Quality of reporting in randomized trials published in high-quality surgical journals. Clinical implications from an exploratory study of postural management of breech presentation. Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone. Epidemiologic studies of adverse effects of anti-retroviral drugs: how well is statistical power reported. Maintenance clinical trials in bipolar disorder: design implications of the divalproex-lithium-placebo study. Suppression of spermatogenesis with desogestrel and testosterone pellets is not enhanced by addition of finasteride. POWER for reproductive health: results from a social marketing campaign promoting female and male condoms. Potential of testosterone buciclate for male contraception: endocrine differences between responders and nonresponders. Searching MEDLINE for randomized clinical trials involving care of the newborn. Problems in conducting economic evaluations alongside clinical trials. Lessons from a study of case management for people with mental disorders. Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in chinese men. Reporting of randomized controlled trials in Hodgkin lymphoma in biomedical journals. Oestradiol enhances testosterone-induced suppression of human spermatogenesis. Secular changes in the quality of published randomized clinical trials in rheumatology. EMDR for panic disorder with agoraphobia: comparison with waiting list and credible attention-placebo control conditions. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations. Randomized controlled trials in pediatric surgery: could we do better? Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review. How easy are randomized controlled trials in epilepsy to find on Medline? The sensitivity and precision of two Medline searches. A prospective, controlled study of the effects of hormonal contraception on bone mineral density. Beyond Medline: reducing bias through extended systematic review search. Improving teenagers' knowledge of emergency contraception: cluster randomised controlled trial of a teacher led intervention. Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach. The quality of randomized controlled trials in major anesthesiology journals. CONSORT adoption and quality of reporting of randomized controlled trials: a systematic analysis in two dermatology journals. Male hormonal contraception: effects of injections of testosterone undecanoate and depot medroxyprogesterone acetate at eight-week intervals in chinese men. Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review. Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism. Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men.
Randomized controlled trials (RCTs) in surgery can provide valuable evidence of the efficacy of interventions if they are well-designed, appropriately executed, and adequately reported. Adequate reporting of methodology in surgical RCTs is known to be poor, and adverse-event reporting in surgical research is inconsistent. The Consolidated Standards of Reporting Trials (CONSORT) statement is a framework to help authors report their findings in a transparent manner. Extensions to the CONSORT statement have been published recently to address deficiencies in adverse-event reporting and in reporting of specific criteria related to nonpharmacologic treatments. The aim of this study was to assess the quality of reporting of trial methodology and adverse events in a sample of general surgical RCTs published in high-quality surgical journals using the criteria specified in the CONSORT statements.
                We used impact factor to identify the top three ranked surgical journals in 2004. We then obtained information on all RCTs published in these journals in the 2005 calendar year. We assessed quality of reporting using Jadad score, compared the quality of RCTs from CONSORT-endorsing journals with nonendorsers, and assessed the number of RCTs adequately reporting key generic methodologic, adverse-event-related, and specific nonpharmacologic criteria.
                Of 42 RCTs analyzed, only 40% (17 of 42) had a Jadad score > or = 3. There was no significant difference in the number of high-quality RCTs published in CONSORT-endorsing journals compared with nonendorsers (p = 0.3). The median percentage of RCTs adequately reporting generic methodologic, adverse-event-related, and specific nonpharmacologic criteria was 32.5%, 17%, and 36.5%, respectively.
                Quality of reporting of generic methodologic, adverse-event-related, and specific nonpharmacologic criteria in surgical RCTs is poor. Increased attention to quality of reporting of surgical RCTs is required if studies are to meet published criteria. The results from an exploratory study of the effectiveness of maternal knee-chest posture for producing cephalic version of breech presentation are shown. Methods are briefly described and clinical implications are presented. Among 25 women, fewer who performed the maternal knee-chest postural intervention experienced fetal cephalic version than women in the control group who did nothing to influence breech presentation. Despite limitations of the underpowered findings, trends in the data may indicate that parity and gestational age were potentially relevant covariates of version. Postural management is not an evidence-based practice. This exploratory study indicates that maternal knee-chest posture may work opposite to the expected direction, but the small sample size precludes generalizations about efficacy of knee-chest postural management. At least one adequately powered trial that controls for parity and gestational age is needed to determine whether knee-chest postural management results in no effect, a small, or small to moderate clinically significant effect. Suppression of spermatogenesis to azoospermia is required for effective hormonal male contraception, but the degree of suppression varies between ethnic groups. We here report the first study of hormonal suppression of spermatogenesis in two African centres using a regimen of oral progestogen with depot testosterone. METHODS A total of 31 healthy men (21 black) were recruited in Cape Town and 21 men in Sagamu, Nigeria. Subjects were randomized to take either 150 or 300 micro g desogestrel daily p.o. with testosterone pellets. In Cape Town, desogestrel was administered for 24 weeks with 400 mg testosterone re-administered 12 weekly. In Sagamu, desogestrel was administered for 52 weeks with 200 mg testosterone (later increased to 400 mg) re-administered 12-weekly.
                In Cape Town, 22 men completed at least 20 weeks treatment. Azoospermia was achieved in 8/10 and 8/12 men in the 150 micro g and 300 micro g desogestrel groups. Four men in Sagamu withdrew. Azoospermia was achieved in all 17 men in the two groups. There were no significant changes in lipoprotein or haemoglobin concentrations in any group.
                These data demonstrate that the combination of oral desogestrel with depot testosterone is an effective regimen for suppression of spermatogenesis in African as in Caucasian and Chinese men, with azoospermia achieved in a total of 83/98 (85%) men. To determine whether there is a difference in average statistical power between pharmacoepidemiologic studies of anti-retroviral adverse drug effects (ADEs) sponsored by for-profit versus non-profit organizations.
                We studied all published pharmacoepidemiologic studies of ADEs associated with the 15 anti-retroviral drugs approved through the end of 1999. A priori, the primary outcome was the power of each study to detect a clinically important difference in the risk for an adverse effect among patients exposed to the study drug(s). We could not evaluate this outcome because of the infrequent reporting of power calculations. We instead report the distribution of studies across a 5-tiered measure of adequacy of reporting of statistical power, as well as the sponsorship of these studies.
