Symptoms Of Testosterone Deficiency Research Articles

Influence of Baseline Serum Testosterone on Changes in Body Composition in Response to Testosterone Therapy

The prognostic value of serum total testosterone (TT) prior to treatment has not been investigated. This study was performed to determine how baseline TT influences changes in body composition in men undergoing testosterone therapy (TTh). Response to TTh in a clinical population of men with symptomatic testosterone deficiency (TD). Retrospective case series of 58 men with TD were treated with TTh. All were naïve to previous TTh. Men were stratified into two groups: group 1 (N = 38) consisted of men with baseline TT > 300 ng/dL (10.4 nmol/L) and group 2 (N = 20) consisted of men with total TT < 300 ng/dL. Men in group 1 were diagnosed with TD on the basis of low values of free testosterone (FT) < 1.5 ng/dL (19.3 pmol/L). Dual-energy X-ray absorptiometry was performed at baseline and follow-up (6.9 ± 4 months) to assess regional and whole body. At baseline, both groups had similar lean mass (LM) and fat mass (FM), but percentage of trunk FM and percentage of total FM were significantly higher in group 2. Both groups demonstrated similar increases in LM for arms, legs, and total body. Percentage of total FM significantly decreased in both groups. Baseline severity of symptomatic TD influences body composition. Similar changes in LM and FM were seen with TTh regardless of baseline severity in TD. Men with TT > 300 ng/dL demonstrated significant positive changes in body composition. The similarity in objective response to TTh in these two groups provides support for the value of FT in the assessment of men with symptoms suggestive of TD.

Baseline Data from the TRiUS Registry: Symptoms and Comorbidities of Testosterone Deficiency

Background: Testosterone deficiency (TD) is prevalent among men seeking medical attention and may be associated with other comorbidities. Objective: The Testim® Registry in the United States (TRiUS), a large, multicenter, prospective, 12-month observational cohort registry, was established to quantify symptoms and comorbidities of hypogonadal men in real-world clinical settings and to evaluate the effect of testosterone replacement therapy (TRT). Methods: Eligible TRiUS participants were hypogonadal men prescribed Testim® (1% testosterone gel) for the first time. Evaluated baseline parameters included: total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), prostate-specific antigen (PSA), anthropometrics (height, weight, waist, hip, and body mass index [BMI]), lipids, blood glucose, sexual dysfunction, mood/depression, and cardiovascular and metabolic risk factors. Parameters were correlated to TT and age using bivariate correlation and to the combination of TT and age using multiple linear regression. Results: TRiUS had 849 registrants (baseline TT: 286.5 ± 151.8 ng/dL; FT: 40.8 ± 62.1 pg/mL; SHBG: 28.2 ± 15.0 nmol/L; PSA: 1.12 ± 1.11 ng/mL). Eighty-six percent were overweight/obese, with a BMI ≥ 25 kg/m2, and 57% were aged 40 to 59 years, with a mean (± standard deviation) age of 52.1 ± 12.3 years. Total testosterone levels were significantly lower in men aged ≥ 65 years. The most common comorbid conditions and cardiovascular risk factors included: smoking, metabolic syndrome, hypertension, dyslipidemia, and coronary artery disease. Weak but statistically significant inverse correlations were noted between TT and sexual dysfunction, fasting glucose, systolic blood pressure, BMI, and Framingham risk scores. Patients with obesity or metabolic syndrome had significantly lower TT levels, particularly among younger and middle-aged patients. Conclusions: Untreated hypogonadal middle-aged men exhibited a high prevalence of cardiometabolic risk factors that were correlated to TT levels. This suggests that TD is associated with adverse medical conditions that pose serious health risks, especially in a younger age demographic than previously thought. Clinicians may want to consider TT testing in unhealthy, middle-aged patients with symptoms of TD.

Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry

To assess the evidence for the concept that the androgen receptor of prostate cancer (PCa) cells becomes saturated when testosterone values exceed castrate levels, so that testosterone administration in hypogonadal men with untreated PCa does not stimulate tumour growth. To propose basic criteria for administration of testosterone to untreated patients with PCa and, as this is a rare clinical situation, to encourage the establishment of an international registry for these patients. Men with a diagnosis of PCa and symptomatic testosterone deficiency received testosterone therapy (TTh). Patients were assessed quarterly. Prostate-specific antigen (PSA) velocity was used as the criterion to discontinue therapy and a return to nadir PSA levels allowed re-initiation of testosterone supplementation. The responses to testosterone supplementation were varied according to each individual and were unpredictable. While some men showed little change after years of treatment, others exhibited a rapid and significant increase in PSA levels. In others, the use of intermittent therapy resulted in synchronous changes in PSA levels. Interruption of TTh invariably translated into a decrease in PSA to pre-therapy levels. Available evidence regarding the effect of testosterone administration to hypogonadal men with untreated PCa is too limited to be considered reliable. In addition, the response to this treatment appears to be varied and unpredictable. Hypogonadism associated with untreated PCa is not common, therefore, we propose the establishment of an international registry as the quickest way to establish the basic parameters for consideration of TTh in this situation and recommendations for follow-up. Until credible evidence becomes available, the current restrictions regarding the administration of testosterone to men with PCa should remain in place.

Low testosterone concentrations and the symptoms of testosterone deficiency according to the Androgen Deficiency in Ageing Males (ADAM) and Ageing Males’ Symptoms rating scale (AMS) questionnaires

First, to assess the association between the concentration of serum testosterone and the symptoms of testosterone deficiency according to two screening questionnaires. Second, to investigate the effects in elderly men with a low-normal testosterone concentration of testosterone supplementation over a period of 6 months on symptoms of testosterone deficiency according to the screening questionnaires. A total of 587 men between 60 and 80 years of age with an eligible serum testosterone measurement and completion of the screening questionnaires were included in the study. Of these 587 men, 237 men with testosterone levels <13·7 nmol/l were included in a double-blind, randomized, placebo-controlled trial of testosterone supplementation. One hundred and sixty milligrams per day of oral testosterone undecanoate or a matching placebo for 6 months. The Androgen Deficiency in Ageing Males (ADAM) and the Ageing Males' Symptoms rating scale (AMS) questionnaires. There was no significant association between the total testosterone concentration and the scores on the two questionnaires. However, age was significantly associated with the scores on the ADAM (OR 1·14, 95% CI 1·05-1·23) and the AMS (OR 1·03, 95% CI 1·01-1·08) questionnaire. After supplementation with testosterone, there were no effects on the scores on the two questionnaires in the testosterone group compared with the placebo group. The findings do not support the use of the ADAM or AMS questionnaire in the evaluation of late-onset hypogonadism in ageing men. Moreover, 6 months of oral testosterone supplementation had no significant effect on scores of the ADAM and AMS questionnaire in this group of elderly men with low-normal testosterone levels.

‘Every obese male with type 2 diabetes should be screened for hypogonadism’

Hypogonadism is a clinical syndrome complex which consists of symptoms with or without signs and biochemical evidence of testosterone deficiency. The symptoms of testosterone deficiency are non-specific which can make the diagnosis difficult. Symptoms which are most commonly associated with testosterone deficiency are reduced or loss of libido, absent morning erections and erectile dysfunction.1 Other common symptoms include tiredness, fatigue, impaired physical endurance, loss of vitality, lack of motivation and mood disturbance. Erectile dysfunction Erectile dysfunction (ED) is a common complication in diabetic men with some reports finding up to 70% have the condition. The pathogenesis of ED in diabetic men is multi-factorial and can be due to a combination of these which include vasculopathy, neuropathy, psychological issues and testosterone deficiency. The presence of hypertension, smoking and higher waist circumference are associated with ED in diabetic men.2 Lower testosterone positively correlates with worsening IIEF (International Index of Erectile Function) in diabetic men. 2 Not all diabetic men with ED have testosterone deficiency but evidence shows that it is present in a significant number. NICE guidelines recommendation is to ‘review the issue of erectile dysfunction annually’.3 The European Association of Urology (EAU) guidelines on ED state that measurement of testosterone is a minimum requirement in the diagnostic evaluation. 4 Penile Doppler ultrasound has shown that basal systolic velocity and dynamic peak velocity after administration of a phosphodiesterase type 5 (PDE-5) inhibitor are significantly reduced in hypogonadal diabetic men when compared to eugonadal men with diabetes.5 Failure to respond to sildenafil is associated with low testosterone in diabetes. 6 Animal work has found that castration leads to reduction in vascular smooth muscle content in the corpus cavernosum, reduced elastic fibres and increased collagen in the tunica albuginea, fat deposition between the tunica and corpus cavernosum and reduced nerve sheath thickness in the cavernosal nerve.7 Prevalence of hypogonadism

