Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis.

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). INTERPRETATION: In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme.

The Her Tribe and His Tribe Aboriginal-Designed Empowerment Programs.

This study documents evaluation of the Her Tribe and His Tribe Aboriginal-designed empowerment pilot programs. The programs were designed to support Victorian Aboriginal people to strengthen mental health, social and emotional wellbeing, community connection, and to reduce psychological distress. A second aim was to explore participants' experiences of the programs, including the feasibility and acceptability of the evaluation component. Her Tribe ran for 16 weeks and His Tribe for 12 weeks. In total, 43 women and 26 men completed assessments at pre- and post-program completion, and 17 and 10, respectively, participated in yarning circles at the 6-month follow up. For both programs, there were significant increases in participants' access to personal strengths and resources, relationship-community-cultural strengths and resources, and decreases in psychological distress. These changes were associated with small to moderate effects that were maintained at the 6-month follow up. There was a significant increase in aerobic fitness for female but not male participants, and no significant changes in weight for either group. Participants described a range of benefits from the programs, including positive elements and areas for improvement. They also viewed the evaluation as feasible and acceptable, and the findings of value. The outcomes from both pilot programs provide evidence that Aboriginal-designed programs, with a focus on physical and cultural activities, can help to strengthen mental health and wellbeing, community connection, and reduce psychological distress in Victorian Aboriginal communities.

Aging and declining testosterone: past, present, and hopes for the future.

As men age, serum testosterone (T) levels decline, whereas serum luteinizing hormone (LH) levels increase somewhat or remain unchanged. Age-related reductions in T levels may be associated with alterations in body composition; energy level; muscle strength; physical, sexual, and cognitive functions; and mood. The predominant contributor to the decline in serum T levels is the decreased ability of the aging testes to make T. As in humans, the Brown Norway rat demonstrates age-related reductions in serum T levels in the setting of unchanged or modestly increased serum LH levels. In this rat model, the ability of aged Leydig cells, the terminally differentiated T-producing cells of the testis, to produce T in response to LH stimulation is significantly diminished. This review begins with a discussion of what is known of the molecular mechanisms by which T synthesis declines with Leydig cell aging. It concludes with a brief history of T replacement therapy, current guidelines, controversies related to T replacement therapy in older men, and proposed future clinical directions.

Temporal artery vasculitis in young: a report of two cases.

Temporal (giant cell) arteritis is a chronic vasculitis of large and medium sized vessels which usually occurs in individuals above 50 years of age. In patients less than 50 years temporal artery vasculitis is extremely rare. The clinical presentations of the vasculitis in younger patients appear to be different from the older patients. We present two case reports of temporal artery vasculitis in patients less than 50 years, one of them with human immunodeficiency virus infection. Both the cases had variable clinical presentations and good response to treatment.

Testicular seminoma 16 years after treatment for CNS germinoma.

Most patients with intracranial germinomas will be cured and become long-term survivors. Physicians caring for these patients should recognize that these patients may be at risk for disease-related and/or treatment-related late sequelae. We report the case of a 27-year-old man who developed testicular seminoma 16 years after treatment for intracranial germinoma. Like their testicular cancer counterparts, long-term survivors of intracranial germinomas may have a susceptibility to develop a subsequent germ cell tumor. These patients require lifelong medical follow-up and should be encouraged to perform testicular self-examination at the appropriate age.