Epidemiological studies have demonstrated that prevalence of hypogonadism in old males increases with every additional decade of life. These males present various symptoms including decrease of sexual function, decrease of cognitive function, altered lipid profile, increased visceral adiposity, changes in bone density and muscular strength secondary to atrophy.Currently, testosterone injections and gel preparations are the most used. Testosterone replacement therapy provides significant symptomatic improvements for men with late start hypogonadism.Long-term benefits and risks of testosterone replacement therapy will be more evident when testosterone effects are studied on all health related parameters over a prolonged period of time. There is a large ongoing multicentric randomized clinical trial sponsored by NIH for testosterone control in old men with low testosterone levels. Its results may give answers to the possible benefits and risks of testosterone replacement in aging males. If an aging male is diagnosed as late-start hypogonadism, the urologist should discuss with the patient potential benefits and risks of testosterone therapy. Aging males with significant erythrocytosis, untreated sleep apnea, prostate cancer and high risk of cardiovascular events must be excluded from testosterone replacement therapy.Currently, there are not enough evidences to clearly state that the benefits of testosterone replacement therapy in aging males are better than the risks of this treatment. A general recommendation cannot be given that testosterone replacement therapy may be applied to al aging males with low testosterone levels independently of significant signs or symptoms.

Androgens play an essential role in the corporo-venous occlusive mechanism that provokes erection. Accordingly to various studies based on animal models, testosterone deficit syndrome causes an endothelial disorder in the corpora cavernosa with diminished secretion of NO, alteration of penile smooth muscle and tunica albuginea structure, and increase of the number of adipocytes within the erectile tissue, which favors fibrosis and impairs erection. All these alterations are reversible with the exogenous administration of androgens. There are not enough studies to get definitive conclusions about androgen supply improving erectile dysfunction in patients with hypogonadism. Studies have been published in which seems that exogenous testosterone could be useful in the treatment of this type of patients. Nevertheless, in most published randomized double blind studies comparing with placebo, testosterone supply does not provide greater benefit on erectile dysfunction than PDE-5 Inhibitors exclusively. All studies coincide in the need to optimize the treatment with PDE-5 Inhibitors since they do have proven to be effective for the treatment of erectile dysfunction in patients with testosterone deficit syndrome

OBJECTIVES: Testosterone deficit syndrome (TDS) is a clinical and biochemical entity characterized by low testosterone levels and androgenic deprivation clinic, which can cause a decrease in the quality of life. However, today there are doubts about its diagnosis and therapeutic management.METHODS: Bibliographic review using the MedLine database and detailed presentation of one clinical case.RESULTS: Testosterone deficit syndrome is associated with metabolic syndrome (visceral obesity, arterial hypertension, diabetes mellitus and dyslipemia). Currently, the performance of TDS screening in all males over the age of 45 years is under discussion. We propose a diagnostic-therapeutic algorithm for the management of TDS and erectile dysfunction.CONCLUSIONS: The treatment of erectile dysfunction associated with late start hypogonadism follows the same steps tha other generic cases of erectile dysfunction.

The progressive aging of the population and the wish to keep a good quality of life in advanced ages makes testosterone deficitsyndrome associated with aging a health issue of increasing relevance. It is a proved fact there is a decrease of androgen levels associated with aging. Nevertheless, there are some difficulties to establish what is the actual prevalence, since there are some ambiguities about which clinical and biochemical parameters allow us to state a correct clinical diagnosis.The figures on prevalence are variable, specially taking into consideration the different age ranges found in the studies, but we could say there would be a global prevalence of around 6% to 12% of symptomatic hypogonadism in the age range between 30/40 and 70 years, with a progressive increase with age.There is a series of factors that may favor androgen deficit increasing the prevalence in different population groups. The main factors are those entities related with metabolic syndrome (obesity, hyperglycemia (insulin resistance, high blood pressure and dyslipemia) in addition to chronic diseases such us AIDS, cancer, and certain pharmacological treatments.

