OnLine First 2013

[Michael Scally MD]

Lindqvist AS, Moberg T, Ehrnborg C, Eriksson BO, Fahlke C, Rosen T. Increased mortality rate and suicide in Swedish former elite male athletes in power sports. Scand J Med Sci Sports. Increased mortality rate and suicide in Swedish former elite male athletes in power sports - Lindqvist - 2013 - Scandinavian Journal of Medicine & Science in Sports - Wiley Online Library

Physical training has been shown to reduce mortality in normal subjects, and athletes have a healthier lifestyle after their active career as compared with normal subjects. Since the 1950s, the use of anabolic androgenic steroids (AAS) has been frequent, especially in power sports. The aim of the present study was to investigate mortality, including causes of death, in former Swedish male elite athletes, active 1960-1979, in wrestling, powerlifting, Olympic lifting, and the throwing events in track and field when the suspicion of former AAS use was high. Results indicate that, during the age period of 20-50 years, there was an excess mortality of around 45%. However, when analyzing the total study period, the mortality was not increased. Mortality from suicide was increased 2-4 times among the former athletes during the period of 30-50 years of age compared with the general population of men. Mortality rate from malignancy was lower among the athletes. As the use of AAS was marked between 1960 and 1979 and was not doping-listed until 1975, it seems probable that the effect of AAS use might play a part in the observed increased mortality and suicide rate. The otherwise healthy lifestyle among the athletes might explain the low malignancy rates.

 

[Michael Scally MD]

Carcaillon L, Brailly-Tabard S, Ancelin ML, et al. Low testosterone and the risk of dementia in elderly men: Impact of age and education. Alzheimers Dement. Low testosterone and the risk of dementia in elderly men: Impact of age and education

OBJECTIVE: The objective of this study was to examine the association of plasma estradiol and testosterone with risk for dementia in elderly men.

METHODS: Within the population based Three-City study, including 3650 men age 65 years and older, a case-cohort design was set up after 4-years of follow-up. Baseline plasma levels of total 17-beta estradiol (Total-E2), total testosterone (total-T) and bioavailable testosterone (bio-T) were measured for all cases of incident dementia (n = 105) and for a random sample of the cohort (n = 413). Cox regression models were used to estimate multivariate steroid sex hormone-associated hazard ratios (HR) and 95% confidence intervals of dementia.

RESULTS: There was a reverse J-shaped relationship between total-T and risk for dementia (P = .007). Compared with the median tertile, the HRs associated with total-T in the lower and upper tertile were increased (HR, 2.33; P = .026; HR, 1.9, P = .126; respectively). Low bio-T was associated with a greater risk for dementia (HR for one standard deviation of decreasing log(bio-T), 1.29; 95% confidence interval, 1.03-1.62). An interaction was found between bio-T and age (P < .0001), and bio-T and education (P = .044). Risk for dementia associated with low bio-T was greater in older men (80 years or older) than in younger men (younger than 80 years; HR, 3.11; P = .011 vs. HR, 1.07, P = .715, respectively) and in men with high level of education compared with those with low level of education (HR, 2.32; P = .0002 vs. HR, 0.95; P = .790, respectively). No significant association was found between Total-E2 and dementia.

CONCLUSIONS: Low levels of testosterone are associated with a risk for dementia in elderly men. The association between low bio-T and dementia may be more relevant to men 80 years or older and men with a high level of education.

 

[Michael Scally MD]

Shelbaia A, Elsaied WM, Elghamrawy H, Abdullah A, Salaheldin M. Effect of selective alpha-blocker tamsulosin on erectile function in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. Urology 2013;82(1):130-5. Elsevier

OBJECTIVE: To study the effect selective of alpha-blocker (tamsulosin HCl) on erectile function in married male patients who are suspected to have benign prostatic hyperplasia (BPH).

MATERIALS AND METHODS: Our study was a prospective randomized single blinded study in one-to-one fashion conducted upon 60 patients, all of them married, between May 2010 and May 2011, the patients under the study were attending the outpatient clinic of the New Kasr Al-Aini Teaching Hospital and Students Hospital, Cairo University, complaining of lower urinary tract symptoms (LUTS) either obstructive, irritative, or both and erectile dysfunction (ED). History was taken from all patients; all patients were examined by digital rectal examination and abdominal examination. We performed pelvic ultrasound, serum prostatic-specific antigen (PSA) measurements, other routine investigations, and uroflowmetry. Assessment of sexual function changes was by the International Index of Erectile Function (IIEF) and penile Doppler ultrasound.

