How to help the aging male? Current approaches to hypogonadism in primary care

Hypogonadism is a common condition which occurs more frequently in older men. It is characterized by low testosterone (T) and is associated with symptoms which are often nonspecific. A key symptom is low libido, but it can also be associated with erectile dysfunction, reduced muscle mass and strength, increased body fat, reduced bone mineral density and osteoporosis, reduced vitality, and depressed mood. Hypogonadism is linked with a variety of comorbid conditions including erectile dysfunction, metabolic syndrome, diabetes, obesity, and osteoporosis. However, the condition is often underdiagnosed. T supplementation in hypogonadism is associated with a range of benefits including improved sexual function, increased lean body mass and/or reduced fat mass, and improved bone mineral density. A variety of T supplementation formulations are available. Although there is no evidence of increased risk of initiating prostate cancer with T supplementation, it is contraindicated in men with prostate cancer. It is important that primary care physicians are aware of both the signs and symptoms of hypogonadism, the monitoring and testing that is required and the merits and advantages of the various T preparations to ensure optimal management of the condition with a treatment approach that best suits patients’ needs.     

A Critical Analysis of Parental Alienation Syndrome and Its Admissibility in the Family Court

Abstract

Over the past three decades, parental alienation syndrome (PAS) has been proposed to explain behaviors by a child who refuses to spend time with a parent and actually denigrates that parent within the context of a child custody dispute. Although some mental health professionals and child custody evaluators, attorneys, and judges have been quick to accept and admit PAS as evidence in these disputes, there has been no consistent empirical or clinical evidence that PAS exists or that the alienator's behavior is the actual cause of the alienated child's behavior towards the target parent. This article attempts to help those working with custody issues understand how the PAS construct fails to meet scientific standards and should not be admissible in courts.     

Comparison of the efficiency of combined extracorporeal shock-wave therapy and triple therapy versus triple therapy itself in Category III B chronic pelvic pain syndrome (CPPS)

The aim of this study is to determine the effect of combining extracorporeal shock-wave therapy (ESWT) and triple therapy versus triple therapy alone, when treating Category III B chronic prostatitis (CPPS). Study included 60 patients, classified as having CPPS, divided into two groups: the first group numbered 30 patients, who were treated with a combination of an α-blocker, an anti-inflammatory agent and a muscle relaxant; the second group consisted of 30 patients who received a combination of ESWT and the fore-mentioned triple therapy. Patients were treated for 12 weeks. The primary criterion of a response to therapy was scoring 2 or less on the NIH-CPSI quality of life item, while the secondary criterion of a response to therapy was a greater than a 50% reduction in NIH-CPSI pain score. Patients who received triple therapy did not show a significant change neither in post void residual urine (PVR) nor in maximum flow rate (Q_MAX), while the second group of patients exhibited significant improvement in both PVR and Q_MAX values. Both groups of patients showed statistically significant improvement in all items of the NIH-CPSI score after the treatment, with significantly better results in the second group.     

Serum sex steroid hormones and frailty in older American men of the Third National Health and Nutrition Examination Survey (NHANES III)

Objective: To determine whether frailty is associated with circulating total and free testosterone, total and free estradiol, and sex hormone-binding globulin (SHBG) in older men. Methods: With NHANES III data of 461 men aged 60 years and older, we used logistic regression to analyze the associations between serum concentrations of sex steroid hormones, SHBG and frailty. Participants meeting any three or more of the five frailty criteria were classified as “frail”, all others were considered as non-frail. Results: 2.5% of men were frail. Men with SHBG ≥66 nmol/L had three times the odds of frailty (OR = 2.97; 95% CI 1.28–6.86) compared to men with SHBG <66 nmol/L. Men with free testosterone levels below 243 pmol/L had an increased odds of frailty (OR = 3.92; 95% CI 1.29–11.89). None of these associations was statistically significant after additionally adjusting for body mass index, smoking and history of cardiovascular diseases (CVD). Total testosterone, and total and free estradiol serum levels were not statistically significantly associated with frailty. Conclusions: In this US nationally representative study of older men, low free testosterone and high SHBG serum levels were associated with a significantly increased odds of frailty after adjustment for age and race/ethnicity. These associations may, however, be explained by confounding due to obesity, smoking, and the higher prevalence of CVD in frail men or by low hormones or high SHBG mediating the association between obesity, smoking, CVD and frailty.     