Testosterone deficit syndrome is a clinical and biochemical syndrome associated with advanced age and characterized by some symptomsassociated with serum testosterone levels deficiency, which may result in a decrease of quality of life and negatively affect the function of multiple organs or systems. Clinical guidelines recommend testosterone replacement therapy (TRT) in patients with testosterone decrease that associate muscle mass and strength loss, lumbar spinal column bone density decrease, or libido and erection decrease.Contraindications for treatment would include active prostate cancer or without treatment, PSA > 4 ng/ml waiting for diagnostic workup, breast cancer, severe sleep apnea, infertility, hematocrit over 50% or severe lower urinary tract symptoms secondary to benign prostatic hypertrophy. In certain situations there is still great controversy, without enough evidence to establish an action. References in case of patientstreated with brachytherapy or radiotherapy are unspecific: they only recommend caution in the treatment with TRT in these patients and strict monitoring of the possible recurrence.In our opinion, low-intermediate risk prostate cancer patients treated with radiotherapy only, without evidence of residual or recurrent disease, are candidates for TRT if symptoms justify it, leaving a free period of never less than one year after nadir (or 24 months after the end of therapy) which guarantees, on the possible means, the absence of biochemical or clinical recurrence,with strict follow up of clinical and biochemical usual parameters (hematocrit, hemoglobin, DRE, PSA).

Testosterone deficit syndrome (TDS) is a clinical and biochemical syndrome associated with advanced age and characterized by some typical symptoms and decrease in serum testosterone levels, which can affect multiple organs and systems, deteriorating the quality of life of the males who suffer it.Due to the low specificity of the clinical picture, as well as that of the commonly used questionnaires, when there is a diagnostic suspicion, serum testosterone determination is necessary, without a current universally accepted determination methodThe increased survival of males in the western world and their demand of a better quality of life,including the preservation of sexual activity, up to increasingly more advanced ages; together with the appearance of new ways of testosterone delivery, make this entity, clinical-biochemical, acquirean increasingly greater importance.From a therapeutic point of view, testosterone replacement therapy has precise indications, with individualized evaluation in each patient on the basis of risk/benefit, and with an adequate, well defined follow up, that will allow the control of possible adverse events.TRT is recommended in patients with diminished testosterone associated with muscle mass and strength loss, decrease of bone density of the lumbar spine or diminished libido and quality of erection.Contraindications for therapy would include active or non treated prostate cancer, PSA > 4 ng/ml before evaluation, breast cancer, severe sleep apnea, infertility, hematocrit over 50% or severe LUTS due to BPH.

The prevalence of diabetes mellitus (DM) is increasing worldwide for all ages due to population growth, aging, and increased prevalence of obesity and physical inactivity. Sexual dysfunction and in particular erectile dysfunction (ED) are frequent complications of DM. In patients with DM, ED can be considered as a useful sign of silent myocardial ischemia. A large body of evidence also supports a strong association between DM, cardiovascular risk (CV) and testosterone deficiency syndrome. Despite this evidence, the screening of ED and hypogonadism in the diabetic population remains poorly implemented. In addition, data regarding the role of testosterone replacement therapy (TRT) for glycometabolic control and CV risk remains contradictory. In the present paper we have reviewed the available evidence and based our discussion on data derived from a specific clinical case.Hypogonadism is frequently observed in subjects with type 2 DM (T2DM) and especially those complaining of ED. Obesity and insulin-resistance are probably the most important pathogenetic factors involved, and, according to the current guidelines, subjects with T2DM should be screened for hypogonadism. TRT is the first line option in hypogonadal subjects with ED, however, the possible role of TRT in improving glycometabolic control and CV outcomes needs to be confirmed through longer and larger studies.

Testosterone déficit síndrome (TDS) is more frequent in males with HIVinfection tan in general population, being in fact the most frequent endocrine disorder in these patients. There are multiple physiopathological mechanisms favoring this testosterone deficit but they are only partially known.Identification of these patients and their adequate treatment will have important consequences not only in their sexual health but also in their general health.

