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The Cochrane Database of Systematic... Jan 2008Excessively heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Eighty per cent of women treated for HMB have no anatomical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Excessively heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Eighty per cent of women treated for HMB have no anatomical pathology, which makes medical therapy, with the avoidance of possibly unnecessary surgery, an attractive alternative. Of the wide variety of medications used to reduce heavy menstrual bleeding, oral progestogens are the most commonly prescribed. This review assesses the effectiveness of two different regimens of oral progestogens in reducing ovulatory HMB.
OBJECTIVES
The primary objective of this review was to investigate the effectiveness of oral progestogen therapy taken either during the luteal phase or for a longer course of 21 days in achieving a reduction in menstrual blood loss in women of reproductive years with heavy menstrual bleeding (HMB).
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2007), MEDLINE (1966 to April 2007) and EMBASE (1985 to April 2007). Attempts were also made to identify trials from citation lists of review articles. In most cases, the first author of each included trial was contacted.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of oral progestogen therapy versus placebo or other medical treatments in women of reproductive years with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic causes for their heavy menstrual blood loss.
DATA COLLECTION AND ANALYSIS
Seven randomised controlled trials (RCTs) were identified that fulfilled the inclusion criteria. The review authors extracted the data independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data.
MAIN RESULTS
No RCTs comparing progestogen treatment with placebo were identified. Comparisons between oral progestogens and other medical therapies were assessed separately according to dosage regimen.Progestogen therapy during the luteal phase was significantly less effective at reducing menstrual blood loss when compared with tranexamic acid, danazol and the progesterone-releasing intrauterine system (IUS). Duration of menstruation was significantly longer with the progesterone IUS when compared with oral progestogen therapy but significantly shorter with danazol treatment. Adverse events were significantly more likely with danazol when compared with progestogen treatment. Progestogen therapy from day 5 to day 26 of the menstrual cycle was significantly less effective at reducing menstrual blood loss than the IUS. A significantly higher proportion of norethisterone (NET) patients taking progestogens found their treatment unacceptable compared to IUS patients. However, the adverse effects of breast tenderness and intermenstrual bleeding were more likely in women with the IUS.
AUTHORS' CONCLUSIONS
Progestogens administered from day 15 or 19 to day 26 of the cycle offer no advantage over other medical therapies such as danazol, tranexamic acid, non-steroidal anti-inflammatory drugs (NSAIDs) and the IUS in the treatment of menorrhagia in women with ovulatory cycles. Progestogen therapy for 21 days of the cycle results in a significant reduction in menstrual blood loss, although women found the treatment less acceptable than intrauterine levonorgestrel. This regimen of progestogen may have a role in the short-term treatment of menorrhagia.
Topics: Administration, Oral; Drug Administration Schedule; Female; Humans; Menorrhagia; Progestins; Randomized Controlled Trials as Topic
PubMed: 18253983
DOI: 10.1002/14651858.CD001016.pub2 -
The Cochrane Database of Systematic... Oct 2007Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments... (Review)
Review
BACKGROUND
Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments for endometriosis aim to remove or decrease the deposits of ectopic endometrium. The observation that hyper androgenic states (an excess of male hormone) induce atrophy of the endometrium has led to the use of androgens in the treatment of endometriosis. Danazol is one of these treatments. The efficacy of danazol is based on its ability to produce a high androgen and low oestrogen environment (a pseudo menopause) which results in atrophy of the endometriotic implants and thus an improvement in painful symptoms.
OBJECTIVES
To determine the effectiveness of danazol compared to placebo or no treatment in the treatment of the symptoms and signs, other than infertility, of endometriosis in women of reproductive age.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials (searched April 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2007), and MEDLINE (1966 to April 2007). In addition, all reference lists of included trials were searched, and relevant drug companies were contacted for details of unpublished trials.
SELECTION CRITERIA
Randomised controlled trials in which danazol (alone or as adjunctive therapy) was compared to placebo or no therapy. Trials which only reported infertility outcomes were excluded.
