Hypogonadotrophic hypogonadism in type 2 diabetes

Recent work shows a high prevalence of low testosterone and inappropriately low luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity in patients with type 2 diabetes. However, the duration of diabetes or HbA1c are not related to HH. Furthermore, recent data show that HH is not associated with type 1 diabetes. C-reactive protein concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and C- reactive protein concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is also relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations are also related to an increase in total and regional adiposity. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates insulin resistance and inflammation. In addition, low testosterone levels are associated with an increase in cardiovascular events. Testosterone therapy may therefore, reduce cardiovascular risk. This important aspect requires further investigation.     

Change in cytokine levels after administration of saikokaryuukotsuboreito or testosterone in patients with symptoms of late-onset hypogonadism

The purpose of this study was to evaluate plasma cytokine levels after treatment with saikokaryukotsuboreito (SKRBT), which is a herbal medicine, or androgen replacement treatment (ART), for patients with late-onset hypogonadism (LOH)-related symptoms. Thirty-one patients over 40 years of age with LOH-related symptoms were included in this study. SKRBT was given orally three times daily to a total of 7.5 g/day for 15 eugonadal patients and ART was give to 16 hypogonadal patients by intramuscular injection of testosterone enanthate at 125?mg each time every 2 weeks. Plasma levels of testosterone and 18 cytokines, as well as LOH-related symptoms scored according to the Aging Males' Symptoms (AMS) scale, were compared before and more than 2 months after treatment. In the ART group, the total AMS score was decreased and testosterone was increased significantly after treatment. No cytokine variables were altered significantly after the treatment. In the SKRBT group, although the total AMS score was significantly decreased, testosterone did not change. From the evaluation of cytokines, a significant increase was found in interleukin (IL)- 8, IL-13, interferon-γ and tumour necrosis factor-α. We conclude that SKRBT might improve LOH-related symptoms in eugonadal patients through the beneficial effect of cytokines, a mechanism that is quite different from ART.     

Testosterone deficiency and the metabolic syndrome

Evidence is presented to link components of the metabolic syndrome to testosterone deficiency and obesity. Testosterone deficiency in hypogonadism or testosterone deprivation in normo-gonadotropic men increases fat mass as well as fasting insulin levels. Testosterone supplementation (TS) in a dose dependent manner, increase lean body mass (LBM), reduces fat mass, body mass index (BMI) and waist hip ratio in both young and elderly hypogonadal men. A negative association between T and insulin resistance as well as impaired glucose intolerance has been demonstrated and in type 2 diabetic men TS improves metabolic parameters. TS improves most components of the metabolic syndrome and also reduces inflammatory cytokines.     

Innate immunity, local inflammation, and degenerative disease

The brain lesions associated with Alzheimer's disease (AD), which are referred to as neurofibrillary tangles and senile plaques, are characterized by the presence of a broad spectrum of inflammatory mediators. Surprisingly, these mediators, which include complement proteins, inflammatory cytokines, prostaglandins, and acute phase reactants such as C-reactive protein and amyloid P, are produced by resident brain cells, including neurons. Although secondary to the fundamental pathology caused by the presence of tangles and plaques, there is strong evidence that inflammation exacerbates the neuronal loss. In particular, AD lesions show evidence of self-attack by the complement system--a part of the immune system that normally functions to rid the body of invading pathogens. However, the lesions are devoid of significant T cell infiltration, a hallmark of an inflammatory immune response, and antibodies. We define this phenomenon as autotoxicity to distinguish it from classical autoimmunity, in which the body raises antibodies to normal endogenous macromolecules. Locally produced inflammatory mediators have also been identified in atherosclerotic plaques, along with evidence of complement self-attack. As was previously shown for heart attacks, epidemiological evidence indicates that extended use of nonsteroidal anti-inflammatory drugs (NSAIDs) results in a reduced risk of AD. NSAIDs inhibit the production of prostaglandin inflammatory mediators, but powerful new therapeutic agents might be developed by targeting more critical inflammatory mechanisms, especially the complement system.     

