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1.
Physiol Rep ; 12(19): e70053, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39370302

RESUMO

Anabolic-androgenic steroids (AASs) impairment of reproduction has been reported. We investigated dose- and time-dependent effects of Nandrolone decanoate (ND) on reproductive system in comparison with Testosterone enanthate (TE). Male Wistar rats were administrated with 1, 3, and 9 mg/kg/weeks ND or 1 and 3 mg/kg/weeks TE for 8 weeks, and testicular phenotype and reproductive hormones were assessed at 4 and 8 weeks post-treatments. AASs × treatment period interaction was significant for gonadosomatic index (GSI), testosterone (T), 17ß-estradiol (E2), and luteinizing hormone (LH). At 4 weeks post-treatment, GSI was decreased in rats treated with 3 mg/kg/weeks ND and T was decreased in all ND-treated groups, while no significant changes in LH levels were observed. At 8 weeks post-treatment, GSI was decreased in rats treated with 1 and 3 mg/kg/weeks ND and with 3 mg/kg/weeks TE, T was decreased in all groups, and E2 and LH were increased and decreased, respectively, in rats treated with 9 mg/kg/weeks ND and with 3 mg/kg/weeks TE. The testes showed histopathological defects in both ND- and TE-treated rats suggesting a delay in seminiferous cycle. This study shows AASs-induced hypogonadism at low-dose that coincided with inhibition of T biosynthesis and disruption of T feedback on pituitary.


Assuntos
Anabolizantes , Hipogonadismo , Hormônio Luteinizante , Decanoato de Nandrolona , Hipófise , Ratos Wistar , Testículo , Testosterona , Animais , Masculino , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Ratos , Hipogonadismo/induzido quimicamente , Hipogonadismo/metabolismo , Testosterona/análogos & derivados , Hormônio Luteinizante/sangue , Anabolizantes/toxicidade , Anabolizantes/farmacologia , Anabolizantes/administração & dosagem , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Estradiol/análogos & derivados , Estradiol/farmacologia , Relação Dose-Resposta a Droga , Nandrolona/análogos & derivados , Nandrolona/toxicidade , Nandrolona/farmacologia
2.
Ann N Y Acad Sci ; 1538(1): 56-70, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39041466

RESUMO

Androgens, formerly known as anabolic-androgenic steroids, mimic the effects of testosterone and are being increasingly abused for nonmedical purposes such as body and performance enhancement. Androgen abuse is associated with increased mortality, and multisystem adverse effects have been reported, including cardiovascular toxicity, infertility, hypogonadism, hepatotoxicity, and mental health disorders. Men may present with the negative health consequences of androgen abuse even despite cessation for a number of years. There is frequently a reluctance to disclose androgen abuse, and substances are often sourced from the black market, which is not regulated and where the products sold may be counterfeit. All men should be encouraged to stop androgen abuse. Managing associated adverse effects will be organ-specific and is complex due to physical and neuropsychiatric symptoms, substance dependence, and high rates of relapse. Given the broad reach and prolonged adverse effects of androgen abuse, clinicians across medical specialties should have an awareness of androgen abuse, its increasing prevalence, and the harms it poses to men and their families. This narrative review aims to summarize the adverse effects and risks associated with androgen abuse.


Assuntos
Androgênios , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Androgênios/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Hipogonadismo/induzido quimicamente , Fatores de Risco
3.
Best Pract Res Clin Rheumatol ; 38(1): 101935, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38429184

RESUMO

The U.S. is grappling with an opioid epidemic, with millions of adults on long-term opioid therapy (LTOT). Although patients often report pain relief and improved daily function with opioids, research shows no significant differences in short-term outcomes between opioid and non-opioid users, as well as no long-term opioid benefits. This scoping review aims to identify lesser-known side effects of long-term opioid use and increase awareness of them, allowing healthcare providers and patients to better assess the risks and benefits of opioid use. Our data search from PubMed and Google Scholar used keywords related to opioids, chronic pain, hypogonadism, endocrinopathies, cancer progression, cardiovascular events, renovascular events, sleep disturbances, mood disorders and others, narrowing down to English-language full articles published from January 2018 to April 2023. This review emphasizes the probable serious adverse consequences of long-term opioid use on various body systems in patients with chronic pain. Given the lack of long-term benefits and significant adverse effects, our review underscores the critical need for healthcare providers to include these risks in discussions with patients when considering the long-term use of opioid therapy.