RESULTS: In the tamsulosin group, a significant statistical improvement was detected in the erectile function score and intercourse satisfaction score with significant improvement in total IIEF beside the improvement in the International Prostatic Symptom Score (IPSS). Although orgasmic function score showed significant worsening.

CONCLUSION: Tamsulosin HCl capsules showed a significant statistical improvement in the erectile function, sexual desire, and intercourse satisfaction score with significant improvement in total IIEF in patients with lower urinary tract symptoms because of benign prostatic hyperplasia.

 

[Michael Scally MD]

The Role of Androgen in the Adipose Tissue of Males

Adipose tissue, where various metabolic hormones are secreted, plays a role in metabolizing different substances including androgen. Within fat tissue, enzymes such as aromatase and aldo-keto reductase 1C are responsible for metabolizing testosterone into estrogen and 5-dihydrotestosterone into inactive metabolites. Adipose tissue can also affect the secretion of gonadotropin, which influences the formation of androgen in the testes. At the same time, androgen has an impact on the distribution and proliferation of adipose tissue. The adrenoreceptors for catecholamines, which have been proven to play an essential role in controlling lipolysis, function by being up-regulated by androgens. Furthermore, androgens regulate the activity of lipoprotein lipase, a key enzyme involved in intracellular esterification of adipose tissue.

Lee HK, Lee JK, Cho B. The Role of Androgen in the Adipose Tissue of Males. World J Mens Health 2013;31(2):136-40.
:: WJMH :: The World Journal of Men's Health

Interplay Between Adipocyte And Androgen

AR: adrenoreceptor, LPL: lipo-protein lipase, TG: triglyceride, ARO: aromatase, DHT: dihydrotestosterone, AKR1C: Aldo-keto-reductase 1C.

 

[Michael Scally MD]

Corrales JJ, Almeida M, Martín-Martín L, Miralles JM, Orfao A. Testosterone replacement therapy in hypogonadal men is associated with increased expression of LAMP-2 (CD107b) by circulating monocytes and dendritic cells. Clinical Endocrinology. Testosterone replacement therapy in hypogonadal men is associated with increased expression of LAMP-2 (CD107b) by circulating monocytes and dendritic cells - Corrales - Clinical Endocrinology - Wiley Online Library

Background Accumulated experimental data indicates that androgen therapy has effects on inflammation and protects from autoimmune disorders. Despite this, the in vivo effects of testosterone replacement therapy on human antigen presenting cells–e.g. monocytes and dendritic cells– remain unknown.

Objective, Design and Patients We monitored the effects of testosterone replacement therapy on the number and the functionality -as assessed by the expression of CD107b (lysosome–associated membrane protein 2, LAMP-2)- of resting and in vitro stimulated peripheral blood (classical and non-classical) monocytes and dendritic cells (myeloid and plasmacytoid) from hypogonadal men.

Results Our results show that testosterone replacement therapy induces over-expression of CD107b by circulating monocytes and dendritic cells from hypogonadal men, both under resting (i.e. non-stimulated) conditions, and after in vitro stimulation. CD107b over-expression mostly involved monocytes and in vitro stimulation with CpG oligodeoxynucleotides. Of note, a strong correlation was found between CD107b expression on monocytes and serum gonadotropins levels,

Conclusion These results support the existence of an effect of testosterone therapy, and potentially also of gonadotropins, on circulating antigen presenting cells. This article is protected by copyright. All rights reserved.

 

[Michael Scally MD]

Corrales JJ, Almeida M, Martín-Martín L, Miralles JM, Orfao A. Testosterone replacement therapy in hypogonadal men is associated with increased expression of LAMP-2 (CD107b) by circulating monocytes and dendritic cells. Clinical Endocrinology. Testosterone replacement therapy in hypogonadal men is associated with increased expression of LAMP-2 (CD107b) by circulating monocytes and dendritic cells - Corrales - Clinical Endocrinology - Wiley Online Library

Background Accumulated experimental data indicates that androgen therapy has effects on inflammation and protects from autoimmune disorders. Despite this, the in vivo effects of testosterone replacement therapy on human antigen presenting cells–e.g. monocytes and dendritic cells– remain unknown.

Objective, Design and Patients We monitored the effects of testosterone replacement therapy on the number and the functionality -as assessed by the expression of CD107b (lysosome–associated membrane protein 2, LAMP-2)- of resting and in vitro stimulated peripheral blood (classical and non-classical) monocytes and dendritic cells (myeloid and plasmacytoid) from hypogonadal men.

