Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

Testosterone deficiency syndrome among males with type 2 diabetes mellitus in East Malaysia.

Type 2 diabetes mellitus (T2DM) may be independently associated with testosterone deficiency syndrome (TDS). Both conditions are linked with reduced quality of life and cardiovascular comorbidities. The magnitude of TDS among T2DM men and its predictors has still not been well established in Malaysia. This study aimed to determine the prevalence of TDS and its predictors among men with T2DM attending a government health clinic in Kuching, Sarawak. TDS severity and level of serum total testosterone were also explored. A cross-sectional study was conducted involving 360 respondents. Aging Males Symptoms Scale (AMS) score > 26 and serum total testosterone ≤ 12 nmol/L were used to diagnose TDS. The prevalence of TDS in current study was 19.7%. Multivariate analysis showed that determinants for TDS included age (Adjusted OR 1.061: 95% CI 1.020; 1.103), Iban ethnicity (Adjusted OR 2.469: 95% CI 1.154; 5.283) and a waist circumference equal or greater than 90 cm (Adjusted OR 3.655: 95% CI 1.472; 9.081). However, there was no significant association between TDS and the level of serum total testosterone (p = 0.581). We concluded that the prevalence of TDS in this study was relatively low. The severity of this condition may not be influenced by testosterone level. Physicians might consider a diagnosis of TDS if elder diabetic men with abdominal obesity present to primary care clinics with clinical features of hypogonadism. Health care providers also might consider lowering their threshold to screen for TDS among Iban men with T2DM.

Clinicopathological features of bladder tumours in a single institution in Malaysia.

OBJECTIVE: To determine the clinicopathological features of bladder tumours encountered over a five year period in Universiti Kebangsaan Malaysia Medical Centre. METHODS: Medical records of bladder tumour cases from 2005 till 2009 were retrospectively reviewed and tabulated. RESULTS: A total of 83 cases were recorded. The incidence was highest among the Chinese (56.6%), followed by Malays (34.9%), Indians (6%) and other races (2.4%). The male-to-female ratio was 9.4:1. The median age was 65 years (range 30-91 years) and median duration of follow up was 17.2 months (range 2-60 months). The main histopathology was transitional cell carcinoma (TCC) (90.4%), followed by adenocarcinoma (6%), squamous cell carcinoma (1.2%), leiomyoma (1.2%) and myeloid sarcoma (1.2%). For the TCCs, 58.6% were superficial while 41.4% were muscle invasive, and 13.3% had nodal metastasis with distant metastasis in 8%. Of the total, 5.3% were papillary urothelial tumours of low malignant potential, 33.3% pTa, 20% pT1, 10.7% pT2, 12.0% pT3 and 18.7% pT4. Of the superficial tumours, 32.5% were high grade tumours. There were ten radical cystectomies performed for transitional cell carcinomas; two had neobladder reconstruction whereas the other eight had ileal conduits. All the adenocarcinomas and squamous cell carcinomas were treated by radiotherapy due to the advanced stage of the disease while the myeloid sarcoma received chemotherapy. Mean survival of patients with muscle invasive cancer was 33+/-5 months. By the end of the study, 18.1% of patients had died of their cancer. CONCLUSION: The incidence of bladder tumours is highest among the Chinese. When compared to other studies, the incidence of muscle invasive and high-grade superficial tumours was greater.

Spontaneous bladder perforation: a rare complication of tuberculosis.

Spontaneous bladder perforation secondary to tuberculosis (TB) is very rare. Only three cases have been reported so far in the literature. Due to its rarity, the diagnosis of spontaneous bladder perforation is often missed. Confirmation of TB via culture takes a long time and starting empirical treatment for TB is necessary. We relate our experience with a young woman who presented with clinical features of a perforated appendix and was only diagnosed with bladder perforation during laparotomy. She also had distal right ureteral stricture and left infundibular stenosis. The provisional diagnosis of TB was attained via typical histopathological features and a positive Mantoux test. She was started empirically on anti-TB treatment and recovered without any complications. Urine culture after 6 weeks confirmed the diagnosis of TB.

Seven-year review of prostate carcinomas diagnosed by TRUS biopsy in a single Malaysian institution.

INTRODUCTION: Analysis of epidemiological as well as survival differences among the multiethnic population of Malaysia with prostate cancer is important. METHODS: Patients confirmed by transrectal-ultrasonographic-guided-biopsy performed from 2002 to 2008 were enrolled and analysed according to ethnicity, age, PSA level, Gleason score, stage of disease and survival. RESULTS: Among 83 patients, there were 38 Malay, 40 Chinese, 3 Indians and 2 others. Median age at diagnosis was 69.9 (range: 59-93), 43 patients (51.8%) being diagnosed before the age of 70. The median PSA level upon diagnosis was 574 ng/ml (range: 1-8632) and the median Gleason score was 7 (range: 2-10). Over half were already in Stage 4 when diagnosed. The most common site of metastasis was the bone. As a result the commonest prescribed treatment was hormonal manipulation. Five patients underwent radical prostatectomy and a further thirteen patients had radical radiotherapy (stage I: 1 patient, stage II: 7 patients and stage III: 5 patients). Ten patients defaulted follow-up. The median disease-specific survival was 21.9 months (range: 1-53). CONCLUSIONS: Prostatic carcinoma is a disease of the elderly and it is frequently diagnosed late in Malaysia. Greater efforts should be made to educate Malaysians regarding prostate cancer.

A prospective, randomized clinical trial comparing bipolar plasma kinetic resection of the prostate versus conventional monopolar transurethral resection of the prostate in the treatment of benign prostatic hyperplasia.

BACKGROUND AND OBJECTIVE: For treatment of benign prostatic hyperplasia (BPH), Plasma Kinetic loop Resection of the Prostate (PKRP) is an alternative to conventional monopolar transurethral resection of prostate (TURP). We compared outcomes with the two treatments in a randomized trial. PATIENTS AND METHODS: Over a one-year period, we randomly assigned patients with an indication for surgery for BPH and who met inclusion criteria to treatment with either PKRP or TURP. We measured prostate volume by transrectal ultrasound, relief of bladder outlet obstruction, operative time, decline in serum sodium and hemoglobin, weight of resected prostatic chips, duration of catheterization and hospital stay. Patients were evaluated one month after discharge for obstructive symptoms. Complications were also recorded. RESULTS: Of 102 patients enrolled, 51 underwent PKRP and 51 underwent TURP. Relief of obstructive symptoms and mean operative time showed no statistically significant difference. The PKRP group had a smaller decline in hemoglobin than the TURP group (0.6 g/dL vs 1.8 g/dL, P=.01), a lower reduction in serum sodium levels (1.03 mmol/L vs 5.01 mmol/L, P=.01), a shorter catheterization time (37.2 hours versus 57.7 hours, P=.03) and a shorter hospital stay (1.5 days versus 2.6 days, P=.02). One patient in the bipolar PKRP group needed recatheterization versus four patients in the TURP group. CONCLUSION: PKRP reduces morbidity with an outcome similar to conventional monopolar TURP in the treatment of BPH.