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The testis expresses the largest number of genes of any mammalian organ, a finding that has long puzzled molecular biologists. Our single-cell transcriptomic data of human and mouse spermatogenesis provide evidence that this widespread transcription maintains DNA sequence integrity in the male germline by correcting DNA damage through a mechanism we term transcriptional scanning. We find that genes expressed during spermatogenesis display lower mutation rates on the transcribed strand and have low diversity in the population. Moreover, this effect is fine-tuned by the level of gene expression during spermatogenesis. The unexpressed genes, which in our model do not benefit from transcriptional scanning, diverge faster over evolutionary timescales and are enriched for sensory and immune-defense functions. Collectively, we propose that transcriptional scanning shapes germline mutation signatures and modulates mutation rates in a gene-specific manner, maintaining DNA sequence integrity for the bulk of genes but allowing for faster evolution in a specific subset.
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Expressão Gênica/genética , Mutação em Linhagem Germinativa/genética , Espermatogênese/genética , Adulto , Animais , Sequência de Bases/genética , Perfilação da Expressão Gênica/métodos , Células Germinativas/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Taxa de Mutação , Testículo/metabolismo , Transcrição Gênica/genética , Transcriptoma/genéticaRESUMO
INTRODUCTION: Priapism is a urologic emergency that may require surgical intervention in cases refractory to supportive care. Exchange transfusion (ET) has been previously used to manage sickle cell disease (SCD), including in priapism; however, its utilization in the context of surgical intervention has not been well-established. AIM: To explore the utilization of ET, as well as other patient and hospital-level factors, associated with surgical intervention for SCD-induced priapism METHODS: Using the National Inpatient Sample (2010-2015), males diagnosed with SCD and priapism were stratified by need for surgical intervention. Survey-weighted regression models were used to analyze the association of ET to surgical intervention. Furthermore, negative binomial regression and generalized linear models with logarithmic transformation were used to compare ET vs surgery to length of hospital stay (LOS) and total hospital charges, respectively. MAIN OUTCOME MEASURES: Predictors of surgical intervention among patients with SCD-related priapism RESULTS: A weighted total of 8,087 hospitalizations were identified, with 1,782 (22%) receiving surgical intervention for priapism, 484 undergoing ET (6.0%), and 149 (1.8%) receiving combined therapy of both ET and surgery. On multivariable regression, pre-existing Elixhauser comorbidities (e.g. ≥2 Elixhauser: OR: 2.20; P < 0.001), other forms of insurance (OR: 2.12; P < 0.001), and ET (OR: 1.99; Pâ¯=â¯0.009) had increased odds of undergoing surgical intervention. In contrast, Black race (OR: 0.45; P < 0.001) and other co-existing SCD complications (e.g. infectious complications OR: 0.52; P < 0.001) reduced such odds. Compared to supportive care alone, patients undergoing ET (adjusted IRR: 1.42; 95% CI: 1.10-1.83; Pâ¯=â¯0.007) or combined therapy (adjusted IRR: 1.42; 95% CI: 111-1.82; P < 0.001) had a longer LOS vs. surgery alone (adjusted IRR: 0.85; 95% CI: 0.74-0.97; Pâ¯=â¯0.017). Patients receiving ET (adjusted Ratio: 2.39; 95% CI: 1.52-3.76; P < 0.001) or combined therapy (adjusted Ratio: 4.42; 95% CI: 1.67-11.71; Pâ¯=â¯0.003) had higher ratio of mean hospital charges compared with surgery alone (adjusted Ratio: 1.09; 95% CI: 0.69-1.72; Pâ¯=â¯0.710). CONCLUSIONS: Numerous factors were associated with the need for surgical intervention, including the use of ET. Those receiving ET, as well as those with combined therapy, had a longer LOS and increased total hospital charges. Ha AS, Wallace BK, Miles C, et al. Exploring the Use of Exchange Transfusion in the Surgical Management of Priapism in Sickle Cell Disease: A Population-Based Analysis. J Sex Med 2021;18:1788-1796.