DATA COLLECTION AND ANALYSIS
Only five trials met the inclusion criteria and two authors independently extracted data from these trials. All trials compared danazol to placebo. Three trials used danazol as sole therapy and three trials used danazol as an adjunct to surgery. Although the main outcome was pain improvement other data relating to laparoscopic scores and hormonal parameters were also collected.
MAIN RESULTS
Treatment with danazol (including adjunctive to surgical therapy) was effective in relieving painful symptoms related to endometriosis when compared to placebo. Laparoscopic scores were improved with danazol treatment (including as adjunctive therapy) when compared with either placebo or no treatment. Side effects were more commonly reported in those patients receiving danazol than for placebo.
AUTHORS' CONCLUSIONS
Danazol is effective in treating the symptoms and signs of endometriosis. However, its use is limited by the occurrence of androgenic side effects.
Topics: Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Pelvic Pain; Randomized Controlled Trials as Topic
PubMed: 17943735
DOI: 10.1002/14651858.CD000068.pub2 -
The Cochrane Database of Systematic... 2001Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments... (Review)
Review
BACKGROUND
Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments for endometriosis aim to remove or decrease deposits of ectopic endometrium. The observation that hyperandrogenic states (an excess of male hormone) induce atrophy of the endometrium has led to the use of androgens in the treatment of endometriosis. Danazol is one of these treatments used. The efficacy of danazol is based on its ability to produce a high androgen/low estrogen environment (a pseudo menopause) which results in the atrophy of endometriotic implants and thus an improvement in painful symptoms.
OBJECTIVES
To determine the effectiveness of danazol compared to placebo or no treatment in the treatment of the symptoms and signs, other than infertility, of endometriosis in women of reproductive age.
SEARCH STRATEGY
The Menstrual Disorders Group search strategy was used to identify randomised controlled trials of the use of danazol in endometriosis. In addition, all reference lists of included trials were searched, and relevant drug companies were contacted for details of unpublished trials
SELECTION CRITERIA
Randomised controlled trials in which danazol (alone or as adjunctive therapy) was compared to placebo or no therapy. Trials which only reported infertility outcomes were excluded.
DATA COLLECTION AND ANALYSIS
Only four trials met the inclusion criteria and two authors extracted data independently from these trials. All four trials compared danazol to placebo. Two trials used danazol as sole therapy and two trials used danazol as an adjunct to surgery. Although the main outcome was pain improvement other data relating to laparoscopic scores and hormonal parameters were also collected.
MAIN RESULTS
Treatment with danazol (including adjunctive surgical therapy) was effective in relieving painful symptoms related to endometriosis when compared to placebo. Laparoscopic scores were improved with danazol treatment (including adjunctive therapy) when compared with either placebo or no treatment. Side effects were more commonly reported in those patients receiving danazol than placebo.
REVIEWER'S CONCLUSIONS
Danazol is effective in treating the symptoms and signs of endometriosis. However, its use is limited by the occurrence of androgenic side effects.
Topics: Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Pelvic Pain; Randomized Controlled Trials as Topic
PubMed: 11687066
DOI: 10.1002/14651858.CD000068 -
The Cochrane Database of Systematic... 2000Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments... (Review)
Review
BACKGROUND
Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments for endometriosis aim to remove or decrease deposits of ectopic endometrium. The observation that hyperandrogenic states (an excess of male hormone) induce atrophy of the endometrium has led to the use of androgens in the treatment of endometriosis. Danazol is one of these treatments used. The efficacy of danazol is based on its ability to produce a high androgen/low estrogen environment (a pseudo menopause) which results in the atrophy of endometriotic implants and thus an improvement in painful symptoms.
OBJECTIVES
To determine the effectiveness of danazol compared to placebo or no treatment in the treatment of the symptoms and signs, other than infertility, of endometriosis in women of reproductive age.
SEARCH STRATEGY
The Menstrual Disorders Group search strategy was used to identify randomised controlled trials of the use of danazol in endometriosis. In addition, all reference lists of included trials were searched, and relevant drug companies were contacted for details of unpublished trials
SELECTION CRITERIA
Randomised controlled trials in which danazol (alone or as adjunctive therapy) was compared to placebo or no therapy. Trials which only reported infertility outcomes were excluded.