                Of 48 studies meeting our inclusion criteria, only 1 (2%) reported either a completed, a priori power calculation or sufficient details for readers to calculate the power to detect a pre-defined, clinically important effect. Thirty-five studies (73%) reported the minimum information required for sophisticated readers to determine the power to detect an event rate of interest to them; 6 additional studies (13%) reported confidence intervals around at least one summary effect measure and 6 (13%) provided no indication of power or uncertainty. Of the 41 studies for which sponsorship was determined, only 3 (7%) were sponsored by for-profit organizations.
                The poor reporting of statistical power in this sample suggests a need for guidelines to improve the reporting of pharmacoepidemiologic studies of ADEs. Future research is needed to determine whether the observed paucity of industry-sponsored observational studies of anti-retroviral ADEs extends to other clinical areas, and if so, to identify the causes of this phenomenon.
                Copyright 2004 John Wiley & Sons, Ltd. Maintenance studies in bipolar disorder have received increased attention in recent years. The interest is driven by apparent contradictions between results of early placebo-controlled trials of lithium and recent open studies, as well as interest in a new group of drugs with mood-stabilizing properties. The multiple outcome indices that require attention in prophylactic bipolar disorder studies add a dimension not present in acute studies of bipolar disorder. We present the methodology of a recently completed randomized, double-blind, placebo-controlled, parallel-group comparison of divalproex and lithium. We examine the consequences of salient design features, along with their implications for future studies. A fundamental conclusion is that such maintenance studies should be designed and executed to emphasize enrollment of patients with relatively active, severe forms of the illness. This goal is not achieved simply, as inherent features of long-term, placebo-controlled studies drive recruitment and enrollment in the direction of patients with milder forms of bipolar disorder. Attention to the frequency of both manic and depressive episodes and the severity of an index manic episode may aid in the selection of patients most suitable for studies designed to achieve adequate statistical power. Conversion of testosterone to dihydrotestosterone (DHT) by the action of 5alpha-reductase can amplify androgen action. This may be of particular importance in the presence of low testosterone concentrations and may contribute to maintenance of spermatogenesis in a proportion of men receiving male contraceptive regimens. We therefore investigated whether the addition of finasteride, a 5alpha-reductase inhibitor, to a prototype male hormonal contraceptive regimen consisting of desogestrel (150 microg orally daily) and repeated administration of testosterone pellets (2 x 200 mg per 12 weeks) would enhance suppression of spermatogenesis. Sixteen normal men were randomized to receive either the standard androgen/progestogen treatment alone (control group) or with finasteride (5 mg orally daily-FIN group) for 24 weeks. Both groups showed profound suppression of spermatogenesis with azoospermia being obtained in 6 of 8 subjects in the control group and in 5 of 7 in the FIN group. There were no significant differences between the groups with respect to sperm concentrations. Significant suppression of luteinizing hormone and follicle-stimulating hormone was achieved within 2 weeks of treatment in both groups, while testosterone concentrations were maintained in the normal physiological range. DHT concentrations fell in both groups but were significantly lower in the FIN group. Gonadotropin and testosterone concentrations were similar for both regimens throughout the study. This study demonstrates the potential for long-term suppression of spermatogenesis using a combination of an oral progestogen with repeated administration of a depot preparation of testosterone. However, these data do not support the involvement of 5alpha-reductase in maintaining residual spermatogenesis during gonadotropin suppression for hormonal male contraception. To evaluate effects of a 6-month social marketing campaign on awareness of, attitudes toward and use of female as well as male condoms for 15-25 year-old-women.
                Using a time-space sampling methodology, we conducted a cross-sectional survey of 3407 women at pre-campaign in 12 western U.S. neighborhoods on female and male condom awareness, attitudes, and use. Six of the 12 study neighborhoods were randomly selected to receive the POWER social marketing campaign designed to impact condom knowledge, attitudes, and use. The campaign was followed with another cross-sectional survey of 3,003 women in all 12 study neighborhoods on condom knowledge, attitudes, use and awareness of POWER materials. We compared pre-and post-campaign surveys to determine the efficacy of POWER and conducted post hoc analyses on post-campaign data to determine if exposure to POWER was related to higher levels of positive condom attitudes and norms and condom use.
                We found no differences between neighborhoods with and without the POWER campaign with regard to our primary outcomes. To diagnose reasons for this null effect, we examined outcomes post hoc examining the influence of POWER exposure. Post hoc analyses show some evidence that exposure to POWER was associated with condom use. In the context of the nested trial, this raises concerns that post test only evaluations are limited.