Acquired immune deficiency syndrome projections in England and Wales: interplay of methodology and data

Since the late 1980s, regular monitoring of the human immunodeficiency virus epidemic in England and Wales has been carried out through the work of successive national working groups. One of their tasks has been to provide short-term projections of the incidence of acquired immune deficiency syndrome. In this paper the data and methods used in this projection work are reviewed and results critically assessed with the aim of highlighting the strong interaction between methodological developments and data acquisition.     

RigiScan data under long-term testosterone therapy: improving long-term blood circulation of penile arteries,penile length and girth,erectile function,and nocturnal penile tumescence and duration

Background: Late-onset hypogonadism (LOH) presents with low serum testosterone (TT) levels and sexual and nonsexual symptoms. Erectile dysfunction affects a man’s self-esteem and as a result partner relationship and quality of life.

Objectives: To investigate the andrological clinical profile outcomes of testosterone therapy (TTh) in men (n?=?88) with symptomatic LOH complaints and symptoms.

Main outcome measures: Erectile function was assessed using the International Index of Erectile Function-5 questionnaire at baseline and at 6 and 12 months of TTh. In addition, penile length was measured at baseline and 12 months. We also evaluated nocturnal penile tumescence (NPT, using RigiScan) and blood flow of cavernous arteries (penile Doppler ultrasonography) at baseline and 12 months of TT.

Materials and methods: Eighty-eight LOH men (M_age 51.1 years) with erectile dysfunction, all with serum TT?<10.4?nmol/L before TTh. Patients received intramuscular long-acting testosterone undecanoate for 12 months.

Results: Following TTh, in all patients, serum TT levels were restored within 3 months to normal levels. Compared with baseline values, erectile function significantly improved at 6 (mean score increase 1.95) and 12 months (mean score increase 2.16). No significant changes in penile length were observed. NPT significantly improved at 12 months in terms of both the frequency (mean increase 1.27 times) and duration of rigidity (mean increase 5.12?min). As regards the blood flow of the cavernous arteries, we observed a significant improvement (decrease of 1.16?cm/s) and end diastolic velocity of the penile arteries.

Conclusion: TTh in men with LOH resulted in improvement of the erectile function, NPT, and to some extent the blood flow of the cavernous arteries.     

Testosterone,testosterone therapy and prostate cancer

Abstract

With prostate cancer not observed in eunuchs and total androgen suppression by castration an effective first-line treatment for advanced prostate cancer, the dramatic regression seen in tumour symptoms after castration, lead to the theory that high levels of circulating androgens were a risk factor for prostate cancer. This theory however, ignored the effects testosterone variations within a physiologic range could have on early tumour events and since the early 2000s, clinical evidence discounting testosterone as a linear mechanistic cause of prostate cancer growth mounted, with alternative mechanistic hypotheses such as the saturation model being proposed. Together with a growing understanding of the negative health effects and decreased quality of life in men with testosterone deficiency or hypogonadism, a paradigm shift away from testosterone as a prostate cancer inducer occurred allowing clinicians to use testosterone therapy as potential treatment for men with difficult and symptomatic hypogonadism that had been previously treated for prostate cancer. In this review we contextualise the idea of testosterone as a risk factor for prostate cancer inducement and compile the most current literature with regards to the influence of testosterone and testosterone therapy in prostate cancer.     

Validation of an Arabic ADAM questionnaire for androgen deficiency screening in the Arab community

Background.?It is well documented that testosterone levels decline with age, this decline is associated with symptoms which could be assessed denoting androgen deficiency. We investigated the validity of an Arabic version of the Saint Louis University androgen deficiency in ageing men (ADAM) questionnaire to screen for androgen deficiency in Saudi and non Saudi Arabic speaking men.

Methods.?It was a cross sectional study of ambulatory community-based Arabic Saudi men recruited from Volunteers in Riyadh city, Capital of Saudi Arabia, aged 18–80 years. Seven hundred thirty men agreed to fill the Arabic ADAM questionnaire, they were invited to a morning blood sample for total testosterone and sex hormone binding globulin and those who agreed to complete the whole study were only 407 men. Low serum bioavailable testosterone (BT) levels (androgen deficiency) were defined as <10th percentile of serum BT levels in young healthy Saudi men (18–30 years).