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Anemia Falciforme , Priapismo , Anemia Falciforme/complicações , Serviço Hospitalar de Emergência , Humanos , Pacientes Internados , Tempo de Internação , Masculino , Priapismo/etiologia , Priapismo/cirurgiaRESUMO
INTRODUCTION: Penile prosthesis infections remain challenging despite advancements in surgical technique, device improvements, and adoption of antibiotic prophylaxis guidelines. AIM: To investigate penile prosthesis infection microbiology to consider which changes in practice could decrease infection rates, to evaluate current antibiotic prophylaxis guidelines, and to develop a proposed algorithm for penile prosthesis infections. METHODS: This retrospective institutional review board-exempt multi-institutional study from 25 centers reviewed intraoperative cultures obtained at explantation or Mulcahy salvage of infected three-piece inflatable penile prostheses (IPPs). Antibiotic usage was recorded at implantation, admission for infection, and explantation or salvage surgery. Cultures were obtained from purulent material in the implant space and from the biofilm on the device. MAIN OUTCOME MEASURES: Intraoperative culture data from infected IPPs. RESULTS: Two hundred twenty-seven intraoperative cultures (2002-2016) were obtained at salvage or explantation. No culture growth occurred in 33% of cases and gram-positive and gram-negative organisms were found in 73% and 39% of positive cultures, respectively. Candida species (11.1%), anaerobes (10.5%) and methicillin-resistant Staphylococcus aureus (9.2%) constituted nearly one third of 153 positive cultures. Multi-organism infections occurred in 25% of positive cultures. Antibiotic regimens at initial implantation were generally consistent with American Urological Association (AUA) and European Association of Urology (EAU) guidelines. However, the micro-organisms identified in this study were covered by these guidelines in only 62% to 86% of cases. Antibiotic selection at admissions for infection and salvage or explantation varied widely compared with those at IPP implantation. CONCLUSION: This study documents a high incidence of anaerobic, Candida, and methicillin-resistant S aureus infections. In addition, approximately one third of infected penile prosthesis cases had negative cultures. Micro-organisms identified in this study were not covered by the AUA and EAU antibiotic guidelines in at least 14% to 38% of cases. These findings suggest broadening antibiotic prophylaxis guidelines and creating a management algorithm for IPP infections might lower infection rates and improve salvage success. Gross MS, Phillips EA, Carrasquillo RJ, et al. Multicenter Investigation of the Micro-Organisms Involved in Penile Prosthesis Infection: An Analysis of the Efficacy of the AUA and EAU Guidelines for Penile Prosthesis Prophylaxis. J Sex Med 2017;14:455-463.
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Antibioticoprofilaxia , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/prevenção & controle , Antibacterianos/uso terapêutico , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Prótese de Pênis/efeitos adversos , Reoperação/efeitos adversos , Estudos RetrospectivosRESUMO
INTRODUCTION: Provoked and spontaneous nocturnal erections are thought to play a role in maintenance of male sexual health through oxygenation of the corpus cavernosa. Conversely, hypoxia is thought to be an etiological factor in the pathogenesis of cavernosal fibrosis and long-term erectile dysfunction. It has been hypothesized that the early penile hypoxia after radical prostatectomy (RP) may lead to fibrosis and consequently a decrease in stretched penile length and long-term erectile dysfunction. AIM: The aim of this study was to assess the changes in penile tissue oxygenation with vacuum erection device (VED) use. METHODS: Twenty men between 2 and 24 months following RP were enrolled prospectively. Each man cycled a VED to achieve full erection 10 consecutive times over a period of approximately 2 minutes without constriction ring. MAIN OUTCOME MEASURES: Tissue oximetry was measured at baseline and immediately after VED using a tissue oximeter at five sites: right thigh, right corpora, glans, left corpora, and left thigh. Additional measurements were captured over the course of an hour. RESULTS: Mean age and time from surgery was 58.2 years and 12.6 months, respectively, and the average Sexual Health Inventory for Men score was 7. Use of the VED significantly increased both glanular and corporal oximetry relative to the baseline values for the entire 60 minutes. An initial increase of 55% was seen in corporal oxygenation with VED use. CONCLUSIONS: This is the first study demonstrating that a single, brief application of the VED without a constriction ring results in significant improvement in penile oxygen saturation. The use of a VED has significant benefits for patients both with regard to cost and invasiveness when compared with other penile rehabilitation protocols.
