How is the semen quality of sexually active men following recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection?
Twenty-five percent of the men with recent SARS-Cov-2 ...infections and proven healing were oligo-crypto-azoospermic, despite the absence of virus RNA in semen.
The presence of SARS-CoV-2 in human semen and its role in virus contagion and semen quality after recovery from coronavirus disease 2019 (COVID-19) is still unclear. So far, studies evaluating semen quality and the occurrence of SARS-CoV-2 in semen of infected or proven recovered men are scarce and included a limited number of participants.
A prospective cross-sectional study on 43 sexually active men who were known to have recovered from SARS-CoV2 was performed. Four biological fluid samples, namely saliva, pre-ejaculation urine, semen, and post-ejaculation urine, were tested for the SARS-CoV-2 genome. Female partners were retested if any specimen was found to be SARS-CoV-2 positive. Routine semen analysis and quantification of semen leukocytes and interleukin-8 (IL-8) levels were performed.
Questionnaires including International Index of Erectile Function and Male Sexual Health Questionnaire Short Form were administered to all subjects. The occurrence of virus RNA was evaluated in all the biological fluids collected by RT-PCR. Semen parameters were evaluated according to the World Health Organization manual edition V. Semen IL-8 levels were evaluated by a two-step ELISA method.
After recovery from COVID-19, 25% of the men studied were oligo-crypto-azoospermic. Of the 11 men with semen impairment, 8 were azoospermic and 3 were oligospermic. A total of 33 patients (76.7%) showed pathological levels of IL-8 in semen. Oligo-crypto-azoospermia was significantly related to COVID-19 severity (P < 0.001). Three patients (7%) tested positive for at least one sample (one saliva; one pre-ejaculation urine; one semen and one post-ejaculation urine), so the next day new nasopharyngeal swabs were collected. The results from these three patients and their partners were all negative for SARS-CoV-2.
Although crypto-azoospermia was found in a high percentage of men who had recovered from COVID-19, clearly exceeding the percentage found in the general population, the previous semen quality of these men was unknown nor is it known whether a recovery of testicular function was occurring. The low number of enrolled patients may limit the statistical power of study.
SARS-CoV-2 can be detected in saliva, urine, and semen in a small percentage of men who recovered from COVID-19. One-quarter of men who recovered from COVID-19 demonstrated oligo-crypto-azoospermia indicating that an assessment of semen quality should be recommended for men of reproductive age who are affected by COVID-19.
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Background
Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) are conditions extremely prevalent in the aging male. Although androgens are involved in prostate growth during ...developmental age, their role in the pathogenesis of BPH/LUTS is debated. Recent data indicate that low testosterone and high estradiol favor disease progression. In addition, the role of other determinants, such as metabolic syndrome or prostate inflammation, is emerging.
Aim
We reviewed the evidence regarding the pathogenesis of BPH/LUTS with particular attention to metabolic influence.
Materials and methods
A review of published evidence was performed using Medline.
Results
Available evidence shows that a three-hit hypothesis can be drawn. An overt, or even a subclinical, bacterial or viral infection could induce prostatic inflammation (first hit) that could be autosustained or exacerbated by the presence of an altered metabolism and in particular by hypercholesterolemia (second hit). Hypogonadism and/or hyperestrogenism could act as a third hit, favoring the maintenance of this inflammatory state. The combined action of all three hits, or even two of them, may result in overexpression of Toll-like receptors (TLRs), transformation of prostatic cells into antigen-presenting cells and activation of resident human prostate-associated lymphoid tissue ending in overproduction of growth factors which, in turn, will induce prostate remodeling and further prostate enlargement. The mechanical obstruction, along with the direct action of the unfavorable metabolic and hormonal milieu on the bladder neck, helps in generating LUTS.
Conclusion
Inflammation, dyslipidemia and altered sex-steroid milieu mutually concur in determining BPH/LUTS.
Metabolic syndrome (MetS) and prostate cancer (PCa) are highly prevalent conditions worldwide. Current evidence suggests the emerging hypothesis that MetS could play a role in the development and ...progression of several neoplasms. The aims of this study are to evaluate the impact of MetS and MetS factors on PCa incidence, on the risk of high-grade PCa and to analyze the role of MetS and single MetS components on the development of aggressive PCa features.