Hypogonadism may affect as much as 70% of the patients with chronic renal failure (CRF) in comparison with general population. Physiopathologically, it is a hypergonadotropic hypogonadism, with alterations in the pulsatile production of GnRH, FSH, LH and testicular testosterone, that is a general disorder of the hypothalamic-hypophysis-testicular axis. This disorder may determine important consequences in this population of patients, with varied sexual dysfunction, trophic and functional muscular and fatty tissue disorders, bone demineralization, anemia and increase of cardiovascular disease associated mortality.Treatment in these patients must be focused from a general point of view, increasing their clinical condition, the systemic complications associated with CRF, complementing in this way with exogenous testosterone replacement therapy. If possible, it seems that the most efficacious therapy will be renal transplantation.

Since 70 years ago testosterone is considered a risk factor for prostate cancer and its supplementation in men with testosterone deficit syndrome is considered a risk for the development of a prostatic neoplasia. We discuss the case of a man with hypogonadism and increased PSA, the indications for biopsy and risks involved in testosterone supplementation, as well as recommended follow up. Over this practical base, we expose the current evidence on prostatic safety in men with testosterone supplementation.

We define dyslipemia as the abnormally elevated presence of lipids in the blood. The main ones are hypercholesterolemia (cholesterol over 240 mg/dl), hypertrigliceridemia (triglicerides level over 200 mg/dl) and hipo-alphalipoproteinemia (High density lipopro-teins, also called HDL Cholesterol, below 40 mg/dl). The presence of excessive lipids contributes to arterios-clerosis and they are an independent cardiovascular risk factor (1) (Table I).It may be primary, if they have genetic origin and they are not associated with other diseases, but in most cases they are secondary to other pathological entities such as diabetes, hypothyroidism, obesity and metabolic syndrome (MS). In our current society, sedentary lifes-tyle and unadequatelly hypercaloric diets are making obesity and MS prevalences grow, and their relation to dyslipemias has become tighter.Obesity is related with all the criteria for MS. But obesity is not at all synonymous of MS. On the one hand neither fat distribution is the same in all individualas nor confers the same risk. Accordingly, we know that abdominal localization of fat is related to higher intensity of insulin resistance (IR) and MS. On the other hand, it seems that certain components of MS are determined by genetic factors, since there are morbid obese persons that are metabolically healthy and other patients develop insu-lin resistance without obesity. So that, it seems that the excess in visceral adiposity in the presence of certain genetic factors would be the most related cause of the appearance of peripheral insulin resistance and diabe-tes mellitus, hyperlipidemia (increase of very low density pipoproteins (VLDL)), decrease of highdensity lipopro-teins (HDL), arterial hypertension, and hypogonadotro-pic hypogonadism, composing what we call metabolic syndrome.In this scenario, we urologists are being first-hand wit-nesses. On the one hand, and in relation with cardio-vascular risk factors, we know that all of them, and in-dependently, not only can produce erectile dysfunction due to endothelial dysfunction (2), but also it generally appears years before the cardiovascular event (3). On the other hand, and in relation to the hypogonadotropic hypogonadism of patients with MS, we urologists may contributein greatly to the detection of patients with MS whose only symptom is erectile dysfunction or diminis-hed libido, but specially we may play a key role in the improvement of these patients, since it is known that testosterone replacement therapy has a major potential to diminish or stop the progression of MS or its cardio-vascular effects. Testosterone treatment not only improves the lipid profile, hypertension, insulin resistance, or reduces the abdomi-nal circumference, but also it may help to get a better adherence to diet and exercise, so contributing to chan-ge unhealthy lifestyle habits whch are the origin of the problem (4).

