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Annals of Internal Medicine Nov 2009Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing in men with ED, are uncertain.
PURPOSE
To evaluate the efficacy and harms of oral phosphodiesterase-5 (PDE-5) inhibitors and hormonal treatments for ED and assess the effect of measuring serum hormone levels on treatment outcomes for ED.
DATA SOURCES
English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, and SCOPUS through April 2009. Trial reference lists also were scanned.
STUDY SELECTION
Randomized, controlled trials (RCTs) of oral PDE-5 inhibitors and hormonal treatment for ED, and observational studies reporting measurement of serum hormone levels, prevalence of hormonal abnormalities, or both in men with ED.
DATA EXTRACTION
Two independent reviewers abstracted data on study, participant, and treatment characteristics; efficacy and harms outcomes; and prevalence of hormonal abnormalities.
DATA SYNTHESIS
Data, primarily from short-term trials (
LIMITATIONS
Many RCTs were of low methodological and reporting quality, particularly those involving hormonal treatments or directly comparing different PDE-5 inhibitors. Most RCTs provided only short-term efficacy and harms data.
CONCLUSION
Oral PDE-5 inhibitors improved erectile functioning and had similar efficacy and safety profiles. Results on the efficacy of hormonal treatments and the value of hormone testing in men with ED were inconclusive.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality.
Topics: Contraindications; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Hormone Replacement Therapy; Humans; Hyperprolactinemia; Hypogonadism; Male; Penile Erection; Prolactin; Testosterone
PubMed: 19884626
DOI: 10.7326/0003-4819-151-9-200911030-00150 -
Maturitas Jun 2011To systematically review the evidence for a relationship between sex hormones and structural changes in osteoarthritis (OA). (Review)
Review
AIM
To systematically review the evidence for a relationship between sex hormones and structural changes in osteoarthritis (OA).
METHODS
Electronic searches of MEDLINE were performed in November-December 2010 and in February 2011 for studies of sex hormones and OA that met a predefined set of criteria. Both controlled trials and observational studies were eligible for inclusion. Two independent reviewers extracted the data and assessed the methodological quality of the included studies. Due to the heterogeneity of the studies, we were unable to perform a best evidence synthesis. However we have provided summaries for each section.
RESULTS
Twenty-seven studies were included in this review, of which 11 were considered high quality. The evidence suggests an association between endogenous oestrogen and cartilage turnover and radiographic OA, and between testosterone and cartilage volume. There is also evidence for an association between exogenous oestrogen and cartilage and bone turnover, although its effects on radiographic and MRI structure as well as joint replacement are unclear. The evidence also supports an association between oestrogen receptor α and β gene polymorphisms and OA.
CONCLUSION
Although the heterogeneity of the studies means that there is insufficient evidence to form strong conclusions, the available evidence supports an effect of endogenous and exogenous oestrogen as well as oestrogen receptor polymorphisms on joint health.
Topics: Cartilage; Estrogens; Gonadal Steroid Hormones; Humans; Joints; Osteoarthritis; Polymorphism, Genetic; Radiography; Receptors, Estrogen; Testosterone
PubMed: 21481553
DOI: 10.1016/j.maturitas.2011.03.019 -
Burns : Journal of the International... Jun 2016The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of using oxandrolone in patients with severe burns. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of using oxandrolone in patients with severe burns.
MATERIALS AND METHOD
PubMed, Medline, Ovid, Cochrane Library, Elsevier Science, ProQuest, and Springer Link databases were searched. Randomized trials were included, and clinically important measures were selected. The outcomes were pooled with Revman 5.2. Other outcomes that could not be pooled were described in detail.
