OnLine First 2013

[Michael Scally MD]

Kanwar P, Kowdley KV. Diagnosis and treatment of hereditary hemochromatosis: an update. Expert Rev Gastroenterol Hepatol 2013;7(6):517-30. An Error Occurred Setting Your User Cookie

Hereditary hemochromatosis is an inherited iron overload disorder caused by inappropriately low hepcidin secretion leading to increased duodenal absorption of dietary iron, most commonly in C282Y homozygous individuals. This can result in elevated serum ferritin, iron deposition in various organs and ultimately end-organ damage, although there is incomplete biochemical and clinical penetrance and variable phenotypic expression of the HFE mutation in hereditary hemochromatosis. An elevated SF <1000 microg/l is associated with an increased risk of cirrhosis and mortality in C282Y homozygotes. Conversely, a SF <1000 microg/l is associated with a very low likelihood of cirrhosis, making liver biopsy unnecessary among C282Y homozygotes in the absence of concomitant risk factors for liver disease. Phlebotomy remains the mainstay of treatment and new treatments being studied include erythrocytapheresis and 'mini-hepcidins'. Iron overload is being recognized to play a carcinogenic role in hepatocellular carcinoma and other cancers, possibly supporting iron depletion in these patients.

 

[Michael Scally MD]

Opioid Overdose: Preventing And Reducing Opioid Overdose Mortality
http://www.who.int/substance_abuse/publications/opioid_overdose.pdf

Although data are limited, an estimated 70,000-100,000 people die from opioid overdose each year. Opioid overdose was the main cause of the estimated 99,000- 253,000 deaths worldwide related to illicit drug use in 2010.

Opioid overdose is both preventable and, if witnessed, treatable (reversible). In its resolution 55/7 on promoting measures to prevent drug overdose, in particular opioid overdose, the Commission on Narcotic Drugs called upon Member States to include effective measures to prevent and treat drug overdose in national drug policies.

In that resolution, the Commission requested the United Nations Office on Drugs and Crime (UNODC), in collaboration with the World Health Organization (WHO), to collect and circulate available best practices on the prevention and treatment of and emergency response to drug overdose, in particular opioid overdose, including on the use and availability of opioid receptor antagonists such as naloxone and other measures based on scientific evidence.

This discussion paper outlines the facts about opioid overdose, the actions that can be taken to prevent and treat (reverse) opioid overdose and areas requiring further investigation.

 

[Michael Scally MD]

Rosen RC, Wu FC, Behre HM, et al. Registry of Hypogonadism in Men (RHYME): design of a multi-national longitudinal, observational registry of exogenous testosterone use in hypogonadal men. Aging Male 2013;16(1):1-7. An Error Occurred Setting Your User Cookie

OBJECTIVE: Despite the prevalence of hypogonadism (HG) and widespread use of testosterone therapy, little is known about the safety/effectiveness of long-term testosterone use. The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry assessing prostate health and other outcomes associated with testosterone treatment in men.

DESIGN: Observational patient disease registry.

METHODS: RHYME is a non-interventional disease registry with longitudinal data collection on a large sample (N = 999) of well-characterized, hypogonadal men aged 18 years or older. The Registry will prospectively evaluate male patients diagnosed with HG, who have not previously been treated with testosterone therapy. Key design features include: (1) broad inclusion/exclusion criteria, (2) standardized central laboratory hormone assays, (3) independent adjudication of prostate biopsies and mortalities, (4) standard of care treatment, (5) comprehensive medical record and questionnaire data at six months and annually post-enrollment and (6) adequate statistical power for assessing prostate endpoints at 36 months.

RESULTS: A total of 25 clinical sites in six European countries (Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom) have completed recruitment for the study. Recruitment was initiated in May 2009, and completed in December 2011. Data collection is ongoing with a minimum of two years of follow-up on all patients.

