Saturday, July 26, 2014

Mozart, Music and Medicine

Pauwels EK, Volterrani D, Mariani G, Kostkiewics M. Mozart, Music and Medicine. Med Princ Pract.   

According to the first publication in 1993 by Rauscher et al., the Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448.

A further evaluation of this effect has raised the question whether there is a link between music-generated emotions and a higher level of cognitive abilities by mere listening. Positron emission tomography and functional magnetic resonance imaging have revealed that listening to pleasurable music activates cortical and subcortical cerebral areas where emotions are processed. These neurobiological effects of music suggest that auditory stimulation evokes emotions linked to heightened arousal and result in temporarily enhanced performance in many cognitive domains.

Music therapy applies this arousal in a clinical setting as it may offer benefits to patients by diverting their attention from unpleasant experiences and future interventions. It has been applied in the context of various important clinical conditions such as cardiovascular disorders, cancer pain, epilepsy, depression and dementia.

Furthermore, music may modulate the immune response, among other things, evidenced by increasing the activity of natural killer cells, lymphocytes and interferon-gamma, which is an interesting feature as many diseases are related to a misbalanced immune system.

Many of these clinical studies, however, suffer from methodological inadequacies. Nevertheless, at present, there is moderate but not altogether convincing evidence that listening to known and liked music helps to decrease the burden of a disease and enhances the immune system by modifying stress.

Leptin in Human Reproductive Disorders

Chou SH-H, Mantzoros C. Leptin in human reproductive disorders. Journal of Endocrinology.  

As a key hormone in energy homeostasis, leptin regulates neuroendocrine function, including reproduction. It has a permissive role in initiating puberty and maintaining the hypothalamic-pituitary-gonadal axis. This is notable in patients with either congenital or acquired leptin deficiency from a state of chronic energy insufficiency.

Hypothalamic amenorrhea is the best-studied with clinical trials confirming a causative role of leptin in hypogonadotropic hypogonadism. Implications of leptin deficiency have also emerged in the pathophysiology of hypogonadism in type 1 diabetes.

At the other end of the spectrum, hyperleptinemia may play a role in hypogonadism associated with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these conditions of energy excess, mechanisms of reproductive dysfunction include central leptin resistance as well as direct effects at the gonadal level. Thus, reproductive dysfunction due to energy imbalance at both ends can be linked to leptin.

Friday, July 25, 2014

Diagnosis of Prolactinoma in Two Male-To-Female Transsexual Subjects Following High-Dose Cross-Sex Hormone Therapy

Cunha FS, Domenice S, C├ómara VL, et al. Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy. Andrologia.

Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-adminstration of cross-sex hormones, doses may be very high.

Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events.

We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years.

Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised.

Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens.

Lean Mass, Muscle Strength and Gene Expression

Patel HP, Al-Shanti N, Davies LC, et al. Lean Mass, Muscle Strength and Gene Expression in Community Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS). Calcif Tissue Int.   

Sarcopenia is associated with adverse health outcomes. This study investigated whether skeletal muscle gene expression was associated with lean mass and grip strength in community-dwelling older men.

Utilising a cross-sectional study design, lean muscle mass and grip strength were measured in 88 men aged 68-76 years. Expression profiles of 44 genes implicated in the cellular regulation of skeletal muscle were determined. Serum was analysed for circulating cytokines TNF (tumour necrosis factor), IL-6 (interleukin 6, IFNG (interferon gamma), IL1R1 (interleukin-1 receptor-1). Relationships between skeletal muscle gene expression, circulating cytokines, lean mass and grip strength were examined. Participant groups with higher and lower values of lean muscle mass (n = 18) and strength (n = 20) were used in the analysis of gene expression fold change.

Expression of VDR (vitamin D receptor) [fold change (FC) 0.52, standard error for fold change (SE) +/- 0.08, p = 0.01] and IFNG mRNA (FC 0.31; SE +/- 0.19, p = 0.01) were lower in those with higher lean mass.

Expression of IL-6 (FC 0.43; SE +/- 0.13, p = 0.02), TNF (FC 0.52; SE +/- 0.10, p = 0.02), IL1R1 (FC 0.63; SE +/- 0.09, p = 0.04) and MSTN (myostatin) (FC 0.64; SE +/- 0.11, p = 0.04) were lower in those with higher grip strength. No other significant changes were observed.

Significant negative correlations between serum IL-6 (R = -0.29, p = 0.005), TNF (R = -0.24, p = 0.017) and grip strength were demonstrated.