RESULTS
Finally, 15 randomized controlled trials (RCTs) were identified for analysis in this review, including 806 participants. 1. Mortality, infection, and hepatic function: Oxandrolone therapy did not affect mortality (relative risk (RR)=0.85, 95% confidence interval (CI)=(0.38, 1.89), P=0.69) or infection (RR=0.87, (0.69, 1.11), P=0.26). The two groups (oxandrolone group vs. control group) showed no significant difference in liver dysfunction (RR=1.15, (0.83, 1.59), P=0.41). All the 15 RCTs reported no incidence of hepatic insufficiency in controls or treatment groups. 2. In the catabolic phase: Treatment with oxandrolone shortened length of stay by 3.02 (2.37, 3.66) days, donor-site healing time by 4.41 (3.41, 5.41) days, the time between surgical procedures by 0.63 (0.11, 1.16) days, as well as reduced weight loss by 5 (3.70, 6.30) kg and nitrogen loss by 8.19 (6.87, 9.52) g/day, with all P<0.00001. 3. In the rehabilitative phase: Treatment with oxandrolone shortened the length of stay to 6.45 (4.20, 8.69) days, as well as decreased weight loss by 0.86 (0.76, 0.96) kg/week and reduction of lean body mass by 5% (3.34, 6.66), with all P<0.00001. 4. Long-term parameters: Oxandrolone treatment led to an additional gain in lean body mass of 3.99% (3.08, 4.89) after 6 months and 10.78% (9.92, 11.64) after 12 months in patients with severe burns, with all P<0.00001.
CONCLUSION
The treatment of severe burns with oxandrolone is significantly effective without obvious side effects.
Topics: Anabolic Agents; Body Composition; Body Weight; Burns; Chemical and Drug Induced Liver Injury; Humans; Infections; Length of Stay; Mortality; Oxandrolone; Trauma Severity Indices; Wound Healing
PubMed: 26454425
DOI: 10.1016/j.burns.2015.08.023 -
The Cochrane Database of Systematic... 2003Hirsutism is a distressing and relatively common endocrine problem in women which may prove difficult to manage. Cyproterone acetate, an anti-androgen, is frequently... (Review)
Review
BACKGROUND
Hirsutism is a distressing and relatively common endocrine problem in women which may prove difficult to manage. Cyproterone acetate, an anti-androgen, is frequently used to treat hirsutism, usually in combination with ethinyl estradiol.
OBJECTIVES
The objective of this review was to investigate the effectiveness of cyproterone acetate alone, or in combination with ethinyl estradiol, in reducing hair growth in women with hirsutism secondary to ovarian hyperandrogenism.
SEARCH STRATEGY
The Cochrane Menstrual Disorders and Subfertility Group trials register was searched (last search - 4 June 2002). The Cochrane Menstrual Disorders and Subfertility Group register is based on regular searches of MEDLINE (1966 to 2002), EMBASE (1980 to 2002), CINAHL (1982 to 2002), PsycINFO (1987 to 2002) and CENTRAL (Issue 2, 2002 of the Cochrane Library) the handsearching of several journals and conference proceedings, and searches of several key grey literature sources. All publications of randomised controlled trials of cyproterone acetate with or without estrogen versus placebo or other drug therapies for hirsutism were identified.
SELECTION CRITERIA
All randomised controlled studies comparing:- cyproterone acetate to placebo- cyproterone acetate with ethinyl estradiol to placebo- cyproterone acetate with ethinyl estradiol to cyproterone acetate alone- cyproterone acetate (with or without estradiol) to other medical therapies for treatment of hirsutism.
