Laura M. Mongioì

Reproductive function in male patients with type 1 diabetes mellitus

This study was undertaken to evaluate conventional and some of the main bio‐functional spermatozoa parameters, serum gonadal hormones and didymo‐epididymal ultrasound features in patients with type 1 diabetes mellitus (DM1). DM1 affects an increasing number of men of reproductive age. Diabetes may affect male reproduction by acting on the hypothalamic–pituitary–testicular axis, causing sexual dysfunction or disrupting male accessory gland function. However, data on spermatozoa parameters and other aspects of the reproductive function in these patients are scanty. Thirty‐two patients with DM1 [27.0 (25.0–30.0 years)] and 20 age‐matched fertile healthy men [28.0 (27.25–30.75 years)] were enrolled. Patients with diabetic neuropathy, other endocrine disorders or conditions known to alter spermatozoa parameters were excluded. Each subject underwent semen analysis, blood withdrawal for fasting and post‐prandial glycaemia, hormonal analysis and didymo‐epididymal ultrasound evaluation before and after ejaculation. Patients with DM1 had a lower percentage of spermatozoa with progressive motility [10.0 (7.0–12.75) vs. 45.0 (42.0–47.75) %; p < 0.01] and a higher percentage of spermatozoa with abnormal mitochondrial function than controls [47.0 (43.0–55.0) vs. 2.0 (1.0–5.0) %; p < 0.01]. Patients also had greater post‐ejaculatory diameters of cephalic [11.5 (10.2–13.6) vs. 6.0 (4.0–7.0) mm; p < 0.01] and caudal epididymis [5.5 (4.00–7.55) vs. 3.0 (2.0–4.0) mm; p < 0.01] compared to controls, suggesting a lack of the physiological post‐ejaculation epididymal shrinkage. Correlation analysis suggested that progressive motility was associated with fasting glucose (r = −0.68; p < 0.01). The other parameters did not show any significant difference. Patients with DM1 had a lower percentage of spermatozoa with progressive motility, impaired mitochondrial function and epididymal post‐ejaculatory dysfunction. These findings may explain why patients with DM1 experience fertility disturbance. Larger multi‐centric studies are necessary to confirm these results.

Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders

Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6–3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4–17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9–17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear.

The role of carnitine in male infertility.

This review explores the role of carnitine in male infertility. The structure of this review is organized into short paragraphs that address the following aspects: antiapoptotic effect of l‐carnitine on germ cells, effects of l‐carnitine on conventional sperm parameters, in vitro effects of l‐carnitine on sperm function, and the role of l‐carnitine on erectile function.

Arterial Erectile Dysfunction and Peripheral Arterial Disease: Reliability of a New Phenotype of Endothelial Progenitor Cells and Endothelial Microparticles

The aim of this study was to evaluate whether the blood concentrations of a new immunophenotype of circulating late endothelial progenitor cells (EPC) and endothelial microparticles (EMP) varies in patients with arterial erectile dysfunction (aED) and abnormalities in other arterial districts. To accomplish this, cavernous artery peak systolic velocity (PSV), acceleration time (AT), and intima-media thickness (IMT) were determined after intracavernous administration of alprostadil by echo-color Doppler in 80 consecutive patients (age range, 50-75 years). Fifteen patients had aED alone (group A) and served as controls; 22 had aED plus atheroma plaques and/or increased IMT of the common carotid artery (group B); 20 had aED plus lower limb artery abnormalities (group C); and 23 had aED plus carotid and lower limb artery abnormalities (group D). EPC and EMP blood concentrations were evaluated by flow cytometry. Blood mononuclear cells with the immunophenotype CD45(neg)/CD34(pos)/CD144(pos) were defined as EPCs, whereas CD45(neg)/CD144(pos)/annexin V(pos) cells were defined as EMPs. Group B and C patients had a similar PSV, AT, and IMT at the level of the cavernous arteries. Their PSV values were significantly lower and mean values of AT and IMT significantly higher compared with group A patients. Patients of group D had a significantly lower PSV and significantly higher AT and IMT compared with all other groups. As far as serum concentrations of EPCs and EMPs, group D patients had significantly higher EPC and EMP mean values compared with all other groups. Group B and C patients had similar EPC and EMP values. This study showed that a more generalized peripheral atherosclerotic process is associated with a more severe penile artery insufficiency and endothelial dysfunction. Moreover, this study confirms the diagnostic reliability of the immunophenotype of EPCs and EMPs chosen in the clinical practice.

Relevance of genetic investigation in male infertility

Genetic causes can be directly responsible for various clinical conditions of male infertility and spermatogenic impairment. With the increased use of assisted reproduction technologies our understanding of genetic basis of male infertility has large implications not only for understanding the causes of infertility but also in determining the prognosis and management of such couples. For these reasons, the genetic investigations represent today an essential and useful tool in the treatment of male infertility. Several evidences are available for the clinical practice regarding the diagnosis; however, there are less information relative to the treatment of the genetic causes of male infertility. Focus of this review is to discuss the main and more common genetic causes of male infertility to better direct the genetics investigation in the treatment of spermatogenic impairment.

Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index

BackgroundInsulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II).ObjectiveThe aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic β-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest.MethodsA comprehensive MEDLINE® search was performed using relevant key terms for PCOS and DM II.ResultsInsulin-induced hyperandrogenism could impair pancreatic β-cell function, the SC abdominal adipocytes’ lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance.ConclusionsMetabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.