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Disfunção Erétil/terapia , Oxigênio/sangue , Pênis/química , Análise de Variância , Disfunção Erétil/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria/métodos , Projetos Piloto , Estudos Prospectivos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , VácuoRESUMO
PURPOSE: Intracorporeal injections have low use rates and high discontinuation rates. We examined factors associated with intracorporeal injection use, long-term satisfaction with intracorporeal injection and reasons for discontinuation in men treated with radical prostatectomy. MATERIALS AND METHODS: Between October 2000 and September 2003, 731 men who underwent open radical retropubic prostatectomy were enrolled in a prospective outcomes study. The 8-year followup evaluation included the UCLA-PCI, and a survey capturing intracorporeal injection use, satisfaction and reasons for discontinuation. Logistic regression was used to determine associations between intracorporeal injection use and preoperative variables. RESULTS: The 8-year self-assessment was completed by 368 (50.4%) men. Of these men 140 (38%) indicated prior or current intracorporeal injection use, with only 34 using intracorporeal injection at 8 years. Overall, 44% of the men were satisfied with intracorporeal injections. Reasons for discontinuation included dislike (47%), pain (33%), return of erection (19%), inefficacy (14%) and no partner (6%). Men trying intracorporeal injections had greater preoperative UCLA-PCI sexual function scores (75.2 vs 65.62, p = 0.00005) as well as greater decreases in this score at 3 months (p = 0.0002) and 2 years (p = 0.003). Higher preoperative sexual function scores were independently associated with the use of intracorporeal injections in a model adjusted for age, marital status, nerve sparing status and body mass index (OR 1.021, 95% CI 1.008-1.035). CONCLUSIONS: Men pursuing intracorporeal injections have better baseline erectile function and experience greater deterioration in erectile function during the early postoperative period. Despite the high efficacy of injections, many men discontinue intracorporeal injections due to dislike or discomfort. Satisfaction rates for intracorporeal injections indicate their long-term role in restoring sexual function in men with post-prostatectomy erectile dysfunction.
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Disfunção Erétil/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Disfunção Erétil/etiologia , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prostatectomia/efeitos adversos , Fatores de TempoRESUMO
While consensus exists regarding risk factors for priapism, predictors of operative intervention are less well established. We assessed patient and hospital-level predictors associated with penile surgical intervention (PSI) for patients admitted with acute priapism, as well as length of stay (LOS) and total hospital charges using the National Inpatient Sample (2010-2015). Inpatients with acute priapism were stratified by PSI, defined as penile shunts, incisions, and placement of penile prostheses, exclusive of irrigation procedures. Survey-weighted logistic regression models were utilized to assess predictors of PSI. Negative binomial regression and generalized linear models with logarithmic transformation were used to compare PSI to LOS and total hospital charges, respectively. Among 14,529 weighted hospitalizations, 4,953 underwent PSI. Non-Medicare insurances, substance abuse, and ≥3 Elixhauser comorbidities had increased odds of PSI. Conversely, Black patients, sickle cell disease, alcohol abuse, neurologic diseases, malignancies, and teaching hospitals had lower odds. PSI coincided with shorter median LOS (adjusted IRR: 0.62; p < 0.001) and lower ratio of the mean hospital charges (adjusted Ratio: 0.49; p < 0.001). Additional subgroup analysis revealed penile incisions and shunts primarily associated with reduced LOS (adjusted IRR: 0.66; p < 0.001) and total hospital charges (adjusted Ratio: 0.49; p < 0.001). Further work is required to understand predictors of poor outcomes in these populations.
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Pacientes Internados , Priapismo , Masculino , Humanos , Priapismo/cirurgia , Tempo de Internação , Fatores de Risco , Modelos LinearesRESUMO
Male circumcision (MC) is one of the oldest surgical procedures still completed today. Medical indications for MC include phimosis, recurrent balanitis, cosmesis, and infection prevention. In this review, we mainly focus on the role of MC in the prevention of human immunodeficiency virus, human papillomavirus, herpes simplex virus, gonorrhea, chlamydia, chancroid, and syphilis, and the subsequent impact of these genitourinary infections on male fertility. Overall, many compelling data support that MC may play an essential role in both genitourinary infection prevention and male fertility.
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Many couples initially deferred attempts at pregnancy or delayed fertility care due to concerns about coronavirus disease 2019 (COVID-19). One significant fear during the COVID-19 pandemic was the possibility of sexual transmission. Many couples have since resumed fertility care while accepting the various uncertainties associated with severe acute respiratory syndrome coronavirus 2, including the evolving knowledge related to male reproductive health. Significant research has been conducted exploring viral shedding, tropism, sexual transmission, the impact of male reproductive hormones, and possible implications to semen quality. However, to date, limited definitive evidence exists regarding many of these aspects, creating a challenging landscape for both patients and physicians to obtain and provide the best clinical care. This review provides a comprehensive assessment of the evolving literature concerning COVID-19 and male sexual and reproductive health, and guidance for patient counseling.