                Establishing the efficacy of a social marketing campaign is challenging. This group randomized trial showed a null effect. Social marketing campaigns may need to have more media channels and saturation before they can show behavioral effects. Using a nested design with randomization at the community level and probability sampling introduces rigor not commonly seen in evaluations of social marketing campaigns. Suppression of serum LH and FSH, by testosterone (T) alone or in combination with other agents, has proved to be the most promising approach to male contraception. T enanthate, the only androgen preparation tested in male contraceptive efficacy trials so far, must be injected every week due to its short terminal elimination half-life of 4.5 days and leads to supraphysiological T serum levels. A new T ester synthesized under WHO and NIH auspices, testosterone buciclate (TB), showed a favorable pharmacokinetic profile, with a terminal half-life of 29.5 days when tested in hypogonadal men. Here we describe the results of the first clinical trial with TB for male contraception. After two control examinations, normal healthy male volunteers were given a single im injection of 600 mg TB (group I; n = 4) and 1200 mg TB (group II; n = 8) on day 0. Follow-up examinations were performed every 2 weeks up to week 32. In both groups mean serum T levels remained in the normal physiological range throughout the study course. Serum levels of dihydrotestosterone (DHT) showed a dose- and time-dependent increase, with serum levels slightly above the normal range in group II for several weeks and a maximal concentration of 3.8 +/- 0.5 nmol/L (mean +/- SE) in week 6. No suppression of spermatogenesis to oligozoospermia was observed in group I. However, in group II, spermatogenesis was suppressed to azoospermia in three of eight volunteers in week 10 that persisted up to weeks 14, 20, and 22, respectively. In these three men, LH and FSH were suppressed by TB injections to the respective assay detection limits, whereas in the other five subjects, mean serum levels were only decreased to values near the lower normal limit for LH and FSH, respectively. In addition, throughout the study course, a significant difference in serum sex hormone-binding globulin was detected between the responders (mean values, 21.2-26.4 nmol/L) and nonresponders (mean values, 36.2-46.3 nmol/L). Serum levels of LH as well as total and free T at baseline and after TB injection were lower in the responders than in the nonresponders. Both subgroups showed similar increases in serum LH and FSH after GnRH stimulation. In a newly introduced GnRH antagonist suppression test, serum LH and T were decreased to significantly lower levels in the responders. These results indicate a different hormonal equilibrium and probably different susceptibility to feedback regulation of the responders compared to the nonresponders.(ABSTRACT TRUNCATED AT 400 WORDS) Randomized clinical trials make up only a small fraction of published articles concerning care of the newborn infant and an even smaller fraction of articles about all human subjects. The busy pediatrician who wants to keep abreast of the medical literature requires strategies to detect such relevant studies promptly and reliably. Computer searching of MEDLINE is an attractive, potentially powerful but not sufficiently validated means of achieving this goal. Therefore, the sensitivity, specificity, and positive predictive value of two MEDLINE search strategies designed to detect randomized clinical trials for prevention and treatment of newborn diseases among all original articles about human subjects appearing in ten pediatric and general medical journals during 1985 were determined. The yield of both MEDLINE searches was compared to that of a manual search. Fifty-three randomized clinical trials of newborn care were identified by hand search among 233 articles concerning care of the newborn and 2,988 original articles about human subjects. The sensitivities of the MEDLINE searches were 53% and 34%, respectively, and the positive predictive values were 82% and 69%, respectively. Specificity of both computer searches was virtually 100%. Twenty-one randomized clinical trials were not identified by either MEDLINE search strategy, 17 of them for failure of the indexer to assign any methodologic terms at all or failure to assign sufficiently stringent methodologic terms. Consequently, sensitivities were higher, 77% and 68% respectively, when no methodologic terms were used during repeat searches. However, positive predictive values decreased concomitantly to 20% or less.(ABSTRACT TRUNCATED AT 250 WORDS) Case management has become the statutory basis of community care in the UK for people with long-term mental disorders, although a randomised controlled trial found no important improvements over standard care. Here we compare the costs and cost consequences of this intervention with standard care.
                Resource-use data were collected over a six-month baseline period and for 14 months after randomisation on all patients in the trial.
                At 14 months the ratio of control group to treatment group weekly costs was 1.09 (95% CI 0.86-1.38) for total costs; 1.12 (0.76-1.65) for state benefits, and 1.21 (0.61-2.42) for health care costs. Costs were thus lower in the treatment group, but these differences were not significant.
                Retrospective power calculations indicated that the trial could have detected differences of 30% in total cost, but would have required 700 patients per arm to detect a 20% difference in health care costs. Hence this study, which had adequate power to detect clinically meaningful differences, was found to be far too small to detect large differences in costs. Funding agencies increasingly request that clinical trials include economic alongside clinical end-points: these findings may have important lessons for that policy. Monthly injections of testosterone undecanoate (TU) act as a male contraceptive by reversibly suppressing spermatogenesis to azoospermia or severe oligoazoospermia in 95% of Chinese men. In 5% of Chinese men, however, monthly TU administered alone fails to suppress spermatogenesis into contraceptive ranges, or sperm "rebound," leading to occurrences of pregnancy during treatment. Since combinations of progestins and androgens are associated with greater degrees of sperm suppression in white men, we hypothesized that the combination of TU and the progestin levonorgestrel (LNG) would result in improved spermatogenic suppression in Chinese men. Sixty-two healthy Chinese men were randomly assigned to one of the following 3 regimens: group I (n = 21) received 4 LNG rods (75 mg each), which were followed 4 weeks later by 500 mg of TU by intra-muscular (IM) injection every 8 weeks for 24 weeks; group II (n = 20) received 4 LNG implants, which were followed 4 weeks later by 1000 mg of TU by IM injection every 8 weeks for 24 weeks; and group III (n = 21) received TU 1000 mg by IM injection every 8 weeks for 24 weeks. Sperm counts, serum testosterone (T), luteinizing hormone, follicle-stimulating hormone, and LNG were measured every 2 weeks before, during, and after treatment. During treatment, group II demonstrated a trend toward a greater attainment of azoospermia than groups I and III (90% vs 62% [group I] vs 67% [group III]; P =.09). Attainments of either azoospermia or oligozoospermia (sperm density, <3 x 10(6)/mL) were 95%, 100%, and 86% for groups I, II, and III, respectively (P >.05 for comparisons between groups). Spermatogenesis in all subjects returned to the normal range after the implants were removed. No serious adverse events and no significant changes in serum chemistry occurred during the study. These results demonstrate that the combination of IM injections of high-dose TU every 2 months and LNG implants is associated with marked suppression of spermatogenesis in Chinese men. The combination of high-dose TU every 2 months and LNG implants is a promising candidate for future large-scale efficacy studies of hormonal male contraception in Chinese men. Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The Consolidated Standards for Reporting Trials (CONSORT) statement was introduced in 1996 to improve reporting of RCTs. We aimed to determine the extent of ambiguity and reporting quality as assessed by adherence to the CONSORT statement in published reports of RCTs involving patients with Hodgkin lymphoma from 1966 through 2002.
