Eng Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland,
Trang 1Re: Functional and Taxonomic Dysbiosis of the Gut, Urine, and Semen
Microbiomes in Male Infertility
S D Lundy, N Sangwan, N V Parekh, M N Panner Selvam, S Gupta, P McCaffrey,
K Bessoff, A Vala, A Agarwal, E S Sabanegh, S C Vij and C Eng
Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, Vastbiome, Millbrae, California, and Department of Genetics and Genome Sciences and Germline High Risk Cancer Focus Group, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
Eur Urol 2021; 79: 826e836.
Editorial Comment: Humans carry many microbial passengers: they in fact outnumber human cells by about 10 to 1 Investigators now have the molecular and computational tools to assess our little hitchhikers in health and disease, and these authors did just that with 25 men with primary infertility and 12 healthy men with proven paternity They collected rectal swabs, semen, urine and controls With these kinds of studies, like the epigenome, researchers seek patterns that are similar
in subjects with disease and that are different from those who are healthy In this study, the in-vestigators did find a microbial fingerprint in the semen that was somewhat similar to that in the urine and that somewhat distinguished infertile from fertile men Interestingly, vasectomy appeared
to alter the microbiome, indicating that the testis or epididmyis likely contributed to it With increasingly sophisticated tools, we’re finding that our microbial tourists play an important role in disease, and that includes infertility
Craig Niederberger, MD
Male and Female Sexual Function and Dysfunction; Andrology
Re: Sperm Count and Hypogonadism as Markers of General
Male Health
A Ferlin, A Garolla, M Ghezzi, R Selice, P Palego, N Caretta, A Di Mambro, U Valente,
M De Rocco Ponce, S Dipresa, L Sartori, M Plebani and C Foresta
Unit of Endocrinology and Metabolism, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy, Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Padova, Italy, Department of Medicine, Clinica Medica I, University of Padova, Padova, Italy, and Unit of Laboratory Medicine, Department of Medicine, University of Padova, Padova, Italy
Eur Urol Focus 2021; 7: 205e213.
Editorial Comment: The authors tested the provocative hypothesis as to whether semen quality and reproductive function could represent a marker of general male health in a retrospective study of 5,177 individuals from a prospectively collected database of 11,516 males of infertile couples who had semen analysis in a tertiary university center Data included reproductive hormones, testis ultra-sound, and biochemical determinations for glucose and lipid metabolism The average patient age was 31.77.9 years
Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2e14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assess-ment index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syn-drome (OR 1.246, 95 CI 1.005e1.545) All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia
Trang 2Please note that this is a young patient cohort Azoospermic patients are more likely to experience worse metabolic parameters such as blood pressure, body mass index etc, and lower sperm counts Interesting data
Suggested Reading
Krzastek SC, Sharma D, Abdullah N et al: Long-term safety and efficacy of clomiphene citrate for the treatment of hypogonadism J Urol 2019; 202: 1029.
Re: Testosterone Treatment to Prevent or Revert Type 2 Diabetes in Men
Enrolled in a Lifestyle Programme (T4DM): A Randomised, Double-Blind,
Placebo-Controlled, 2-Year, Phase 3b Trial
G Wittert, K Bracken, K P Robledo, M Grossmann, B B Yeap, D J Handelsman,
B Stuckey, A Conway, W Inder, R McLachlan, C Allan, D Jesudason, M Ng Tang Fui,
W Hague, A Jenkins, M Daniel, V Gebski and A Keech
Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, South Australia, Australia, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia, Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia, Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia, Medical School, University of Western Australia, Perth, Western Australia, Australia, ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, New South Wales, Australia, Medical School, University of Western Australia, Perth, Western Australia, Australia, Keogh Institute for Medical Research, Perth, Western Australia, Australia, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia, Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Queensland, Australia, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia, Hudson Institute of Medical Research and Monash University, Clayton, Victoria, Australia, Department of Endocrinology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia, and Health Research Institute, University of Canberra, Canberra, Australian Capital Territory, Australia
Lancet Diabetes Endocrinol 2021; 9: 32e45.