International web survey shows high prevalence of symptomatic testosterone deficiency in men

Introduction. Though the clinical significance of testosterone deficiency is becoming increasingly apparent, its prevalence in the general population remains unrecognised. A large web-based survey was undertaken over 3 years to study the scale of this missed diagnosis.Methods. An online questionnaire giving the symptoms characterising testosterone deficiency syndrome (Aging Male Symptoms – AMS – scale) was set up on three web sites, together with questions about possible contributory factors.Results. Of over 10,000 men, mainly from the UK and USA, who responded, 80% had moderate or severe scores likely to benefit from testosterone replacement therapy (TRT). The average age was 52, but with many in their 40s when the diagnosis of ‘late onset hypogonadism’ is not generally considered. Other possible contributory factors to the high testosterone deficiency scores reported were obesity (29%), alcohol (17.3%), testicular problems such as mumps orchitis (11.4%), prostate problems (5.6%), urinary infection (5.2%) and diabetes 5.7%.Conclusions. In this self-selected large international sample of men, there was a very high prevalence of scores which if clinically relevant would warrant a therapeutic trial of testosterone treatment. This study suggests that there are large numbers of men in the community whose testosterone deficiency is neither being diagnosed nor treated.

Testosteron und Infertilität

About 15% of men and women in their reproductive years remain childless; in 50% of cases the reasons can be found in the male partner. It is important to define as exactly as possible the reasons for infertility to select those men who can be treated by a causal treatment option and to find the optimum treatment strategy. While FSH is the key hormone for intact spermatogenesis, testosterone as an important modifier of quantitative normal sperm production may sometimes be underestimated. Exogenous substitution with testosterone will suppress spermatogenesis and is thus not indicated in hypogonadal males with hypogonadism and infertility at the same time. In males with normal to elevated gonadotrophins and symptomatic testosterone deficiency, treatment is difficult and evidence-based recommendations are missing. The situation in males presenting with secondary hypogonadotropic hypogonadism exhibiting one of the clearly defined and treatable reasons of male infertility is totally different. To stimulate the gonadal function in secondary hypogonadal patients wishing to father a child, pulsatile GnRH or subcutaneous gonadotrophin treatment are used. They stimulate both testosterone production and spermatogenesis. After the end of successful fertility treatment, substitution is continued by exogenous testosterone treatment with oral, transdermal or intramuscular physiological preparations.

EFFECT OF ANDROGENIC ACTIVITY OF ONION ON FSH, LH, TESTESTRONE HORMONE AND SPERMATOGENESIS IN RAT

Objectives: Testosterone deficiency is having an increasing impact on men’s health because of global aging, increasing obesity, diabetes and environmental factors and an explanation is needed why so few androgen deficient men are being treated. Methods: Demographic data for men over the age of 50 from different regions of the world have been compared with the number of men in that age group estimated from sales figures to be receiving testosterone treatment. Results: Based on the 20% of men over 50 in the general population who are expected to have testosterone deficiency symptoms, on average only 0.69% these men in most European countries were receiving treatment. The proportion was higher in the UK (1.00%) and Germany (1.89%), but lower in France (0.49%), Italy (0.51%) and Russia (0.54%). Australia had higher figures (1.64%), in spite of tight state control measures on androgen use. The USA has the highest treatment rate (7.96%) and this is increasing rapidly. Based on symptoms plus low total and free testosterone levels, androgen deficiency would be diagnosed in at least 5% of men over 50, and percentage treatment rates therefore four times higher. However, even on that basis, only in the USA do these exceed 10%. Conclusions: International action is urgently needed to raise awareness in the medical profession in the various countries of these unacceptably low levels of testosterone treatment. Improvement in this requires education and motivation of doctors and those regulating the healthcare systems.