                We analyzed 242 published full-text reports of RCTs in patients with Hodgkin lymphoma. Quality of reporting was assessed using a 14-item questionnaire based on the CONSORT checklist. Reporting was studied in two pre-CONSORT periods (1966-1988 and 1989-1995) and one post-CONSORT period (1996-2002).
                Only six of the 14 items were addressed in 75% or more of the studies in all three time periods. Most items that are necessary to assess the methodologic quality of a study were reported by fewer than 20% of the studies. Improvements over time were seen for some items, including the description of statistics methods used, reporting of primary research outcomes, performance of power calculations, method of randomization and concealment allocation, and having performed intention-to-treat analysis.
                Despite recent improvements, reporting levels of CONSORT items in RCTs involving patients with Hodgkin lymphoma remain unsatisfactory. Further concerted action by journal editors, learned societies, and medical schools is necessary to make authors even more aware of the need to improve the reporting RCTs in medical journals to allow assessment of validity of published clinical research. The aim of this study was to determine for the first time in humans, the efficacy of adding a low dose oestradiol to a suboptimally suppressive testosterone dose in a depot hormonal regimen to suppress spermatogenesis in healthy eugonadal men. Twenty-six healthy men were randomized into groups that were treated by a single subdermal implantation of either 600 mg testosterone alone (T; n = 11) or together with 10 mg (TE10, n = 7) or 20 mg (TE20, n = 8) oestradiol. Administration of oestradiol produced a dose-dependent increase in peak plasma oestradiol at 1 month and prolonged suppression of plasma LH and FSH leading to significantly enhanced suppression of sperm output. Despite the augmented spermatogenic suppression, there was no significant difference in the proportions achieving azoospermia (6/26, 23%) or severe oligozoospermia (<1 or <3 x 10(6) spermatozoa per ml, 7/26, 27%) and overall these proportions were inadequate to provide reliable contraception according to the standards identified in World Health Organization male contraceptive efficacy studies. Total and free testosterone remained within the eugonadal reference range for young men throughout the study. While the lower oestradiol dosage had minimal spermatogenic suppression effects, the higher dose produced dose-limiting adverse effects of androgen deficiency and/or oestrogen excess between the fourth and sixth month of the study. This appeared to be due to the unexpectedly prolonged, low concentration of oestradiol release from the oestradiol implants. There were no significant treatment-related changes in body composition, lipids, prostate-specific antigen, haematological or biochemical variables. Thus oestradiol has a low therapeutic window and dose-limiting side-effects at dosages that fail to achieve the uniform azoospermia required of an effective male hormonal contraceptive regimen. To assess the quality of published randomized clinical trials (RCTs) in rheumatology and to determine whether there has been improvement in quality between 2 time periods, 1987-1988 and 1997-1998.
                Using MEDLINE and a hand search of selected rheumatology journals, we identified RCTs of adult rheumatic diseases published in English in 1987-1988 or 1997-1998. We examined trial quality with an expanded version of the Jadad scale, which assesses the adequacy of reported random sequence generation, allocation concealment, blinding, and analysis. All trials were read by 1 reviewer, with prior standardization using a random sample read by 2 reviewers. We also evaluated "high"- versus "low"-impact journals based on citation index.
                Two hundred forty RCTs (1987-1988 119 RCTs, 1997-1998 121 RCTs) were assessed. Results showed improvement in the quality of the trials, but the rates of reported random sequence generation, allocation concealment, power, and intent-to-treat analyses were persistently low. Low rates of reports of random sequence generation, allocation concealment, and intent-to-treat analyses were present even in the high-impact journals.
                There has been improvement in the quality of reporting of RCTs in rheumatology between 1987-1988 and 1997-1998. However, methodologic problems such as lack of allocation concealment, inadequate random sequence generation, lack of reporting of power, and lack of intent-to-treat analyses remain common. Many of these problems are established sources of bias in RCTs and are easily rectifiable. In a randomized controlled trial, eye movement desensitization and reprocessing (EMDR) for panic disorder with agoraphobia (PDA) was compared with both waiting list and credible attention-placebo control groups. EMDR was significantly better than waiting list for some outcome measures (questionnaire, diary, and interview measures of severity of anxiety, panic disorder, and agoraphobia) but not for others (panic attack frequency and anxious cognitions). However, low power and, for panic frequency, floor effects may account for these negative results. Differences between EMDR and the attention-placebo control condition were not statistically significant on any measure, and, in this case, the effect sizes were generally small (eta2 = .00-.06), suggesting the poor results for EMDR were not due to lack of power. Because there are established effective treatments such as cognitive-behavior therapy for PDA, these data, unless contradicted by future research, indicate EMDR should not be the first-line treatment for this disorder. Suppression of spermatogenesis to azoospermia is the goal of hormonal male contraception based on T combined with gestagens. The combination of the long-acting T, ester testosterone undecanoate (TU), with norethisterone (NET) enanthate (E) showed high efficacy. In the present study, we tested the validity of this approach by varying the NET dose and mode of application. The aim of the study was to achieve high rates of suppression of spermatogenesis as reflected by sperm counts, monitor gonadotropins as well as other hormones, and evaluate any possible side effects. In a phase II clinical trial, groups of normal volunteers received: 1000 mg TU im at wk 2, 6, 12, and 18 combined with 200 mg NETE im at wk 0, 6, 12, and 18 (group I); 1000 mg TU im and 400 mg NETE im at wk 0, 6, 12, and 18 (group II); and 1000 mg TU im at wk 0, 6, 12, and 18 with daily oral NET acetate (NETA) from wk 0 to 24 (group III). In all groups marked suppression of gonadotropins resulted in a significant decrease of spermatogenesis and azoospermia in 13/14, 11/12, and 12/14 men in groups I to III, respectively. The remaining men all had less than 1 million sperm/ml. Reversible side effects included increase in body weight, erythrocytes, hemoglobin, and hematocrit and decrease in high-density lipoprotein cholesterol and alkaline phosphatase in all groups and increase in liver enzymes in the oral NETA group. This study documents the high efficacy of TU in combination with NET and confirms that this dose and mode of application (1000 mg TU im every 6 wk plus 400 mg NETE im every 6 wk or plus 10 mg daily oral NETA) is as effective as the previously reported regimen containing 1000 mg TU + 200 mg NETE im every 6 wk. The contraceptive efficacy of this combination of TU and NETE should be evaluated in further clinical trials. Randomized controlled trials (RCTs) are accepted as the gold standard for assessing the effectiveness of clinical interventions but are rarely reported in pediatric surgery. Have RCTs submitted to the British Association of Paediatric Surgeons (BAPS) Annual Congress during the last 5 years been adequately designed and large enough to produce a valid result?