DATA COLLECTION AND ANALYSIS
Only four trials met the inclusion criteria and two authors extracted data independently from these trials. All four trials compared danazol to placebo. Two trials used danazol as sole therapy and two trials used danazol as an adjunct to surgery. Although the main outcome was pain improvement other data relating to laparoscopic scores and hormonal parameters were also collected.
MAIN RESULTS
Treatment with danazol (including adjunctive surgical therapy) was effective in relieving painful symptoms related to endometriosis when compared to placebo. Laparoscopic scores were improved with danazol treatment (including adjunctive therapy) when compared with either placebo or no treatment. Side effects were more commonly reported in those patients receiving danazol than placebo.
REVIEWER'S CONCLUSIONS
Danazol is effective in treating the symptoms and signs of endometriosis. However, its use is limited by the occurrence of androgenic side effects.
Topics: Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Pelvic Pain
PubMed: 10796483
DOI: 10.1002/14651858.CD000068 -
Current Opinion in Hematology Nov 2016Dyskeratosis congenita is an inherited bone marrow failure syndrome caused by defects in telomere maintenance. Hematopoietic stem cell transplantation (HSCT) is the only... (Review)
Review
PURPOSE OF REVIEW
Dyskeratosis congenita is an inherited bone marrow failure syndrome caused by defects in telomere maintenance. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure because of dyskeratosis congenita. The present review summarizes the literature with respect to the diagnosis and treatment of patients with dyskeratosis congenita who received HSCT, and discusses the recent progress in the management of dyskeratosis congenita.
RECENT FINDINGS
The recent systematic review of the literature showed poor long-term outcome, with 10-year survival estimates of only 23% in 109 patients with dyskeratosis congenita who received HSCT. Multivariate analysis identified age greater than 20 years at HSCT, HSCT before 2000, and alternative donor source to be poor prognostic markers. HSCT for dyskeratosis congenita is characterized by a marked decline in long-term survival because of late deaths from pulmonary complications. However, a prospective study using danazol showed promising results in gain in telomere length and hematologic responses.
SUMMARY
A recent prospective study may support the recommendation that HSCT is not indicated for patients with dyskeratosis congenita; instead, they should receive androgen, particularly danazol, as a first-line therapy. Another option may be routine use of androgen after HSCT for the prophylaxis of pulmonary fibrosis.
Topics: Combined Modality Therapy; Disease Management; Dyskeratosis Congenita; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome
PubMed: 27607446
DOI: 10.1097/MOH.0000000000000290 -
The Cochrane Database of Systematic... Jan 2013Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.
OBJECTIVES
The primary objective of this review was to investigate the effectiveness of NSAIDs in achieving a reduction in menstrual blood loss in women of reproductive years with HMB.
SEARCH METHODS
We searched the Cochrane Menstrual Disorders & Subfertility Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL in July 2012 and reference lists of articles. We also contacted manufacturers and researchers in the field.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with either each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their heavy menstrual blood loss.
DATA COLLECTION AND ANALYSIS
Eighteen RCTs were identified that fulfilled the inclusion criteria for this review and data were extracted independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data and one trial with missing variances were described in data tables.
MAIN RESULTS
As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than either tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There were no statistically significant differences between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system (Progestasert), oral contraceptive pill (OCC)) but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB.
AUTHORS' CONCLUSIONS
NSAIDs reduce HMB when compared with placebo but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or another type of intrauterine system, Progestasert.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Menorrhagia; Randomized Controlled Trials as Topic
PubMed: 23440779
DOI: 10.1002/14651858.CD000400.pub3 -
La Revue de Medecine Interne Aug 2019Ten to 15% of common variable immunodeficiencies (CVID) develop auto-immune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Treatment is based on...
INTRODUCTION
Ten to 15% of common variable immunodeficiencies (CVID) develop auto-immune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Treatment is based on immunosuppressants, which produce blocking effects in the CVID. Our objective was to assess their risk-benefit ratio in these immunocompromised patients.
METHODS
We identified 17 articles detailing the treatment of AIHA and/or ITP in patients suffering from CVID through a systematic review of the MEDLINE database.