Results.?Cronbach's Alpha of 0.71 (n?=?730) showed a good internal consistency of the Arabic ADAM questionnaire. Among participants, 18.2% and 77.6% had low serum BT levels and a positive ADAM questionnaire, respectively. The prevalence of positive ADAM and low serum BT is increasing with age. The Arabic ADAM questionnaire had a high sensitivity of 86.5%, a low specificity of 24.3%, and positive predictive values (+PVs) and negative (?PVs) of 20.3% and 89%, respectively.

Conclusion.?The Arabic ADAM questionnaire has a very good sensitivity but very low specificity for screening of androgen deficiency in Saudi men, therefore biological confirmation is needed especially when clinical symptoms of androgen deficiency are present.     

Effects of long-term testosterone replacement therapy,with a temporary intermission,on glycemic control of nine hypogonadal men with type 1 diabetes mellitus – a series of case reports

Abstract

Type 2 diabetes mellitus (T2DM) is often associated with obesity and subnormal serum testosterone (T) levels. Until 5 years ago there was no indication that men with type 1 diabetes mellitus (T1DM) had subnormal serum T. But recent studies indicate that about 10% of men with T1DM suffer from hypogonadism, as a rule aged men and men with obesity. While hypogonadal men with T2DM benefit from normalization of their serum T, this has not been investigated in men with T1DM. Nine men with T1DM, erectile dysfunction and hypogonadism (total testosterone?≤?12?nmol/L) received testosterone replacement therapy (TRT). In seven men TRT was intermitted: one man with prostate malignancy and six men because of problems of reimbursement. Incidentally, this provided an opportunity to monitor the effects of withdrawal and of the reinstatement of TRT. In all men, glycemic control (serum glucose and HbA_1c), weight, waist circumference, lipid profiles and erectile function improved upon TRT. The seven men whose TRT was intermitted showed a deterioration which improved again upon reinstatement of TRT. The data suggest that aging and obese men with T1DM might have subnormal T levels and that their glycemic control, lipid profiles and erectile function might benefit from TRT.     

Adding to the controversy: Pitfalls in the diagnosis of testosterone deficiency syndromes with questionnaires and biochemistry

Purpose. To determine the value of available questionnaires used for the diagnosis of testosterone deficiency syndromes (TDS) by correlating their ratings with a panel of hormonal determinations in a male population.

Materials and methods. Participants completed the ADAM questionnaire and underwent biochemical evaluation at the local site. Assessments determined entry into Group A (symptomatic) or Group B (non-symptomatic). After stratification, subjects provided a morning sample of blood, completed the Aging Male Survey (AMS) and the newly developed Canadian Society for the Study of the Aging Male (CSAM-Q) questionnaires. Serum aliquots were analysed at a central lab for 8 putative markers commonly associated with symptomatic testosterone deficiency associated with aging: total testosterone (T); bioavailable T (BT); dehydroepiandrosterone sulphate (DHEA-S); sex-hormone binding globulin (SHBG); luteinizing hormone (LH), prolactin (PRL); thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1).

Results. 92 men were screened; of these 59 (mean age of 58 ± 11 years) completed the study, 30 (51%) scored positively (mean 61.5 years) to the ADAM while 29 (49%) did not (mean 54.1 years). For the AMS the weight of the three domains (psychological, somato-vegetative and sexual) was significantly greater in Group A (p < 0.001) than in Group B. Equally, for the CAS questionnaire, the scores for the variables energy, global performance, frequency of intercourse, mood and quality of sleep were lower in Group A than in their asymptomatic counterparts (p < 0.001). The domain of memory assessment within the CSSAM-Q was not discriminatory. ADAM and AMS are self-administered and completed within 10 minutes. CSSAM-Q is more time consuming, requires an investigator to administer, and memory domain is biased in favour of specific professional training.

No difference was found between the two groups in 6 of 8 biochemical tests. However, significant lower values (p < 0.001) were found for DHEA-S and IGF-1 in the symptomatic group as compared with the non-symptomatic cohort.

Conclusions. This study confirms that newer, more complex tools perform similarly to the simpler ADAM questionnaire. The lack of correlation between the clinical picture and the most commonly used biochemical confirmatory tests, again, clearly points to the paramount importance of the clinical evaluation. An emphasis and reliance on serum T alone hinders the clinician's ability to manage testosterone deficiency syndromes (TDS).