                Abstracts accepted by the Annual BAPS Congress meetings between 1996 and 2000 were examined in collaboration with a senior health services researcher. The quality of the design, methodology, statistical analysis and conclusions, and the adequacy of the sample size were assessed for all identifiable clinical RCTs.
                From 760 accepted abstracts, there were only 9 RCTs (1%) of clinical interventions. In only 4 trials was the relevant primary end-point specified at the outset of the study, and none documented the method of randomization. Only one abstract mentioned blinding with respect to the intervention or outcome measure. Sample sizes were inadequate to detect even large clinical differences. To date, only one of these RCTs has been published in an English-language, peer-reviewed journal.
                Clear guidelines exist for the conduct of RCTs, yet compliance with these standards was rarely documented in abstracts of pediatric surgical RCTs presented at BAPS. Sample sizes were inadequate. RCTs in pediatric surgery are difficult to perform, but the specialty would benefit from well-designed, carefully conducted, multicentre, clinical RCTs to advance evidence-based practice.
                Copyright 2003, Elsevier Science (USA). All rights reserved. To assess the clinical effectiveness and cost-effectiveness of bone morphogenetic protein (BMP) for the treatment of spinal fusions and the healing of fractures compared with the current standards of care.
                Electronic databases, related journals and references from identified studies were searched in January 2006, with an updated search only for randomised controlled trials (RCTs) in November 2006.
                A systematic review of available data was conducted. The data from selected studies were then analysed and graded according to quality and processed to give a value to the efficacy of BMP. Existing models were modified or updated to evaluate the cost-effectiveness of BMP for open tibial fractures and spinal fusion.
                All selected trials were found to have several methodological weaknesses. Insufficient sample size in most trials, meant that patient baseline comparability between trial arms was not achieved and the statistical power to detect a moderate effect was low. Data did indicate that BMP increased fracture union among patients with acute tibial fractures and found that high-dose BMP is more effective than a lower dose for open tibial fractures. The healing rate in the BMP group was not found to be statistically significantly different from that in the autogenous bone grafting group for patients with tibial non-union fractures, but BMP reduced the number of secondary interventions in patients with acute tibial fractures compared with controls. There was very limited evidence that BMP in scaphoid non-union was safe and may help to accelerate non-union healing when used in conjunction with either autograft or allograft. There was evidence that BMP-2 is more effective than autogenous bone graft for radiographic fusion in patients with single-level degenerative disc disease. No significant difference was found when BMP-7 was compared with autograft for degenerative spondylolisthesis with spinal stenosis and spondylolysis. The use of BMP was associated with a reduced operating time, improvement in clinical outcomes and a shorter hospital stay as compared with autograft. The proportion of secondary interventions tended to be lower in the BMP group than the control, but not of statistical significance. Trial data on time to return to work postoperatively were sometimes difficult to interpret because of unclear or inappropriate data analysis methods. The incremental cost of BMP for open tibial fractures was estimated to be about 3.5 million pounds per year in the UK. The estimated incremental cost per quality-adjusted life-year (QALY) gained is 32,603 pounds. The probability that cost per QALY gained is less than 30,000 pounds for open tibial fracture is 35.5%. The cost-effectiveness ratio is sensitive to the price of BMP and the severity of open tibial fractures. The use of recombinant human bone morphogenetic protein for spinal fusion surgery may increase the cost to the UK NHS by about 1.3 million pounds per year. The estimated incremental cost per QALY gained was about 120,390 pounds. The probability that BMP is cost-effective (i.e. cost/QALY less than 30,000 pounds) was only 6.4%. From the societal perspective, the estimated total cost of using BMP for spinal fusion is about 4.2 million pounds per year in the UK.
                Additional BMP treatment plus conventional intervention is more effective than conventional intervention alone for union of acute open tibial fractures. The cost-effectiveness of additional BMP may be improved if the price of BMP is reduced or if BMP is mainly used in severe cases. BMP may eliminate the need for autogenous bone grafting so that costs and complications related to harvesting autograft can be avoided. In non-unions, there is no evidence that BMP is more or less effective than bone graft; however, it is currently used when bone graft and other treatments have failed. The use of BMP-2 in spinal fusion surgery seems to be more effective than autogenous bone graft in terms of radiographic spinal fusion among patients with single-level degenerative disc disease. There is a lack of evidence about the effectiveness of BMP for other spinal disorders including spondylolisthesis and spinal stenosis. There was limited evidence showing that BMP is associated with greater improvement in clinical outcomes. According to the results of economic evaluation, the use of BMP for spinal fusion is unlikely to be cost-effective. The following areas would benefit from further research: clinical trials of BMP that include formal economic evaluation, a multicentre RCT of fracture non-union and of interbody and/or posterolateral spinal fusion, trials of non-tibial acute long bone fractures, and RCTs comparing BMP-2, BMP-7 and controls. Recognition of the need for more scientifically acceptable review strategies is increasing. Systematic reviews have rarely been performed on randomized controlled trials (RCTs) in the field of epilepsy. We have 355 published RCTs on a database, which will be used as a data source from systematic reviews. We wished to test the sensitivity and precision of two Medline search strategies, and to identify reasons why RCTs were missed. Both a basic and a comprehensive search strategy were used to search Medline from 1966 to 1993. Three journals (Epilepsia, Epilepsy Research, Acta Neurological Scandinavica) were searched by hand. The sensitivity and precision of these Medline search strategies in these three journals was calculated. We investigated articles missed by our comprehensive search to ascertain why they had been missed. Of the 308 RCTs on the database published between 1966 and 1993, 275 were found by our comprehensive Medline search, whereas 103 were found by our basic search. The overall precision of our comprehensive and basic searches was 35 and 72%, respectively. The overall sensitivity of our comprehensive and basic searches was 86 and 66%, respectively. Our comprehensive search failed to find 16 RCTs published in the three journals searched by hand. Articles were missed because they were inadequately indexed on Medline and/or did not contain adequate methodological information in their titles or abstracts. To find all relevant trials, a search strategy must be as sensitive as possible, but this sensitivity inevitably involves loss of precision. The National Library of Medicine is addressing indexing problems with Medline, but the quality of reports also must be improved to enhance retrieval. To compare the effect of depot medroxyprogesterone acetate (DMPA) and two types of oral contraceptives (OC) on bone mineral density (BMD) among women 18-33 years of age with those not using hormonal contraception.