Summary.- Prevalence of depression in men increases with age, so does the prevalence of hypogonadism. Depression and anxiety are the most common psychopathological symptoms associated with male hypogonadism. The question is whether the age-related gradual decline in testosterone levels contributes to the rising rate of depression in older men. Many studies have demonstrated the improvement in depressive symptoms in hypogonadal men with testosterone supplementation. However, a subpopulation of hypogonadal men appear to be better responders to TRT when treated for depression.Testosterone deficiency is associated with numerous nonspecific symptoms including decline in libido, erectile dysfunction, increased fat deposition, decreased muscle mass, decreased energy and depression. The relationship between increased depressive symptoms and declining testosterone levels is complex because many conditions are independently associated with depression and testosterone deficiency. These conditions include medical illnesses, such as HIV/AIDS, and obesity, stress, smoking, and alcohol abuse.While the literature does not support a consistent relationship between testosterone levels and depressive symptoms most studies do suggest that lower testosterone levels are associated with depressive symptoms. Furthermore, TRT has been shown to improve depressive symptoms in most men. This could be due to the fact that testosterone is a modulator of GABAA receptors and inhibits 5-HT3 receptors centrally. However there appears to be a subpopulation of depressed male patients that tend to respond best to TRT. These patients include men who have HIV/AIDS, mild depression, more severe testosterone deficiency, use transdermal testosterone as opposed to IM testosterone, and those not responding to SSRIs. However, patients taking SSRIs also experience a significant improvement in depressive symptoms once treated with TRT.Men with depressive symptoms and testosterone deficiency syndrome should be given a trial of testosterone replacement therapy for at least 3 months as TRT alone may improve clinical symptoms of depression. Furthermore, men already on SSRIs may also experience further improvement in depressive symptoms after initiating TRT.

Spermatogenesis is a well defined, complex, long and very orderlyprocess of cellular division and differentiation that is under regulation by endocrine signals (GnRH, LH, Inhibin and FSH): paracrine signals, derived from the interrelation of the various types of cells in the tubules and interstitium (even in a juxtacrine way), and autocrine signals of self communication of the cell with itself. Testosterone plays an essential role in this process. In the testicular tubules, testosterone reaches concentrations 100 times higher than circulating testosterone in the blood stream.From a reproduction point of view, we can find two completely different scenarios in relation to testosterone deficit syndrome with a similar final clinical result: The difficulties of the male to have children. On one side the presence of hypogonadism, which requires a different management depending of the clinical priority and wishes of parenthood of the patient an his partner. On the other side, the opposite situation, the patient who requires or is already under testosterone therapy.In patients with hypogonadotropic hypogonadism, when patient`s clinical priority is fertility, the treatment to restore normal spermatogenesis requires external administration of gonadotropins. Treatment must be prolonged, at least 12-18 months.95% of the cases will have a favorable response, meaning the finding of spermatozoids in ejaculation sperm as a consequence of spermatogenesis restoration.

Testosterone Deficiency Syndrome is associated with age. Recent studies advocate for the safety of hormonal treatment with testosterone in patients with history of Prostate Cancer (PC), once disease-free survival is confirmed. A total of five publications describe 110 patients treated with testosterone replacement therapy, having a history of PC, who had undergone radical prostatectomy (RP). Only one patient had biochemical recurrence during replacement therapy.Testosterone replacement therapy must be indicated in selected patients with history of low risk localized prostate cancer treated satisfactorily who are symptomatic and have good oncological control. The testosterone levels to achieve should be the minimum effective to obtain a symptomatic response. Adequate information on the benefits and potential risks must be understood and accepted by the patient.

OBJETIVE: New investigations focus on the relationship between benign prostatic hyperplasia, lower urinary tract symptoms, erectile dysfunction and testosterone deficit; giving to this last one a common role in all of them. In this paper, we present a typical patient who complains of symptoms related to BPH, to treat him in terms of micturition quality, sexual function and hypogonadism. METHODS/RESULTS: 61 year-old male, with obesity, hypertension and hypercholesterolemia, who complains of long term mixed urinary symptoms, with an IPSS of 12 and IIEF-5 of 22. DRE: II/IVprostate, adenomatous. Blood parameters: PSA 1.9 ng/dl, total testosterone 238 ng/dl, triglycerides 213 mg/dl, glucose 89 mg/dl. Uroflowmetry: total volume 256 ml, maximum flow 12 ml/s, average 5.7 ml/s and post-void volume of 15 ml. Urinary ultra- sound: 5 mm detrusor and prostate volume of 39 cm3. Nowadays, LUTS are considered multietiologic, including testosterone as one of the causes. According to the classic criteria, this patient fits for treatment with combination therapy, as well as for daily PDE5i, recently approved for LUTS therapy. Administration of testosterone to treat LUTS is still controversial. It could restore the patient’s levels of testosterone, improving the metabolic syndrome and creating an optimal environment for the 5PDEi. Nevertheless, according to some current scientific evidences, it could help improving LUTS.CONCLUSIONS: Given the necessity of larger studies, testosterone supplementation therapy seems to not worsen the evolution of BHP. It could even improve them if the testosterone deficit is documented.