RESULTS
The increased infectious risk with corticosteroids does not call into question their place in the first line of treatment of ITP and AIHA in CVID. High-doses immunoglobulin therapy remain reserved for ITP with a high risk of bleeding. In second-line treatment, rituximab appears to be effective, with a lower infectious risk than the splenectomy. Immunosuppressants (azathioprine, methotrexate, mycophenolate, cyclophosphamide, vincristine, ciclosporine) are moderately effective and often lead to severe infections, meaning that their use is justified only in resistant cases and steroid-sparing. Dapsone, danazol and anti-D immunoglobulins have an unfavorable risk-benefit ratio. The place of TPO receptor agonists is still to be defined. The establishment of immunoglobulin replacement in the place of immunosuppressants (except for short-term corticotherapy) or splenectomy appears to be essential to limit the risk of infections, including in the absence of previous infections.
CONCLUSION
The presence of CVID does not mean that it is necessary to give up on corticosteroids as a first-line treatment and rituximab as a second-line treatment for AIHA and ITP, but it should be in addition to immunoglobulin replacement. A splenectomy should be reserved as a third-line treatment.
Topics: Anemia, Hemolytic, Autoimmune; Common Variable Immunodeficiency; Danazol; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Rituximab; Splenectomy
PubMed: 31101329
DOI: 10.1016/j.revmed.2019.02.006 -
The Cochrane Database of Systematic... Oct 2009Menorrhagia (heavy menstrual bleeding) is a benign yet debilitating social and health condition. Treatments prescribed in order to reduce excessive menstrual blood loss... (Review)
Review
BACKGROUND
Menorrhagia (heavy menstrual bleeding) is a benign yet debilitating social and health condition. Treatments prescribed in order to reduce excessive menstrual blood loss include prostaglandin synthetase inhibitors, antifibrinolytics, the oral contraceptive pill and other hormones. The combined oral contraceptive pill (OCP) is claimed to have a variety of beneficial, inducing a regular shedding of a thinner endometrium and inhibiting ovulation thus having the effect of treating menorrhagia and providing contraception.
OBJECTIVES
To determine the effectiveness of oral contraceptive pills compared with other medical therapies, placebo or no therapy in the treatment of heavy menstrual bleeding.
SEARCH STRATEGY
We searched the Menstrual Disorders and Subfertility Group trials register (search dates: Oct 1996, May 2002, June 2004, April 2006 and June 2009) for all publications which describe randomised trials of OCP for the treatment of menorrhagia. This register is based on regular searches of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, the hand searching of 20 relevant journals and conference proceedings, and searches of several key grey literature sources.
SELECTION CRITERIA
All randomised controlled comparisons of OCP versus other medical therapies, placebo or no treatment for the treatment of menorrhagia. Women of reproductive years with regular heavy periods, measured either objectively or subjectively and greater than, or equal to, two months follow up.
DATA COLLECTION AND ANALYSIS
All assessments of trial quality and data extraction were performed unblinded by at least two reviewers. Only one trial of 45 women met the inclusion criteria and none were excluded.
MAIN RESULTS
As the trial used a cross-over design, only data from the first treatment period (cycles three and four) were analysed. The results from all the three mefenamic acid groups were combined. There was no significant difference in menstrual blood loss (MBL) between those women treated with the OCP and danazol, mefenamic acid or naproxen.
AUTHORS' CONCLUSIONS
One small study found no significant difference between groups treated with OCP, mefenamic acid, low dose danazol or naproxen. Overall, the evidence from the one study is not sufficient to adequately assess the effectiveness of OCP.This review was unable to achieve its stated objectives because of the paucity of the data.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Contraceptives, Oral; Danazol; Drug Therapy, Combination; Female; Humans; Mefenamic Acid; Menorrhagia; Naproxen
PubMed: 19821266
DOI: 10.1002/14651858.CD000154.pub2 -
Obstetrics and Gynecology Mar 2013To compare the effectiveness of nonsurgical abnormal uterine bleeding treatments for bleeding control, quality of life (QOL), pain, sexual health, patient satisfaction,... (Comparative Study)
Comparative Study Review
OBJECTIVE
To compare the effectiveness of nonsurgical abnormal uterine bleeding treatments for bleeding control, quality of life (QOL), pain, sexual health, patient satisfaction, additional treatments needed, and adverse events.
