Double trouble: Co-occurrence of testosterone deficiency and body fatness associated with all-cause mortality in US men.

BACKGROUND: Testosterone deficiency (TD, total testosterone ≤350 ng/dL [12.15 nmol L-1 ]) and obesity epidemic are growing in parallel in the United States. Yet, the sequelae of TD and obesity on the risk of mortality remain unclear. OBJECTIVE: To investigate whether the co-occurrence of TD and overall obesity (body mass index ≥30 kg/m2 ), and abdominal obesity (waist circumference ≥102 cm), is associated with a risk of all-cause mortality in American men. DESIGN: The data were obtained from the NHANES 1999-2004 and the Linked Mortality File (December 31, 2011). A total of 948 participants aged ≥20 years old with endogenous sex hormones and adiposity measurements data were included in this study. RESULTS: Over a median of 9.5 years of follow-up, 142 men died of any cause in this cohort. Multivariable analysis showed a 2.60 fold increased risk of death among men with TD compared with men without TD (Hazard Ratio [HR] = 2.60; 95% confidence interval [CI] = 1.20-5.80). No evidence for interaction between TD and overall or abdominal obesity with risk of death (Pinteraction ≥ .80). However, only after comparing men with TD and abdominal obesity with men without TD and no abdominal obesity, we found a 3.30 fold increased risk of death (HR = 3.30, 95% CI = 1.21-8.71). CONCLUSION: Men with co-occurrence of TD and abdominal obesity have a higher risk of mortality. The effect of co-occurrence of TD and abdominal obesity should be further explored with a larger and longer follow-up time study.

Measurement of endothelial dysfunction via peripheral arterial tonometry predicts vasculogenic erectile dysfunction.

Endothelial cell dysfunction is associated with cardiovascular disease and vasculogenic erectile dysfunction (ED). Measured via peripheral artery tonometry (PAT), endothelial dysfunction in the penis is an independent predictor of future cardiovascular events. The aim of the study was to determine whether measurement of endothelial dysfunction differentiates men with vasculogenic ED identified by duplex ultrasound from those without. A total of 142 men were retrospectively assessed using patient history, penile duplex ultrasonography (US) and PAT (EndoPAT 2000). ED was self-reported and identified on history. Vasculogenic ED was identified in men who exhibited a peak systolic velocity (PSV) of ⩽ 25 cm s(-1) at 15 min following vasodilator injection. The reactive hyperemia index (RHI), a measurement of endothelial dysfunction in medium/small arteries, and the augmentation index (AI), a measurement of arterial stiffness, were recorded via PAT. Penile duplex US was used to categorize men into those with ED (n = 111) and those without ED (n = 31). The cohort with ED had a PSV of 21 ± 1 cm s(-1) (left cavernous artery) and 22 ± 1 cm s(-1) (right cavernous artery). The control group without ED had values of 39 ± 2 cm s(-1) (left) and 39 ± 2 cm s(-1) (right). Given the potential for altered endothelial function in diabetes mellitus, we confirmed that hemoglobin A1c, urinary microalbumin and vibration pulse threshold were not different in men with vasculogenic ED and those without. RHI in patients with ED (1.85 ± 0.06) was significantly decreased compared to controls (2.15 ± 0.2) (P<0.05). The AI was unchanged when examined in isolation, and when standardized to heart rate. Measurement of endothelial function with EndoPAT differentiates men with vasculogenic ED from those without. RHI could be used as a non-invasive surrogate in the assessment of vasculogenic ED and to identify those patients with higher cardiovascular risk.

Depression is correlated with the psychological and physical aspects of sexual dysfunction in men.

Few studies have objectively examined the relationship between depression and various stages of sexual function. Here we associate depression and sexual function using validated questionnaires. A retrospective review of 186 men was performed; demographics and serum hormone levels were obtained. Responses to questionnaires evaluating depressive symptoms (Patient Health Questionnaire (PHQ-9)), sexual function (International Index of Erectile Function (IIEF)) and hypogonadal symptoms (quantitative Androgen Decline in the Aging Male (qADAM)) completed by each patient were correlated using Spearman's rank correlation. Mean±s.d. subject age: 52.6±12.7 years; mean serum hormone levels: TT 429.8±239.2 ng dl(-1), free testosterone 9.72±7.5 pg ml(-1) and estradiol 34.4±22.8 pg ml(-1). Negative correlations were observed between total PHQ-9 score and the sexual desire (ρ=-0.210, P=0.006), intercourse satisfaction (ρ=-0.293, P<0.0001) and overall satisfaction (ρ=-0.413, P<0.0001) domains of the IIEF and individual IIEF questions pertaining to erectile function. Men with a PHQ-9 score 10 (mild depression or worse), had lower sexual desire and sex life satisfaction. A negative correlation between PHQ-9 score and qADAM score (ρ=-0.634, P<0.0001) was observed and men with higher PHQ-9 score had lower qADAM scores. Depressive symptoms in men correlate with both psychological as well as physical aspects of sexual function.