 

[Michael Scally MD]

Papanicolaou DA, Ather SN, Zhu H, et al. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J Nutr Health Aging 2013;17(6):533-43. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia - Springer

BACKGROUND: Sarcopenia, the age-related loss of muscle mass [defined as appendicular LBM/Height2 (aLBM/ht2) below peak value by>1SD], strength and function, is a major contributing factor to frailty in the elderly. MK-0773 is a selective androgen receptor modulator designed to improve muscle function while minimizing effects on other tissues.

OBJECTIVES: The primary objective of this study was to demonstrate an improvement in muscle strength and lean body mass (LBM) in sarcopenic frail elderly women treated with MK-0773 relative to placebo. DESIGN: This was a randomized, double-blind, parallel-arm, placebo-controlled, multicenter, 6-month study. Participants were randomized in a 1:1 ratio to receive either MK-0773 50mg b.i.d. or placebo; all participants received Vitamin D and protein supplementation.

SETTING: General community.

PARTICIPANTS: 170 Women aged >/=65 with sarcopenia and moderate physical dysfunction.

MEASUREMENTS: Dual energy X-ray absorptiometry, muscle strength and power, physical performance measures.

RESULTS: Participants receiving MK-0773 showed a statistically significant increase in LBM from baseline at Month 6 vs. placebo (p<0.001). Participants receiving both MK-0773 and placebo showed a statistically significant increase in strength from baseline to Month 6, but the mean difference between the two groups was not significant (p=0.269). Both groups showed significant improvement from baseline at Month 6 in physical performance measures, but there were no statistically significant differences between participants receiving MK-0773 and placebo. A greater number of participants experienced elevated transaminases in the MK-0773 group vs. placebo, which resolved after discontinuation of study therapy. MK-0773 was generally well-tolerated with no evidence of androgenization.

CONCLUSIONS: The MK-0773-induced increase in LBM did not translate to improvement in strength or function vs. placebo. The improvement of strength and physical function in the placebo group could be at least partly attributed to protein and vitamin D supplementation.

 

[Michael Scally MD]

Tsang AH, Barclay JL, Oster H. Interactions between endocrine and circadian systems. Journal of Molecular Endocrinology. http://jme.endocrinology-journals.org/content/early/2013/08/30/JME-13-0118.abstract

In most species endogenous circadian clocks regulate 24-hour rhythms of behaviour and physiology. Clock disruption has been associated with decreased cognitive performance and increased propensity to develop obesity, diabetes, and cancer. Many hormonal factors show robust diurnal secretion rhythms, some of which are involved in mediating clock output from the brain to peripheral tissues. In this review we describe the mechanisms of clock-hormone interaction in mammals, the contribution of different tissue oscillators to hormonal regulation, and how changes in circadian timing impinge on endocrine signalling and downstream processes. We further summarize recent findings suggesting that hormonal signals may feed-back on circadian regulation and how this crosstalk interferes with physiological and metabolic homeostasis.

 

[Michael Scally MD]

Flechtner-Mors M, Schick A, Oeztuerk S, et al. Associations of Fatty Liver Disease and Other Factors Affecting Serum SHBG Concentrations: A Population Based Study on 1657 Subjects. Horm Metab Res. https://www.thieme-connect.de/ejournals/abstract/10.1055/s-0033-1354369

Sex hormone binding globulin (SHBG) is a glycoprotein expressed predominantly in the hepatocytes. It regulates the transport of sex steroid hormones in the blood stream to their target tissues. The expression of the SHBG gene is subject to multifactorial regulation including hormonal, metabolic, and nutritional aspects. Against this background, we investigated the effect of fatty liver and metabolic syndrome, together with other parameters, on serum SHBG concentrations in a population-based cohort in Germany.

This cross-sectional study included 870 women and 787 men (average age 42.3+/-12.8 years), who underwent ultrasound screening for fatty liver in addition to providing a complete medical history and undergoing physical and laboratory examination. Fatty liver was diagnosed on ultrasound criteria in 159 women (18.3%) and 287 men (36.5%).

Fatty liver was shown to exert a significant influence on serum SHBG concentrations in men and in premenopausal women. Men with grade 1 fatty liver had a 1.96-fold increased risk (95%-confidence interval=1.28-3.02; p=0.0022) and postmenopausal women with grade 1 fatty liver a 2.4-fold risk (95%-confidence interval=1.11-5.27; p=0.0267) for low SHBG concentrations.