Results Our results show that testosterone replacement therapy induces over-expression of CD107b by circulating monocytes and dendritic cells from hypogonadal men, both under resting (i.e. non-stimulated) conditions, and after in vitro stimulation. CD107b over-expression mostly involved monocytes and in vitro stimulation with CpG oligodeoxynucleotides. Of note, a strong correlation was found between CD107b expression on monocytes and serum gonadotropins levels,

Conclusion These results support the existence of an effect of testosterone therapy, and potentially also of gonadotropins, on circulating antigen presenting cells. This article is protected by copyright. All rights reserved.

 

[Michael Scally MD]

Sanchez V, Wistuba J, Mallidis C. Semen analysis: update on clinical value, current needs and future perspectives. Reproduction. http://www.reproduction-online.org/content/early/2013/09/23/REP-13-0109.abstract

At present, evaluation of male reproductive function consists primarily of routine semen analysis, a collection of conventional microscopic assessments ideally performed following the guidelines set by the World Health Organization. Whilst providing some insight into testicular function, these long performed tests are limited in the information that they impart, more specifically, they are unable to predict true fertility potential. As a consequence, there is a need for the appraisal and consideration of newer semen parameters that may be more indicative of reproductive success. Although various novel assays have been introduced which broaden the scope of information available to both researcher and clinician, the utility of these tests remains limited due to the lack of standardization of protocols and the absence of clinically established, dependable reference ranges. As such, it is not surprising that most of these parameters and their associated methods remain recommended for "research purposes only". With the burgeoning "omics" revolution, nanotechnology and the development of new analytical instruments, there is now an opportunity for the identification and measurement of previously unknown features which may prove to be more indicative of each sperm's true functional status and capability. Once optimized, simplified, clinically validated and made more readily accessible, these new approaches hold the promise of forming the fulcrum upon which andrological investigations can enter a new era.

 

[Michael Scally MD]

Tal R, Stember DS, Logmanieh N, Narus J, Mulhall JP. Erectile Dysfunction In Men Treated For Testicular Cancer. BJU Int. Erectile Dysfunction In Men Treated For Testicular Cancer - Tal - BJU International - Wiley Online Library

OBJECTIVE: To study the unique characteristics of erectile dysfunction (ED) in men who developed ED following testis cancer (TC) diagnosis and treatment.

PATIENTS AND METHODS: All men treated for TC who presented for sexual function evaluation were included in an institutional database. All men underwent standard evaluation including history/physical examination, completion of the International Index of Erectile Function (IIEF) questionnaire, testosterone/gonadotropin measurement and a penile duplex Doppler ultrasonography (DUS).

RESULTS: 76 men constituted the population. Mean age was 29+/-8 years. 25% were partnered. 39% had seminoma (S) and 61% non-seminomatous germ cell tumor (NSGCT). 66% of S patients had radiation. 79% of NSGCT had chemotherapy, 18% primary retroperitoneal lymph node dissection (RPLND) and 20% post-chemotherapy RPLND. The mean time to seek sexual medicine consultation was 12+/-7 months after treatment completion. Median number of vascular risk factors was 0 (range 0-2). Mean remaining testis size was 16+/-8 ml. Mean total testosterone, LH, FSH levels were 312+/-186 ng/dl, 9+/-7 IU/ml, 17+/-12 IU/ml. 26% had total testosterone levels <300 ng/dl. 84% complained primarily of loss of erection sustaining capability. 24% had episodes of transient ED prior to TC diagnosis. Mean IIEF erectile function domain (EFD) score was 16+/-7. 100% of patients had a normal DUS. Mean peak systolic and end diastolic velocities were 48+/-16 and 1.2+/-2.2cm/s respectively. 88% responded with penetration hardness erections to PDE5 inhibitor (PDE5i) use (mean EFD score 27+/-5), however 12% did not (mean EFD score 17+/-6). No difference in hemodynamics existed between those men with and without hypogonadism.

CONCLUSIONS: Men with TC presenting with ED after treatment appear to uniformly have normal erectile hemodynamics, suggesting adrenaline-mediated ED. While the majority of TC survivors with ED respond successfully to PDE5i, a significant minority do not.

 

[Michael Scally MD]

van Exel E, Eikelenboom P, Comijs H, Deeg DJ, Stek ML, Westendorp RG. Insulin-like growth factor-1 and risk of late-onset Alzheimer's disease: findings from a family study. Neurobiol Aging. Elsevier

Insulin-like growth factor-1 (IGF-1), part of an evolutionary conserved signaling pathway in both mammalian and non-mammalian species, is inferred in neurodegenerative disorders including Alzheimer's disease (AD). A murine model for AD shows that reduced IGF-1 signaling prevents AD-like characteristics. However, variation in serum levels of IGF-1 and risk of AD in humans has yet to be determined.