Effects of tadalafil treatment combined with physical activity in patients with low onset hypogonadism: results from a not-randomized single arm phase 2 study

Abstract Purpose: To investigate a possible relation between penile Doppler ultrasound examination (PDUE) parameters and efficacy of chronic therapy with tadalafil (TAD) combined with a protocol of aerobic physical activity (PA) in patients with late onset hypogonadism (LOH). Methods: The study evaluated 30 patients consecutively enrolled with LOH and erectile dysfunction which present contraindication to hormonal replacement therapy for concomitant prostate disease. These patients were subjected to a combined protocol with phosphodiesterase V selective inhibitors (TAD 5 mg daily) and aerobic PA. Results: After three months, we observed significant improvements in erectile function [IIEF-5, median (IQR) = 13.0 (7.0–18.0) versus 6.0 (5.0–6.75); p < 0.01] and of the main metabolic [homeostatic model assessment index, median (IQR) = 2.5 (1.62–3.37) versus 3.0 (2.0–3.75); p < 0.01; body mass index, median (IQR) = 27.0 (24.0–28.75) versus 27.5 (24.0–29.5)] and vascular parameters [peak systolic velocity, median (IQR) = 29.5 (24.25–31.0) versus 28.0 (23.0–24.25); acceleration time, median (IQR) = 114 (105.25–134.0) versus 115.0 (106.5–134.0)], assessed by PDUE. Conclusion: PA in association with phosphodiesterase V inhibitors could compensate the effects of hypogonadism on erectile function and facilitate the clinical response to these drugs even in the absence of adequate serum concentrations of total testosterone.

Impact of thyroid disease on testicular function

IntroductionTestis was considered unresponsive to thyroid hormone for a long time. However, like in animals, the presence of thyroid hormone receptors in different testicular cell types was demonstrated also in humans. Accordingly, thyrotoxicosis and hypothyroidism have remarkable effects on testicular function and more extensively on fertility.ReviewThyrotoxicosis and hypothyroidism are associated with changes affecting the endocrine, sexual, or reproductive functions. Particularly, compared with controls, hyperthyroid patients have higher serum SHBG and lower free and bioavailable testosterone concentrations, a higher rate of astheno-zoospermia, oligo-zoospermia, and terato-zoospermia, and a higher prevalence of sexual disturbances, such as premature ejaculation. In hypothyroid patients, hormonal changes are in the opposite direction compared with hyperthyroid patients.SummaryThyroid hormone regulates a number of functions in the testis, such as proliferation and differentiations of non-germ cells, steroidogenesis, and sperm motility. Furthermore, thyroid hormone regulates testicular redox status. Consequently, thyroid hormone excess or deficiency can affect testicular function at different levels.ConclusionsIn view of the high prevalence of thyrotoxicosis and hypothyroidism, a considerable part of infertile patients may harbor overt or subclinical thyroid disease. Identification and management of thyrotoxicosis/hypothyroidism associated infertility needs the collaboration of andrologists, endocrinologists, gynecologists, and general practitioners.

Human Papilloma Virus Infection in Patients with Male Accessory Gland Infection: Usefulness of the Ultrasound Evaluation

This study evaluated the ultrasound (US) features of 20 patients with MAGI and concomitant papilloma virus (HPV) infection compared to 20 patients with microbial (presence of Chlamydia trachomatis alone) MAGI and 20 patients with amicrobial (inflammatory) MAGI. Patients with HPV infection showed significantly (p < 0.05) higher total prostate, seminal vesicles, and epididymal US signs (18.0 ± 2.0) compared to the other 2 groups (12.0 ± 4.0 versus 10.0 ± 3.0, resp.). In addition, patients with MAGI and HPV had a higher prevalence of complicated forms of MAGI [prostatovesiculitis (PV) and prostate-vesiculo-epididymitis (PVE)] and a higher frequency of the fibrosclerotic variant compared to the other groups (70.0 ± 10.0% versus 48.0 ± 5.0% versus 15.0 ± 10.0%). Moreover, HPV infected patients had a higher number of US criteria suggestive for MAGI in the periurethral region of the prostate compared to the other groups. In particular, the patients showed a higher ratio between periurethral and lobar US criteria distribution (5.0 versus 0.5). Finally, the seminal fluid concentration of CD45pos leukocytes (2.0 ± 0.2 versus 1.3 ± 0.3 versus 1.0 ± 0.3 mil/mL) was significantly higher and sperm progressive motility was significantly lower in these patients compared to other groups.

Consequences on aging process and human wellness of generation of nitrogen and oxygen species during strenuous exercise

Abstract Impairment of antioxidant defense system and increase in metabolic rate and production of reactive oxygen species have been demonstrated in strenuous exercise. Both at rest and during contractile activity, skeletal muscle generates a very complex set of reactive nitrogen and oxygen species; the main generated are superoxide and nitric oxide. The nature of the contractile activity influences the pattern and the magnitude of this reactive oxygen and nitrogen species (ROS) generation. The intracellular pro-oxidant/antioxidant homeostasis undergoes alteration owing to strenuous exercise and the major identified sources of intracellular free radical generation during physical activity are the mitochondrial electron transport chain, polymorphoneutrophil, and xanthine oxidase. Reactive oxygen species increased tissue susceptibility to oxidative damage and pose a serious threat to the cellular antioxidant defense system. The possible dangerous consequences of the aging process and human wellness are emphasized in this review.