Among metabolic parameters, HDL-C represented as affecting factor in men (p=0.0058) and premenopausal women (p=0.0002), while cholesterol only showed an association in premenopausal women (p=0.0439) and triglyceride in postmenopausal women (p=0.0436). No association of concentrations of SHBG and metabolic syndrome was observed. Age, BMI and waist-to-hip ratio also influence the SHBG concentration.

Based on these findings, we conclude that fat accumulation in the liver influences SHBG concentrations in men and premenopausal women.

 

[Michael Scally MD]

Redmon JB, Thomas W, Ma W, et al. Semen parameters in fertile US men: the Study for Future Families. Andrology. Semen parameters in fertile US men: the Study for Future Families - Redmon - 2013 - Andrology - Wiley Online Library

Establishing reference norms for semen parameters in fertile men is important for accurate assessment, counselling and treatment of men with male factor infertility. Identifying temporal or geographic variability in semen quality also requires accurate measurement of semen parameters in well-characterized, defined populations of men. The Study for Future Families (SFF) recruited men who were partners of pregnant women attending prenatal clinics in Los Angeles CA, Minneapolis MN, Columbia MO, New York City NY and Iowa City IA. Semen samples were collected on site from 763 men (73% White, 15% Hispanic/Latino, 7% Black and 5% Asian or other ethnic group) using strict quality control and well-defined protocols. Semen volume (by weight), sperm concentration (hemacytometer) and sperm motility were measured at each centre. Sperm morphology (both WHO, 1999 strict and WHO, 1987) was determined at a central laboratory. Mean abstinence was 3.2 days.

Mean (median; 5th–95th percentile) values were: semen volume, 3.9 (3.7; 1.5–6.8) mL; sperm concentration, 60 (67; 12–192) × 106/mL; total sperm count 209 (240; 32–763) × 106; % motile, 51 (52; 28–67) %; and total motile sperm count, 104 (128; 14–395) × 106 respectively. Values for sperm morphology were 11 (10; 3–20) % and 57 (59; 38–72) % normal forms for WHO (1999) (strict) and WHO (1987) criteria respectively.

Black men had significantly lower semen volume, sperm concentration and total motile sperm counts than White and Hispanic/Latino men. Semen parameters were marginally higher in men who achieved pregnancy more quickly but differences were small and not statistically significant. The SFF provides robust estimates of semen parameters in fertile men living in five different geographic locations in the US. Fertile men display wide variation in all of the semen parameters traditionally used to assess fertility potential.

 

[Michael Scally MD]

Highlights
• We evaluated the validity of a commercial dihydrotestosterone (DHT) immunoassay.
• Immunoassay overestimated DHT concentrations by 79%-1000% compared with LC-MS/MS.
• Immunoassay did not detect reductions in DHT following finasteride treatment.
• Cross-reactivity of the DHT immunoassay ranged from 18-99% with testosterone (T).
• This immunoassay is invalid for DHT assessment in biological fluids containing T.


Yarrow JF, Beck DT, Conover CF, Beggs LA, Goldberger BA, Borst SE. Invalidation of a commercially available human 5alpha-dihydrotestosterone immunoassay. Steroids. Invalidation of a commercially available human 5?-dihydrotestosterone immunoassay