We used a proven family design, comparing middle-aged offspring with and without a parental history of AD. The offspring under study carry an increased risk of AD but do not yet experience cognitive impairment. A total of 206 offspring from 92 families with a parental history of AD were compared with 200 offspring from 97 families without a parental history of AD. Apolipoprotein-E (APOE) genotypes and serum IGF-1 levels were compared in subjects with and without a parental history of AD using linear regression, adjusted for APOE genotype and other possible demographic and clinical confounders.

Offspring with a parental history of AD were more likely to be an APOE epsilon4 allele carrier (46.5% vs. 21%, p = 0.001) than were offspring without such a parental history. Offspring with a parental history of AD had higher IGF-1 levels than subjects without such a history, in both unadjusted and adjusted analyses (18.3 mmol/L vs. 16.7 mmol/L, p = 0.001).

In conclusion, higher serum IGF-1 levels in middle age are associated with risk of AD disease in older age, independent of APOE genotype.

 

[Michael Scally MD]

Duron E, Funalot Bt, Brunel Ng, et al. Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 in Alzheimer's Disease. Journal of Clinical Endocrinology & Metabolism 2012;97(12):4673-81. Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 in Alzheimer's Disease

Context: Few large studies have been conducted to assess the relationship between circulating IGF and late-life cognition.

Objective: The aim of the study was to assess the relationship between IGF-I and IGF binding protein-3 (IGFBP-3) serum levels and cognitive impairment, including Alzheimer's disease (AD).

Methods: In this multicentric cross-sectional study, 694 elderly subjects (218 men, 476 women; 78.6 ± 6.7 yr old) were included; 481 had memory complaints and were diagnosed, after comprehensive cognitive assessment, with AD (n = 224) or mild cognitive impairment (MCI) (n = 257). The control group was comprised of 213 subjects without memory complaint and with normal cognition (recruited among patients' caregivers). IGF-I and IGFBP-3 serum levels were determined by ELISA.

Results: IGF-I and IGFBP-3 serum levels were significantly associated with cognitive status in men (IGF-I, 137 ± 69 ng/ml for AD vs. 178 ± 88 ng/ml for MCI and 172 ± 91 ng/ml for controls, P = 0.01; IGFBP-3, 3675 ± 1542 ng/ml for AD vs. 4143 ± 1828 ng/ml for MCI and 4488 ± 1893 ng/ml for controls, P = 0.04). In women, IGFBP-3 was significantly associated with cognitive status (3781 ± 1351 ng/ml for AD vs. 4190 ± 1408 ng/ml for MCI and 4390 ± 1552 ng/ml for controls; P < 0.001), but no significant differences between groups for IGF-I occurred. After adjustment for confounding variables (age, educational level, body mass index, diabetes, apolipoprotein E ?4 status), logistic regression indicated that IGF-I [odds ratio (95% confidence interval) = 0.48 (0.26–0.88)] and IGFBP-3 [odds ratio (95% confidence interval) = 0.71 (0.52–0.97)] serum levels were independently associated with AD in men, but not in women.

Conclusions: We report a significant association between low IGF-I and IGFBP-3 serum levels and AD in men, but not in women.

 

[Michael Scally MD]

Poliwczak AR, Tylinska M, Broncel M. Testosterone Therapy Improves the Heart Rate Turbulence Without Effect on NT-proBNP Level in Men with Metabolic Syndrome. Horm Metab Res. https://www.thieme-connect.de/ejournals/abstract/10.1055/s-0033-1355380

It is now known that BNP and NT-proBNP levels are decreasing with increased BMI, regardless of other metabolic syndrome (MS) constituents. Additionally, testosterone deficiency may intensify frequency of ventricular rhythm disorders in obese individuals by inhibition of the parasympathetic system. Determination of heart rhythm turbulence (HRT) is a useful, noninvasive method used for evaluation of equilibrium of the vegetative system.

The aim of the study was to evaluate effect of testosterone therapy on HRT and NT-proBNP levels in MS patients.

Eighty males were qualified for the study. They were divided into 3 groups:
I (n=30), males with testosterone deficiency syndrome and metabolic syndrome (MS+TDS+);
II (n=25), males with MS+TDS-;
III (n=25), healthy males.

The patients with MS+TDS+ received Omnadrem 250 in the form of intramuscular injections for 9 weeks.

Laboratory tests and 24-h Holter ECG were taken twice before the therapy and directly after completion of the therapy.