DATA SOURCES
MEDLINE, Cochrane databases, and Clinicaltrials.gov were searched from inception to May 2012. We included randomized controlled trials of nonsurgical treatments for abnormal uterine bleeding presumed secondary to endometrial dysfunction and abnormal uterine bleeding presumed secondary to ovulatory dysfunction. Interventions included the levonorgestrel intrauterine system, combined oral contraceptive pills (OCPs), progestins, nonsteroidal anti-inflammatory drugs (NSAIDs), and antifibrinolytics. Gonadotropin-releasing hormone agonists, danazol, and placebo were allowed as comparators.
METHODS OF STUDY SELECTION
Two reviewers independently screened 5,848 citations and extracted eligible trials. Studies were assessed for quality and strength of evidence.
TABULATION, INTEGRATION, AND RESULTS
Twenty-six articles met inclusion criteria. For reduction of menstrual bleeding in women with abnormal uterine bleeding presumed secondary to endometrial dysfunction, the levonorgestrel intrauterine system (71-95% reduction), combined OCPs (35-69% reduction), extended cycle oral progestins (87% reduction), tranexamic acid (26-54% reduction), and NSAIDs (10-52% reduction) were all effective treatments. The levonorgestrel intrauterine system, combined OCPs, and antifibrinolytics were all superior to luteal-phase progestins (20% increase in bleeding to 67% reduction). The levonorgestrel intrauterine system was superior to combined OCPs and NSAIDs. Antifibrinolytics were superior to NSAIDs for menstrual bleeding reduction. Data were limited on other important outcomes such as QOL for women with abnormal uterine bleeding presumed secondary to endometrial dysfunction and for all outcomes for women with abnormal uterine bleeding presumed secondary to ovulatory dysfunction.
CONCLUSION
For the reduction in mean blood loss in women with heavy menstrual bleeding presumed secondary to abnormal uterine bleeding presumed secondary to endometrial dysfunction, we recommend the use of the levonorgestrel intrauterine system over OCPs, luteal-phase progestins, and NSAIDs. For other outcomes (QOL, pain, sexual health, patient satisfaction, additional treatments needed, and adverse events) and for treatment of abnormal uterine bleeding presumed secondary to ovulatory dysfunction, we were unable to make recommendations based on the limited available data.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antifibrinolytic Agents; Contraceptives, Oral, Combined; Dysmenorrhea; Female; Humans; Intrauterine Devices, Medicated; Menorrhagia; Patient Satisfaction; Quality of Life; Randomized Controlled Trials as Topic; Reproductive Health; Tranexamic Acid
PubMed: 23635628
DOI: 10.1097/AOG.0b013e3182839e0e -
Obstetrical & Gynecological Survey Jun 2008To examine the need for and evaluate the method of menses suppression in women at risk for thrombocytopenia. A systematic review of the published literature in MEDLINE... (Review)
Review
To examine the need for and evaluate the method of menses suppression in women at risk for thrombocytopenia. A systematic review of the published literature in MEDLINE using the search terms thrombocytopenia, menorrhagia, therapeutic amenorrhea, progestin intrauterine device, combination oral contraceptive--extended and cyclic, gonadotropin releasing hormone agonist, danazol, and progestins. There are an increased number of reproductive age women at risk for thrombocytopenia who would benefit from menses suppression. A number of effective medical regimens are available. In patients who fail medical therapy, endometrial ablation appears to be effective in women with thrombocytopenia. As a result of the increased number of women at risk for thrombocytopenia, there is a need for therapeutic amenorrhea. The type of regimen selected depends upon the patients need for contraception and the ability to tolerate estrogen-containing medications. For women who fail medical therapy, there are surgical options, which are associated with less morbidity than hysterectomy.
Topics: Adult; Comorbidity; Contraceptive Agents, Female; Danazol; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Hematopoietic Stem Cell Transplantation; Humans; Hysterectomy; Intrauterine Devices; Levonorgestrel; Menorrhagia; Menstruation; Thrombocytopenia
PubMed: 18492296
DOI: 10.1097/OGX.0b013e3181706620