A systematic literature search and analysis on PubMed, EMBASE, Cochrane and Academic One File databases until September 2015 was performed by 2 independent reviewers to evaluate the associations between MetS and PCa incidence, and between MetS and high-grade PCa incidence (bioptical Gleason Score⩾8, Prognostic Group 4-5 according to the novel prostate cancer grading system). Also the association between MetS and individual MetS components with pathological Gleason Score⩾8, extra-capsular extension, seminal vesicle invasion, positive surgical margins and biochemical recurrence (defined as two consecutive PSA values ⩾0.2 ng ml
after radical prostatectomy) was evaluated.
24 studies were selected including a total of 132 589 participants of whom 17.35% had MetS. There was a slight association between MetS and PCa incidence (odds ratio (OR)=1.17 (1.00-1.36), P=0.04) and between high-grade PCa and MetS (OR= 1.89 (1.50-2.38), P<0.0001) but the studies were statistically heterogeneous. No association was found between MetS components and PCa risk except for hypertension. MetS was significantly associated with pathologic Gleason Score⩾8 (OR= 1.77 (1.34-2.34); P<0.01), extra-capsular extension (OR=1.13 (1.09-1.18); P<0.01), seminal vesicle invasion (OR=1.09 (1.07-1.12); P<0.01), positive surgical margins (OR=1.67 (1.47-1.91); P<0.01) and biochemical recurrence (OR=1.67 (1.04-2.69); P<0.01).
The presence of MetS is associated with worse oncologic outcomes in men with PCa, in particular with more aggressive tumor features, and biochemical recurrence.
Purpose
The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological ...consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated.
Methods
All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (
n
= 19), as well as those reporting data on semen analysis (
n
= 5) and hormonal parameters (
n
= 11) in infected/recovered patients without any arbitrary restriction were included.
Results
Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality.
Conclusions
The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.
Abstract
STUDY QUESTION
When is the investigation and treatment of midline prostatic cysts (MPC) of clinical value in the work-up of males of infertile couples?
SUMMARY ANSWER
With a prevalence of ...10.2% in infertile men, MPC should be investigated according to a seminal algorithm detecting a MPC volume >0.117 ml, which may impair semen parameters, and could be treated to improve sperm count and achieve natural pregnancy.
WHAT IS KNOWN ALREADY
MPC are frequent and are considered a correctable cause of male infertility. However, they have been poorly investigated in an infertility setting. In addition, no study has investigated clinical and ultrasound (US) characteristics of men with MPC.
STUDY DESIGN, SIZE, DURATION
A cross-sectional analysis was carried out of 693 consecutive subjects consulting for couple infertility from September 2012 to March 2017. As a control group, 103 age-matched healthy, fertile men were studied. Furthermore, a longitudinal evaluation of 11 infertile men undergoing trans-rectal ultrasonically-guided cyst aspiration (TRUCA), semen analyses 1 and 3 months after TRUCA and a follow-up 1 year after TRUCA to assess natural pregnancy were performed.
PARTICIPANTS/MATERIALS, SETTING, METHODS
All subjects underwent, in our outpatient clinic, clinical, hormonal, scrotal and transrectal US evaluation and semen analysis within the same day. Of 693 males of infertile couples, 648 (37.1 ± 7.9 years, mean+SD) without genetic abnormalities were studied, along with 103 fertile men (36.6 ± 5.0 years). Eleven infertile men underwent TRUCA and were followed-up as reported above.