Enzyme immunoassays (EIA) are commonly utilized for the evaluation of androgens in biological fluids; however, careful consideration must be given to cross-reactivity with other endogenous sex-steroid hormones. Our purpose was to determine the validity of a commonly-utilized commercially-available dihydrotestosterone (DHT) EIA. Serum samples obtained from older hypogonadal men who participated in a 12-month randomized controlled trial evaluating the effects of testosterone-enanthate (125mg/week) or vehicle in combination with finasteride (5mg/day) or placebo were assayed for DHT via EIA and using a validated gold-standard LC-MS/MS approach. Additionally, commercially-available (DHT-free) buffer containing graded testosterone doses was evaluated by DHT immunoassay. DHT concentrations measured via EIA were 79% to >1000% higher than values obtained by LC-MS/MS (p<0.05), with the largest differences (415-1128%) occuring in groups receiving finasteride. Both LC-MS/MS and EIA indicated that testosterone-enanthate increased serum DHT to a similar magnitude. In contrast, finasteride-induced reductions in DHT were detected by LC-MS/MS, but not EIA (p<0.05). No significant associations were present for DHT concentrations between measurement techniques. Cross-reactivity of testosterone with the immunoassay ranged from 18-99% and DHT concentrations measured by EIA were highly associated with the spiked testosterone concentrations in DHT-free buffer (r=0.885, p<0.001). In conclusion, we provide evidence invalidating a commonly-utilized commercially-available DHT immunoassay because significant cross-reactivity exists between testosterone and the EIA and because the changes in DHT observed via EIA were not associated with a validated gold-standard measurement technique. The cross-reactivity of testosterone is particularly concerning because testsoterone is present in 100-fold greater concentrations than is DHT within the circulation.

 

[Michael Scally MD]

Rose SR, Kim MO, Korbee L, et al. Oxandrolone for the treatment of bone marrow failure in Fanconi anemia. Pediatr Blood Cancer. Oxandrolone for the treatment of bone marrow failure in Fanconi anemia - Rose - 2013 - Pediatric Blood & Cancer - Wiley Online Library

BACKGROUND: A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization.

PROCEDURE: A single arm, Phase I/II study was designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic response was noted at 16 weeks, a single dose escalation was offered. Subjects were regularly assessed for toxicity, including determinations of virilization, behavioral changes, and liver and kidney function. At 32 weeks, those who demonstrated hematologic response were allowed to continue study treatment, and those without improvement were deemed non-responsive.

RESULTS: Nine subjects completed the study and were followed for a median of 99 weeks (46-136 weeks). Three (33.3%) subjects developed mild sub-clinical virilization and continued treatment with a dose reduction. None (0%) had adverse behavioral changes. Two (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven (77.8%) subjects had a hematologic response.

CONCLUSION: Oxandrolone appears to be well-tolerated, has limited toxicities at the administered doses in FA with patients, and may be an alternative androgen for the treatment of BMF in FA.

 

[Michael Scally MD]

Kraemer WJ, Solomon-Hill G, Volk BM, et al. The effects of soy and whey protein supplementation on acute hormonal responses to resistance exercise in men. J Am Coll Nutr 2013;32(1):66-74. An Error Occurred Setting Your User Cookie

Objective: For many resistance-trained men concerns exist regarding the production of estrogen with the consumption of soy protein when training for muscle strength and size. Thus, the purpose of this investigation was to examine the effects of soy and whey protein supplementation on sex hormones following an acute bout of heavy resistance exercise in resistance trained men.

Methods: Ten resistance-trained men (age 21.7 +/- 2.8 [SD] years; height 175.0 +/- 5.4 cm; weight 84.2 +/- 9.1 kg) volunteered to participate in an investigation. Utilizing a within subject randomized crossover balanced placebo design, all subjects completed 3 experimental treatment conditions supplementing with whey protein isolate (WPI), soy protein isolate (SPI), and maltodextrin placebo control for 14 days with participants ingesting 20 g of their assigned supplement each morning at approximately the same time each day. Following supplementation, subjects performed an acute heavy resistance exercise test consisting of 6 sets of 10 repetitions in the squat exercise at 80% of the subject's one repetition maximum.

Results: This investigation observed lower testosterone responses following supplementation with soy protein in addition to a positive blunted cortisol response with the use of whey protein at some recovery time points. Although sex hormone binding globulin (SHBG) was proposed as a possible mechanism for understanding changes in androgen content, SHBG did not differ between experimental treatments. Importantly, there were no significant differences between groups in changes in estradiol concentrations.