Pituitary radiographic abnormalities and clinical correlates of hypogonadism in elderly males presenting with erectile dysfunction

The prevalence of erectile dysfunction rises rapidly with age and is a frequent complaint presented in clinical practice. Although the etiology of erectile dysfunction is multifactorial, 10-20% of evaluations demonstrate testosterone deficiency. Testosterone deficiency due to secondary hypogonadism increases with age. Despite a higher prevalence of secondary hypogonadism in the elderly, there are no studies addressing hypothalamic-pituitary structural abnormalities in elderly impotent men with testosterone deficiency. We retrospectively reviewed the records of all elderly men who presented for general outpatient evaluation of erectile dysfunction from 1996 to 1999. To obtain a cohort control population, the records of 300 patients without erectile dysfunction were also reviewed. Amongst the erectile dysfunction patients, 225 were found to be testosterone deficient (testosterone < 300 ng/dl). Of these patients, 29 were additionally diagnosed with secondary hypogonadism based on a luteinizing hormone (LH) < 13 mIU/ml. Magnetic resonance imaging (MRI) or computed tomography (CT) imaging was available and reviewed in all patients diagnosed with secondary hypogonadism. Ten per cent of these patients had hypothalamic-pituitary imaging abnormalities. The prevalence of pituitary tumors within our population was not significantly elevated compared to the previous general population studies. Small-vessel white matter disease, hyperlipidemia and history of compression fractures were significantly increased in both univariate and multivariate analysis in the erectile dysfunction group compared with the control cohort. This study does not suggest that the use of hypothalamic-pituitary imaging in the evaluation of impotence in elderly men, in the absence of clinical characteristics of other hormonal loss or sella compression symptoms, will increase diagnosis of structural hypothalamic-pituitary abnormalities over that of the general population. However, the yield may increase with very low testosterone levels. These data suggest that there is an increase in ischemic white matter disease in elderly men with hypogonadism that may reflect microvascular injury to the hypothalamic-pituitary. Furthermore, these data confirm that low testosterone is associated with hyperlipidemia in the elderly. Future studies are required to assess the role of hypogonadism and hyperlipidemia, and to determine if treatment of the hormone deficiency improves the lipid profile.     

Clinical experiences with testosterone therapy: prostate safety

Due to a decrease in Leydig cell function, a considerable proportion of men over 50 years of age will develop hypogonadism. Consequently, loss of libido and several other testosterone-dependent symptoms may become evident. When decreased levels of biologically available testosterone are found, and corresponding symptoms are present, these men could be eligible for testosterone substitution therapy. Testosterone treatment in testosterone-deprived men has been shown to improve general well-being, osteoporosis, muscle atrophy, libido and - if present - anemia. Despite these positive effects, testosterone treatment has to be performed with caution. Although it has not been proven that elevation of the serum testosterone level to the normal range results in a greater risk of developing prostate cancer, the effects of testosterone on a prostate cancer already present are well established. Several studies have demonstrated that testosterone treatment does not result in a significant increase in serum levels of prostate-specific antigen (PSA) or prostate volume. The long-term effects, however, are currently unknown. For these reasons, testosterone treatment should be performed only when the presence of prostate cancer is unlikely; i.e. when PSA levels are within normal limits and digital rectal examination does not reveal any suspicious findings. These examinations may still miss some small prostate cancers that could be promoted by testosterone treatment. The determination of PSA levels under testosterone treatment is necessary every 3 months, at least for the first year. Steadily rising PSA levels require immediate cessation of testosterone administration and the initiation of further diagnostic procedures (prostate biopsy), to rule out prostate cancer.     

