Pharmacological treatment of lower urinary tract symptoms in benign prostatic hyperplasia: consequences on sexual function and possible endocrine effects.

INTRODUCTION: Benign prostate hyperplasia (BPH) is one of the most prevalent diseases in aging men. It may adversely affect quality-of-life due to the presence of low urinary tract symptoms (LUTS) and its effects on sexuality. AREAS COVERED: The impact of α1-blockers, 5α-reductase inhibitors (5-ARI), and phosphodiesterase 5 inhibitors (PDE-5i) on erectile and ejaculatory functions in men with BPH are covered. Endocrinological aspects have also been addressed, including the management of hypogonadism, which affects many patients with BPH, and the impact of the use of 5-ARI use on bone health. EXPERT OPINION: The adverse-event profile of α1-blockers depends on their affinity for the α1-adrenoceptors rather than selectivity. The probability of ejaculatory dysfunction is highest with silodosin than other nonselective drugs (tamsulosin, alfuzosin, doxazosin, and terazosin). Concerning the impact of finasteride and dutasteride on sexual desire, erectile function, and ejaculation, the vast majority of the studies have shown a low prevalence of treatment-related adverse events. Due to the benefits of erection, PDE5i represents the perfect class of drugs for the treatment of LUTS-BPH in patients with erectile dysfunction. Testosterone replacement therapy could be considered in some hypogonadal patients with BPH. Finally, current evidence support the safety of 5-ARI on bone tissue.

FSH therapy for idiopathic male infertility: four schemes are better than one.

OBJECTIVE: The aim of this article is to propose an algorithm that aids the clinician to choose the best therapeutic scheme of follicle-stimulating hormone (FSH) in the treatment of men with idiopathic infertility, based on testicular volume (TV) and serum total testosterone concentrations; highlighting the potential role of additional therapy with hCG in a sequential temporal scheme. MATERIALS AND METHODS: We subdivided patients in four clinical groups: patients with normal TV and serum testosterone concentrations (A); patients with normal TV and reduced serum testosterone concentrations (B); patients with reduced TV and serum testosterone concentration (C); patient with low TV e normal serum testosterone concentrations (D). Then, we administered to each group a specific therapeutic scheme. Group A: treated with FSH alone for at least 3 months; group B: treated with hCG alone twice a week for 3 months and addition of FSH for poor responders (unmodified sperm parameters); group C: treated ab initio with FSH and hCG until the pregnancy was reached; group D: treated with FSH alone for 3 months and addition of hCG for moderate poor responders (increased TV but unmodified sperm parameters) or second cycle of FSH for 3 months for severe poor responders (unmodified TV and sperm parameters). After 6 months we evaluated the therapeutic response in term of sperm parameters normalization rate, spontaneous pregnancy rate, and sperm DNA fragmentation normalization rate. RESULTS: 40% of patients became normozoospermic after treatment, while 30% achieved spontaneous pregnancy. B was the group that best responded to treatment in terms of normalization of seminal parameters; while the highest spontaneous pregnancy rate was obtained from the D group. B group also obtained the highest sperm DNA fragmentation normalization rate. CONCLUSIONS: To date, no reliable predictors of response to treatment with FSH exist, but TV and serum testosterone concentrations can help the clinician to choose the best therapeutic scheme for men with idiopathic infertility. The groups treated with a sequential temporal scheme (B and D groups) showed better clinical results compared with two groups treated with conventional schemes (A and C groups).

Early male aging or poor clinical consideration for males in IVF centers? An original study.

The Italian law 40/2004 allows the use of assisted reproduction techniques only if there are no other effective therapeutic approaches to overcome infertility. According to article 4 paragraph 1, the impossibility of removing the otherwise impeding causes to achieve a pregnancy must be ascertained before the couple undergoes assisted reproduction techniques. On this premises, we sought to evaluate the percentage of couples who underwent or were addressed to assisted reproduction techniques despite a known and potentially treatable male infertility factor in fertility centers in the city of Catania, Italy. To accomplish this, andrologists, urologists and endocrinologists were asked to report the number of couples already addressed to assisted reproduction techniques which they counseled in the trimester April-June 2018 having a under 35-year-old female partner and at least one among the following untreated conditions: (A) oligoasthenoteratozoospermia and FSH <8 mIU/ml, (B) third-degree varicocele (mono or bilateral form), and (C) leukocytospermia or urogenital infections. Of the 320 enrolled couples, 75 (23%) met the criterion A, 45 (14%) the criterion B, and 62 (19%) the criterion C. More than a half couples were addressed to assisted reproduction techniques despite a potentially treatable male infertility factor.

Testicular Function of Childhood Cancer Survivors: Who Is Worse?