The diagnosis of testosterone deficit (TD)in adult men is made upon the finding of consistentsymptoms or signs associated with confirmed lowTestosterone levels. TD can be caused by primarytesticular failure, decreased LH secretion (secondary) ora combination of both (mixed type).The clinical features of TD depend on the age of onset.Before completion of pubertal development it results ineunuchoid traits that can be easily detected. The clinicalexpression of adult onset TD is protean, with variedsymptoms and signs often overlapping with those ofaging and several chronic conditions. Sexual problemsas low desire and difficult erections are frequentlyreported by TD patients. Several symptom questionnaireshave been proposed for detecting TD. However, poorspecificity and weak correlation with serum testosteronemake them unsuitable as diagnostic tools, although theirscores can help for monitoring future treatments. Physicalexamination usually yields few significant data but it canhelp for detecting unidentified cases of early onset TD.Measuring serum total testosterone(TT) levels ismandatory. It is available in most laboratories althoughcommonly used methods are not fully satisfactory. Inadult men the lower limit for the normal reference rangeis around 10 nmol/ L, but this figure can vary amonglaboratories. “Grey zone” values falling within a ± 20%interval around this limit need further clarification. To thisaim most hospital laboratories can calculate the free(FT) or bioavailable fractions (BioT) of TT, SHBG, andalbumin levels.When TD diagnosis is confirmed, a number ofadditional tests, such as measuring gonadotropins andprolactin, should be used to find out its etiology. Theyare summarized here in a diagnostic algorithm. There isa need for laboratory tests giving a reliable estimate ofthe androgen sensitivity of each subject

Elderly patients present testosterone deficit syndrome (TDS) in a prevalent manner. TDS is defined as a clinical and biochemical syndrome with total fasting testosterone below normal levels in two consecutive measurements. A significant relationship with comorbidities such as diabetes mellitus, obesity or metabolic syndrome has been observed in these patients. These latter are recognized risk factors of coronary artery disease (CAD) and arteriosclerosis. It seems logical to think that CAD is more frequent in patients with TDS, and it is supported on multiple works demonstrating the correlation of theses two pathologies.We intend to illustrate the management of patients with TDS and CAD presenting a clinical case and the recommended diagnostic and therapeutic approach.A Sixty-four year old male with hypertension, non-insulin dependent diabetes mellitus and obesity consulted for erectile dysfunction and diminished sexual desire. Fasting total testosterone and glycosylate hemoglobin were determined.IIEF-5 was 12, ErectionHardness Score was 2 and IIEF item 12 1 point over 5. His total testosterone was 150 ng/dl, which was confirmed in a second test; HDL cholesterol level was 30 mg/dl. Interrogated again, the patient referred oppressive chest pain appearing after running 50 meters for the last three months that never happened in rest or with minor efforts.APPROACH: It is a patient with high cardiovascular risk and atypical chest pain so recommendation was given to consult a cardiologist. Stress test was performed. It was a submaximal, evaluable test (reached 80% of his maximum theoretical heart rate) stopped due to angina. Clinically and electrically it was positive at medium charge. Coronary angiogram was indicated showing a severe (85%) lesion at the medial third of anterior descendant artery. Balloon angioplasty was performed and a 3.0 x 24 mm drug-coated stent was placed. Cardiologic treatment was prescribed as well as combination therapy for his erectile dysfunction and diminished libido with testosterone and a PDE 5 inhibitor.