                Data from 155 women were analyzed. Depot medroxyprogesterone acetate was administered to 33 women; 63 women who chose oral contraception were randomly assigned to receive either a norethindrone-containing pill (n = 28) or a desogestrel-containing pill (n = 35). Fifty-nine women who did not use hormonal contraception served as controls. Lumbar spine BMD was determined using dual-energy x-ray absorptiometry at baseline and after 12 months of contraceptive use. We analyzed method-related percent change in BMD while controlling for body mass index, calcium intake, exercise, and smoking. We had approximately 90% power to detect a 2.5% difference between any two groups.
                Users of DMPA experienced a mean BMD loss of 2.74% over 12 months compared with controls who sustained a 0.37% loss (P = .01). Users of OCs generally demonstrated a gain (2.33% for norethindrone-containing pills, 0.33% for desogestrel-containing pills), which was different from controls among users of norethindrone-containing pills (P = .01), but not among users of desogestrel-containing pills (P = .99). Observed changes in BMD among DMPA users differed from women who used either type of pill (P < .002).
                Depot medroxyprogesterone acetate has an adverse effect on BMD, in comparison with OCs or nonhormonal methods, when used for 12 months. Results must be interpreted cautiously until it is determined whether these effects endure or are reversible. To evaluate the sensitivity and precision of various extended search methods in identifying randomized controlled trials (RCTs) for systematic reviews.
                Prospective analysis of extended search methods (specialized databases or trial registries, reference lists, hand-searching, personal communication, and Internet) used in two systematic reviews of RCTs. The gold standard was the total number of RCTs identified by major databases (MEDLINE, EMBASE, etc.) and extended search strategies combined. Sensitivity was the proportion of all known RCTs identified by any extended search method. Precision reflected the proportion of all items uncovered by any extended search method that actually were RCTs.
                The extended search identified 94 additional RCTs for the systematic reviews beyond those identified with the major databases. Specialized databases and trial registries had the highest sensitivity and precision for the lipid-lowering project (13.6% and 52.7%, respectively; p < .05) followed by scanning of reference lists (7.2% sensitivity and 41.9% precision; p <.05). Hand-searching was more effective than personal communication and Internet searching (1.7% sensitivity and 12.2% precision; p < .05). The acupuncture project had slightly different results, with the specialized databases and trial registries tied with the review of reference lists for highest sensitivity (14.2%). The precision followed the same trend as the lipid-lowering project (17.6% specialized databases; 8.3% reference lists; p < .05). A post-hoc analysis showed that 75 of the 94 RCTs were indexed in the major databases but missed by the major database search.
                Extended searching identified additional RCTs for the systematic reviews beyond those found in major databases. Specialized databases and trial registries were most effective. An important number of RCTs were missed by the major database search. Timing and accuracy of indexing may explain this finding. The definitive measure, whether there is an association between the method used to uncover RCTs, the quality of the items uncovered and their impact on systematic review results, is yet to be determined. To assess the effectiveness of a teacher led intervention to improve teenagers' knowledge about emergency contraception.
                Cluster randomised controlled trial.
                24 mixed sex, state secondary schools in Avon, south west England.
                1974 boys and 1820 girls in year 10 (14-15 year olds).
                Teachers gave a single lesson on emergency contraception to year 10 pupils. The teachers had previously received in-service training on giving the lesson. The pupils were actively involved during the lesson.
                Questionnaires distributed to pupils at baseline and six months after the intervention assessed their knowledge of the correct time limits for hormonal emergency contraception and for use of the intrauterine device as emergency contraception, the proportion of pupils who were not virgins, the proportion who had used emergency contraception, and the pupils' intention to use emergency contraception in the future.
                The proportion of pupils knowing the correct time limits for both types of emergency contraception was significantly higher in the intervention group than in the control group at six months' follow up (hormonal contraception: proportion of boys 15.9% higher (95% confidence interval 6.5% to 25.3%), girls 20.4% (10.4% to 30.4%); intrauterine device used as emergency contraception: boys 4.2% (0.7% to 7.7%), girls 10.7% (0.4% to 21.0%). The number of pupils needed to be taught for one more pupil to know the correct time limits was six for boys and five for girls. The intervention and control groups did not differ in the proportion of pupils who were not virgins, in the proportion who had used emergency contraception, and in the proportion intending to use emergency contraception in the future.