Assuntos
Analgésicos Opioides , Dor Crônica , Humanos , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Hipogonadismo/tratamento farmacológico , Hipogonadismo/induzido quimicamente , Doenças Cardiovasculares
4.
Cancer ; 130(15): 2611-2620, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38549441

RESUMO

BACKGROUND: It is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK-positive cancer and in murine models. METHODS: In this study, three groups, including an experimental group of male patients with ALK-positive, advanced non-small cell lung cancer (ANSCLC) who were receiving alectinib (cohort A), a control group of female patients with ALK-positive ANSCLC who were receiving alectinib (cohort B), and a control group of male patients with ALK-negative ANSCLC (cohort C), prospectively underwent a full hormone assessment for androgen deficiency at 8 weeks after the start of treatment and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to an endocrinologist. RESULTS: Ninety-five patients were consecutively enrolled onto the study. Among sixty-eight male patients, both median total testosterone levels (2.93 vs. 4.92 ng/ml; p = .0001) and free testosterone levels (0.11 vs. 0.17 pg/ml; p = .0002) were significantly lower in ALK-positive ANSCLC patients in cohort A compared with ALK-negative patients in cohort C; conversely, median FSH (10.32 vs. 17.52 mUI/ml; p = .0059) and LH levels (4.72 vs. 7.49 mUI/ml; p = .0131) were significantly higher in cohort C compared to cohort A. Median inhibin B levels were higher in ALK-positive male patients (74.3 vs. 44.24 pg/ml; p = .0038), but all patients had inhibin B values within the normal range. The percentage of male patients who had positive scores on the Androgen Deficiency in Aging Males (ADAM) questionnaire was 62% in cohort A and 26.8% in cohort C, including eight patients who reported at least one major symptom and were referred to Andrology Unit. No significant differences in the endocrine assessment were reported between cohorts A and B. CONCLUSIONS: Symptoms of androgen deficiency should be tracked in male patients with ALK-positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate.


Assuntos
Quinase do Linfoma Anaplásico , Carbazóis , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piperidinas , Testosterona , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Carbazóis/uso terapêutico , Carbazóis/efeitos adversos , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Idoso , Adulto , Testosterona/sangue , Testosterona/deficiência , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Disfunções Sexuais Fisiológicas/induzido quimicamente , Feminino , Androgênios/deficiência , Estudos Prospectivos , Hipogonadismo/induzido quimicamente , Hipogonadismo/tratamento farmacológico , Receptores Proteína Tirosina Quinases
5.
Oncologist ; 29(6): e728-e740, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38518107

RESUMO

BACKGROUND: In male patients with cancer treated with antineoplastic drug, hypogonadism is a neglected cause of diminished quality of life. This condition may be cancer related as well as toxicity related. The role of antineoplastic drug in causing hypogonadism is poorly understood. The aim of this systematic review was to establish the prevalence, nature (primary/secondary), and impact of hypogonadism on quality of life in male patients with cancer on antineoplastic therapy. METHODS: The search strategy used PubMed, Embase, and Cochrane databases to select articles in English language that described hypogonadism in male patients with cancer. The search period was from January 1, 1945 to February 28, 2023. We included observational studies, case reports or case series and excluded studies concerning hematological malignancies, prostate cancer, female patients, and survivors. FINDINGS: Of 4488 records identified, 28 studies met inclusion criteria (17 observational studies, 11 case reports or case series). Anti-angiogenic drugs and crizotinib were found to have a role in the development of hypogonadism. Patients treated with immune checkpoint-inhibitors developed secondary hypogonadism due to immune-related hypophysitis or orchitis. As for active chemotherapy, platinum salts were often associated with hypogonadism, followed by antimetabolites and taxanes. Selected studies were heterogeneous for populations, interventions, and outcomes assessments. Thus, a generalization is difficult. Moreover, the role of concurrent etiologies cannot be excluded in most studies. CONCLUSION: Our research emphasizes the importance of evaluating the gonadal axis before treatment in patients considered at risk and testing it at regular intervals or in case of clinical suspicion.


Assuntos
Antineoplásicos , Hipogonadismo , Neoplasias , Humanos , Masculino , Hipogonadismo/induzido quimicamente , Hipogonadismo/tratamento farmacológico , Hipogonadismo/complicações , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Qualidade de Vida
6.
Am J Drug Alcohol Abuse ; 50(2): 132-138, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38320237