TIME FOR INTERNATIONAL ACTION ON TREATING TESTOSTERONE DEFICIENCY SYNDROME

Aim. Testosterone deficiency is having an increasing impact on men's health because of global aging, higher levels of obesity, diabetes and metabolic syndrome and adverse environmental factors such as stress xenoestrogens and anti-androgens. The question addressed is to what extent the large body of evidence on the benefits and safety of testosterone therapy is applied in clinical practice.Methods. Demographic data for men over the age of 50 from different regions of the world have been compared with the number of men in that age group estimated from sales figures to be receiving testosterone treatment.Results. On the basis of estimate that 20% of men over 50 in the general population of each region could be expected to have testosterone deficiency symptoms, on average only these men (0.69%) in most European countries were receiving treatment. Proportion was higher in the UK (1.00%) and Germany (1.89%), but lower in France (0.49%), Italy (0.51%) and Russia (0.54%). Interestingly, Australia had higher figu...

Therapeutic Potential of Testosterone Gels

A large number of men over 60 years of age have low bioavailable or free testosterone levels and symptoms of testosterone deficiency. These symptoms include loss of energy, depressed mood, decreased libido, erectile dysfunction, decreased muscle mass and strength, increased fat mass, frailty, osteopenia and osteoporosis. Clinical trials indicate that testosterone therapy can improve many of these findings. In the past, androgen use in clinical practice was impeded or limited, since efficient oral or parental administration of testosterone was impossible. The introduction of modern transdermal testosterone-delivery systems has changed this situation fundamentally. Its clinical efficacy in reversing symptoms of hypogonadism has been demonstrated. The main advantage of the transdermal testosterone gel is easy handling or applicability, lack of visibility, flexibility in dosing and the low rate of minimal skin irritation resulting in good compliance. Current experiences suggest that testosterone gel may be the most physiological and well-tolerated transdermal testosterone-delivery system yet. Application of the gel is simple, practicable for the patient and replaces painful intramuscular injections. Owing to the short action of testosterone gel, application can be ceased in case of the appearance of side effects, such as an excessive increase in hematocrit, prostate-specific antigen or an abnormal digital rectal examination.

Time for international action on treating testosterone deficiency syndrome

Aim. Testosterone deficiency is having an increasing impact on men's health because of global aging, higher levels of obesity, diabetes and metabolic syndrome and adverse environmental factors such as stress xenoestrogens and anti-androgens. The question addressed is to what extent the large body of evidence on the benefits and safety of testosterone therapy is applied in clinical practice.Methods. Demographic data for men over the age of 50 from different regions of the world have been compared with the number of men in that age group estimated from sales figures to be receiving testosterone treatment.Results. On the basis of estimate that 20% of men over 50 in the general population of each region could be expected to have testosterone deficiency symptoms, on average only these men (0.69%) in most European countries were receiving treatment. Proportion was higher in the UK (1.00%) and Germany (1.89%), but lower in France (0.49%), Italy (0.51%) and Russia (0.54%). Interestingly, Australia had higher figures (1.64%), in spite of tight state control measures on androgen use. The USA has the highest treatment rate (7.96%) and this is increasing rapidly.If the basis for the diagnosis was the more conventional combination of symptoms plus biochemical evidence of low total and free testosterone levels, androgen deficiency would be expected in at least 5% of men over 50, and percentage treatment rates therefore four times higher. However, even on that basis, only in the USA do these exceed 10%.Conclusions. International action is urgently needed to raise awareness in the medical profession in the various countries of these remarkably low levels of testosterone treatment. Improvement in this requires education and motivation of doctors and those regulating the healthcare systems. A public awareness campaign is needed to educate men about the symptoms of testosterone deficiency and its impact on their health.

