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The substitution of testosterone is basic andrological treatment. Beside the "when and how," knowledge of possible side effects is mandatory. Therefore, we highlight the effects of testosterone replacement therapy on bones, cardiac function, sexuality, gynacomatia, fertility, and contraception, but also areas of concern regarding prostate carcinoma and testosterone replacement therapy., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Androgen-deprivation therapy (ADT) is the standard therapy used for advanced or metastatic prostate cancer, either alone or in association with additional procedures and substances. The optimum value of testosterone postulated more than 40 years ago was arbitrarily set to be < 50 ng/dL or < 1.7 nmol/L and, from today's perspective, was defined by more insensitive measurement methods. Since then, more and more data has been generated, suggesting that a value of < 20 ng/dL would be prognostically relevant. Yet no guideline has been changed so far despite the call for lowering the target value. Measuring testosterone to evaluate the response to androgen suppression is not yet established in clinical routine. There are no specific recommendations in national and international guidelines. Based on the evolving evidence, the question about testosterone management during ADT is gaining importance. The current data is summarised in this paper., Competing Interests: S. Zastrow: Apogepha - Beratungsleistung; T. N. Mudra: APOGEPHA Arzneimittel GmbH; H. Suttmann: Berater- und Referenentätigkeit sowie Unterstützung von Kongressteilnahmen: Sanofi, Janssen, Astellas, Bayer, Ipsen, Apogepha, (Thieme. All rights reserved.)

Testosterone is a natural hormone which is essential to maintaining physical and emotional wellbeing in men, regardless of age. Male hypogonadism is an endocrine condition of testosterone deficiency with the potential to cause multiple morbidities and psychosocial problems. The condition can be of primary (testicular), secondary (hypothalamic-pituitary) or so-called functional origin (as a result of inflammatory conditions, obesity or chronic illness). Testosterone deficiency can cause symptoms of a sexual nature, foster metabolic dysfunction and impair physical abilities as well as cause osteopenia/osteoporosis and anemia. Testosterone replacement therapy should not be initiated in the case of desired paternity, unclear processes of the prostate or mammary gland and high hematocrit. Diagnosis and treatment as well as monitoring of hypogonadism treatment are clearly regulated by international guidelines and replacement therapy is proven to be effective in ameliorating the above-mentioned symptoms when performed according to these guidelines. In functional hypogonadism, which is most often, but not exclusively, found in older men, treatment of the underlying condition/co-morbidity is mandatory prior to starting testosterone substitution.

Testosterone is a natural hormone which is essential to maintain physical and emotional wellbeing in men. Male hypogonadism is an endocrine condition of testosterone deficiency with the potential to cause multiple morbidities and psychosocial complaints. The condition can be of primary (testicular), secondary (hypothalamic-pituitary) or so-called functional origin (as a result of inflammatory conditions, obesity or chronic illness). Testosterone deficiency can cause symptoms of sexual nature, insulin resistance, osteoporosis, anemia among others. A replacement of testosterone should not be initiated in case of desired paternity, unclear processes of the prostate, mammary gland, or high hematocrit. Diagnosis and treatment as well as surveillance of the therapy of hypogonadism are clearly regulated by international guidelines and replacement therapy is proven to be effective to ameliorate the above-named complaints when performed according to these guidelines., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Hypogonadism refers to reduced endocrine function of the testicles and leads to testosterone deficiency. It is often observed in older and obese men. Symptoms with the highest predictive value are reduced sexual thoughts, decreased spontaneous erections, and erectile dysfunction. After excluding contraindications (e.g., desire for children), various forms of replacement therapy are available. Studies have shown that testosterone therapy is safe if regularly checked.