Influence of testosterone substitution on glycemic control and endothelial markers in men with newly diagnosed functional hypogonadism and type 2 diabetes mellitus: a randomized controlled trial

Abstract

Effects of testosterone (T) on the cardiovascular system of men remain controversial. The impact of T-replacement therapy (TRT) in men with functional hypogonadism and type 2 diabetes mellitus (T2DM) has to be elucidated. This study included 80 men (mean age 51.5?±?6.3 years) with newly diagnosed T2DM (according to ADA criteria) and functional hypogonadism (according to EAU criteria). Randomization: Group1 (n?=?40): TRT using 1%-transdermal T-gel (50?mg/day), Group2 (n?=?40) no TRT (controls). Dietary treatment applied to both. Parameters at baseline/after 9?months: anthropometric parameters, lipids and indicators of carbohydrate metabolism (fasting glucose, insulin, HbA1c, HOMA-IR), markers of adipose tissue and EnD (leptin, resistin, p- and e-selectin, ICAM- 1, VCAM- 1 and CRP). ANCOVA for repeated measurements revealed TRT to cause a significant decrease in waist circumference (WC), HOMA-IR and HbA1c vs controls (p?<?.001, p?=?.002, p?=?.004, respectively). Leptin declined in subjects receiving TRT vs controls (p?=?.04). Concentrations of resistin, ICAM-1, p-selectin and CRP decreased significantly vs controls (all p?<?.001); no effects for e-selectin and VCAM-1. Advanced age attenuated effects, higher delta testosterone levels augmented effects. Decrement of WC was related to decreasing markers of adipose tissue secretion/EnD. TRT in men with functional hypogonadism and T2DM improved carbohydrate metabolism and markers of endothelial dysfunction.     

Testosterone therapy in erectile dysfunction

Studies in animals have indicated that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction and a reduction in nitric oxide synthase-stained nerves in erectile tissue. Furthermore, castration adversely affects penile hemodynamics and smooth muscle content, leading to veno-occlusive dysfunction. Testosterone replenishment reverses these physiological, biochemical and structural changes. Several clinical studies have demonstrated the benefits of a combination of testosterone and sildenafil. A recently published, multicenter study evaluated the safety and efficacy of testosterone gel 1% (Testogel®; Schering AG, Germany/AndroGel®; Solvay Pharmaceuticals) vs. placebo gel in conjunction with sildenafil, in producing an erectile response in hypogonadal men who did not respond to treatment with sildenafil alone for erectile dysfunction. The selection criteria required subjects to have had erectile dysfunction for at least 3 months, to be non-responsive to 100 mg sildenafil and to have low testosterone levels (&lt;?400 ng/dl). The primary efficacy measurement was the mean change from baseline in the Erectile Function domain of the International Index of Erectile Function (IIEF). Secondary outcome measures included the mean change from baseline in the other domains and the total sum of the IIEF. Subjects were randomized to receive either testosterone gel + sildenafil, or placebo gel + sildenafil for 12 weeks. Testosterone therapy with testosterone gel improved the erectile response to sildenafil. Therefore, testosterone therapy may be considered for the treatment of erectile dysfunction in men with low to low-normal testosterone levels, who have failed prior treatment with sildenafil alone. Consequently, it is important to screen for hypogonadism in men who fail PDE5 inhibitors.     

Testosterone is not associated with mortality in older African-American males

Introduction.?Although testosterone and its association with disease progression and mortality is a widely studied topic, no studies have evaluated mortality risks related to testosterone levels in an older African-American population. The mechanisms for known racial differences in mortality risk for certain cancers and cardiovascular risk factors are largely unknown. Elucidating a mortality risk associated with testosterone levels may give insight into the elevated risk for certain diseases in African-Americans.