Editorial Comment: Men who are overweight or obese frequently have low serum testosterone concentrations, which are associated with increased risk of type 2 diabetes The authors aimed to determine whether testosterone treatment prevents progression to or reverses early type 2 diabetes, beyond the effects of a community-based lifestyle program
The study was termed “testosterone treatment to prevent or revert type 2 diabetes in men enrolled
in a lifestyle program” (T4DM) The study of 19,022 men took place between February 5, 2013 and February 27, 2017 It was a randomized, double-blind, placebo-controlled, 2-year, phase 3b trial done
at 6 Australian tertiary care centers Men aged 50e74 years with a waist circumference of 95 cm or higher, a serum testosterone concentration of 14.0 nmol/L or lower but without pathological hypo-gonadism, and impaired glucose tolerance (oral glucose tolerance test 2-hour glucose 7.8e11.0 mmol/L)
or newly diagnosed type 2 diabetes (provided oral glucose tolerance test 2-hour glucose15.0 mmol/L) were enrolled in a lifestyle program and randomly assigned (1:1) to receive an intramuscular injection
of testosterone undecanoate (1,000 mg) or placebo at baseline, 6 weeks, and then every 3 months for 2 years
Testosterone treatment for 2 years reduced the proportion of participants with type 2 diabetes beyond the effects of a lifestyle program Increases in hematocrit might be treatment limiting Longer-term durability, safety, and cardiovascular effects of the intervention remain to be further investigated Timely data
Suggested Reading
Mulhall JP, Trost LW, Brannigan RE et al: Evaluation and management of testosterone deficiency: AUA guideline J Urol 2018; 200: 423.
Trang 3Re: Transdermal Testosterone Attenuates Drug-Induced Lengthening of Both
Early and Late Ventricular Repolarization in Older Men
E Tomaselli Muensterman, H A Jaynes, K M Sowinski, B R Overholser, C Shen,
R J Kovacs and J E Tisdale
College of Pharmacy, Purdue University, Indianapolis, Indiana, Division of Clinical Pharmacology, School of Medicine, Indiana University, Indianapolis, Indiana, The Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massa-chusetts, and Krannert Institute of Cardiology, School of Medicine, Indiana University, Indianapolis, Indiana
Clin Pharmacol Ther 2021; 109: 1499e1504.
Editorial Comment:The authors have previously reported that transdermal testosterone attenu-ates drug-induced QT interval lengthening in older men However, it is unknown whether this is due
to modulation of early ventricular repolarization, late repolarization, or both In a secondary analysis
of a prospective, randomized, double-blind, placebo-controlled 3-way crossover study, the authors determined if transdermal testosterone and oral progesterone attenuate drug-induced lengthening of early and late ventricular repolarization, represented by the electrocardiographic measurements
Male volunteers 65 years of age (14) were randomized to receive transdermal testosterone
100 mg, oral progesterone 400 mg, or matching transdermal/oral placebo daily for 7 days On the morning following the seventh day, subjects received intravenous ibutilide 0.003 mg/kg, after which electrocardiograms were performed serially
Transdermal testosterone attenuates drug-induced lengthening of both early and late ventricular repolarization in older men Important data
Re: Testosterone Ameliorates Age-Related Brain Mitochondrial Dysfunction
W Yan, T Zhang, Y Kang, G Zhang, X Ji, X Feng and G Shi
Department of Neurobiology, Hebei Medical University, Shijiazhuang, China, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China, Hebei Laboratory Animal Center, Hebei Medical University, Shijiazhuang, China, and Hebei Key Laboratory of Forensic Medicine, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
Aging (Albany NY) 2021; 13: 16229e16247.