Males with MS+TDS+ more often presented irregular HRT parameters and were characterised by lower NT-proBNP levels compared to the healthy individuals.

Testosterone replacement therapy caused improvement of HRT and had no significant effect on the NT-proBNP level. Testosterone replacement therapy and body weight reduction may significantly decrease negative consequences of MS and TDS.

 

[Michael Scally MD]

Ho CH, Yu HJ, Wang CY, et al. Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and metabolic syndrome. PLoS One 2013;8(9):e74173. PLOS ONE: Prediabetes Is Associated with an Increased Risk of Testosterone Deficiency, Independent of Obesity and Metabolic Syndrome

OBJECTIVE: The association between type 2 diabetes and low testosterone has been well recognized. However, testosterone levels in men with prediabetes have been rarely reported. We aimed to investigate whether prediabetes was associated with an increased risk of testosterone deficiency.

METHODS: This study included 1,306 men whose sex hormones was measured during a medical examination. Serum total testosterone and sex hormone-binding globulin were measured; free and bioavailable testosterone concentrations were calculated by Vermeulen's formula. Prediabetes was defined by impaired fasting glucose (IFG), impaired postprandial glucose (IPG), or glycated hemoglobin (HbA1c) 5.7%-6.4%. Logistic regression was performed to obtain the odds ratios (OR) for subnormal total testosterone (<300 ng/dL) or free testosterone (<6 ng/dL) in prediabetic and diabetic men compared with normoglycemic individuals, while adjusting for age, BMI, waist circumference, and metabolic syndrome (MetS).

RESULTS: Normoglycemia, prediabetes, and diabetes were diagnosed in 577 (44.2%), 543 (41.6%), and 186 (14.2%) men, respectively. Prediabetes was associated with an increased risk of subnormal total testosterone compared to normoglycemic individuals (age-adjusted OR=1.87; 95%CI=1.38-2.54). The risk remained significant in all multivariate analyses. After adjusting for MetS, the OR in prediabetic men equals that of diabetic patients (1.49 versus 1.50). IFG, IPG, and HbA1c 5.7%-6.4% were all associated with an increased risk of testosterone deficiency, with different levels of significance in multivariate analyses. However, neither prediabetes nor diabetes was associated with subnormal free testosterone in multivariate analyses.

CONCLUSIONS: Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and MetS. After adjusting for MetS, the risk equals that of diabetes. Our data suggest that testosterone should be measured routinely in men with prediabetes.

 

[Michael Scally MD]

Yuan J, Zhang R, Yang Z, et al. Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction: a systematic review and network meta-analysis. Eur Urol 2013;63(5):902-12. Comparative Effectiveness and Safety of Oral Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction: A Systematic Review and Network Meta-analysis

CONTEXT: Phosphodiesterase type 5 inhibitors (PDE5-Is) are currently the first-line therapy for erectile dysfunction (ED), but available studies investigating the comparative effects of different PDE5-Is are limited.

OBJECTIVE: To compare the efficacy and safety of different classes of oral PDE5-Is for ED.

EVIDENCE ACQUISITION: A systematic search was performed in PubMed, Cochrane Library, and Embase to identify randomized controlled trials that compared different PDE5-Is or PDE5-Is with a placebo for ED. The methodological quality of included studies was appraised with the Cochrane Collaboration bias appraisal tool, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation system.

EVIDENCE SYNTHESIS: A total of 118 trials (31 195 individuals) were included. There was no major difference in the results between the traditional meta-analysis and the network meta-analysis. Network meta-analysis demonstrated that PDE5-Is were superior to placebo to improve erectile function. Compared with tadalafil (relative risk [RR]: 0.61; 95% confidence interval [CI], 0.33-0.90) and vardenafil (RR: 0.63; 95% CI, 0.35-0.92), avanafil was less effective on Global Assessment Questionnaire question 1. Tadalafil was more effective than vardenafil (mean difference [MD]: 1.49; 95% CI, 0.50-2.50) and udenafil (MD: -1.84; 95% CI, -3.31 to -0.33) as measured by the erectile function domain of the International Index of Erectile Function. For all efficacy outcomes, the absolute effects and the rank tests indicated that tadalafil and vardenafil were the most effective agents. After adjusting for dosage, the conclusion remained the same. Safety analysis showed there was no major difference among different agents.

CONCLUSIONS: In recommended doses, oral PDE5-Is are more effective than placebo for ED, and tadalafil seems to be the most effective agent, followed by vardenafil. PDE5-Is are generally safe and well tolerated, and there is no major difference on the safety profile.