Methods and results.?Study data were derived from a cohort 622 African-Americans (age 80.05?±?6.4, range 68–102) from Saint Louis, Missouri that includes 190 males (age 79.38?±?6.2, range 70–102). The eligible sample for this report includes 56 of the 190 males (age 78.89?±?6.9, range 70–102) who donated blood at baseline in 1992–1994 and subsequently tested for total testosterone and bioavailable testosterone. Covariates for adjusted analyses were lower body functional limitations, physician visits and comorbidities, also collected at baseline. Males' mean bioavailable testosterone levels (ng/dl) were 33.33?±?24.4 (n above 70?ng/dl?=?5) and mean total testosterone levels (ng/dl) were 246.63?±?118.7 (n above 300?ng/dl?=?20). Vital status was determined through 2002; 41 males (73%) were deceased and 15 were alive. Mortality did not differ among males with testosterone levels?<300 versus 300+ (p?=?0.42) or with bioavailable testosterone levels?<70 versus > 70 (p?=?0.34). Total testosterone levels did not predict mortality when adjusted for age (Adjusted Hazard Ratio [AHR]?=?0.998; 95% confidence interval [CI] 0.995–1.001; p?=?0.28) or adjusted for age and other covariates (AHR?=?0.099; 95% CI 0.996, 1.002; p?=?0.35). Bioavailable testosterone levels did not predict mortality when adjusted for age (AHR?=?0.992; 95% CI .977–1.007; p?=?0.30) or when adjusted for age and other covariates (AHR 0.991; 95% CI .976–1.006; p?=?0.261).

Conclusion.?In older African-American males, total and bioavailable testosterone levels, with and without adjustment for covariates, are not independently associated with mortality risk.     

Association of bioavailable estradiol levels and testosterone levels with serum albumin levels in elderly men

Estrogens are reported to be the essential sex steroid acting on some male physiological functions, and bioavailable estrogens comprise the free and albumin-bound fractions. Moreover, most of the bioavailable sex steroid is made up of albumin-bound fraction. We examined the age-related change in serum free, albumin-bound and bioavailable estradiol levels in comparison with each fraction of testosterone and its relationship with serum albumin level in elderly men. Albumin-bound as well as bioavailable estradiol levels declined with age, and their decreases were associated much more with the decrease of albumin level than the increase of sex-hormone binding globulin (SHBG) level in sixties and seventies, and similar results were recognized in the level of each fraction of testosterone, suggesting albumin levels have an important role for maintaining bioavailable sex steroid levels in males aged over sixty. Moreover, our study showed that SHBG levels associated inversely with bioavailable sex steroid levels particularly when serum albumin level was low. It seems likely that the decrease of bioavailable estradiol as well as testosterone is induced by the decrease of albumin-bound fractions in combination with the increase of SHBG-bound fractions in males aged over sixty, and that their physical characteristics of aging could be induced by the decrease of albumin-bound fractions caused by the decrease of serum albumin regardless of total sex steroid levels.     

Interleukin-18 and testosterone levels in men with metabolic syndrome

Objective: Interleukin 18 (IL-18) is an adipokine associated with obesity. Data about the relationship of IL-18 to the metabolic syndrome (MS) are still scarce. Low testosterone (T) levels are common in men with MS, but we did not find data about the levels of IL-18 in men with low T. The aim of this study was to determine the levels of IL-18 in men with MS with or without low T.

Patients and methods: A total of 251 men were included in the study. Of them 218 had MS (IDF 2005) and they were divided according to their morning total testosterone (TT) level (cutoff 10.4?nmol/l) into two groups: MS-low T (N?=?84) and MS-normal T (N?=?134). The control group consisted of 33 men without MS and low T. IL-18 was determined in serum using enzyme-linked immunosorbent assay. A small group of eight men with MS and low T levels received testosterone therapy for three months and physical and laboratory parameters were monitored at the end of that period.

Results: MS men were at mean age (±SD)?=?53.77?±?9.59 years; body mass index (BMI)?=?34.0?±?6.3?kg/m²; and TT?=?12.59?±?5.66?nmol/l. The control group was at age?=?52.12?±?5.2 years (NS); BMI?=?25.6?±?2.4?kg/m² (p?p?p?p?p?p?Conclusions: In this study, higher IL-18 levels were found in the presence of MS compared to healthy men, but they did not differ between men having MS with or without LOH.     