This novel skeletal muscle gene expression study carried out within a well-characterized epidemiological birth cohort has demonstrated that lower expression of VDR and IFNG is associated with higher lean mass, and lower expression of IL-6, TNF, IL1R1 and myostatin is associated with higher grip strength.

These findings are consistent with a role of proinflammatory factors in mediating lower muscle strength in community-dwelling older men.

Male Facial Attractiveness and Masculinity May Provide Sex- And Culture-Independent Cues to Semen Quality

Soler C, Kekalainen J, Nunez M, et al. Male facial attractiveness and masculinity may provide sex- and culture-independent cues to semen quality. J Evol Biol.   

Phenotype-linked fertility hypothesis (PLFH) predicts that male secondary sexual traits reveal honest information about male fertilization ability. However, PLFH has rarely been studied in humans. The aim of the present study was to test PLFH in humans and to investigate whether potential ability to select fertile partners is independent of sex or cultural background. We found that on the contrary to the hypothesis, facial masculinity was negatively associated with semen quality. As increased levels of testosterone have been demonstrated to impair sperm production, this finding may indicate a trade-off between investments in secondary sexual signalling (i.e. facial masculinity) and fertility or status-dependent differences in investments in semen quality. In both sexes and nationalities (Spanish and Colombian), ranked male facial attractiveness predicted male semen quality. However, Spanish males and females estimated facial images generally more attractive (gave higher ranks) than Colombian raters, and in both nationalities, males gave higher ranks than females. This suggests that male facial cues may provide culture- and sex-independent information about male fertility. However, our results also indicate that humans may be more sensitive to facial attractiveness cues within their own populations and also that males may generally overestimate the attractiveness of other men to females.

Pharmacokinetics and Drying Time of Testosterone 2% gel

Morgentaler A, McGettigan J, Xiang Q, Danoff TM, Gould EM. Pharmacokinetics and drying time of testosterone 2% gel in men with hypogonadism: a multicenter, open-label, single-arm trial. Int J Impot Res.   

The objective of this study was to assess drying time after application of testosterone 2% gel (Fortesta Gel, Endo Pharmaceuticals), time needed for serum total testosterone (TT) to reach the eugonadal range (300 ng dl-1), and time to steady-state serum TT. Thirty-four men with primary or secondary hypogonadism were enrolled in the study; 31 men were included in the pharmacokinetics (PKs) population. Testosterone 2% gel (40 mg) was applied once daily in the morning to the front and inner thighs for 14 days. Median gel drying time was 2.4 min (95% confidence interval (CI), 1.7-3.4 min; n=31). Serum TT concentrations reached the target eugonadal range with a median time of 2.9 h (95% CI, 1.9-4.3 h; n=24). Median time to steady-state serum TT concentration was 1.1 days (95% CI, 0.7-3.4 days; n=31). Six patients (17.6%; n=34) reported treatment-related adverse events; all were mild. The results from this 14-day PK study in men with hypogonadism suggest that testosterone 2% gel dries, on average, in <3 min after application and that testosterone 2% gel rapidly reaches the target eugonadal range and attains steady-state serum TT concentrations in about 1 day.

Wednesday, July 23, 2014

Validity of Midday Total Testosterone Levels in Erectile Dysfunction

Welliver RC, Jr., Wiser HJ, Brannigan RE, Feia K, Monga M, Kohler TS. Validity of Midday Total Testosterone Levels in Older Men with Erectile Dysfunction. The Journal of Urology 2014;192(1):165-9.   

Purpose - Based on studies showing the circadian rhythmicity of testosterone the optimal time of day to draw total testosterone in men has classically been reported as between 8 and 11 a.m. However, further studies demonstrated that the testosterone circadian rhythmicity becomes blunted with age.

Materials and Methods - We retrospectively reviewed the charts of 2,569 men who presented with erectile dysfunction for total testosterone and draw times. We compared the men by age group, including less than 40 years and 5-year groupings after age 40 years. Total testosterone was analyzed for variability during the most common draw time hours (7 a.m. to 2 p.m.).

Results - Mean total testosterone at 7 to 9 a.m. and 9 a.m. to 2 p.m. clinically and statistically differed only in men younger than 40 vs 40 to 44 years old (mean difference 207 ng/dl, 95% CI 98–315, p = 0.0004 vs 149 ng/dl, 95% CI 36–262, p = 0.01). No other group showed a clinically and statistically significant difference between those periods.

Conclusions - Total testosterone in men with erectile dysfunction who are younger than 45 years should be drawn as close to 7 a.m. as possible because a statistically and clinically relevant decrease in testosterone will occur during the course of the day. Men older than 45 years with erectile dysfunction can have total testosterone drawn at any time before 2 p.m. without misleading results.