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COVID-19/epidemiologia , Genitália Masculina/virologia , Saúde do Homem/tendências , Reprodução/fisiologia , Saúde Reprodutiva/tendências , SARS-CoV-2/isolamento & purificação , COVID-19/prevenção & controle , Humanos , Infertilidade Masculina/epidemiologia , Infertilidade Masculina/prevenção & controle , MasculinoRESUMO
OBJECTIVE: To determine if there has been a change in empirical medical therapy (EMT) practices since a 2010 American Urological Association survey reported that 25% of urologists treated infertile men who were pursuing a pregnancy with testosterone (T). DESIGN: Survey-based cohort study of AUA members. SETTING: Practice patterns were evaluated of urologists in academic and nonacademic hospital centers. PATIENTS: Practice patterns were evaluated in the treatment of men with idiopathic infertility. INTERVENTIONSS: None. MAIN OUTCOME MEASURES: Subgroup analysis by means of univariate analysis between means (Fisher exact test) and descriptive proportions was used to compare male infertility fellowship-trained urologists (RUs) to general urologists (non-RUs). RESULTS: A total of 191 urologists responded (4.7%). Excluding trainees, 164 responses (85.9%) were analyzed: 134 (82.3%) were from non-RUs and 29 from (17.7%) RUs. Over all, 65.9% treated male infertility with a combination of EMT and surgery (93.1% of RU vs. 60.4% of non-RUs). The most common medications used by RUs were clomiphene (100%), anastrozole (85.7%), and hCG/LH (82.1%). Non-RUs used these less frequently. Overall, 24.4% of the urologists reported that they would use T to treat male infertility: 14.4% (n = 4) of RUs and 24.4% (n = 30) of non-RUs. CONCLUSIONS: A total of 65.9% of urologists would treat male infertility with the use of EMT and surgery. The most common EMTs were clomiphene, anastrozole, and hCG/LH. Of concern, 24.4% of urologists considered T to treat male infertility, a medication with known contraceptive potential. This is unchanged from the 2010 survey, and confirms the need for reproductive medicine guidelines that include the topic of EMT use in infertile men.
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OBJECTIVE: To describe detection of severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) in seminal fluid of patients recovering from coronavirus disease 2019 (COVID-19) and to describe the expression profile of angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) within the testicle. DESIGN: Observational, cross-sectional study. SETTING: Tertiary referral center. PATIENT(S): Thirty-four adult Chinese males diagnosed with COVID-19 through confirmatory quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) from pharyngeal swab samples. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets. RESULT(S): Six patients (19%) demonstrated scrotal discomfort suggestive of viral orchitis around the time of COVID-19 confirmation. Severe acute respiratory syndrome-CoV-2 was not detected in semen after a median of 31 days (interquartile range, 29-36 days) from COVID-19 diagnosis. Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression. CONCLUSION(S): Severe acute respiratory syndrome-CoV-2 was not detected in the semen of patients recovering from COVID-19 1 month after COVID-19 diagnosis. Angiotensin-converting enzyme 2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression. The long-term effects of SARS-CoV-2 on male reproductive function remain unknown.
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Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Sêmen/virologia , Adolescente , Adulto , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/genética , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/diagnóstico , Pneumonia Viral/enzimologia , Pneumonia Viral/genética , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Serina Endopeptidases/genética , Testículo/enzimologia , Testículo/virologia , Fatores de Tempo , Transcriptoma , Internalização do Vírus , Adulto JovemRESUMO
Gender dysphoria, or the incongruence between gender identification and sex assigned at birth with associated discomfort or distress, manifests in transgender patients, whose multifaceted care includes puberty suppression, cross-sex hormonal therapy, and gender-affirming surgery. Discussion of fertility preservation (FP) is paramount because many treatments compromise future fertility, and although transgender patients demonstrate desire for children, use of FP remains low for a plethora of reasons. In transgender women, established FP options include ejaculated sperm cryopreservation, electroejaculation, or testicular sperm extraction. Further research is needed regarding reproductive health and FP in transgender patients.
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Preservação da Fertilidade , Procedimentos de Readequação Sexual , Transexualidade , Feminino , Humanos , MasculinoRESUMO
In vitro fertilization used in combination with intracytoplasmic sperm injection allows otherwise sterile couples to become parents. Despite recent studies on the safety of these technologies, there is still only an incomplete picture of the risks associated with the usage of these assisted reproductive techniques to offspring. The risk of multiple gestations continues to be of major concern because of its association with low birth weight, preterm delivery, and increased perinatal mortality. This article outlines the risks associated with in vitro fertilization/intracytoplasmic sperm injection as a well-defined treatment for couples with severe male factor infertility.