MAIN RESULTS AND THE ROLE OF CHANCE
A MPC was present in 66/648 (10.2%) males of infertile couples and in 6/103 (5.8%) fertile men. MPC occurrence and volume were higher in patients with severe oligo- or azoospermia than in fertile men (all P < 0.05). Infertile men with a MPC showed a lower seminal volume and sperm count and a higher prevalence of azoospermia than the rest of the infertile sample or fertile men, and a higher frequency of US signs suggestive of ejaculatory duct obstruction. MPC volume was negatively associated with total sperm count (r = -0.452, P < 0.0001). In fertile men, the highest MPC volume was 0.117 ml, suggesting it as a biological threshold not compromising semen quality. In infertile men, using receiver operating characteristic curve analyses, a MPC volume >0.117 ml identified subjects with severe oligo- or azoospermia with an overall accuracy of ~75% (both P < 0.005). Eleven men with infertility, semen abnormalities and large MPC (>0.250 ml) underwent TRUCA, which led to sperm count improvement in all patients 1 month after surgery. Three months after TRUCA a lower sperm count and a higher MPC volume than 2 months before were observed (P < 0.005 and P < 0.05, respectively), although improved when compared to baseline. After TRUCA a natural pregnancy occurred in four couples. Finally, we propose an algorithm, based on semen parameters, useful in identifying a MPC in males of infertile couples.
LIMITATIONS, REASONS FOR CAUTION
Although in line with the sample size of previous studies (n = 7-20), the number of infertile men with MPC evaluated longitudinally after treatment is limited (n = 11). In addition, although a MPC volume >0.117 ml can negatively affect the sperm count, only MPC > 0.250 ml have been treated in this study.
WIDER IMPLICATIONS OF THE FINDINGS
First, the algorithm proposed is easy to use and useful for selecting patients who can benefit from a prostate US in the infertility work-up. Second, a MPC volume ≤0.117 ml may not impair semen quality, while a larger volume can lead to severe oligo- or azoospermia and could be treated. Third, TRUCA is effective, and simpler and less invasive than other surgical techniques for MPC treatment. Finally, since the MPC can increase in size and sperm count decrease over time after TRUCA, semen cryopreservation should be considered 1 month after TRUCA.
STUDY FUNDING/COMPETING INTEREST(S)
Grants from the Ministry of University and Scientific Research (SIR project to F.L., protocol number: RBSI14LFMQ). No conflicts of interest.
Summary
Despite their efficacy in the treatment of benign prostatic hyperplasia, the popularity of inhibitors of 5α‐reductase (5ARIs) is limited by their association with adverse sexual side effects. ...The aim of this study was to review and meta‐analyze currently available randomized clinical trials evaluating the rate of sexual side effects in men treated with 5ARIs. An extensive Medline Embase and Cochrane search was performed including the following words: ‘finasteride’, ‘dutasteride’, ‘benign prostatic hyperplasia’. Only placebo‐controlled randomized clinical trials evaluating the effect of 5ARI in subjects with benign prostatic hyperplasia were considered. Of 383 retrieved articles, 17 were included in this study. Randomized clinical trials enrolled 24,463 in the active and 22,270 patients in the placebo arms, respectively, with a mean follow‐up of 99 weeks and mean age of 64.0 years. No difference was observed between trials using finasteride or dutasteride as the active arm considering age, trial duration, prostate volume or International Prostatic Symptoms Score at enrollment. Overall, 5ARIs determined an increased risk of hypoactive sexual desire OR = 1.54 (1.29; 1.82); p < 0.0001 and erectile dysfunction OR = 1.47 (1.29; 1.68); p < 0.0001. No difference between finasteride and dutasteride regarding the risk of hypoactive sexual desire and erectile dysfunction was observed. Meta‐regression analysis showed that the risk of hypoactive sexual desire and erectile dysfunction was higher in subjects with lower Qmax at enrollment and decreased as a function of trial follow‐up. Conversely, no effect of age, low urinary tract symptom or prostate volume at enrollment as well as Qmax at end‐point was observed. In conclusion, present data show that the use of 5ARI significantly increases the risk of erectile dysfunction and hypoactive sexual desire in subjects with benign prostatic hyperplasia. Patients should be adequately informed before 5ARIs are prescribed.
Purpose
Adrenocortical carcinoma (ACC), a rare malignancy of the adrenocortex, is characterized by a crosstalk between the adipose microenvironment and tumor. Here, we assessed the involvement of ...carbonic anhydrase (CA) enzymes III and IX (CAIII and CAIX), in the metabolic alterations of the adipose tissue characterizing obesity and in the local crosstalk between the tumor adipose microenvironment and ACC.
