The increase in platelet levels was associated to an increase in fibrinogen levels and a decrease in the activity of ALT. By contrast, patients without SVR presented a delayed response to increased platelet levels and showed no significant improvement in liver function when they received Danazol.
CONCLUSION
Danazol can be used along with PEG-INF and ribavirin to treat thrombocytopenia in patients with HCV.
Topics: Adult; Aged; Alanine Transaminase; Antiviral Agents; Biomarkers; Danazol; Drug Therapy, Combination; Female; Fibrinogen; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon-alpha; Male; Mexico; Middle Aged; Odds Ratio; Pilot Projects; Platelet Count; Polyethylene Glycols; Prospective Studies; RNA, Viral; Recombinant Proteins; Ribavirin; Thrombocytopenia; Time Factors; Treatment Outcome; Viral Load
PubMed: 21911886
DOI: No ID Found -
Fertility and Sterility Aug 1977Danazol was found to inhibit multiple enzymes of steroidogenesis directly in the pregnant mare serum (PMS)-treated hamster ovary and the rat testis and adrenal in vitro....
Danazol was found to inhibit multiple enzymes of steroidogenesis directly in the pregnant mare serum (PMS)-treated hamster ovary and the rat testis and adrenal in vitro. In the PMS-treated hamster ovary, danazol inhibited 17alpha-hydroxylase, 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase. In the rat testis, danazol inhibited 17alpha-hydroxylase, 17,20-lyase, 3beta-hydroxysteroid dehydrogenase, and 17beta-hydroxysteroid dehydrogenase. In the rat adrenal, danazol inhibited 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11beta-hydroxylase. Two hours after a subcutaneous injection of 5 mg/kg of danazol to adult male rats, serum luteinizing hormone levels were significantly increased and serum testosterone levels were significantly suppressed. These findings suggest that in the rodent one of danazol's major pharmacologic effects is the direct inhibition of steroidogenesis.
Topics: Adrenal Glands; Adult; Animals; Child; Cricetinae; Danazol; Female; Humans; In Vitro Techniques; Luteinizing Hormone; Lyases; Male; Mixed Function Oxygenases; Ovary; Oxidoreductases; Pregnadienes; Rats; Steroids; Testis; Testosterone
PubMed: 885271
DOI: No ID Found -
Annals of the Rheumatic Diseases Jan 1993The menstrual cycle is characterised by variations in the absolute and relative concentrations of the hormones of the hypothalamic pituitary ovarian axis, which in turn...
The menstrual cycle is characterised by variations in the absolute and relative concentrations of the hormones of the hypothalamic pituitary ovarian axis, which in turn affect cell function and cytokine and heat shock protein production. Menstruation involves the shedding of the secretory endometrium, which is part of the mucosal associated lymphoid tissue and hence is rich in immunologically competent cells such as CD8 T cells and macrophages. The case is reported here of a patient presenting with a recurrent but transient symmetrical inflammatory polyarthritis which only occurred at menstruation with no residual damage. The disease was suppressed by danazol. Endometrial degradation products are suggested as the trigger of this 'menstrual arthritis'.
Topics: Adult; Arthritis; Danazol; Female; Humans; Menstruation; Recurrence
PubMed: 8427519
DOI: 10.1136/ard.52.1.65