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Anormalidades Congênitas/etiologia , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Feminino , Humanos , Fatores de RiscoRESUMO
Assisted reproductive technologies are increasingly used in the treatment of both male and female infertility. The techniques, including in vitro fertilization, with or without intracytoplasmic sperm injection as an adjunctive treatment, represent a tremendous step forward for infertile couples who previously had no treatment options. As we move towards the 30(th) anniversary of the birth of the first baby conceived by in vitro fertilization, questions about the safety of these procedures linger. We review here the available literature regarding the safety of assisted reproductive technologies; these data are made far more robust by the inclusion of long-term follow-up data from the first generation of children arising after the introduction of these technologies.
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Anormalidades Congênitas/epidemiologia , Técnicas de Reprodução Assistida/efeitos adversos , Criança , Anormalidades Congênitas/etiologia , Anormalidades Congênitas/genética , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/genética , Feminino , Fertilização in vitro/efeitos adversos , Fertilização in vitro/tendências , Humanos , Masculino , Gravidez , Técnicas de Reprodução Assistida/tendências , Fatores de RiscoRESUMO
OBJECTIVES: The aim of this study was to compare testicular metabolite concentrations between fertile control subjects and infertile men. MATERIALS AND METHODS: Single voxel proton magnetic resonance spectroscopy (H-MRS) was performed in the testes with and without water suppression at 3 T in 9 fertile control subjects and 9 infertile patients (8 with azoospermia and 1 with oligospermia). In controls only, the T1 and T2 values of water and metabolites were also measured. Absolute metabolite concentrations were calculated using the unsuppressed water signal as a reference and correcting for the relative T1 and T2 weighting of the water and metabolite signals. RESULTS: Testicular T1 values of water, total choline, and total creatine were 2028 ± 125 milliseconds, 1164 ± 105 milliseconds, and 1421 ± 314 milliseconds, respectively (mean ± standard deviation). T2 values were 154 ± 11 milliseconds, 342 ± 53 milliseconds, and 285 ± 167 milliseconds, respectively. Total choline concentration was lower in patients (mean, 1.5 mmol/L; range, 0.9-2.1 mmol/L) than controls (mean, 4.4 mmol/L; range, 3.2-5.7 mmol/L; P = 4 × 10). Total creatine concentration was likewise reduced in patients (mean, 1.1 mmol/L; range, undetectable -2.7 mmol/L) compared with controls (mean, 3.6 mmol/L; range, 2.5-4.7 mmol/L; P = 1.6 × 10). The myo-inositol signal normalized to the water reference was also lower in patients than controls (P = 4 × 10). CONCLUSIONS: Testicular metabolite concentrations, measured by proton spectroscopy at 3 T, may be valuable as noninvasive biomarkers of spermatogenesis.
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Infertilidade/diagnóstico , Espectroscopia de Ressonância Magnética/métodos , Espermatogênese , Testículo/diagnóstico por imagem , Adulto , Biomarcadores/metabolismo , Colina/metabolismo , Creatina/metabolismo , Estudos de Avaliação como Assunto , Feminino , Humanos , Infertilidade/metabolismo , Infertilidade/fisiopatologia , Inositol/metabolismo , Masculino , Pessoa de Meia-Idade , Testículo/metabolismo , Testículo/fisiopatologiaRESUMO
Male hormonal physiology plays an important role in the function and development of the prostate. Moreover, benign prostatic hyperplasia and prostate cancer, two common and bothersome conditions of the prostate, are also influenced by hormonal activity. This article reviews the existing data regarding these complex relationships.
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Próstata/fisiopatologia , Hiperplasia Prostática/fisiopatologia , Neoplasias da Próstata/fisiopatologia , Testosterona/deficiência , Testosterona/fisiologia , Humanos , Masculino , Próstata/efeitos dos fármacos , Próstata/fisiologia , Testosterona/sangue , Testosterona/uso terapêuticoRESUMO
Testosterone supplementation therapy (TST) has become increasingly popular since the turn of the century. Most prescriptions in the U.S. are written by primary care providers, endocrinologists, or urologists. The FDA has requests pharmaceutical companies provide more long term data on efficacy and safety of testosterone products. Results from these studies will help define the appropriate population for TST going forward. It is hoped that these data combined with physician and public education will minimize inappropriate prescribing and allow those likely to benefit from TST to receive it.
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Hipogonadismo/tratamento farmacológico , Saúde Pública , Testosterona/uso terapêutico , Humanos , Masculino , Padrões de Prática MédicaRESUMO
The concept of unilateral care of the female partner has gained momentum in the reproductive health community, especially with the advent of in vitro fertilization and intracytoplasmic sperm injection. Herein, the authors examine the existing evidence in support of evaluating and treating the male patient as part of the routine evaluation of the infertile couple. This evidence includes assessments of efficacy, cost-effectiveness, and safety, and-- when considered broadly--argues strongly against unilateral care.