History and Clinical Presentation: A 27-year-old man was admitted to our outpatient clinic with symptoms of loss at libido, erectile dysfunction and fatigue. He had been playing soccer from the age of 7, for the last 10 years as a high-level professional. During that time repeated mild head-trauma without loss of consciousness had occurred, mainly triggered by excessive header-training and occasional collisions., Investigations: Serum levels of testosterone and luteinizing hormone were low. A gonadotropin releasing hormone loading test revealed significant gonadotropin responses, therefore pituitary gonadotropic insufficiency was unlikely. Further pituitary insufficiency of any other axis was also excluded by insulin hypoglycemia test. Magnetic resonance imaging of the brain revealed no significant abnormalities of the hypothalamic-pituitary unit., Treatment and Course: Testosterone substitution, at first applied transdermally, then intramuscularly, was initiated after approval by the National Anti Doping Agency. Four months later most of the symptoms had regressed., Conclusion: Pituitary deficiency in the course of craniocerebral trauma is frequent and may be transient or permanent, mostly affecting somatotropic or gonadotropic function. Hormonal imbalances may also be observed after mild but repeated trauma without loss of consciousness and should be considered in cases of isolated pituitary dysfunction, since such traumas may often occur in contacts sports such as boxing or intensive soccer play., (© Georg Thieme Verlag KG Stuttgart · New York.)

Contrasting the relatively abrupt hormonal changes during female menopause, male reproductive function gradually declines during aging. This leads to the formal diagnosis of androgen deficiency in many apparently healthy 80-year-old men, when conventional thresholds are applied, and consequently to the question of androgen substitution in geriatric medicine. Although many clinical studies have documented a correlation between low plasma testosterone levels and mortality a clear causal relationship - which would imply immanent substitution therapy - has not been demonstrated. With this in mind, the diagnosis of late-onset hypogonadism (LOH) should only be made when testosterone-deficiency related symptoms concur with low testosterone levels. Which exact symptoms justify the diagnosis of LOH, however, is not sharply defined. Using criteria defined in the recent EMAS study, LOH might even be an over-diagnosed entity without huge relevance in geriatrics. Low testosterone levels are associated with frailty, but testosterone supplementation has only shown limited effects on age-related sarcopenia. Moreover: the increased incidence of cardiovascular events in the TOM study should be a caveat and lead to a moratorium for uncritical testosterone supplementation in aging men with cardiovascular diseases., (© Georg Thieme Verlag KG Stuttgart · New York.)

The expert questioning of when a treatment with testosterone is medically necessary has increased by several 100% in the daily work of the insurance medical expert in the past years. The reason for this is that testosterone is prescribed a lot more often nowadays than it was 10 years ago. One can suspect that testosterone has become part of a popular lifestyle medication. However, the clinical meaning of the age-dependent decrease of testosterone in men is controversial. Unfortunately, there are only few study data about hypogonadism in ageing men. Testosterone treatment has a very narrow application field and is only medically necessary if the low testosterone level has been clinically proven as well as in a medical lab examination. This is decisive because testosterone treatment has numerous limitations of application and has a wide range of side effects. This article shows the controversy surrounding the discussion on testosterone treatment and the pitfalls of issuing the insurance medical expert's report.

The Kallmann syndrome is a very rare congenital association of gonadotropin-releasing hormone deficiency and hyposmia or anosmia. Clinically it is characterized by low serum concentrations of testosterone and inadequate low levels of luteinizing hormone and follicle-stimulating hormone as well as incomplete sexual maturation, lack of secondary sexual features (facial and body hair growth, deepening of the voice), micropenis and sometimes even cryptorchidism. The reduced or absent sense of smell is typical for the Kallmann syndrome and distinguishes this syndrome from other causes of hypogonadotropic hypogonadism. Additional findings may include synkinesia, hearing loss, unilateral renal aplasia, brachy- or syndactyly, agenesis of corpus callosum, cleft palate and dental agenesis. A 19-year-old man presented to our male infertility clinic with delayed sexual maturation, eunuchoid habitus, micropenis, cryptorchidism, erectile dysfunction and absence of ejaculation, anemia and osteoporosis as well as low serum concentrations of luteinizing hormone, follicle-stimulating hormone and testosterone in combination with hyposmia.