DATA COLLECTION AND ANALYSIS
Eleven studies were identified which fulfilled the inclusion criteria. Nine randomised studies were included in the review, and two were excluded because of insufficient information. Only one study had more than 100 women included in the analysis. The major outcomes included: subjective improvement in hirsutism, changes in Ferriman Gallwey scores, changes in linear hair growth and hair shaft diameter, alterations in endocrine parameters, side effects to treatment, withdrawals during therapy
MAIN RESULTS
There were no clinical trials comparing cyproterone acetate alone with placebo. There was one small study comparing cyproterone acetate in combination with ethinyl estradiol to placebo. In this study there was a significant subjective reduction in hair growth with cyproterone acetate therapy, although the confidence limits were large. There were no studies comparing cyproterone acetate alone with cyproterone acetate in combination with ethinyl estradiol to treat hirsutism. In studies where cyproterone acetate was compared to other drug modalities (ketoconazole, spironolactone, flutamide, finasteride, GnRH analogues) no difference in clinical outcome was noted. There were, however, endocrinological differences in androgen and estrogen levels between different drug therapies. There were insufficient data to assess differences in side effects between women treated with cyproterone acetate and other medical therapy.
REVIEWER'S CONCLUSIONS
Cyproterone acetate combined with estradiol results in a subjective improvement in hirsutism compared to placebo. Clinical differences in outcome between cyproterone acetate and other medical therapies were not demonstrated in the studies included in this review. This may be because of the small size of the studies, lack of standardized assessment and lack of objective determinants of improvement in hirsutism. The endocrinological effects of the different drug therapies reflect the mode of action. Larger carefully designed studies are needed to compare efficacy and safety profiles between drug therapies for hirsutism.
Topics: Androgen Antagonists; Cyproterone Acetate; Drug Therapy, Combination; Ethinyl Estradiol; Female; Hirsutism; Humans; Hyperandrogenism; Randomized Controlled Trials as Topic
PubMed: 14583927
DOI: 10.1002/14651858.CD001125 -
The Cochrane Database of Systematic... Mar 2012Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so 'add-back' therapy is needed.
OBJECTIVES
To summarize all randomized controlled trials (RCTs) of male hormonal contraception.
SEARCH METHODS
In January and February 2012, we searched the computerized databases CENTRAL, MEDLINE, POPLINE, and LILACS. We also searched for recent trials in ClinicalTrials.gov and ICTRP. Previous searches included EMBASE. We wrote to authors of identified trials to seek additional unpublished or published trials.
SELECTION CRITERIA
We included all RCTs that compared a steroid hormone with another contraceptive. We excluded non-steroidal male contraceptives, such as gossypol. We included both placebo and active-regimen control groups.
DATA COLLECTION AND ANALYSIS
The primary outcome measure was the absence of spermatozoa on semen examination, often called azoospermia. Data were insufficient to examine pregnancy rates and side effects.
MAIN RESULTS
We found 33 trials that met our inclusion criteria. The proportion of men who reportedly achieved azoospermia or had no detectable sperm varied widely. A few important differences emerged. 1) Levonorgestrel implants (160 μg daily) combined with injectable testosterone enanthate (TE) were more effective than levonorgestrel 125 µg daily combined with testosterone patches. 2) Levonorgestrel 500 μg daily improved the effectiveness of TE 100 mg injected weekly. 3) Levonorgestrel 250 μg daily improved the effectiveness of testosterone undecanoate (TU) 1000 mg injection plus TU 500 mg injected at 6 and 12 weeks. 4) Desogestrel 150 μg was less effective than desogestrel 300 μg (with testosterone pellets). 5) TU 500 mg was less likely to produce azoospermia than TU 1000 mg (with levonorgestrel implants). 6) Norethisterone enanthate 200 mg with TU 1000 mg led to more azoospermia when given every 8 weeks versus 12 weeks. 7) Four implants of 7-alpha-methyl-19-nortestosterone (MENT) were more effective than two MENT implants. We did not conduct any meta-analysis due to intervention differences.Several trials showed promising efficacy in percentages with azoospermia. Three examined desogestrel and testosterone preparations or etonogestrel and testosterone, and two examined levonorgestrel and testosterone.
AUTHORS' CONCLUSIONS
No male hormonal contraceptive is ready for clinical use. Most trials were small exploratory studies. Their power to detect important differences was limited and their results imprecise. In addition, assessment of azoospermia can vary by sensitivity of the method used. Future trials need more attention to the methodological requirements for RCTs. More trials with adequate power would also be helpful.