Conclusion: Our main findings demonstrate that 14 days of supplementation with soy protein does appear to partially blunt serum testosterone. In addition, whey influences the response of cortisol following an acute bout of resistance exercise by blunting its increase during recovery. Protein supplementation alters the physiological responses to a commonly used exercise modality with some differences due to the type of protein utilized.

 

[Michael Scally MD]

Finkelstein JS, Lee H, Burnett-Bowie S-AM, et al. Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men. New England Journal of Medicine 2013;369(11):1011-22. MMS: Error

BACKGROUND - Current approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both account for clinical manifestations.

METHODS - We provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin acetate, placebo gel or testosterone gel, and anastrozole (to suppress the conversion of testosterone to estradiol). Changes in the percentage of body fat and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were also assessed.

RESULTS - The percentage of body fat increased in groups receiving placebo or 1.25 g or 2.5 g of testosterone daily without anastrozole (mean testosterone level, 44±13 ng per deciliter, 191±78 ng per deciliter, and 337±173 ng per deciliter, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and in those receiving 1.25 g of testosterone daily without anastrozole. Leg-press strength fell only with placebo administration. In general, sexual desire declined as the testosterone dose was reduced.

CONCLUSIONS - The amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varied widely in men. Androgen deficiency accounted for decreases in lean mass, muscle size, and strength; estrogen deficiency primarily accounted for increases in body fat; and both contributed to the decline in sexual function. Our findings support changes in the approach to evaluation and management of hypogonadism in men.

 

[Michael Scally MD]

Stubbe JH, Chorus AM, Frank LE, de Hon O, van der Heijden PG. Prevalence of use of performance enhancing drugs by fitness centre members. Drug Test Anal. Prevalence of use of performance enhancing drugs by fitness centre members - Stubbe - 2013 - Drug Testing and Analysis - Wiley Online Library

Studies on the use of performance enhancing drugs (PED) in fitness centres rely predominately on conventional survey methods using direct questioning. However, research indicates that direct questioning of sensitive information is characterized by under-reporting.

The aim of the present study was to contrast direct questioning of different types of PED use by Dutch fitness centre members with results obtained with the Randomized Response Technique (RRT). Questionnaires were conducted among members of fitness centres. PED were classified into the following categories: anabolic steroids, prohormones, substances to counteract side-effects, growth hormone and/or insulin, stimulants (to reduce weight), and miscellaneous substances.

A total of 718 athletes from 92 fitness centres completed the questionnaire. The conventional method resulted in prevalences varying between 0% and 0.4% for the different types of PED with an overall prevalence of 0.4%. RRT resulted in prevalences varying between 0.8% and 4.8% for the different types of PED with an overall prevalence of 8.2%. The overall prevalence of the two survey methods differed significantly.

The current study showed that the conventional survey method using direct questioning led to an underestimation of the prevalence. Based on the RRT results, the percentage of users of PED among members of fitness centres is approximately 8.2%. Stimulants to lose weight had the highest prevalence, even higher than anabolic steroids. The key task for future preventive health work is to not only focus on anabolic steroid use, but also include interventions focusing on the use of stimulants to lose weight.

 

[Michael Scally MD]

Pastuszak AW, Badhiwala N, Lipshultz LI, Khera M. Depression is correlated with the psychological and physical aspects of sexual dysfunction in men. Int J Impot Res 2013;25(5):194-9. International Journal of Impotence Research - Abstract of article: 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 (?=?0.210, P=0.006), intercourse satisfaction (?=?0.293, P<0.0001) and overall satisfaction (?=?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 (?=?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.

 

[Michael Scally MD]

Rossow LM, Fukuda DH, Fahs CA, Loenneke JP, Stout JR. Natural bodybuilding competition preparation and recovery: a 12-month case study. Int J Sports Physiol Perform 2013;8(5):582-92. http://journals.humankinetics.com/ijspp-current-issue/ijspp-volume-8-issue-5-september/natural-bodybuilding-competition-preparation-and-recoverynbsp-a-12-month-case-study

Bodybuilding is a sport in which competitors are judged on muscular appearance. This case study tracked a drug-free male bodybuilder (age 26-27 y) for the 6 mo before and after a competition.

