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.
METHODS: A retrospective review of all TDT patients treated in Haematology Unit, Hospital Pulau Pinang (HPP) was conducted.
RESULTS: Of the 45 adult TDT patients, 22 were males and 23 were females with mean age of 28.8±6.9 years old. Majority of TDT in HPP were beta thalassemia major (71.1%), followed by E-Beta thalassemia (24.4%) and HbH-Constant Spring (4.4%). Frequency of transfusion was 3-4 weekly. 40.0% of adult TDT suffered from at least one endocrine complication. Among the adult TDT patients with endocrine complication, 50% have one endocrinopathy, 38.9% with two types of endocrinopathies and 11.1% of them have three or more types of endocrinopathies. Hypogonadism (22.2%) was the commonest endocrine complication, followed by osteoporosis (20%), hypothyroidism (13.3%), diabetes mellitus (6.7%) and hypocortisolism (4.4%). Patients with endocrine complications were significantly older. Mean serum ferritin level and LIC was higher among patients with endocrine complications but both were not statistically significant.
CONCLUSION: Endocrinopathy is still prevalent in 40% of adult TDT patients. This leads to higher health-care resource utilization, cost and significant morbidities among patients with TDT. Therefore, regular monitoring and early detection with intensification of chelation therapy is essential.
AIM: To assess plasma testosterone and sexual function in Southeast Asian men on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT).
METHODS: 76 sexually active men on MMT (mean age = 43.30 ± 10.32 years) and 31 men on BMT (mean age = 41.87 ± 9.76 years) from a Southeast Asian community were evaluated using plasma total testosterone (TT) and prolactin levels, body mass index, social demographics, substance use measures, and depression severity scale.
OUTCOMES: Prevalence and associated factors of TT level lower than the reference range in men on MMT or BMT.
RESULTS: More than 1 third of men (40.8%, n = 31) on MMT had TT levels lower than the reference range, whereas 1 fourth of men (22.6%, n = 7) on BMT did. At univariate analysis, MMT vs BMT (β = 0.298, adjusted R2 = 0.08, P = .02) and body mass index (β = -0.23, adjusted R2 = 0.12, P = .02) were associated with changes in TT after stepwise regression. There were no significant associations with age; Opiate Treatment Index Q scores for alcohol, heroin, stimulant, tobacco, or cannabis use and social functioning domain; education levels; hepatitis C status; and severity of depression. Prolactin level did not differ between the MMT and BMT groups.
CLINICAL IMPLICATIONS: The sex hormonal assay should be used regularly to check men on MMT.
STRENGTHS AND LIMITATIONS: This is the first study conducted in the Southeast Asian community. Our study was limited by the lack of a healthy group as the reference for serum levels of testosterone and prolactin.
CONCLUSIONS: The findings showed that plasma testosterone levels are lower in MMT than in BMT users. Hence, men who are receiving MMT should be screened for hypogonadism routinely in the clinical setting. Yee A, Loh HS, Danaee M, et al. Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment. J Sex Med 2018;15:159-166.
METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.
RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.
CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.
AIM: The aim of this review is to analyze current data regarding options of treatment for men with hypogonadism and infertility.
MAIN OUTCOMES MEASURES: A comprehensive review of the current literature on management of infertility among hypogonadal men.
METHODS: A literature search using PubMed from 1980 to 2012 was done on articles published in the English language. The following medical subject heading terms were used: "infertility," "infertile," "hypogonadism;" "testosterone deficiency" and "men" or "male;" and "treatment" or "management."
RESULTS: The options for hypogonadal testicular failure are limited. Hormonal treatment is by and large ineffective. For secondary hypogonadism (hypogonadotropic/normogonadotropic hypogonadism), the options include gonadotropin-releasing hormone, human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), and anti-estrogens and aromatase inhibitors. Dopamine antagonist is indicated for prolactinoma. Artificial reproductive technique is indicated for primary testicular failure and also when medical therapy fails.
CONCLUSION: The most suitable option with the current data available is hCG with or without hMG/FSH. Testosterone supplementation should be avoided, but if they are already on it, it is still possible for a return of normal sperm production within 1 year after discontinuing testosterone. Ho CCK and Tan HM. Treatment of the hypogonadal infertile male-A review. Sex Med Rev 2013;1:42-49.