 

[Michael Scally MD]

Baykan EK, Erdogan M, Ozen S, Darcan S, Saygili LF. Aromatase deficiency, a rare syndrome: case report. J Clin Res Pediatr Endocrinol 2013;5(2):129-32. http://www.jcrpe.org/eng/makale/422/46/Full-Text

Aromatase deficiency (AD) is a rare autosomal recessive inheritance syndrome. Its worldwide incidence is unknown, and there are few case reports in the literature. Aromatase dysfunction develops due to CYP19A1 gene mutation and a decrease in estrogen synthesis. Estrogen deficiency can induce delayed epiphyseal closure, eunuchoid body habitus, osteopenia, and osteoporosis in both genders.

Our patient was a 27-year-old male who presented with bone pain, recurrent bone fractures associated with minimal trauma starting in puberty, and a progressive increase in height. Laboratory tests revealed that the blood levels of follicle-stimulating hormone and luteinizing hormone were above normal, testosterone level was normal, and estrogen was undetectable.

Plain bone radiography of the left wrist and hand demonstrated that the epiphyses were still unfused. Lumbar osteoporosis was detected in bone densitometry.

In the genetic analysis, homozygous R375H guanine-adenine (G-A) mutation was detected in the CYP19A1 gene, and a diagnosis of AD was reached.

Treatment with 25 mug transdermal estradiol was started.

All family members were examined. Homozygous R375H G-A mutation was detected in the patient's younger brother. Heterozygous R375H G-A mutation was found in his mother, father, and older brother.

In conclusion, this AD patient requires lifetime estrogen replacement in order to provide sufficient bone mineralization, to reduce the risk of bone fractures, and to lead a healthy life. The best method to prevent the possible complications is to diagnose the AD syndrome at early ages and to provide adequate estrogen replacement starting at puberty.

 

[Michael Scally MD]

Wang F, Vihma V, Soronen J, et al. 17β-ESTRADIOL AND ESTRADIOL FATTY ACYL ESTERS AND ESTROGEN-CONVERTING ENZYME EXPRESSION IN ADIPOSE TISSUE IN OBESE MEN AND WOMEN. Journal of Clinical Endocrinology & Metabolism. 17?-ESTRADIOL AND ESTRADIOL FATTY ACYL ESTERS AND ESTROGEN-CONVERTING ENZYME EXPRESSION IN ADIPOSE TISSUE IN OBESE MEN AND WOMEN

Context: Obesity is associated with increased circulating 17?-estradiol (E2) but less is known about E2 concentrations in adipose tissue. In addition to E2, adipose tissue synthesizes E2 fatty acyl esters (E2-FAE).

Objective: The aim was to compare estrogen concentrations and expression of estrogen-converting enzymes in adipose tissue between severely obese men and women.

Design and Setting: Tissue samples were obtained during elective surgery in University Central Hospital in the years 2008–2011.

Patients: We studied 14 men and 22 premenopausal women undergoing bariatric surgery and 10 control women operated for non-malignant reasons.

Interventions: Paired samples were taken from abdominal subcutaneous and visceral adipose tissue and serum and analyzed for E2 and E2-FAE by fluoroimmunoassay and liquid chromatography-tandem mass spectrometry. mRNA expression of genes was analyzed by qPCR.

Results: Compared to men, E2 levels in subcutaneous adipose tissue in obese women were higher, along with higher relative mRNA expressions of steroid sulfatase and 17?-hydroxysteroid dehydrogenases 1, 7, and 12. In men, E2-FAE concentrations in adipose tissue were similar to E2 but in women significantly lower compared to E2. Adipose tissue E2-FAE and serum E2-FAE levels correlated positively in obese subjects. Serum E2 did not significantly correlate with E2 concentration or mRNA expression of genes in adipose tissue in obese men or women.

Conclusions: The production of E2 by the large adipose mass was not reflected by increased circulating E2 concentrations in severely obese men or women. However, adipose tissue may contribute to concentrations of serum E2-FAE.

 

[Michael Scally MD]

Li BJ, Zhang C, Li K, et al. Clinical analysis of the characterization of magnetic resonance imaging in 102 cases of refractory haematospermia. Andrology. Clinical analysis of the characterization of magnetic resonance imaging in 102 cases of refractory haematospermia - Li - 2013 - Andrology - Wiley Online Library

To analyze the pathogenesis of persistent and refractory haematospermia and to evaluate the aetiological diagnostic value of magnetic resonance imaging (MRI) for this type of haematospermia.