Inverse association of testosterone and sex hormone binding globulin levels with leukocyte count in middle-aged and elderly men

Objective: The inverse associations of testosterone and sex hormone-binding globulin (SHBG) levels with cardiometabolic diseases are well established and are increasingly viewed as inflammatory diseases. This study aimed to examine the associations of testosterone and SHBG levels with leukocyte count in 451 Korean men aged ≥50 years.

Methods: Serum testosterone and SHBG levels were categorized into tertiles. High leukocyte count was defined as ≥7340 cells/μl, which corresponded to the 75th percentile of the current sample. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for high leukocyte count were calculated across testosterone and SHBG tertiles using multiple logistic regression analysis.

Results: The mean leukocyte counts significantly decreased with increasing testosterone and SHBG tertiles. The ORs (95% CIs) of high leukocyte count for the first tertile of testosterone and SHBG were 3.27 (1.34–7.95) and 2.38 (1.05–5.96), respectively, compared with the referent third tertile, after adjusting for age, smoking status, alcohol drinking, regular exercise, body mass index, blood pressure, fasting plasma glucose, triglyceride, and high-density lipoprotein (HDL) cholesterol level.

Conclusion: We found inversely graded associations of low testosterone and SHBG levels with leukocyte count. These findings suggest that low testosterone and SHBG levels may be interpreted as a state of low-grade inflammation.     

Testosterone and the breast

Although women have been treated with testosterone (T) for female sexual dysfunction since the 1950s, the role of T in normal female physiology is not yet fully defined. One of the major safety concerns of androgen therapy is whether androgens have a stimulatory effect on the breast that could lead to breast carcinomas. The proposed mechanisms for such stimulation include local estrogen production from the aromatase enzyme complex present in the breast tissue or by the direct stimulation of the androgen receptor. Predominant data from in vitro studies have shown that androgens actually have apoptotic and antiproliferative effects and not stimulatory effects. Animal models have shown similar results to in vitro studies, finding that androgens inhibit breast cancer growth. Prospective and retrospective epidemiological analyses have shown mixed outcomes, with no clear consensus regarding androgen use and breast cancer risk. Hyperandrogenism in patients with polycystic ovarian syndrome with elevated levels of endogenous T is not associated with an increased risk of breast cancer and may, in fact, be protective. Another human model with excess of T is female-to-male transgenderism, in which genotypic women are treated with large doses of exogenous T with no increased risk. High-dose androgen therapy also has been effective in treating patients with advanced breast cancer. Thus, the preponderance of data suggests that T use in females is not associated with an increased risk of breast carcinoma.     

Testosterone and body functions

Testosterone supplementation can help reduce many of the symptoms associated with androgen deficiency in the aging male by its effects on various parts of the body. Bone mineral density can decrease in the hypogonadal man and this may contribute to the increased fracture rate in the elderly. Testosterone therapy can improve bone mineral density and bone architecture by increasing bone formation and decreasing bone resorption – the possible benefits on fracture rate are unknown. Testosterone also improves body composition by reducing body fat mass and increasing lean body mass, and by increasing epidermal thickness, but its effects on muscle strength are still debated. In patients with diabetes and androgen deficiency, testosterone supplementation appears to reduce blood glucose and this could have important implications for cardiovascular risk reduction in patients with diabetes or the metabolic syndrome. The wide-ranging benefits of testosterone therapy in young and old men are clear and it appears that the route of administration (intramuscular, oral, or transdermal) does not alter this fact, but future work could illustrate even more profound effects of testosterone (e.g., in reducing cardiovascular risk) that could result in its recommended use in a wider range of patients.     