Results/methods
CAIII and CAIX expression is altered in visceral adipose tissue (VAT) in obesity and in ACC. A significant CAIX upregulation was present in ACC at advanced stages (
n
= 14) (fold increase FI = 7.4 ± 0.1,
P
< 0.05) associated with lower CAIII levels (FI = 0.25 ± 0.06,
P
< 0.001), compared with lower stages (
n
= 9). In vitro coculture between visceral adipose stem cells (ASCs) and ACC cell lines, H295R and MUC-1, mimicking the interaction occurring between VAT and advanced ACC, showed a significant CAIX upregulation in H295R but not in MUC-1 cells, and a decreased expression of CAIII. The effect on adipose cells was different when cocultured with H295R or MUC-1 cells. Coculture did not modulate CAIII expression in ASCs, which, however, was significantly downregulated with H295R (FI = 0.34 ± 0.11,
P
< 0.05) and upregulated by MUC-1 when cocultured ASCs were induced to differentiate toward adipocytes, with an expression profile similar to what found in VAT of obese subjects. CAIX expression was markedly increased in ASCs cocultured with H295R and to a less extent following adipogenesis induction (FI = 150.9 ± 46.5 and FI = 4.6 ± 1.1,
P
< 0.01, respectively).
Conclusion
Our findings highlight a modulation of CAIII and CAIX in the metabolic crosstalk between ACC and its local adipose microenvironment, suggesting that CAs might represent a potential target for novel anticancer therapies.
Epidemiological data indicate that lower urinary tract symptoms (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation has been proposed as a candidate mechanism at the ...crossroad between these two clinical entities.Aim of study is to examine the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens.
A total of 271 consecutive men treated with simple prostatectomy were retrospectively selected for this study in two tertiary referral centers for LUTS/BPH. Prostate diameters and volume were measured by transrectal ultrasound, LUTS scored by International Prostate Symptom Score (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and American Heart Association and the National Heart, Lung and Blood Institute was used to define MetS. The inflammatory infiltrate was investigated combining anatomic location, grade and extent of flogosis into the overall inflammatory score (IS); the glandular disruption (GD) was used as a further marker.
Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior-posterior (AP) diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum high-density lipoprotein) was associated with an increased risk of having a prostatic volume >60 cm(3) (hazard ratio (HR) = 3.268, P < 0.001). A significant positive correlation between the presence of MetS and the IS was observed. MetS patients presented lower uroflowmetric parameters as compared with those without MetS (Maximum flow rate (Q(max)): 8.6 vs 10.1, P = 0.008 and average flow rate (Q(ave)): 4.6 vs 5.3, P = 0.033, respectively), and higher obstructive urinary symptoms score (P = 0.064). A positive correlation among both IS-GD and IPSS Score was also observed (adjusted r = 0.172, P = 0.008 and adjusted r = 0.128, P = 0.050).
MetS is associated with prostate volume, prostatic AP diameter and intraprostatic IS. The significantly positive association between MetS and prostatic AP diameter could support the observation that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS can be regarded as a new determinant of prostate inflammation and BPH progression.
The purpose of this narrative review is to evaluate the role of prostatic inflammation as a treatment target for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) and ...provide an update on the available therapies.
An extensive literature search was conducted for studies on established and investigational treatments with anti-inflammatory mechanism of action that has been assessed for the management of male LUTS due to BPO.
Data on phosphodiesterase 5 inhibitors, nonsteroidal anti-inflammatory drugs, vitamin D3 receptor analogs, phytotherapy, statins, and lifestyle changes have been reviewed and analyzed. Preclinical evidence has shown the anti-inflammatory effect of these treatments on prostate. However, there is a wide variation in the degree of mature of each therapy. In addition, there are significant differences between the studies in terms of design, number of patients, and duration of follow-up.
Several drugs classes have been investigated for their impact on prostatic inflammation and improvement of male LUTS. The reviewed data support the rationale for use of agents that may alter and improve the inflammatory environment in the prostate in men with LUTS, but further high-quality long-term studies are required for the exact positioning of the new drugs in daily practice.
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