                The intervention significantly improved the proportion of boys and girls knowing the correct time limits for both types of emergency contraception. The intervention did not change the pupils' sexual activity or use of emergency contraception. Hormonally induced azoospermia induced by weekly im injections of testosterone enanthate provides effective and reversible male contraception, but more practical regimens are needed. Given our previous findings that six 200-mg pellets implanted subdermally produced more stable, physiological T levels and reduced the delivered T dose by more than 50% while maintaining equally effective suppression of sperm output with fewer metabolic side-effects than weekly 200-mg testosterone enanthate injections, we sought in this study to determine 1) whether further dose-sparing could be achieved by lower testosterone doses while maintaining efficacy and 2) the efficacy of adding a depot progestin to a suboptimally suppressive depot testosterone dose as a model depot progestin/androgen combination male contraceptive. Healthy volunteers were randomized into groups (n = 10) who received either of two lower T doses (two or four 200-mg T pellets) or four 200-mg T pellets plus a single im injection of 300 mg depot medroxyprogesterone acetate (DMPA). Two T pellets (400 mg, 3 mg/day) had a negligible effect on sperm output. Four T pellets (800 mg, 6 mg/day) suppressed sperm output between the second to fourth postimplant months; output returned to normal by the seventh postimplant month, although only 4 of 10 men became azoospermic or severely oligozoospermic (< 3 mol/L/mL). The addition of a depot progestin markedly increased the extent, but not the rate, of sperm output suppression, with 9 of 10 becoming azoospermic and 10 of 10 becoming severely oligozoospermic. There were no serious adverse effects during the study. Plasma total and free testosterone levels remained within the eugonadal range at all times with each treatment. Plasma epitestosterone was suppressed by all 3 regimens, consistent with a dose-dependent inhibition of endogenous Leydig cell steroidogenesis. Plasma LH and FSH measured by a two-site immunoassay were suppressed in a dose-dependent fashion by T and further suppressed by the addition of DMPA. Sex hormone-binding globulin levels were decreased by DMPA, but not by either T dose. Prostate-specific antigen and lipids (total, low or high density lipoprotein cholesterol, and triglycerides) were not significantly changed in any group. Thus, a depot testosterone preparation with zero order release must be delivered at between 6-9 mg/day to provide optimal (but not uniform) efficacy at inducing azoospermia. The addition of a single depot dose of a progestin to a suboptimal testosterone dose (6 mg/day) markedly enhances the extent, but not the rate, of spermatogenic suppression, with negligible biochemical androgenic side-effects. These findings provide a basis for the use of a progestin/androgen combination depot for hormonal male contraception. Efforts to develop a hormonal contraceptive regimen for men have focused on administration of testosterone (T), alone or together with other agents. Previous regimens have successfully induced azoospermia in only 50-70% of subjects, however. GnRH antagonists, alone or in combination with T, have been shown to induce azoospermia in a very high percentage of nonhuman primates. We tested the hypothesis that the addition of a GnRH antagonist to a high-dose T regimen would lead to a higher percentage of men developing azoospermia than would T alone. We administered the GnRH antagonist, Nal-Glu (100 micrograms/kg.day sc), plus T enanthate, 200 mg im weekly or placebo sc injections daily plus T enanthate, 200 mg im weekly, to separate groups of healthy men for 16-20 weeks. Seven of 10 men who received Nal-Glu plus T and 6 of 9 men who received T alone became azoospermic; gonadotropin levels were suppressed and T levels were increased similarly in both groups. There was a trend toward higher pretreatment gonadotropin levels and lower sperm counts in men who became azoospermic. Weight gain, development of acne, and increases in hematocrit and hemoglobin were similar in the two groups. In the majority of the men, sperm counts returned to the baseline levels within 4-5 months after treatment ended. We conclude that with the dosages of Nal-Glu and T we used in this study, the addition of GnRH antagonist to a high-dose T regimen does not increase the ability of T to suppress spermatogenesis in healthy men. Use of a higher dose of Nal-Glu, a lower dose of T, delaying the start of T replacement until several weeks after Nal-Glu injections are initiated, or prolonged hormonal administration might lead to a combination regimen that will suppress spermatogenesis more fully than does T alone. Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18) group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus LNG also suppressed sperm production more rapidly than T alone. Time to azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P < 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and 2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in hemoglobin were similar in the two groups. We conclude that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligospermia than T alone. Increased attention has been directed at the quality of randomized controlled trials (RCTs) and how they are being reported. We examined leading anesthesiology journals to identify if there were specific areas for improvement in the design and analysis of published clinical studies. All RCTs that appeared between January 2000 and December 2000 in leading anesthesiology journals (Anesthesiology,Anesthesia & Analgesia,Anaesthesia, and Canadian Journal of Anaesthesia) were retrieved by a MEDLINE search. We used a previously validated assessment tool, including 14 items associated with study quality, to determine a quality score for each article. The overall mean weighted quality score was 44% +/- 16%. Overall average scores were relatively high for appropriate controls (77% +/- 7%) and discussions of side effects (67% +/- 6%). Scores were very low for randomization blinding (5% +/- 2%), blinding observers to results (1% +/- 1%), and post-beta estimates (16% +/- 13%). Important pretreatment clinical predictors were absent in 32% of all studies. Significant improvement in the reporting and conduct of RCTs is required and should focus on randomization methodology, the blinding of investigators, and sample size estimates. Repeat assessments of the literature may improve the adoption of guidelines for the improvement of the quality of randomized controlled trials. CONSORT (Consolidated Standards for Reporting Trials) guidelines were constructed to ensure optimal reporting quality of randomized controlled trials (RCTs).
                To determine the effect of the adoption of CONSORT on the reporting quality of RCTs, we performed a systematic evaluation of RCTs published in two dermatology journals pre- and post-CONSORT adoption.
                The journals selected for the study were the Journal of the American Academy of Dermatology and the British Journal of Dermatology. We selected RCTs published in 1997 and 2006 using both Medline and hand searching. The following critical CONSORT criteria were recorded: sample size, type of disease studied, type of control, single-centre or multicentre study, type of funding, blinding, methods and type of randomization, definition of a primary endpoint, justification for sample size selection and power calculation, population for analysis, and adequacy of group comparison. A multivariable analysis was conducted to determine factors associated with optimal reporting quality.
                In total, 98 studies were included. Improvement in reporting quality was evident for the specification of the randomization method (20% in 1997 vs. 45% in 2006, P < 0.01) and for the justification of sample size (22% in 1997 vs. 43% in 2006, P = 0.027). The percentage of studies with optimal reporting quality increased from 11% in 1997 to 28% in 2006 (P = 0.03). Factors significantly associated with a good methodological quality were pharmaceutical industry funding and publication in 2006 vs. 1997.