BACKGROUND: A multi-disciplinary approach has led to an improvement in prognosis of childhood cancers. However, in parallel with the increase in survival rate, there is a greater occurrence of long-term toxicity related to antineoplastic treatment. Hypogonadism and infertility are among the most frequent endocrinological sequelae in young adult childhood cancer survivors. The aim of this study was to identify which category of patients, grouped according to diagnosis, therapy, and age at treatment, shows the worst reproductive function in adulthood. METHODS: We evaluated morpho-volumetric development of the testis, endocrine function of the hypothalamic-pituitary-gonadal axis, and sperm parameters in 102 young adult childhood cancer survivors. RESULTS: Overall, about one-third of patients showed low total testicular volume, total testosterone (TT) <3.5 ng/mL, and altered sperm count. Hodgkin's disease, hematopoietic stem cell transplantation, and non-cranial irradiation associated to chemotherapy were risk factors for poor gonadal function. Patients treated in pubertal age showed lower total testicular volume; however, the difference was due to more gonadotoxic treatment performed in older age. Testicular volume was more predictive of spermatogenesis than follicle-stimulating hormone (FSH), while anti-Müllerian hormone (AMH) was not useful in the evaluation of testicular function of male childhood cancer survivors. CONCLUSIONS: Pre-pubertal subjects at high risk of future infertility should be candidates for testicular tissue cryopreservation.

Corrigendum: Hypogonadism and Sexual Dysfunction in Testicular Tumor Survivors: A Systematic Review.

[This corrects the article DOI: 10.3389/fendo.2019.00264.].

Testosterone levels after treatment with urofollitropin in infertile patients with idiopathic mild reduction of testicular volume.

INTRODUCTION: A reduction of testicular volume (TV) represents an important clinical sign, which may hide sperm abnormalities and predispose to hypogonadism. AIM: The primary purpose of this study was to evaluate the serum levels of total testosterone after treatment with urofollitropin in selected patients with male infertility and idiopathic mild reduction of testicular volume. METHODS: In this 1-year-long prospective design, patients with abnormal sperm parameters, mild reduction in TV (8-12 mL) and normal gonadotropin, and total testosterone (TT) serum levels were recruited in this study. Patients treated for 4 months with urofollitropin were included in group A, those treated with intracytoplasmatic sperm injection due to a female-factor infertility were included in group B. Hormone values, sperm parameters, and TV were detected at baseline (T0), after 4 (T1) and 12 months (T2) in group A and at T0 and T2 in group B. RESULTS: Group A (n = 80) showed increased follicle-stimulating hormone (FSH) at T1 and sperm morphology at T1 and T2 compared to T0 (all p < 0.05). Group B (n = 50) had lower TT and higher FSH levels at T2 compared to T0 (all p < 0.05). At T2, TT, VT, total sperm count, progressive motility, total motility, and sperm morphology were higher in group A compared to group B (all p < 0.05). CONCLUSION: Reduced TV may predispose to infertility and hypogonadism. FSH treatment may improve Sertoli and Leydig cell function and prevent the development of hypogonadism.

Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications.

The age-related decline of serum T occurs in ~20-30% of adult men and it is today defined as late-onset hypogonadism (LOH). In the elderly, such decline becomes more prevalent (up to 60%) and shows-up with erectile dysfunction (ED) and hypoactive sexual desire. A large body of experimental evidences have shown that the combination of T replacement therapy (TRT) and phosphodiesterase type 5 inhibitors (PDE5i) is, usually, effective in restoring erectile function in patients with LOH and ED who have not responded to monotherapy for sexual disturbances. In fact, PDE5is potentiate the action of nitric oxide (NO) produced by endothelial cells, resulting in a vasodilator effect, while T facilitates PDE5i effects by increasing the expression of PDE5 in corpora cavernosa. Meta-analytic data have recognized to PDE5i a protective role on the cardiovascular health in patients with decreased left ventricular ejection fraction. In addition, several studies have shown pleiotropic beneficial effects of these drugs throughout the body (i.e., on bones, urogenital tract and cerebral, metabolic, and cardiovascular levels). TRT itself is able to decrease endothelial dysfunction, oxidative stress and inflammation, thus lowering the cardiovascular risk. Furthermore, untreated hypogonadism could be the cause of PDE5i ineffectiveness especially in the elderly. For these reasons, aging men complaining ED who have LOH should undergo TRT before or at the moment when PDE5i treatment is started.

Substance Abuse and Male Hypogonadism.