Purpose: The aim of this study was to provide the most comprehensive physiological profile of bodybuilding competition preparation and recovery ever compiled.

Methods: Cardiovascular parameters, body composition, strength, aerobic capacity, critical power, mood state, resting energy expenditure, and hormonal and other blood parameters were evaluated.

Results: Heart rate decreased from 53 to 27 beats/min during preparation and increased to 46 beats/min within 1 mo after competition. Brachial blood pressure dropped from 132/69 to 104/56 mmHg during preparation and returned to 116/64 mmHg at 6 mo after competition. Percent body fat declined from 14.8% to 4.5% during preparation and returned to 14.6% during recovery. Strength decreased during preparation and did not fully recover during 6 months of recovery. Testosterone declined from 9.22 to 2.27 ng/mL during preparation and returned back to the baseline level, 9.91 ng/mL, after competition. Total mood disturbance increased from 6 to 43 units during preparation and recovered to 4 units 6 mo after competition.

Conclusions: This case study provides a thorough documentation of the physiological changes that occurred during natural bodybuilding competition and recovery.

 

[idmd]

Didn't we have a new low T person around here starving themselves while doing intense exercise? This was quite a sharp drop in testosterone levels!

 

[Michael Scally MD]

Didn't we have a new low T person around here starving themselves while doing intense exercise? This was quite a sharp drop in testosterone levels!

And, if we are thinking of the same person, they were/are in a hurry for TRT (50+ years).

 

[Michael Scally MD]

Xu P, He H, Chen Y, Wang C, Zhu Y, Ye X. Osteoporotic fractures and persistent non-fusion of the hand epiphyses caused by empty sella syndrome in an adult: A case report. J Int Med Res. Osteoporotic fractures and persistent non-fusion of the hand epiphyses caused by empty sella syndrome in an adult: A case report

We report a case of primary empty sella syndrome (ESS) resulting in osteoporotic fractures and persistent non-fusion of the hand epiphyses, and discuss the potential pathogenesis of this disease. A 41-year-old man presented with pain in the right hand and back after a fall. X-radiographs revealed persistent epiphyses and severe osteoporosis. Serum phosphorus and prolactin levels were above normal levels, and free triiodothyronine, free thyroxine and testosterone levels were below normal limits. Magnetic resonance imaging of the head revealed empty sella. A lumbar bone mineral density examination indicated severe osteoporosis. ESS caused a systemic hormone disorder in this patient, resulting in osteoporotic fractures and persistent non-fusion of the hand epiphyses. Possible causes of this anomaly are chronic or congenital abnormities of the pituitary gland.

 

[Michael Scally MD]

Tuin J, Sanders JS, Buhl BM, van Beek AP, Stegeman CA. Androgen deficiency in male patients diagnosed with ANCA-associated vasculitis: a cause of fatigue and reduced health-related quality of life? Arthritis Res Ther 2013;15(5):R117. http://arthritis-research.com/content/15/5/R117/abstract

INTRODUCTION: Low testosterone levels in men are associated with fatigue, limited physical performance and reduced health-related quality of life (HRQOL); however this relationship has never been assessed in patients with anti-neutrophil cytoplasmic antibodies (ANCA) -associated vasculitides (AAV). The aim of this study was to assess the prevalence of androgen deficiency and to investigate the role of testosterone in fatigue, limited physical condition and reduced HRQOL in men with AAV.

METHODS: Male patients with AAV in remission were included in this study. Fatigue and HRQOL were assessed by the multi-dimensional fatigue inventory (MFI)-20 and RAND-36 questionnaires.

RESULTS: 70 male patients with a mean age of 59 years (SD 12) were included. Scores of almost all subscales of both questionnaires were significantly worse in patients compared to controls. Mean total testosterone and free testosterone levels were 13.8 nmol/L (SD 5.6) and 256 pmol/L (SD 102) respectively. Androgen deficiency (defined according to Endocrine Society Clinical Practice Guidelines) was present in 47% of patients. Scores in the subscales of general health perception, physical functioning and reduced activity were significantly worse in patients with androgen deficiency compared to patients with normal androgen levels. Testosterone and age were predictors for the RAND-36 physical component summary in multiple linear regression analysis. Testosterone, age, vasculitis damage index (VDI) and c-reactive protein (CRP) were associated with the MFI-20 subscale of general fatigue.