Clinical data from 102 patients with persistent and refractory haematospermia was retrospectively analysed. Data collected included history, symptoms, as well as ultrasound and MRI of the morphological features of the bilateral seminal vesicles (SV) and ejaculatory duct (ED) areas.

Criteria for inclusion were haematospermia symptoms that occurred more than six times, that lasted more than 6 months, and that did not improve after >1 month of conservative treatment.

Patients underwent seminal vesiculoscopy with a post-surgery follow-up of 3–48 months [average (18.1 ± 10.3) months]. Of the 102 patients that underwent MRI examination, data from 88 patients (86.3%) showed typical and characteristic changes in the ED area, including the signal intensity changes in 60 (58.8%), SV volume changes in 32(31.4%), the formation of cysts such as prostatic utricular cysts in 27 (26.5%), Müllerian cysts in 4 (3.9%), ED cysts in 5 (4.9%) and a SV cyst in 1(1.0%). The MRI findings were confirmed by seminal vesiculoscopy and all patients received appropriate treatment.

In 14 patients (13.7%), no obvious abnormal changes were observed with MRIs, however, these patients were diagnosed and successfully managed using seminal vesiculoscopy. Some degrees of ED obstruction was usually found during surgery.

The symptoms of haematospermia disappeared 1–2 months after surgery in all patients. Two patients had a recurrence of haematospermia, underwent the same treatment, and recovered during the follow-up period.

The aetiology of the most cases of the refractory haematospermia can be distinguished using the three-dimensional MRI. Typical abnormalities observed on MR images are signal intensity, SV volume changes and cyst formation. MRI has significant etiological diagnostic value and provides reliable information for the subsequent treatment of patients with persistent and refractory haematospermia.

 

[Michael Scally MD]

An J, Cheetham TC, Van Den Eeden S. PS3-36: Testosterone Replacement Therapy Patterns for Aging Males in a Managed Care Setting. Clin Med Res 2013;11(3):141. PS3-36: Testosterone Replacement Therapy Patterns for Aging Males in a Managed Care Setting

Background/Aims Testosterone replacement therapy is a widespread and growing practice for treating androgen deficiency. Characteristics of males receiving testosterone and treatment patterns in a managed care setting are relatively unexplored. The purpose of this study was to describe the characteristics and treatment patterns of males receiving testosterone therapy.

Methods We identified patients who received a testosterone prescription from January 1999 to December 2010 in Kaiser Permanente Southern California (KPSC). We excluded patients receiving testosterone therapy for indications other than androgen deficiency, including: 1) age <30, 2) genetic indications, 3) hypothalamic or pituitary dysfunction, and 4) testicular or pituitary trauma. Twelve months continuous membership prior to the index date was required for inclusion in the cohort. We investigated demographics, testosterone prescriptions, baseline diagnoses, total serum testosterone laboratory results, and physician specialty. Descriptive statistics and paired t-test were used.

Results Among testosterone users (N = 10,159) the mean (SD) age was 56.8 (11.6) and 67.7% were white.

On an annual basis, from 1999 to 2010, the treatment rate increased by 183% and number of prescriptions per patient increased by 22%. The most frequently prescribed testosterone products were transdermal gels (55.7%), patches (26.2%), and intramuscular injections (14.4%). The average duration of exposure was close to one year [mean (SD) days supply = 320.0 (504.2) days].

Baseline testosterone levels were obtained in 91.0% of patients and the mean (SD) serum testosterone level was 259.7 (179.5) ng/dL. Follow-up testosterone levels were drawn in 59.8% of patients within one year of the index date and the mean (SD) serum testosterone level was 395.0 (275.3) ng/dL. The mean increase from the baseline was 151.9 (95% CI = 160.5, 143.3) for transdermal gels, 118.0 (129.5, 106.5) for patches, and 200.7 (237.0, 164.3) for intramuscular injections.

The most frequent diagnoses at baseline were hypertension (43.7%), hyperlipidemia (43.1%), erectile dysfunction (33.5%), testicular dysfunction (26.7%), and diabetes (20.3%).

Testosterone prescriptions were most frequently written by primary care providers (family practice [36.0%] or internal medicine [20.1%]) followed by specialists (endocrinology [13.5%] and urology [6.6%]).

Conclusions Testosterone therapy is rapidly increasing treatment among aging males in KPSC, and most frequently prescribed by primary care physicians.