                There is a need to improve the reporting quality of RCTs published in dermatology journals. Surveys indicate that one form of acceptable male hormonal contraception would consist of injections given at 2- to 3-month intervals. This report describes a study of depot medroxyprogesterone acetate (DMPA) and testosterone undecanoate (TU) injected at 8-wk intervals for suppression of spermatogenesis in healthy Chinese men. After screening, 30 healthy volunteers were enrolled and randomly assigned to one of three dose groups (n = 10/group): 1000 mg TU (group A); 1000 mg TU plus 150 mg DMPA (group B); 1000 mg TU plus 300 mg DMPA (group C). All doses were given as im injections at 8-wk intervals. The study consisted of an 8-wk control (baseline) period, a 24-wk treatment period, and a 24-wk recovery period. Consistent azoospermia or severe oligozoospermia was achieved and maintained in all volunteers during the treatment period, except for two men in the TU-alone group who experienced a rebound in sperm concentrations. An 8-wk regimen of TU plus DMPA at both tested combination doses effectively suppressed spermatogenesis to azoospermia in Chinese men. All volunteers tolerated the injections; no serious adverse effects were reported. The lower-dose combination is recommended for further testing in an expanded clinical trial or contraceptive efficacy study. Several randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS.
                Reports of RCTs assessing analgesics in postoperative pain after TOS were systematically searched from electronic databases. The quality of reports was assessed using the CONSORT checklist (scoring range from 0 to 22). The quality was considered poor when scoring was 12 or lesser. The publication year and the impact factor of journals were recorded.
                A total of 92 reports of RCTs were identified and 69 (75%) scored 12 or lesser in CONSORT checklist (range 5-17). The mean (SD) CONSORT score of all reports was 10.6 (2.7). Missing CONSORT items included primary and secondary outcome measures (11%), the specific objectives and hypothesis definition (12%), the sample size calculation (12%), the dates defining the periods of recruitment (12%), the discussion of external validity of findings (14%), the allocation sequence generation (24%), and the interpretation of potential bias or imprecision of results (25%). There was a little improvement in CONSORT scores over time (r = 0.62; p < 0.001) and with impact factor of journals (r = 0.30; p < 0.001).
                Quality of reporting RCTs on analgesics after TOS is poor. Reporting of those RCTs should be improved according to methodological standard checklists in the next years. The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male contraception. Twenty-four healthy male volunteers (33.2 +/- 0.9 yr) were randomly assigned to 3 groups (n = 8) to receive: 1) 300 microg DSG orally daily and 100 mg T enanthate, i.m., weekly; 2) 300 microg DSG and 50 mg T enanthate; or 3) 150 microg DSG and 100 mg T enanthate for 24 weeks. To investigate the individual contribution to the combined action, DSG was administered alone for the first 3 weeks, and T enanthate was added on day 22. After 24-week treatment, sperm density in 78% (18 of 23) of the subjects became azoospermic, whereas 91.7% (22 of 24) and 95.8% (23 of 24) suppressed to less than 1 million/mL and less than 3 million/mL, respectively. The 300 microg DSG with 50 mg T enanthate combination induced azoospermia in 8 of 8 subjects, and the suppression of sperm density was significantly greater than that in the 300 microg DSG/100 mg T enanthate group, but was not different from that in the 150 microg DSG/100 mg T enanthate group. DSG (300 or 150 microg daily) alone in the first 3 weeks suppressed LH, FSH, and T to 60.6%, 48.0%, and 35.4%, respectively, of the baseline. Addition of T enanthate (50 and 100 mg weekly) raised plasma T to the physiological range and induced a further fall in LH and FSH to the limits of assay detection. There was no consistent difference in mean LH and FSH levels among the three groups during treatment or recovery, except that FSH remained detectable in a higher proportion of samples from the group receiving 300 microg DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol decreased by 9.3 +/- 1.7%, 10.3 +/- 2.6%, and 7.7 +/- 2.8%, respectively, during treatment with DSG alone with no difference between 300 and 150 microg. Addition of T enanthate (both 50 and 100 mg weekly) induced a further fall only in high density lipoprotein cholesterol to 22.6 +/- 3.7% from the baseline. In summary, the combined actions of oral DSG with low doses of T enanthate were highly effective in suppressing pituitary-testicular functions in adult men. The optimal regimen for inducing azoospermia was 300 microg DSG daily with 50 mg T enanthate weekly. Oral DSG exerted discernible effects on lipid metabolism. We conclude that the combination of oral progestogens with low dose T is a promising approach to achieve effective reversible male contraception. Effective hormonal male contraception requires a high prevalence of spermatogenic suppression, which has proved particularly difficult in Caucasian populations. We have investigated the combination of oral desogestrel with depot testosterone in Caucasian and Chinese men.
                Thirty men in Edinburgh and 36 men in Shanghai received 150 or 300 microg desogestrel p.o. daily for 24 weeks with 400 mg testosterone pellets s.c. on day 1 and at 12 weeks.
                Eight men withdrew before completing 24 weeks treatment. Testosterone concentrations remained within the normal range. Spermatogenesis was profoundly suppressed in all men. Azoospermia was achieved by a higher proportion of men in the 300 microg desogestrel group: 28/28 men versus 22/31 men (P < 0.05). All Caucasian men in the 150 microg group achieved sperm concentrations of < 1 x 10(6)/ml whereas three men in the Shanghai group maintained sperm concentrations of > 3 x 10(6)/ml. Fifteen men continued on this regimen for a subsequent 24 weeks: all remained azoospermic for the duration of treatment. High-density lipoprotein cholesterol fell by 15% in Caucasian men, but was unchanged in the Chinese men; both groups showed some weight gain.
                This combination of oral desogestrel with depot testosterone maintains physiological testosterone concentrations with consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men and therefore has many of the properties necessary for a contraceptive preparation for men.
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.