Testosterone replacement therapy in the setting of prostate cancer treated with radiation.

A lack of consensus and few data support testosterone replacement therapy (TRT) in hypogonadal men who have been treated for prostate cancer (CaP), particularly those who have received radiation therapy. We performed retrospective review of 13 hypogonadal men with CaP, treated with brachytherapy or external beam radiotherapy who were subsequently treated with testosterone (T) between 2006 and 2011. Serum T, free T (FT), estrogen (E), sex hormone-binding globulin (SHBG), prostate-specific antigen (PSA), hemoglobin (Hgb) and hematocrit (Hct) values were evaluated approximately every 3 months after TRT initiation up to 67 months of follow-up. Prostate biopsies demonstrated four men with Gleason (Gl) 6, 7 with Gl 7 and 2 with Gl 8 disease. Median (interquartile range) age at TRT initiation was 68.0 (62.0-77.0) years, initial T 178.0 (88.0-263.5) ng dl(-1), FT 10.1 (5.7-15.0) pg ml(-1) and PSA 0.30 (0.06-0.95) ng ml(-1). Median follow-up after TRT initiation was 29.7 months (range 2.3-67.3 months). At median follow-up, a significant increase in mean T (368.0 (281.3-591.0) ng dl(-1), P=0.012) and SHBG were observed, with no significant increases in Hgb, Hct, E, FT, or PSA (0.66 (0.16-1.35) ng ml(-1), P=0.345). No significant increases in PSA or CaP recurrences were observed at any follow-up interval. TRT in the setting of CaP after treatment with radiation therapy results in a rise in serum T levels and improvement in hypogonadal symptoms without evidence of CaP recurrence or progression.

Emerging concepts in erectile preservation following radical prostatectomy: a guide for clinicians.

Radical prostatectomy (RP) is a commonly performed procedure for the management of prostate cancer. While documented oncologic outcome for early stage disease is excellent, functional impairments such as incontinence and erectile dysfunction (ED) are common after the procedure. Recent evidence has implicated cavernous nerve damage and subsequent corporal oxygen deprivation, as well as corporal inflammation, in the pathogenesis of post-RP ED. Targeted therapies such as oral phosphodiesterase-5 inhibitors, mechanical vacuum erection devices, local alprostadil delivery and testosterone replacement (for hypogonal patients) have demonstrated some efficacy in the management of post-RP ED. This review aggregates much of the recent data in support of these therapies and critically reviews them. The article then presents tools to assess patients and partner sexual function to aid in identifying and monitoring post-RP ED. Finally, the article describes a protocol in use at Baylor College of Medicine as a guide toward the development of a protocol for erectile preservation (EP). The purpose of this work is to educate clinicians on emerging concepts in EP and provide an implementable protocol for use in practice.

IGF-1 levels are significantly correlated with patient-reported measures of sexual function.

Growth hormone (GH) supplementation may help to preserve erectile function. We assessed whether serum insulin-like growth factor 1 (IGF-1) levels, a surrogate for GH levels, correlate with sexual function scores in 65 men who completed the Sexual Health Inventory for Men (SHIM) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires, and had serum IGF-1 and testosterone levels determined. Median±s.d. IGF-1 level, SHIM and EPIC scores were 235.0±86.4, 19.5±8.7 and 56.4±28.3 mg ml(-1), respectively. IGF-1 levels and total SHIM score correlate significantly (r=0.31, P=0.02), as do IGF-1 levels and all individual SHIM question scores, and IGF-1 levels and the sexual domain of the EPIC questionnaire (r=0.30, P=0.02). No correlation was observed between IGF-1 levels and Gleason score, IGF-1 and testosterone level or SHIM score and testosterone level. These data support a potential role for the GH axis in erectile function.

The quantitative ADAM questionnaire: a new tool in quantifying the severity of hypogonadism.