 

[Michael Scally MD]

Kulshreshtha B, Khadgawat R, Gupta N, Ammini A. Progression of puberty after initiation of androgen therapy in patients with idiopathic hypogonadotropic hypogonadism. Indian J Endocrinol Metab 2013;17(5):851-4. http://www.ijem.in/temp/IndianJEndocrMetab175851-2585898_071058.pdf

BACKGROUND: Onset of puberty in boys usually occurs by 14 years of age. Some boys may exhibit delayed sexual maturation till about 17-18 years of age. However, pubertal onset beyond 18 years of age is exceedingly rare.

MATERIALS AND METHODS: Patients diagnosed as idiopathic hypogonadotropic hypogonadism (IHH) who had onset of puberty (increase in testicular volume >10 ml) while on androgen therapy were studied. These patients were evaluated prospectively.

RESULTS: There were nine subjects that were included in the study. The pre-therapy testicular volumes ranged from 3 to 6 ml. Luteinizing hormone (LH) levels increased from 1.2 +/- 0.96 to 2.8 +/- 1.0 IU/L, follicular stimulating hormone (FSH) levels increased from 1.5 +/- 0.79 to 3.5 +/- 1.9 IU/L, and testosterone increased from 0.36 +/- 0.16 to 3.4 +/- 2.1 ng/ml. Three out of nine patients had testosterone levels below 3 ng/ml.

CONCLUSION: Our present study indicates that pubertal development can occur in patients presenting with hypogonadotropic hypogonadism after 18 years of age. However, acquired pubertal status may be subnormal.

 

[Michael Scally MD]

Samplaski MK, Loai Y, Wong K, Lo KC, Grober ED, Jarvi KA. Testosterone use in the male infertility population: prescribing patterns and effects on semen and hormonal parameters. Fertil Steril. Testosterone use in the male infertility population: prescribing patterns and effects on semen and hormonal parameters

OBJECTIVE: To analyze how frequently and why men presenting with infertility take testosterone (T) and if negative effects of T on semen parameters are reversed following cessation.

DESIGN: Analysis of a prospectively collected database.

SETTING: Male Infertility clinic.

PATIENT(S): Men presenting for fertility evaluation from 2008 to 2012.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): The frequency and reason for T use in the infertile male population, and semen and hormonal parameters while on T and following discontinuation.

RESULT(S): A total of 59/4,400 men (1.3%) reported taking T. T was prescribed by a variety of physicians, including endocrinologists (24%), general practitioners (17%), urologists (15%), gynecologists (5%), and reproductive endocrinologists (3%). Only one of the men admitted that he had obtained T from an illicit source. More than 82% of men were prescribed T for the treatment of hypogonadism, but surprisingly, 12% (7/59) were prescribed T to treat their infertility. While on T, 88.4% of men were azoospermic, but by 6 months after T cessation, 65% of the men without other known causes for azoospermia recovered spermatogenesis.

CONCLUSION(S): In Canada, T was not commonly used by men presenting for fertility investigation (1.3%). Close to 2/3 of infertile men using T recovered spermatogenesis within 6 months of T discontinuation.

 

[Michael Scally MD]

Ng Tang Fui M, Hoermann R, Cheung AS, Gianatti EJ, Zajac JD, Grossmann M. Obesity and age as dominant correlates of low testosterone in men irrespective of diabetes status. Andrology. Obesity and age as dominant correlates of low testosterone in men irrespective of diabetes status - Ng Tang Fui - 2013 - Andrology - Wiley Online Library

Although men with type 2 diabetes (T2D) frequently have lowered testosterone levels, it is not well established whether this is ascribable to the diabetic state per se, or because of other factors, such as obesity. Our objective was to determine the prevalence and correlates of low testosterone in middle-aged men with diabetes. We conducted a cross-sectional study in 240 men including 80 men with type 1 diabetes (T1D), 80 men with T2D and 80 men without diabetes. Prevalence of a total testosterone </=8 nmol/L was low, occurring in none of the men with T1D, 6.2% of men with T2D and 2.5% of men without diabetes. Men with T1D had higher testosterone levels compared with men without diabetes (p < 0.001), even after adjustment for body mass index (BMI) and age (p < 0.02). While men with T2D had lower testosterone compared with controls (p = 0.03), this was no longer significant when BMI and age were taken into account (p = 0.16). In the entire cohort, TT remained inversely associated with BMI independent of age, sex hormone-binding globulin and diabetic status (p = 0.01), whereas calculated free testosterone (cFT) was independently and inversely associated with age (p < 0.001), but not with BMI (p = 0.47). These results suggest that marked reductions in circulating testosterone are uncommon in middle-aged men with diabetes. Increasing BMI and age are dominant drivers of lowered total and cFT, respectively, independent of the presence or absence of diabetes.