Progressive deterioration of male reproductive function is occurring in Western countries. Environmental factors and unhealthy lifestyles have been implicated in the decline of testosterone levels and sperm production observed in the last fifty years. Among unhealthy lifestyles, substance and drug abuse is a recognized cause of possible alterations of steroidogenesis and spermatogenesis. Alcohol, opioids and anabolic-androgenic steroids are capable to reduce testosterone production in male interfering with testicular and/or hypothalamic-pituitary function. Other substances such as nicotine, cannabis, and amphetamines alter spermatogenesis inducing oxidative stress and subsequent apoptosis in testicular tissue. Substance and drug abuse is a potentially reversible cause of hypogonadism, defined as the failure of the testis to produce physiological concentrations of testosterone and/or a normal number of spermatozoa. The identification of the abuse is important because the withdrawal of substance intake can reverse the clinical syndrome. This review summarizes the most important clinical and experimental evidence on the effect of substance abuse on testosterone and sperm production.

Hypogonadism and Sexual Dysfunction in Testicular Tumor Survivors: A Systematic Review.

Testicular tumor is the most common malignancy in men of reproductive age. According to the tumor histology and staging, current treatment options include orchiectomy alone or associated with adjuvant chemo- and/or radiotherapy. Although these treatments have considerably raised the percentage of survivors compared to the past, they have been identified as risk factors for testosterone deficiency and sexual dysfunction in this subgroup of men. Male hypogonadism, in turn, predisposes to the development of metabolic and cardiovascular impairment that negatively affects general health. Accordingly, longitudinal studies report a long-term risk for cardiovascular diseases after radiotherapy and/or cisplatin-based chemotherapy in testicular tumor survivors. The aim of this review was to summarize the current evidence on hypogonadism and sexual dysfunction in long-term cancer survivors, including the epidemiology of cardiovascular and metabolic disorders, to increase the awareness that serum testosterone levels, sexual function, and general health should be evaluated during the endocrinological management of these patients.

Erectile dysfunction, physical activity and physical exercise: Recommendations for clinical practice.

Erectile dysfunction could be an early sign of endothelial dysfunction and, therefore, of cardiovascular disease, with which it shares many risk factors. Among reversible risk factors, physical inactivity is one of the most important. Regular physical exercise has been shown to improve erectile function through different mechanisms involving glucose and lipid metabolism, regulation of arterial pressure, production of nitric oxide and hormonal modulation. Furthermore, exercise shows a synergistic effect with the drugs commonly used in the treatment of impotence. Since many patients with erectile dysfunction may have underlying cardiovascular disease, the evaluation of individual cardiovascular risk is mandatory before prescribing physical exercise. When exercise is not contraindicated, the most appropriate protocol must be chosen, considering the individual characteristics of the patient. Both aerobic and anaerobic/resistance protocols have proven effective. However, meta-analytic studies show that aerobic exercise with moderate-to-vigorous intensity is the most effective in improving erection. Testosterone is an important modulator of physical performance, and its blood levels must always be evaluated in patients with erectile dysfunction.

New insights into the genetics of spermatogenic failure: a review of the literature.

Genetic anomalies are known to affect about 15% of infertile patients with azoospermia or severe oligozoospermia. Despite a throughout diagnostic work-up, in up to the 72% of the male partners of infertile couples, no etiological factor can be found; hence, the cause of infertility remains unclear. Recently, several novel genetic causes of spermatogenic failure (SPGF) have been described. The aim of this review was to collect all the available evidence of SPGF genetics, matching data from in-vitro and animal models with those in human beings to provide a comprehensive and updated overview of the genes capable of affecting spermatogenesis. By reviewing the literature, we provided a list of 60 candidate genes for SPGF. Their investigation by Next Generation Sequencing in large cohorts of patients with apparently idiopathic infertility would provide new interesting data about their racial- and ethnic-related prevalence in infertile patients, likely raising the diagnostic yields. We propose a phenotype-based approach to identify the genes to look for.

Current and emerging medical therapeutic agents for idiopathic male infertility.

INTRODUCTION: Infertility is one of the great challenges of modern healthcare. It afflicts about 8-12% of reproductive-aged couples worldwide, but the prevalence is even higher in industrialized countries. In 50% of cases, a male factor of infertility underlies the problem, but in about 30% of these cases the etiology of male infertility remains unknown. This eventuality, called idiopathic infertility, requires empirical medical therapy and/or assisted reproductive techniques. AREAS COVERED: This article reviews the literature about the medical treatments available for idiopathic male infertility. These treatments can be divided into two main categories: hormonal therapies and non-hormonal therapies. The compounds with the strongest evidence of efficacy and the most used in clinical practice for the treatment of idiopathic male infertility are follicle-stimulating hormone (FSH) and estrogen receptor selective modulators (SERMs). Non-hormonal treatments include a series of compounds with antioxidant and prokinetic properties, supported by variable degrees of evidence of clinical efficacy. EXPERT OPINION: Patients with idiopathic infertility have peculiar clinical features that differentiate them from each other. Therapy must, therefore, be personalized to each patient. Furthermore, scientific research must investigate the pathophysiological mechanisms that underlie infertility; only in this way, new targeted therapies can be developed.