Androgen deficiency is a pervasive problem in the older male population and is thought to be responsible for many symptoms once considered to be the result of normal aging. Numerous methods have been proposed to facilitate the detection of men at risk for androgen deficiency. In this article, we propose a novel screening tool, the quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire and report its successful use in quantifying the severity of androgen deficiency in a group of older men. Fifty-seven males scheduled to undergo radical prostatectomy for prostate cancer completed the qADAM as well as the Sexual Health Inventory for Men (SHIM) and the Expanded Prostate Cancer Index Composite hormonal/sexual (EPICh/EPICs) questionnaires. Thirty-four men also had serum testosterone levels measured for comparison. The qADAM showed statistically significant correlation to the SHIM (P=0.001), EPICh (P=0.016), EPICs (P= <0.001), and serum testosterone (P=0.046). The qADAM represents a viable alternative to existing questionnaires used to detect androgen deficiency and to assess response to treatment.

Efficacy of changing testosterone gel preparations (Androgel or Testim) among suboptimally responsive hypogonadal men.

The study objective was to evaluate the efficacy of changing testosterone gel preparations among suboptimally responsive hypogonadal men. The records of all hypogonadal men on gel (Testim or Androgel) testosterone replacement therapy (TRT) were reviewed to identify men who underwent a brand substitution in gel TRT due to initial suboptimal response. Total and free serum testosterone levels and the presence of hypogonadal symptoms (ADAM) were compared pre- and post-gel substitution. Of the 370 hypogonadal men on testosterone gel replacement therapy, 75 (20%) underwent a brand substitution. Prior to substitution, among patients initially treated with Androgel, the mean total and free testosterone levels were 311 ng dl(-1) and 10.4 pg ml(-1), respectively. Total testosterone levels were below 300 ng dl(-1) in 58% of these patients. Following a change to Testim, mean total and free testosterone levels increased to 484 ng dl(-1) (P<0.001) and 14.6 pg ml(-1) (P=0.01), respectively. Total testosterone levels remained below 300 ng dl(-1) in only 17% of these patients. Among patients initially treated with Testim, the mean total and free testosterone levels were 544 ng dl(-1) and 18.0 pg ml(-1), respectively. Total testosterone levels were below 300 ng dl(-1) in 15% of men. Following testosterone gel change to Androgel, mean total and free testosterone levels were 522 ng dl(-1) (P=0.7) and 16.1 pg ml(-1) (P=0.6), respectively. Total testosterone levels remained below 300 ng dl(-1) in 27% of these patients. Hypogonadal symptoms improved in a significant proportion of men who underwent a brand substitution following an initial suboptimal biochemical or symptomatic response. A change in testosterone gel preparation among initially unresponsive hypogonadal men is justified prior to abandoning or considering more invasive TRT. Changing from Androgel to Testim offers hypogonadal men the potential for improved clinical and biochemical responsiveness. Changing from Testim to Androgel is indicated to eliminate or minimize unwanted side effects.

Correlation between simultaneous PSA and serum testosterone concentrations among eugonadal, untreated hypogonadal and hypogonadal men receiving testosterone replacement therapy.

The primary objective of this study was to correlate simultaneous measures of prostate-specific antigen (PSA) and serum testosterone among large samples of eugonadal, untreated hypogonadal and hypogonadal men treated with testosterone replacement therapy (TRT). From 2001 to 2007, laboratory records were reviewed to identify men who underwent simultaneous measurement of PSA and serum testosterone levels. The data were stratified based on three groups of men: group 1 consisted of eugonadal men (T>300 ng per 100 ml) evaluated for BPH, reproductive failure or sexual dysfunction; group 2 consisted of untreated hypogonadal men (T<300 ng per 100 ml); and group 3 comprised symptomatic hypogonadal men receiving TRT. Correlations were found between PSA (total and free fractions) and total serum testosterone levels among the three groups. Group 1: eugonadal men (n=385 patients), mean PSA and serum testosterone were 1.60 ng ml(-1) and 484 ng 100 ml, respectively. There was no significant correlation between PSA and total serum testosterone levels (r=-0.01, P=0.8). Group 2: untreated hypogonadal men (n=229 patients), mean PSA and serum testosterone were 1.49 ng ml(-1) and 269 ng per 100 ml, respectively. There was no significant correlation between PSA and total serum testosterone levels (r=0.03, P=0.6). Group 3: hypogonadal men on TRT (n=229 patients and 994 individual samples analyzed) mean PSA and serum testosterone were 1.50 ng ml(-1) and 555 ng per 100 ml, respectively. There was no significant correlation between PSA and serum testosterone levels (r=-0.005, P=0.9). Mean total serum testosterone levels were increased significantly (P<0.001) following treatment. Mean PSA levels did not increase in a statistically or clinically significant manner following TRT (mean PSA increase from baseline 0.05 ng ml(-1), P=0.6). In conclusion, TRT does not appear to significantly influence serum PSA expression and no significant correlation was identified between PSA and serum testosterone among eugonadal, untreated hypogonadal and hypogonadal men receiving TRT.