Topics: Azoospermia; Contraception; Contraceptive Agents, Male; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Synthetic; Desogestrel; Drug Implants; Humans; Levonorgestrel; Male; Norethindrone; Oligospermia; Randomized Controlled Trials as Topic; Testosterone
PubMed: 22419294
DOI: 10.1002/14651858.CD004316.pub4 -
The Cochrane Database of Systematic... Jan 2007The synthetic androgen Danazol, was developed in the 1970's as a treatment for endometriosis. Its use was soon advocated in women with unexplained subfertility. Two... (Review)
Review
BACKGROUND
The synthetic androgen Danazol, was developed in the 1970's as a treatment for endometriosis. Its use was soon advocated in women with unexplained subfertility. Two randomised trials were subsequently conducted to assess the effectiveness of danazol in this population.
OBJECTIVES
The objective of this review was to assess the effect of danazol on live birth rate in women with unexplained subfertility.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Sub-fertility Group's specialised register of trials (searched November , 2006) the Cochrane Register of Controlled Trials (The Cochrane Library, Issue 4, 2006), MEDLINE (1966-November 2006), EMBASE (1980 - November 2006) and reference lists of articles.
SELECTION CRITERIA
Randomised trials of danazol compared with placebo or no treatment in women with unexplained subfertility.
DATA COLLECTION AND ANALYSIS
Data were extracted by two reviewers EH and GT.
MAIN RESULTS
Two trials involving seventy-one women were included. There was no statistically significant difference in the live birth/ ongoing pregnancy rate between danazol and placebo at the end of treatment (OR 1.16, 95% CI 0.0 to 8.29; P=0.36) or at the end of follow-up (OR 2.41; 95% CI 0.59, 9.82; P=0.22). There was no significant difference in clinical pregnancies following treatment (OR 0.14, 95% CI 0.01, 2.26; P=0.17), however there were significantly more clinical pregnancies during the follow-up period in the danazol group compared with the placebo group (OR 3.15, 95%CI 0.98, 10.10; P<0.05). Multiple side effects were reported.
AUTHORS' CONCLUSIONS
Available data demonstrate no evidence of the benefit of danazol for unexplained subfertility. Although there is insufficient evidence to be certain of this, the need for contraception during treatment and the adverse effects and costs of danazol, make its use for this problem unwarranted. The increased pregnancy rate in the long term follow-up data may be attributable to additional therapies and did not influence the live birth/ongoing pregnancy data.
Topics: Danazol; Estrogen Antagonists; Female; Humans; Infertility, Female
PubMed: 17253444
DOI: 10.1002/14651858.CD000069.pub2 -
Testosterone Supplementation and Cognitive Functioning in Men-A Systematic Review and Meta-Analysis.Journal of the Endocrine Society Aug 2019Testosterone supplementation (TS) is assumed important for cognitive functioning in men, but conflicting results have prevented firm conclusions. The current study...
Testosterone supplementation (TS) is assumed important for cognitive functioning in men, but conflicting results have prevented firm conclusions. The current study systematically reviewed available randomized controlled trials (RCTs) on effects of TS on cognitive functioning in men, subjected the findings to meta-analysis, and explored between-study differences as possible moderators of the effects. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, two authors independently searched for eligible records in the electronic databases of PubMed, PsycINFO, Web of Science, the Cochrane Library, Cumulative Index of Nursing and Allied Health, and Embase and determined eligibility using the following (population, intervention, comparison, outcome) criteria: population, male adults (>18 years); intervention, TS; comparison, placebo; and outcome, results of standardized neuropsychological tests. Following duplicate removal, 3873 records were screened with 92 remaining for full-text screening. Twenty-one papers reporting results of 23 independent RCTs were included, of which none treated samples of clinically hypogonadal men. The small improvement found in overall cognitive functioning (Hedges = 0.09; CI 95%: -0.02 to 0.19) failed to reach statistical significance ( = 0.108) and approached zero when adjusting for possible publication bias ( = 0.04). The effects for the 11 individual cognitive domains did not reach statistical significance (: -0.04 to 0.19, : 0.061 to 0.989). Small statistically significant ( < 0.05) effects were found for five study subsets but failed to meet the fail-safe criterion. The available evidence indicates that effects of TS on cognitive functioning in men with testosterone levels within normal ranges are less robust and of insufficient magnitude to be of clinical relevance. The effects in clinically hypogonadal men remain to be investigated.