Testosterone and erectile physiology

The role of testosterone deficiency in sexual dysfunction is an important aspect of aging, because it affects such a large proportion of men over 50 years old. A number of age-related factors can cause sexual dysfunction (in particular erectile dysfunction) and testosterone deficiency, such as chronic illness and multiple medications, and the causative link between hypogonadism and erectile dysfunction is still debated. However, studies in castrated animals have proven that addition of testosterone, and its conversion to dihydrotestosterone, can restore erectile function. It appears that testosterone achieves this by peripheral mechanisms (endothelial dependent and independent) and central mechanisms. Testosterone replacement therapy is therefore effective for erectile dysfunction in men with hypogonadism, with success rates of 35–40%. Testosterone supplementation is also important in men who fail on phosphodiesterase type-5 inhibitors, because a minimum plasma concentration of testosterone is required for the successful restoration of erectile function with these agents. Testosterone gels are now the preferred formulation for testosterone supplementation and they can be highly beneficial in a proportion of men with erectile dysfunction.     

The Philippine Male Aging Survey

The aging male is fast becoming a global concern. The problem is predicted to become a major health issue that should be addressed immediately in order to prevent disability, morbidity, and, more importantly, mortality. As part of its commitment to increase awareness and create interest in the care of Filipino aging males, The Philippine Society for the Study of the Aging Male Foundation, Inc. (PhiSSAM), a multi-specialty society established in 2000, embarked on a survey among Filipino physicians to determine their knowledge, attitudes, and practices regarding male aging. Results showed that the majority of doctors (about 87%) thought that men may experience andropause. Most would diagnose patients based on symptoms alone, while only 20–30% used testosterone levels to make a diagnosis of andropause. Decreased libido and less strong erections were the symptoms very closely associated with low testosterone. Of those doctors responding, 89% agreed that andropause can affect the quality of a man's life as much as menopause can affect a female; only 38% had already prescribed/instituted treatment for andropause. Of the 62% non-prescribers, 58% said they were either very likely or fairly likely to institute treatment in the future if there were more clinical trials, more medical information, and more information on drugs. Major concerns on testosterone replacement therapy included prostate cancer, benign prostatic hypertrophy, and heart disease. The findings in this pilot survey indicate a need among the doctors in the Philippines for education about andropause and the available treatments.     

Testosterone supplementation: what and how to give

Several epidemiological studies have demonstrated a gradual decrease of serum testosterone with aging in men. A considerable number of men will experience hypogonadal androgen levels, defined by the normal range for young men. Thus, in addition to the long-standing use of androgen replacement therapy in the classical forms of primary and secondary hypogonadism, age-associated testosterone deficiency has led to considerable developments in application modes for testosterone. Since oral preparations of testosterone are ineffective, due to the first-pass effect of the liver, or, in case of 17 α-alkylation, cause hepatotoxicity, intramuscular injection of long-acting esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. However, the large fluctuations of serum testosterone levels cause unsatisfactory shifts of mood and sexual function in some men; combined with the frequent injections, this delivery mode is thus far from being ideal. In contrast, the transdermal testosterone patches are characterized by favorable pharmacokinetic behavior and have proven to be an effective mode of delivery. Safety data over 10 years indicate no negative effect on the prostate. Nevertheless, the scrotal testosterone patch system is hampered by the application site, which is not easily accepted by many subjects; the non-scrotal patch has a high rate of skin irritations. In view of the drawbacks of the currently available preparations, the most recent developments in testosterone supplementation appear to be highly promising agents. Androgen, which has been available in the United States since mid-2000, will be introduced this year in most European markets as Testogel ® , a hydroalcoholic gel containing 1% testosterone. Doses of 50-100 mg gel applied once daily on the skin deliver sufficient amounts of testosterone to restore normal hormonal values and to correct the signs and symptoms of hypogonadism. The gel has shown to be very effective and successful in American patients, who have benefited from its availability for almost 3 years. Furthermore, in phase II and III clinical studies, the intramuscular injection of 1000 mg testosterone undecanoate every 12-15 weeks has led to extremely stable serum testosterone levels for a prolonged period of time and has resulted in excellent efficacy. It is very likely in the future that these products will be the mainstay of testosterone supplementation. Whereas the indication for testosterone substitution for men with classical forms of hypogonadism is unequivocal, the use of testosterone in men with ageassociated hypogonadism is less uniformly accepted. Yet, the few studies addressing this question indicate that men with testosterone serum levels below the lower normal limit for young adult men and with lack of energy, libido, depressed mood and osteoporosis may benefit from testosterone supplementation. However, it should be kept in mind that the experience documented in studies is limited. Nevertheless, serious side-effects, especially in regard to the prostate, did not occur, with the longest study extending over 3 years.     