The Paradox Dividing Testosterone Deficiency Symptoms and Androgen Assays: A Closer Look at the Cellular and Molecular Mechanisms of Androgen Action

Central to the diagnosis and treatment of testosterone deficiency syndrome in the adult male is the remarkable paradox that there is a very poor correlation between the characteristic symptoms and levels of serum androgens. Because androgen deficiency can be associated with severe symptomatology, as well as diverse conditions such as coronary heart disease, diabetes, and metabolic syndrome, the aim was to present an evidence-based working hypothesis to resolve this confusing clinical paradox. A review of the possible mechanisms in testosterone deficiency syndrome was carried out, and a hypothesis to explain this paradox and associated problems in the diagnosis and clinical management of androgen deficiency was established on the basis of a review of the literature. The mechanisms by which androgen deficiency could arise were studied at five different levels: 1. Impaired androgen synthesis or regulation. 2. Increased androgen binding. 3. Reduced tissue responsiveness. 4. Decreased androgen receptor activity. 5. Impaired transcription and translation. As with insulin in maturity onset diabetes mellitus, there can be both insufficient production and variable degrees of resistance to the action of androgens operating at several levels in the body simultaneously, with these factors becoming progressively worse with aging, adverse lifestyle, other disease processes, and a wide range of medications. Using this model, androgen deficiency can be redefined as an absolute or relative deficiency of androgens or their metabolites according to the needs of that individual at that time in his life. There are important ways in which the considerations raised by this hypothesis affect the etiology, terminology, diagnosis, and treatment of androgen-deficient states.

Recent perspectives on the age-related decline of testosterone

A pivotal question is whether the age-related decline of testosterone should be viewed as hypogonadism, i.e. a deficiency of testosterone manifesting itself by the signs and symptoms of insufficient androgen action and, in the best case, reversed by testosterone treatment. There is no clear dividing line between normal and subnormal blood testosterone levels for establishing with certainty whether a man is hypogonadal or not. Rather, symptoms accumulate gradually with decreasing testosterone level, with these levels of testosterone differing between individuals, while within a subject not all symptoms of testosterone deficiency will manifest themselves at the same blood testosterone level. The diagnosis of late onset hypogonadism (LOH) and, certainly, the decision to provide androgen treatment must be made with caution, taking the specific increment of symptoms in relation to testosterone levels into account. The various symptoms of LOH might start at various concentrations of androgens. With a given plasma testosterone level, some complaints might be present and others not. This has also been confirmed in studies establishing symptom-specific thresholds of androgen levels. Symptoms of LOH do not manifest themselves at uniform threshold values of testosterone. Therefore, symptoms of testosterone deficiency are not uniformly and predictably related to blood testosterone values, which may lead to different diagnostic criteria for testosterone deficiency. So, the conclusion seems inevitable that the clinical manifestations of hypogonadism are multifactorially determined and that the diagnosis should not only depend on the measurement of testosterone but a proper assessment should comprise somatic and psychological aspects in addition to measurement of testosterone.

Clinical experience with Andriol® Testocaps®– The first Austrian surveillance study on the treatment of late-onset hypogonadism

Objective. The objective of this study was to document the efficacy and tolerability of the new formulation of Andriol® Testocaps® in the treatment of late-onset hypogonadism in a clinical practice setting.Methods. The primary inclusion criterion was symptomatic testosterone deficiency, as confirmed by laboratory testing (morning total testosterone <12 nmol/L) on two separate occasions. The study was performed in 43 centres in Austria and a dosage of oral testosterone undecanoate of 2×80 mg/day was used for three months. The ADAM questionnaire, the AMS scale and the SF-36 questionnaire were administered by the patients and specific questions were asked to the prescribers.Results. A total of 189 patient report forms and 185 doctor report forms were completed. The average age of the participants was 54.7 ± 12.3 years and average treatment duration was 13.9 ± 2.2 weeks. Serum testosterone level increased by more than 50% from 8.7 ± 4.3 nmol/L to 13.2 ± 6.7 nmol/L (p < 0.001). Treatment improved symptoms on the ADAM and AMS scales, whereas no changes were observed on the SF-36. There were no significant effects on serum PSA levels.Conclusion. Short-term treatment with oral testosterone undecanoate in a clinical practice setting improved late-onset hypogonadism symptoms in aging men with low testosterone levels.