PubMed: 31384712
DOI: 10.1210/js.2019-00119 -
Human Reproduction Update Jul 2018Testicular sperm extraction (TESE) is a surgical procedure to retrieve spermatozoa from the testes of men with azoospermia to help them achieve biological parenthood.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Testicular sperm extraction (TESE) is a surgical procedure to retrieve spermatozoa from the testes of men with azoospermia to help them achieve biological parenthood. Although effective, the surgical procedure is not without complications and haematoma, devascularization, inflammation and a decrease in testosterone levels have been described as such. The prevalence and duration of hypogonadism and associated symptoms after TESE have not been studied systematically.
OBJECTIVE AND RATIONALE
In this systematic review we addressed the following research questions: Are serum testosterone levels decreased after TESE and, if so, do these levels recover over time? What is the prevalence of symptoms and signs related to hypogonadism after TESE and are they related to testosterone levels?
SEARCH METHODS
We searched the databases Pubmed and Embase from 1 January 1993 to 26 June 2017. We combined subject headings with terms in title and/or abstract for participants, intervention and outcomes. We included all studies that reported on TESE, regardless of the specific technique used, that measured testosterone and/or LH, and/or had information on signs or symptoms related to hypogonadism as defined by hypogonadism guidelines. An additional inclusion criterion was that studies described these measurements both before and after TESE. The quality of the included studies was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions tool.
OUTCOMES
We identified 15 studies reporting on total testosterone levels of which five studies also reported on testicular volume and one study on erectile dysfunction. Men with Klinefelter syndrome and men with non-obstructive azoospermia had the strongest decrease in total testosterone levels 6 months after TESE, with a mean decrease of 4.1 and 2.7 nmol/l, respectively, which recovered again to baseline levels 26 and 18 months after TESE, respectively. At 6 months after TESE, some studies reported serum total testosterone concentrations below a cut-off value of 12 nmol/l, where symptoms and signs related to hypogonadism may appear. Furthermore, an increased prevalence of erectile dysfunction related to decreased total testosterone levels 6 months after TESE was reported. Also, in some men a decrease in testicular volume was reported. However, it is not clear if this is related to low testosterone levels.
WIDER IMPLICATIONS
The transient, but statistically significant, decrease in total testosterone levels indicates that men are at risk of developing a temporary hypogonadism after TESE, but there is insufficient evidence for whether patients actually experience clinical symptoms in case of decreased serum testosterone levels. To be able to properly counsel TESE patients, more large-scale monitoring on signs and symptoms of hypogonadism, in combination with testosterone measurements, needs to be performed in men undergoing TESE.
Topics: Adult; Azoospermia; Humans; Hypogonadism; Klinefelter Syndrome; Male; Risk Factors; Sperm Retrieval; Spermatozoa; Testosterone
PubMed: 29726895
DOI: 10.1093/humupd/dmy015 -
Maturitas Jun 2024Prostate cancer survivors treated with androgen deprivation therapy may be at increased risk of cardiovascular disease. Dietary recommendations for the prevention and/or... (Review)
Review
The effect of dietary interventions or patterns on the cardiometabolic health of individuals treated with androgen deprivation therapy for prostate cancer: A systematic review.