We present the case of a patient with suspected congenital hypopituitarism first diagnosed at the age of 38 years. Despite partial insufficiency of all pituitary-regulated hormonal axes, the patient never suffered from severe health problems. However, the patient was disfigured, and his intellectual and physical capacities were clearly impaired. The initiation of a hormone replacement therapy with hydrocortisone and thyroid hormones is essential in such a patient, but the substitution of sex hormones can create ethical problems.

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.

Abdominal obesity as a key cardiovascular risk factor as well as metabolic syndrome and type 2 diabetes mellitus are associated with low testosterone levels. In line with these facts, investigations of patients undergoing androgen ablation therapy for prostate cancer have shown a negative effect of this treatment approach on insulin sensitivity and body fat mass. The effects of physiological doses of testosterone seem to have less impact on the parameters of lipid metabolism. However, supraphysiological levels of testosterone can lower HDL levels. At present data on glycemic control in patients with type 2 diabetes are not yet uniform, but negative effects on glycemic control in type 2 diabetics have not been reported. In fact two studies were able to demonstrate a positive effect of testosterone on glycemic control in patients with type 2 diabetes. It is currently not yet possible to conclusively evaluate the significance of testosterone treatment in patients with metabolic syndrome and type 2 diabetes mellitus. Only larger, randomized prospective trials will show whether testosterone therapy is helpful in metabolic syndrome or type 2 diabetes. However, administration of testosterone in hypogonadal men with metabolic syndrome appears to be a promising treatment option to improve metabolic control.

In the age of nerve-sparing radical prostatectomy, rates of postoperative erectile dysfunction (ED) have significantly decreased. However, on comparing open retropubic, laparoscopic and robot-assisted procedures, none of these techniques seem to show specific advantages in this respect. PDE5 inhibitors are considered to be the gold standard in the first-line therapy of postoperative ED, as far as relevant contraindications can be excluded. Intraurethral and intracavernosal injections with prostaglandin E1 represent the second-line treatment. Implantation of penile prostheses still remains as the third-line and ultima ratio. Meanwhile, the administration of PDE5 inhibitors has been proven to be most effective. When applying this therapy regimen, these substances are highly useful when they are administered early after the intervention. After curative treatment of prostate cancer, testosterone substitution can be an efficient way to reduce hypo-gonadal symptoms in patients with manifest testosterone deficiency. It may even contribute to the improvement of post- interventional erectile disorders. According to the recent literature, testosterone substitution therapy is safe and does not show any additional risk of recurrence when there is a well considered indication and when patients are carefully selected., (Georg Thieme Verlag Stuttgart * New York.)

Hypogonadism is highly prevalent in the elderly and in men with prostate cancer. Symptoms of hypogonadism, such as depression, lack of libido, and decreased bone mineral density, can significantly impair quality of life. In addition, testosterone plays an important role in erectile preservation and in growth and function of the cavernosal and penile nerves. There are compelling data showing that testosterone replacement therapy (TRT) does not increase the risk of prostate cancer. The literature (four published studies) concerning men treated with TRT after definitive therapy for prostate cancer reports only one biochemical recurrence. Based on these data, physicians cannot really justify withholding TRT from symptomatic patients after they have been successful treated for prostate cancer. This review gives the practising urologist an overview of the latest literature and useful advice on this controversial topic.

Hyperprolactinaemia is a frequent but often neglected side effect of typical, but also of many atypical antipsychotics such as amisulpiride, risperidone or ziprasidone. Besides galactorrhoea, potential consequences are suppression of the hypothalamic-pituitary-gonadal axis with hypogonadism, sexual dysfunction, infertility and in women also irregularities of the menstrual cycle and amenorrhoea. Potential long term consequences are mainly osteopenia and osteoporosis with an enhanced risk of fractures. Hyperprolactinaemia, if not clearly caused by a prolactin inducing antipsychotic, should always be thoroughly investigated. Ideally, prolactin should be measured before starting a patient on a new antipsychotic. Furthermore, before neuroleptic treatment is begun, and also in regular intervals after that, patients should be asked about potential clinical signs of hyperprolactinaemia. Hyperprolactinaemia which is clearly due to antipsychotics but without clinical symptoms only requires regular controls of bone mineral density. However, if clinical symptoms occur, switching to a prolactin sparing antipsychotic may be necessary. In these cases fertility is often regained and the women concerned have to be informed about the enhanced risk of pregnancy and counselled regarding contraception. If switching is not possible, estradiol has to be substituted in women. Also in men with hypogonadism hormonesubstitution (with testosterone) is usually indicated. Generally hyperprolactinaemia in psychiatric patients should be taken more seriously in the future.

