Because of the paucity of studies and inconsistencies regarding the impact of diabetes mellitus (DM) on semen quality, this disease is seldom looked for in the infertile patient. Recently, this view has been challenged by findings showing that DM induces subtle molecular changes that are important for sperm quality and function. This brief review shows the main sperm parameters in patients with DM and presents the mechanisms hypothesized to explain the changes observed in these patients. The data available suggest that DM alters conventional sperm parameters. In addition, DM causes histologic damage of the epididymis, with a negative impact on sperm transit. Various mechanisms may explain the sperm damage observed in patients with DM. These include endocrine disorders, neuropathy, and increased oxidative stress. Many authors suggest that DM decreases serum testosterone levels. This is associated with a steroidogenetic defect in Leydig cells. In addition, diabetic neuropathy seems to cause atonia of seminal vesicles, bladder, and urethra. Furthermore, DM is associated with an increased oxidative stress, which damages sperm nuclear and mitochondrial DNA. Finally, spermatogenesis derangement and germ cell apoptosis in type 1 DM may relate to a local autoimmune damage, whereas insulin resistance, obesity, and other related comorbidities may impair sperm parameters and decrease testosterone serum levels in patients with type 2 DM.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease (COVID-19) appears to have a higher mortality rate in presence of comorbidities and in men. The latter suggests the presence of a possible sex-dependent susceptibility. An enzymatic system involved in this different predisposition could be represented by angiotensin converting enzyme 2 (ACE2). ACE2 is activated and down-regulated by the spike protein of the virus and allows the penetration of SARS-CoV-2 into epithelial cells and myocardium. Data on the experimental animal have shown that 17ß-estradiol increases the expression and activity of ACE2 in both adipose tissue and kidney. Spontaneously hypertensive male mice have a higher myocardial ACE2 expression than females and its levels decrease after orchiectomy. In addition to this first aspect, the recent evidence of an increased frequency of venous thromboembolism in patients with COVID-19 (a clinical element associated with a worse prognosis) calls the attention on the safety of treatment with testosterone, in particular in hypogonadal men with greater genetic predisposition. Evidence that sex hormones are able to modulate the expression of ACE2 could help in interpreting epidemiological results and in designing more appropriate intervention strategies. Moreover, the vitamin D deficiency in elderly men may be worthy of further study regarding the epidemiological aspects of this different susceptibility and lethality between sexes.

Although the prevalence of sub-infertility in diabetic patients in childbearing age is known, the mechanisms by which diabetes mellitus (DM) causes male infertility are not completely explained. This detrimental effect is achieved with a variety of mechanisms that include pre-testicular, testicular, and post-testicular pathogenetic moments and can be different in type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) patients because of type of diabetes, duration of disease, and glycemic metabolic compensation. Aim of this study was to evaluate whether diabetic disease can be considered a risk factor for infertility considering the etiopathogenetic differences between DM1 and DM2 on sperm function. We enrolled 38 DM1 patients and 55 DM2 patients with idiopathic infertility history >12 months, and 100 healthy fertile subjects. The following outcomes were evaluated in optical microscopy and flow cytometry: sperm function (by conventional and biofunctional sperm parameters) and signs of urogenital infection/inflammation (by sperm leukocyte concentrations and indices of oxidative stress). Moreover, an andrological evaluation (by didymo-epididymal ultrasound evaluation, serum total testosterone, LH, and FSH measurements) was performed in DM1 and DM2 patients compared to controls. Diabetic patients showed a higher risk of becoming infertile and the pathophysiological mechanisms of damage were different in DM1 and DM2. Conventional sperm parameters of diabetic patients are worse than controls (p < 0.05). The DM2 caused an inflammatory condition with increased oxidative stress resulting in decreased sperm vitality and increased sperm DNA fragmentation. DM1 altered epididymal voiding causing low ejaculate volume and mitochondrial damage resulting in decreased sperm motility. These findings and evidences support the contention that DM could be regarded as cause of male infertility suggesting that the prevention of diabetic disease in DM2 and the follow-up of seminal parameters in DM1 could prevent fertility decline in these categories of patients.

Benign prostatic hyperplasia (BPH) is very common in aging men and causes lower urinary tract symptoms (LUTS), which decrease health-related quality of life. A number of evidence suggests that other than ageing, modifiable factors, such as increasing prostate volume, obesity, diet, dyslipidemia, hormonal imbalance, hypertension, metabolic syndrome, alcohol, and smoking, also contribute to the development of BPH and/or LUTS. More recently, erectile dysfunction (ED) has been linked to LUTS/BPH as a part of this syndrome, suggesting that patients with BPH or LUTS easily develop ED, and that LUTS/BPH symptoms often coexist with ED. This article focuses on the epidemiology and risk factors of the combined phenotype LUTS/BPH – ED.

Male accessory gland infection (MAGI) has been identified among those diagnostic categories which have a negative impact on the reproductive function and fertility in males ( Rowe et al., World Health Organization Manual for the Standardised Investigation and Diagnosis of the Infertile Couple, Cambridge University Press, Cambridge, 1993 ). MAGI is a hypernym which groups the following different clinical categories: prostatitis, prostate‐vesiculitis and prostate‐vesiculo‐epididymitis. Some of the characteristics they share are: common diseases, mainly have a chronic course, rarely cause obstruction of the seminal pathways, can have an unpredictable intracanicular spread to one or more sexual accessory glands of the reproductive tract, as well as to one or both sides. In this review, we show that all components involving the inflammatory response (from the agents which first trigger it to each component of the inflammatory response dynamic) can deteriorate conventional and/or non‐conventional sperm parameters arising from one or more of the following mechanisms: altered secretory function of the epididymis, seminal vesicles, and prostate which reduce the antioxidant properties or scavenging role of the seminal plasma; deterioration of spermatogenesis; and (unilateral or bilateral) organic or functional sub‐obstruction of the seminal tract.