Testosterone replacement therapy improves erythrocyte membrane lipid composition in hypogonadal men

Aim: The aim of this study was to investigate the effects of testosterone replacement therapy (TRT) on erythrocyte membrane (EM) lipid composition and physico-chemical properties in hypogonadal men. Methods: EM isolated from three patients before and after TRT with injectable testosterone undecanoate or testosterone gel were used for analysis of the phospholipid and fatty acid composition, cholesterol/phospholipid ratio, membrane fluidity, ceramide level and enzyme acivities responsible for sphingomyelin metabolism. Results: TRT induced increase of phosphatidylethanolamine (PE) in the EMs and sphingomyelin. Reduction of the relative content of the saturated palmitic and stearic fatty acids and a slight increase of different unsaturated fatty acids was observed in phosphatidylcholine (PC). TRT also induced decrease of the cholesterol/total phospholipids ratio and fluidization of the EM. Discussion: The TRT induced increase of PE content and the reduction of saturation in the PC acyl chains induced alterations in the structure of EM could result in higher flexibility of the erythrocytes. The increase of the SM-metabolizing enzyme neutral sphingomyelinase, which regulates the content of ceramide in membranes has a possible impact on the SM signaling pathway. Conclusion: We presume that the observed effect of TRT on the composition and fluidity of the EM contributes for improvement of blood rheology and may diminish the thrombosis risk. Larger studies are needed to confirm the findings of this pilot study.     

Androgen replacement therapy in aging men with secondary hypogonadism

Many animal and human studies show that supraphysiological doses of dehydroepiandrosterone (DHEA) can influence body composition and carbohydrate and lipid metabolism. Most studies have concentrated on women and have not been randomized, thus creating controversial results. With this in mind, we designed a cross-over double-blind placebo-controlled study of 12 men aged 59.0 ± 4.8 years, who received either 50 mg/24 h DHEA or placebo for 3 months to assess the influence of DHEA on the content and distribution of fat tissue and serum insulin, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels, as well as testosterone, estradiol, DHEA-sulfate (S), prostate-specific antigen (PSA) concentrations and indexes of insulin sensitivity and resistance. Patients were recruited from university employees attending for periodic health checks, with normal hepatic and renal function with endogenous DHEA-S level < 1500 ng/dl. Our results did not reveal any significant changes in study parameters, apart from a statistically significant increase in DHEA-S levels after therapy with active substance.     

Testosterone and the brain

Gender differences in spatial recognition, and age-related declines in cognition and mood, point towards testosterone as an important modulator of cerebral functions. Testosterone appears to activate a distributed cortical network, the ventral processing stream, during spatial cognition tasks, and addition of testosterone improves spatial cognition in younger and older hypogonadal men. In addition, reduced testosterone is associated with depressive disorders. The relationship between depression and testosterone appears to partly depend upon the androgen receptor genotype of the patient, and in appropriate patients with low testosterone levels, testosterone substitution can increase positive mood and decrease negative mood. The much publicized link between testosterone and aggression is probably only of importance in athletes who supplement their testosterone levels to excessively high levels, whereas in hypogonadal men, testosterone supplementation only enhances the positive aspects of aggression such as vigour and energy. Current data suggest that testosterone supplementation in hypogonadal men of all ages will enhance many aspects of mood and cognition.