Prostate cancer survivors treated with androgen deprivation therapy may be at increased risk of cardiovascular disease. Dietary recommendations for the prevention and/or management of cardiovascular disease for these individuals are lacking. This review synthesizes the evidence on the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk in prostate cancer survivors receiving androgen deprivation therapy. A systematic review was conducted across PubMed, CINAHL, Embase, and Cochrane CENTRAL. Intervention or observational cohort studies evaluating diets, nutrients, or nutraceuticals with or without concurrent exercise interventions on cardiovascular disease, cardiovascular events, or cardiovascular disease biomarkers in those treated with androgen deprivation therapy were included. Confidence in the body of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations. Twelve studies reported across fifteen papers were included. Interventions were heterogenous, with most studies including an exercise co-intervention (n = 8). Few significant findings for the effects of diet on cardiometabolic markers were likely due to weak methodology and sample sizes. Strongest evidence was for the effect of a healthy Western dietary pattern with exercise on improved blood pressure (Confidence: moderate). The healthy Western dietary pattern with exercise may improve high-density lipoprotein cholesterol (Confidence: Low) and flow-mediated dilation. Soy may improve total cholesterol (Confidence: Very low). A low-carbohydrate diet with physical activity may improve high-density lipoprotein cholesterol, incidence of metabolic syndrome, and Framingham cardiovascular disease risk score. Evidence of the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk of prostate cancer survivors receiving androgen deprivation therapy is insufficient to inform practice. Well-designed dietary interventions aimed at improving cardiometabolic outcomes of this population are warranted to inform future dietary recommendations.
Topics: Humans; Male; Prostatic Neoplasms; Androgen Antagonists; Cardiovascular Diseases; Exercise; Diet; Dietary Supplements
PubMed: 38430616
DOI: 10.1016/j.maturitas.2024.107940 -
European Urology Jan 2010The well-known side-effect profile of androgen-deprivation therapy (ADT) has significant quality-of-life (QoL) implications. Intermittent androgen deprivation (IAD)... (Review)
Review
CONTEXT
The well-known side-effect profile of androgen-deprivation therapy (ADT) has significant quality-of-life (QoL) implications. Intermittent androgen deprivation (IAD) alternates androgen blockade with treatment cessation to allow hormonal recovery between treatment cycles, thus potentially improving tolerability and QoL.
OBJECTIVE
To evaluate available evidence regarding the efficacy and tolerability of IAD and assess its value in the treatment of prostate cancer (PCa).
EVIDENCE ACQUISITION
Key phase 2/3 clinical trials of IAD in PCa published within the last 10 yr were identified on Medline using the terms prostatic neoplasms [MeSH], intermittent androgen suppression, intermittent hormonal deprivation, intermittent androgen deprivation, and intermittent hormonal therapy. Abstracts from trials reported at 2008-2009 conferences were also included.
EVIDENCE SYNTHESIS
Data from 19 phase 2 studies are discussed with respect to prostate-specific antigen values for treatment suspension/reinitiation, treatment regimens, cycle lengths, testosterone normalisation, and tolerability. Outcome data were promising: Most trials reported an improvement in QoL during the off-therapy periods. Interim data from eight phase 3 trials comparing IAD and continuous androgen deprivation (CAD) support the phase 2 results. IAD generally showed comparable efficacy to CAD with respect to various outcomes, including biochemical progression, progression-free survival, and overall survival. However, IAD was significantly better than CAD with respect to 3-yr risk of progression in one study, and it demonstrated tolerability benefits, particularly with respect to sexual function. Patients most likely to benefit from IAD and factors predictive of poor response are also discussed.
CONCLUSIONS
IAD seems to be as effective as CAD while showing tolerability and QoL advantages, especially recovery of sexual potency; however, there are as yet insufficient data to determine whether IAD has the potential to prevent or reverse the long-term complications associated with ADT.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Evidence-Based Medicine; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Time Factors; Treatment Outcome
PubMed: 19683858
DOI: 10.1016/j.eururo.2009.07.049