Evidence-based drug therapy for male infertility is often difficult because 30% of all cases of male infertility are classified as idiopathic, and another 30% need surgical treatment. Without knowledge of the underlying pathology, there is no foundation for a specific and causal treatment. Most of the currently used drug therapies are empirical at best; moreover, many of the studies on drug treatment for male infertility do not fulfill the required standards of evidence-based medicine (randomized, prospective, placebo-controlled), and the statistical endpoints used (sperm quality, pregnancy rate, baby take-home rate) are not uniform. This article, which is based on a literature survey and the current guidelines concerning drug therapy for male infertility, covers the most common treatment options. Regarding the currently insufficient scientific data for drug therapy and dietary supplements on male infertility, there is a demand for critical indications that take into consideration the possible side effects and the treatment costs. In the case of insufficient drug therapy for male infertility, reproductive medicine seems to be promising.

Testosterone substitution is used to treat the symptoms of low testosterone in men who do not produce enough natural testosterone. Hypogonadism is associated with a range of disease states that have significant effects on morbidity and mortality and also affect quality of life. The regular investigation of PSA, prostate, and ultrasound is necessary.

Managing the clinical features of hormone insufficiency in aging men is an important field of activity for dermatologists and in particular for dermatologists specialized in andrology. Potential consequences of age-associated decrease in plasma testosterone levels include long-term changes in diverse organ systems including changes of bone architecture, body composition, muscular strength, cognitive functions, and mood as well as negative effects on skin and hair. Indications and contraindications for a hormone replacement therapy as well as therapy monitoring are well-defined. Replacement of testosterone in the case of late-onset hypogonadism is not a standardized therapy. Previous studies suggest that testosterone replacement therapy has positive clinical effects. Dermatologic effects of testosterone replacement therapy have not yet been investigated. Further research is required to identify potential benefits and risks of hormone replacement therapy in aging men.

Introduction: Torsion of the spermatic cord is a urological emergency. The torsion of a fixed testis is rare. In the differential diagnosis of acute scrotum it remains a true challenge., Case Report: A 13-year-old boy presented in the emergency service with acute left testicular pain and vomiting. In the patient's history a right orchiectomy due to testicular torsion and a left prophylactic orchidopexy were remarkable. Due to the clinical suspicion of re-torsion an immediate surgical exposure of the testis was performed. Intraoperatively a torsion of the left spermatic cord was found. After detorquation, there was no significant sign of recovery observed. In order to preserve the endocrine function, the single testis was maintained. During follow-up, necrosis of the left testis was noticed, and a secondary left orchiectomy was necessary three weeks after first operation. After loss of both testes the patient was referred to a paediatric endocrinological consultant and testosterone substitution was started., Conclusion: Even though very rare, orchidopexy does not exclude re-torsion of a fixed testis, regardless of the employed operative technique and sutures used. It should be considered in the differential diagnosis of acute scrotum. Operative detorquation should not be delayed and, in order to avoid loss of the affected testis, diagnostic procedures should kept short. After orchidopexy the patient and his relatives must be informed about the possibility of a re-torsion.