Sport, doping and female fertility.

This article is a review that addresses the following topics, divided by paragraphs. The first paragraph investigates the effects of physical activity on ovarian function, analyzing in particular the changes concerning the serum concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, growth hormone, thyroid hormones, leptin, ghrelin, neuropeptide Y. The second paragraph analyzes the effects of doping on the hypothalamic-pituitary-ovarian axis. Finally, the last paragraph analyzes the PCOS category, evaluating the effects of hyperandrogenism in relation to athletic performance.

Nicotine Receptors as a Possible Marker for Smoking-related Sperm Damage.

BACKGROUND: Several studies demonstrate that cigarette smoking has a negative effect on the reproductive health of both genders. The mechanisms by which it alters male gonadic function are not entirely clear. The combustion of cigarette produces a lot of chemical compounds that may be responsible for the negative impact of cigarette smoke on sperm parameters. In particular, the effects on semen of nicotine, a substance present in the tobacco plant and the main constituent of cigarette smoke, have been studied, showing that this alkaloid alters sperm parameters. Recently we investigated the mechanism by which nicotine damages sperm through the evaluation of the expression of nicotinic receptors subunits in human spermatozoa. CONCLUSION: 8 nAChR subunits found to date in mammals are expressed in human spermatozoa but, in non-smokers subjects, only α7 subunit is translated. Cigarette smoking may stimulate the expression of some subunits, not translated in non-smokers. Therefore, the presence in sperm of other nAChR subunits than α7 could represent a marker for smoking-related sperm damage.

Endothelial progenitor cells and erectile dysfunction: a brief review on diagnostic significance and summary of our experience.

The article provides a brief review of the literature concerning the diagnostic use of endothelial progenitor cells in patients with erectile dysfunction. In particular, patients with arterial erectile dysfunction could benefit from the use of this diagnostic marker, which in clinical practice can be used together with more conventional methods such as the penile Doppler. It is very important to acquire diagnostic tools for the diagnosis of sub clinical form of endothelial dysfunction in these patients, in particular when the erectile dysfunction is associated with cardiovascular risk factors.

Post-orchidectomy retroperitoneal seminoma: A case report.

Between 2 and 5% of malignant germ cell tumors in males arise at extragonadal sites. The origin of extragonadal retroperitoneal germ cell tumors remains controversial. Whether these develop primarily in the retroperitoneum or are metastases of a primary testicular tumor has long been debated. We report a 38-year-old male who presented with abdominal pain and was diagnosed with retroperitoneal seminoma. The patient gave a history of having undergone a right orchidectomy for an undescended testis via the inguinal route 10 years previously with a reported histology of benign inflammatory mass.

Arterial erectile dysfunction: different severities of endothelial apoptosis between diabetic patients "responders" and "non responders" to sildenafil.

BACKGROUND: The low pharmacological response to phosphodiesterase type 5 inhibitors represents an expression of higher endothelial damage in certain categories of patients with erectile dysfunction and high cardiovascular risk. The present study evaluated this objective in type 2 diabetic patients with erectile dysfunction, classified as "non responders" to Sildenafil. METHODS: Eighteen "responder" and twelve "non responder" type 2 diabetic patients were evaluated, relatively to different levels of endothelial damage, through the diagnostic use of a new immunophenotype of circulating endothelial progenitor cells (CD45neg/CD34pos/CD144pos) and endothelial microparticles (CD45neg/CD144pos/Annexin Vpos), recently developed and published by our group. RESULTS: "Non responder" patients showed a significant higher severity [8.0±3.0 (International Index of Erectile Function-abbreviated version with 5 questions) vs 14.0±3.0] and duration (10.0±2.0 vs 7.0±2.0 years) of erectile dysfunction, higher level of penile arterial insufficiency (peak systolic velocity=13.0±16.0 vs 28.0±26.0cm/s; acceleration time=153±148 vs 125±128 mm/s) and finally a significant higher level of endothelial apoptosis [0.15±0.13 vs 0.05±.0.03% (serum concentrations of endothelial microparticles)] associated with higher serum concentrations of circulating late immunophenotype of endothelial progenitor cells (0.40±0.35 vs 0.12±.0.10%). CONCLUSIONS: The results of this study corroborate the clinical value of the low clinical response to phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction in the patients with high cardiovascular risk profile, such as diabetics. In addition, the markers used in this study confirm their potential application in clinical practice as useful indicators of endothelial alteration. However, in the future we will have to assess a larger number of patients and for a longer period of observation in order to better understand the causal and temporal relations.