RESUMO

Hypogonadism is a highly prevalent complication of chronic opioid use associated with a constellation of affective, algesic, and cognitive symptoms as well as decreased quality of life. Given that the mainstays of pharmacologic opioid use disorder (OUD) treatment - methadone and buprenorphine - are themselves agonists or partial agonists at the mu opioid receptor, opioid-induced hypogonadism (OIH) remains an underappreciated clinical concern throughout the course of OUD treatment. Prominent theoretical frameworks for OUD emphasize the importance of negative reinforcement and hyperkatifeia, defined as the heightened salience of negative emotional and motivational states brought on by chronic opioid use. In this perspective article, we highlight the striking parallels between the symptom domains of hyperfakifeia and hypogonadism in males, who comprise the vast majority of existing clinical research on OIH. By extension we propose that future research and ultimately clinical care should focus on the identification and treatment of OIH in OUD patients to help address the longstanding paradox of poor treatment retention despite efficacious therapies, particularly in the setting of the current opioid overdose epidemic driven by high potency synthetic opioids such as fentanyl. We then review evidence from chronic pain patients that testosterone replacement provides clinically significant benefits to men with OIH. Finally, using this framework, we compare extant OUD therapeutics and discuss critical gaps in the clinical literature-including the relative dearth of data regarding hypothalamic-pituitary-gonadal function in females who use opioids-where future study should be focused.


Assuntos
Analgésicos Opioides , Hipogonadismo , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Buprenorfina/efeitos adversos , Hipogonadismo/induzido quimicamente , Hipogonadismo/tratamento farmacológico , Metadona/uso terapêutico , Metadona/efeitos adversos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Reforço Psicológico
7.
Medicina (Kaunas) ; 60(2)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38399562

RESUMO

Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind, especially as we age. However, traditional testosterone replacement therapy has been shown to lead to male infertility, caused by negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis. Recent advances in research have led to the discovery of many new methods of administration, which can have more or less suppressive effects on the HPG axis. Also, the usage of ancillary medications instead of or after testosterone administration might help maintain fertility in hypogonadal patients. The goal of this narrative review is to summarize the newest methods for optimizing fertility parameters in patients undergoing treatment for hypogonadism and to provide the necessary information for healthcare providers to make the right treatment choices.


Assuntos
Hipogonadismo , Infertilidade Masculina , Humanos , Masculino , Testosterona/efeitos adversos , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Hipogonadismo/induzido quimicamente , Infertilidade Masculina/tratamento farmacológico , Fertilidade , Terapia de Reposição Hormonal
8.
Expert Opin Pharmacother ; 25(1): 25-35, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38229462

RESUMO

INTRODUCTION: As an increasingly popular therapeutic option, testosterone replacement therapy (TRT) has gained significant notoriety for its health benefits in indicated populations, such as those suffering from hypogonadism. AREAS COVERED: Benefits such as improved libido, muscle mass, cognition, and quality of life have led to widened public interest in testosterone as a health supplement. No therapy exists without side effects; testosterone replacement therapy has been associated with side effects such as an increased risk of polycythemia, benign prostate hypertrophy (BPH), prostate cancer, gynecomastia, testicular atrophy, and infertility. Testosterone replacement therapy is often accompanied by several prophylactic co-therapies aimed at reducing the prevalence of these side effects. Literature searches for sections on the clinical benefits and risks associated with TRT were performed to include clinical trials, meta-analyses, and systematic reviews from the last 10 years. EXPERT OPINION: Data from clinical studies over the last decade suggest that the benefits of this therapy outweigh the risks and result in overall increased quality of life and remission of symptoms related to hypogonadism. With this in mind, the authors of this review suggest that carefully designed clinical trials are warranted for the investigation of TRT in symptomatic age-related hypogonadism.


Assuntos
Hipogonadismo , Neoplasias da Próstata , Masculino , Humanos , Qualidade de Vida , Testosterona/efeitos adversos , Hipogonadismo/tratamento farmacológico , Hipogonadismo/induzido quimicamente , Hipogonadismo/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Libido
9.
Int J Impot Res ; 36(4): 403-407, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38129694

RESUMO

Male hypogonadism is not a risk associated with attention-deficit hyperactivity disorder (ADHD) stimulant medications, but recent studies have explored this connection. Though the pathophysiologic connection remains unclear, we predicted that long-term use of ADHD stimulant medications could increase the risk of hypogonadism in post-pubertal males. Utilizing TriNetX, LLC Research Network data from January 2000 through December 2019, men older than 18 with ADHD receiving long-term stimulant medication (>36 monthly prescriptions) were selected for the study population. Two control groups were constructed: individuals with ADHD but no stimulant medication use, and individuals without ADHD or stimulant medication use. A diagnosis of testicular hypofunction (ICD-10: E29.1) within five years of long-term ADHD stimulant medication use was the chosen primary outcome. After propensity score matching, 17,224 men were analyzed in each group. Of the men with long-term ADHD stimulant medication use, 1.20% were subsequently diagnosed with testicular hypofunction compared to 0.67% of individuals with ADHD without stimulant medication use (RR: 1.78, 95% CI: 1.42-2.23) and 0.68% in men without ADHD or stimulant medication use (RR: 1.75, 95% CI: 1.39-2.19). Therefore, chronic ADHD stimulant medication use was found to be significantly associated with a subsequent diagnosis of testicular hypofunction.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Bases de Dados Factuais , Hipogonadismo , Testosterona , Humanos , Masculino , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Adulto , Hipogonadismo/tratamento farmacológico , Hipogonadismo/induzido quimicamente , Testosterona/efeitos adversos , Pessoa de Meia-Idade , Adulto Jovem , Estados Unidos/epidemiologia , Adolescente , Estudos Retrospectivos
10.
Eur J Endocrinol ; 189(6): 601-610, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38102386