Background: Testosterone levels decline gradually with age in men. A number of manifestations such as reduced libido or depression have been attributed to subphysiological testosterone levels. Hence, testosterone supplementation has been proposed in these cases., Objective: To assess the efficacy and safety of testosterone supplementation therapy in hypogonadal healthy men., Methods: Non-systematic review of randomised controlled trials (RCTs), systematic reviews/meta-analyses and HTA reports investigating testosterone supplementation in hypogonadal healthy men., Results: Five systematic reviews/meta-analyses and seven additional RCTs were included. The evidence suggests a consistent but weak positive effect on sexual function, lean body mass and vertebral bone mass. However, the clinical significance of these findings remains unclear and some clinically relevant outcomes were not included in these studies. On the other hand, testosterone substitution was associated with an increase in prostata-related adverse events, increased hematocrit and allergic skin reactions due to testosterone patches., Conclusions: The efficacy of testosterone supplementation for healthy hypogonadal men remains unclear. Only sexual function may improve in men with unequivocally reduced testosterone levels after supplementation therapy, but the clinical significance of this finding remains unclear. Long-term experience (i.e. more than three years) with effects and side effects is lacking.

The following review presents recent diagnostic and therapeutic developments in the field of endocrinology. With the development of strontium ranelate and teriparatide (human recombinant parathyroid hormone) two new drugs are now available for the treatment of postmenopausal osteoporosis. In addition, the therapeutic use of the calcimimetic agent cinacalcet in the treatment of primary and secondary hyperparathyroidism is discussed. The recent introduction of a novel, long-acting testosterone formulation (testosterone undecanoate) which only requires one intramuscular injection every 3 months, together with the already available hydroalcoholic testosterone gels, appear to be promising alternatives to the previous standard substitution therapy for male hypogonadism. Recently, the mineralocorticoid hormone aldosterone has gained much interest due to its central pathophysiological role in secondary hypertension and its potential deleterious role as a cardiovascular risk factor in nonepithelial target tissues. In this context, the therapeutic potential of a new selective mineralocorticoid receptor antagonist, eplerenone, will be ventilated. In addition, (18)F-DOPA positron emission tomography ((18)F-DOPA-PET), a new functional imaging modality for the diagnostic localization of chromaffin tumors, will be presented and the role of the somatostatin receptor radionuclide therapy with (90)Y-[DOTA](0)-Tyr(3)-octreotide ((90)Y-DOTATOC) for the treatment of advanced neuroendocrine tumors discussed. Furthermore, the ongoing controversy about the diagnosis and treatment of subclinical hypothyroidism will be summarized.

The Klinefelter syndrome is characterized by one or more extra X-chromosomes, deficient androgens, increased gonadotropines, fibrosis and hyalinization of the seminiferous tubules, small testes, gynecomastia, disproportionately long legs, sparse facial hair, and diminished sexual activity. The incidence of Klinefelter syndrome in the general population is 0.1-0.2%, some 3% among infertile patients, and approximately 11% in patients with aspermia. In very rare cases, these patients may manifest focal residua of spermatogenesis. Employing the ICSI method (intracytoplasmic sperm injection into an oocyte), a patient may be helped to father a child. There is, however an increased risk of such a child being born with a chromosomal aberration.

Underlying causes of hypogonadotropic hypogonadism are acquired or congenital disorders of the hypothalamus or pituitary (e.g. pituitary adenoma, craniopharyngioma, prior radiotherapy, trauma, severe general diseases, extreme stress, genetic mutations). In addition to a comprehensive history and physical examination, the diagnostic work-up includes measurement of testosterone, LH and FSH, with the aim of differentiating between primary and secondary hypogonadism. Where indicated, investigation of pituitary function, the use of imaging procedures, possibly an olfactory test, a GnRH stimulation test or genetic analyses may be added. Depending upon the indication, treatment is effected with testosterone, GnRH or gonadotropines.

Serum testosterone levels decline in men with increasing age. Late-onset hypogonadism with its characteristic symptoms can occur in men as they age. Typical symptoms of late-onset hypogonadism are decreased libido and sexual function, osteoporosis, altered distribution of body fat, overall reduction in physical strength, and alterations in general mood. Late-onset hypogonadism can be treated with testosterone, and different forms of testosterone have become available for this indication. The aim of testosterone replacement therapy is to produce serum testosterone levels within the physiological range avoiding levels above and below this range. Although hormone replacement therapy has become accepted in aging males, careful consideration of the indications and therapy monitoring are still required since there are major concerns about the long-term outcome of this therapy and particularly its effects on the prostate gland.