CONCLUSION: This study showed that androgen deficiency was present in a substantial number of patients with AAV. Testosterone was one of the predictors for physical functioning and fatigue. Testosterone may play a role in fatigue, reduced physical performance and HRQOL in male patients with AAV.

 

[Michael Scally MD]

Mieritz MG, Sorensen K, Aksglaede L, et al. Elevated serum IGF-I, but unaltered sex steroid levels, in Healthy Boys with Pubertal Gynaecomastia. Clinical Endocrinology. Elevated serum IGF-I, but unaltered sex steroid levels, in Healthy Boys with Pubertal Gynaecomastia - Mieritz - Clinical Endocrinology - Wiley Online Library

Objective Pubertal gynaecomastia is a very common condition. Although the underlying etiology is poorly understood, it is generally accepted that excess of estrogens and/or deficit of androgens are involved in the pathogenesis. Furthermore, adiposity as well as the GH/IGF-I axis may play a role. In the present study we elucidate the association of adiposity and levels of FSH, LH, SHBG, testosterone, E2, IGF-I, and IGFBP-3 with the presence of pubertal gynaecomastia in a large cohort of healthy boys.

Patients 501 healthy Danish school boys (aged 6.1-19.8 yr) from the COPENHAGEN Puberty Study.

Measurements Anthropometry and pubertal stages (PH1-6 and G1-5) were evaluated, and the presence of gynaecomastia was assessed. Body fat percentage was calculated by means of four skin folds and impedance. Non-fasting blood samples were analyzed for FSH, LH, testosterone, SHBG, estradiol, IGF-I, IGFBP-3 and prolactin.

Results We found that 23% (31/133) of all pubertal boys had gynaecomastia. More specifically 63% (10/16) of boys in genital stage 4 had gynaecomastia. Boys with gynaecomastia had significantly higher IGF-I levels compared to controls (IGF-I SD-score 0.72 vs. -0.037, p<0.001). This difference was maintained after adjusting for confounders (age and pubertal stage). Sex steroid levels, estradiol/testosterone-ratio, or free testosterone were not associated with the presence of gynaecomastia with or without adjustment for confounders.

Conclusions IGF-I levels were elevated in healthy boys with pubertal gynaecomastia compared to boys without gynaecomastia, whereas sex steroid levels did not differ. We speculate that the GH-IGF-I axis may be involved in the pathogenesis of pubertal gynaecomastia.

 

[Michael Scally MD]

Maattanen I, Jokela M, Hintsa T, et al. Testosterone and temperament traits in men: Longitudinal analysis. Psychoneuroendocrinology 2013;38(10):2243-8. Testosterone and temperament traits in men: Longitudinal analysis

Testosterone is the main male hormone that has been associated with various behavioral traits in humans and other animals. We investigated whether levels of total testosterone, free testosterone, and sex hormone binding globulin were associated with temperament traits in a population-based sample of Finnish men at two measurement times taken 6 years apart (n = 686 in year 2001, n = 727 in year 2007). Temperament was assessed using the Temperament and Character Inventory that consists of four temperament traits: novelty seeking, harm avoidance, reward dependence, and persistence. Higher levels of total and free testosterone were associated with higher novelty seeking (standardized B = 0.103,p < 0.001). This association was also observed in a longitudinal within-person analysis (B = 0.084,p = 0.008), suggesting that the association is not confounded by stable between-individual differences in other characteristics. Within-individual variation in total testosterone was associated with higher reward dependence, and higher levels of free testosterone were marginally associated with higher reward dependence. Reward dependence reflects the importance of social rewards to an individual. These results provide additional evidence for the stable and time-varying associations between testosterone and temperament in humans.