Adding to the controversy: Pitfalls in the diagnosis of testosterone deficiency syndromes with questionnaires and biochemistry

Purpose. To determine the value of available questionnaires used for the diagnosis of testosterone deficiency syndromes (TDS) by correlating their ratings with a panel of hormonal determinations in a male population.Materials and methods. Participants completed the ADAM questionnaire and underwent biochemical evaluation at the local site. Assessments determined entry into Group A (symptomatic) or Group B (non-symptomatic). After stratification, subjects provided a morning sample of blood, completed the Aging Male Survey (AMS) and the newly developed Canadian Society for the Study of the Aging Male (CSAM-Q) questionnaires. Serum aliquots were analysed at a central lab for 8 putative markers commonly associated with symptomatic testosterone deficiency associated with aging: total testosterone (T); bioavailable T (BT); dehydroepiandrosterone sulphate (DHEA-S); sex-hormone binding globulin (SHBG); luteinizing hormone (LH), prolactin (PRL); thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1).Results. 92 men were screened; of these 59 (mean age of 58 ± 11 years) completed the study, 30 (51%) scored positively (mean 61.5 years) to the ADAM while 29 (49%) did not (mean 54.1 years). For the AMS the weight of the three domains (psychological, somato-vegetative and sexual) was significantly greater in Group A (p < 0.001) than in Group B. Equally, for the CAS questionnaire, the scores for the variables energy, global performance, frequency of intercourse, mood and quality of sleep were lower in Group A than in their asymptomatic counterparts (p < 0.001). The domain of memory assessment within the CSSAM-Q was not discriminatory. ADAM and AMS are self-administered and completed within 10 minutes. CSSAM-Q is more time consuming, requires an investigator to administer, and memory domain is biased in favour of specific professional training.No difference was found between the two groups in 6 of 8 biochemical tests. However, significant lower values (p < 0.001) were found for DHEA-S and IGF-1 in the symptomatic group as compared with the non-symptomatic cohort.Conclusions. This study confirms that newer, more complex tools perform similarly to the simpler ADAM questionnaire. The lack of correlation between the clinical picture and the most commonly used biochemical confirmatory tests, again, clearly points to the paramount importance of the clinical evaluation. An emphasis and reliance on serum T alone hinders the clinician's ability to manage testosterone deficiency syndromes (TDS).

The characteristics of late-onset hypogonadism, its prevalence, symptoms, and diagnosis

With aging in most but not all men • Total testosterone levels decline • Even more so free testosterone levels • This is associated with symptoms of testosterone deficiency, not only of sexual functioning but also of bone density, muscle mass and metabolic risk factor for cardiovascular disease and diabetes • The diagnosis is based both on clinical symptoms and on laboratory measurements, more so of free testosterone than of total testosterone. • Treatment with testosterone is acceptably safe provided established guidelines are adhered to

Investigation, Treatment, and Monitoring of Late‐Onset Hypogonadism in Males: ISA, ISSAM, and EAU Recommendations

Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.

Effect of 12 month oral testosterone on testosterone deficiency symptoms in symptomatic elderly males with low-normal gonadal status

Relative androgen deficiency in ageing males is assumed to have adverse health effects. This study assessed the effect of 12 months' standard dose, oral testosterone, on symptoms attributed to testosterone deficiency in older men with plasma testosterone levels in the low-normal range for young men. Testosterone undecanoate (TU, 80 mg bid) or placebo was administered for one year to 76 healthy men, 60 years or older, with a free testosterone index (FTI) of 0.3-0.5 and significant symptoms on a questionnaire designed to evaluate androgen deficiency (ADAM). The ADAM was completed at baseline, 6 and 12 months. Hormone and safety data were collected at baseline, 1, 3, 6 and 12 months. After 12 months, plasma total testosterone was unchanged in both groups and sex hormone binding globulin decreased in the testosterone group (P = 0.01). FTI and calculated bioavailable testosterone (cBT) were greater in the testosterone group as compared with the placebo group (P = 0.021 and 0.025, respectively). There was no significant difference in total symptom score between testosterone and placebo groups after 12 months of oral TU. However, there were trends toward improvements in sadness/grumpiness (P = 0.063), reduced erection strength (P = 0.059) and decreased work performance symptoms (P = 0.077), particularly in men with baseline cBT levels below 3.1 nmol/l. This study concludes that 80 mg bid oral TU does not improve overall ADAM questionnaire scores in older men with low-normal gonadal status. Oral TU may preserve mood and erectile function, as assessed by this questionnaire, particularly in men with the lowest testosterone levels.