Editorial Comment:Brain mitochondrial dysfunction and reduced testosterone levels are common features of aging in men Although evidence suggests that the 2 phenomena are interrelated, it is unclear whether testosterone supplementation ameliorates mitochondrial dysfunction in the aging male brain
The authors show that testosterone supplementation significantly alleviates exploratory behav-ioral deficits and oxidative damage in the substantia nigra and hippocampus of aging male rats These effects were consistent with improved mitochondrial function, reflected by testosterone-induced increases in mitochondrial membrane potential, antioxidant enzyme (GSH-PX, catalase, and Mn-SOD) expression/activity, and mitochondrial respiratory complex activities in both brain regions This is an interesting laboratory study that has clinical application
Re: Intralesional Low-Dose Methylprednisolone for the Treatment of Active
Phase Peyronie’s Disease: A Single-Centre, Preliminary Prospective
Non-Randomised Study
I Ure and A Ozen
Department of Urology, Faculty of Medicine, Osmangazi University, Eskisehir, Turkey
Int J Clin Pract 2021; 75: e13754.
Editorial Comment: The authors aimed to evaluate the effect of intralesional low-dose methyl-prednisolone treatment on patients in the active phase of Peyronie’s disease
Forty-eight patients suffering from Peyronie’s disease active phase symptoms were included in the study Methylprednisolone was administered intralesionally for 8 weeks, once per week, at a dose of
Trang 440 mg Methylprednisolone was injected into the plaque The plaque that caused maximal curvature was selected for injection Patients were evaluated before and after treatment for plaque size, angle of curvature, and erectile dysfunction according to the International Index of Erectile Function-5 and Peyronie’s Disease Questionnaire
The mean age of the patients was 61.1 years (range 43e78) The mean duration of the symptoms was 3.4 months (range 0e9) The average plaque size before treatment was 13.6 mm (range 7.1e16.8), and after treatment this value decreased to 10.8 mm (4.3e14.6, p <0.025) The average scores of Peyronie’s Disease Questionnaire elements symptom severity, penile pain, and bother/discomfort were 12.3, 19.1, and 6.2, respectively, before the treatment These scores were decreased to 8.9, 9.6, and 4.4, respec-tively, after treatment All subgroups of Peyronie’s Disease Questionnaire scores were significantly improved after treatment (p[0.001, p <0.001, p[0.045, respectively) No adverse events were observed during or after treatment Interesting study
Suggested Reading
Kuja-Halkola R, Henningsohn L, D'Onofrio BM et al: Mental disorders in Peyronie's disease: a Swedish cohort study of 3.5 million men J Urol 2021; 205: 864.
Allen D Seftel, MD
Pediatric Urology
Re: Does Renal Function Remain Stable after Puberty in Children Who Underwent Ureteral Reimplantation Due to Ureterovesical Junction Obstruction?
B B Neeman, J Jaber, S Kocherov, A Farkas and B Chertin
Department of Urology and Pediatric Urology, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel
Eur J Pediatr Surg 2021; 31: 187e190.
Editorial Comment: The authors share a series of 21 children with mean age of surgery at 14.3 months (range: 3 to 60 months) who underwent open reimplantation for ureterovesical junction obstruction with followup into adulthood Indications for surgery included hydronephrosis and decreased relative renal function on MAG3 renal scan Reimplantation resulted in increased relative renal function not only in the short-term but also remained stable after puberty in all 21 patients
Relative renal function improvement following surgery for ureterovesical junction obstruction appears to be stable long-term
Re: Pyeloplasty Is a Safe and Effective Surgical Approach for Low Functioning Kidneys with Ureteropelvic Junction Obstruction
D K Bowen, S Mittal, A Aghababian, S Eftekharzadeh, L Dinardo, J Weaver, C Long,
A Shukla and A K Srinivasan
Department of Urology, Ann & Robert H Lurie Children’s Hospital of Chicago, Chicago, Illinois, Division of Urology, Children’s Hospital of Philadelphia, Phila-delphia, Pennsylvania, and Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, PhilaPhila-delphia, Pennsylvania
J Pediatr Urol 2021; 17: 233.e1e233.e7.
Editorial Comment: The authors share a large series of 364 children with ureteropelvic junction obstruction in whom 8 children had affected kidneys with 0% to 10% relative renal function, 24 with greater than 10% to 20% relative renal function and 332 with greater than 20% function Following robotic pyeloplasty there were no differences in 30-day postoperative complications, overall success