Diagnostik und Therapie des Hypogonadismus bei erwachsenen M�nnern

Hypogonadism in men is defined as endocrine dysfunction of the testes, and due to reduced serum testosterone levels leads to symptoms of testosterone deficiency. Depending on the location of disruption in the endocrinological cycle, hypogonadism is classified as primary, secondary, or tertiary. In primary hypogonadism, the production of testosterone in the Leydig's cells of the testes does not function properly. Serum LH concentrations are elevated in the sense of counterregulation (hypogonadotropic hypogonadism). In secondary hypogonadism, LH secretion (and usually also FSH) from the hypophysis is impaired so that Leydig's cells are not stimulated, while in tertiary hypogonadism the hypothalamus is damaged. The clinical course in cases of reduced serum testosterone levels is determined essentially by the point in time when hypogonadism becomes manifest. Delayed puberty, eunuchoid stature, and underdeveloped secondary sex characteristics suggest prepubertal onset of hypogonadism.

Beneficial Effects of Testosterone Replacement for the Nonmotor Symptoms of Parkinson Disease

To investigate whether a single daily dose of testosterone replacement gel has beneficial effects on testosterone deficiency symptoms, cognitive function, nonmotor symptoms of Parkinson disease (PD), and motor symptoms of PD. Recently it has been observed that testosterone replacement therapy improves refractory nonmotor symptoms in testosterone-deficient men with PD. Many of the symptoms of testosterone deficiency are nonspecific and overlap with the nonmotor symptoms of PD, such as decreased enjoyment of life, lack of energy, sexual dysfunction, and depression. Replacement therapy for men with PD and comorbid testosterone deficiency may be an important addition to antiparkinsonian management strategies. A prospective open-labeled pilot study of testosterone topical gel (5 g of AndroGel; Unimed Pharmaceutical Inc, Deerfield, Ill) administered daily to testosterone-deficient (free testosterone <80 pg/mL) men with PD. All 10 patients were followed up for 1 month and 6 patients were followed up for a total of 3 months. Patients were administered a battery of testosterone deficiency questionnaires, cognitive studies, and scales of PD nonmotor and motor function at baseline, 1, and 3 months. With the daily transdermal testosterone gel, patients had an average increase in levels of free testosterone from baseline (53 pg/mL) to a 1-month follow-up visit (131 pg/mL; P =.06) and to a 3-month follow-up visit (98 pg/mL; P =.04). Testosterone deficiency symptoms improved in these patients (St Louis Testosterone Deficiency Questionnaire) from baseline (7.9 deficiency symptoms) to 1 month (5.6 deficiency symptoms, P =.04) and 3 months (5.8 deficiency symptoms, P =.08). The Unified Parkinson's Disease Rating Scale IV showed improvement at 1 month (P =.008). Additionally, there were trends toward improvement in the following scales: Unified Parkinson's Disease Rating Scale I at the 3-month follow-up (P =.09), Letter Fluency at the 3-month follow-up (P =.08), and the Hamilton Anxiety Scale at the 1-month follow-up (P =.09). A daily dose of transdermal testosterone gel improved testosterone deficiency symptoms in men with PD. Although there were trends in improvement in other nonmotor and motor symptoms of PD, future placebo control studies will need to be powered to answer these important questions. Whether testosterone deficiency is simply a comorbidity in PD or whether it plays a role in the pathogenesis of disease also remains for future study.