RESUMO

OBJECTIVE: Symptomatic hypogonadism discourages men from stopping anabolic-androgenic steroids (AAS). Some men illicitly take drugs temporarily stimulating endogenous testosterone following AAS cessation (post-cycle therapy; PCT) to lessen hypogonadal symptoms. We investigated whether prior PCT use was associated with the normalization of reproductive hormones following AAS cessation. METHODS: Retrospective analysis of 641 men attending a clinic between 2015-2022 for a single, nonfasting, random blood test <36 months following AAS cessation, with or without PCT. Normalized reproductive hormones (ie, a combination of reference range serum luteinizing hormone, follicle-stimulating hormone, and total testosterone levels) were the surrogate marker of biochemical recovery. RESULTS: Normalization of reproductive hormones was achieved in 48.2% of men. PCT use was associated with faster biochemical recovery (13.0 (IQR8.0-19.0) weeks, PCT; 26.0 (IQR10.5-52) weeks, no-PCT; P < .001). Odds of biochemical recovery during multivariable analysis were: (1) higher with PCT (OR3.80) vs no-PCT (P = .001), in men stopping AAS ≤3 months previously; (2) reduced when 2 (OR0.55), 3 (OR0.46), or 4 (OR0.25) AAS were administered vs 1 drug (P = .009); (3) lower with AAS >6 vs ≤3 months previously (OR0.34, P = .01); (4) higher with last reported AAS >3 months (OR 5.68) vs ≤3 months (P = .001). PCT use was not associated with biochemical recovery in men stopping AAS >3 months previously. CONCLUSION: Without evidence-based withdrawal protocols, men commonly try avoiding post-AAS hypogonadism with PCT, which is illicit, ill-defined, and not recommended. Only half of men had complete biochemical testicular recovery after stopping AAS. The surprising association of self-reported PCT use with short-term biochemical recovery from AAS-induced hypogonadism warrants further investigation.


Assuntos
Anabolizantes , Hipogonadismo , Masculino , Humanos , Estudos Retrospectivos , Esteróides Androgênicos Anabolizantes , Anabolizantes/efeitos adversos , Congêneres da Testosterona/efeitos adversos , Testosterona , Hipogonadismo/induzido quimicamente , Hipogonadismo/tratamento farmacológico , Hipogonadismo/diagnóstico , Androgênios/efeitos adversos
11.
Expert Opin Investig Drugs ; 32(11): 1071-1084, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37943011

RESUMO

INTRODUCTION: The specific role of testosterone (T) replacement therapy in patients with late onset hypogonadism is still conflicting. Several available preparations have been developed to restore either fertility and normal testosterone (T) levels (secondary hypogonadism) or just T levels (primary hypogonadism). AREAS COVERED: Advantages and limitations related to available new treatments will be discussed in detail. In addition, possible news related to preparations in the pipeline will be discussed. EXPERT OPINION: The selection of a specific T preparation should be adequately discussed with each subject. Transdermal T preparations are those that can preserve, after a unique morning administration, the circadian rhythmicity of T secretion. Conversely, short-acting preparations (such as oral or intranasal) need two- or three-times daily administration, potentially reducing patient compliance. Long acting T preparations, such as injectable T undecanoate have the advantage of bimestrial or trimestral administration, reducing the required number of administrations. The use of non-steroidal selective androgen receptor modulators (SARM), a heterogeneous class of compounds selectively acting on androgen receptor targets, remains investigational due to the lack of the full spectrum of T's action and the possible risk of side effects, despite their potential use in the treatment of muscle wasting and osteoporosis.


Assuntos
Hipogonadismo , Receptores Androgênicos , Humanos , Masculino , Testosterona , Androgênios , Hipogonadismo/tratamento farmacológico , Hipogonadismo/induzido quimicamente , Administração Cutânea
12.
Subst Abuse Treat Prev Policy ; 18(1): 66, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951896

RESUMO

BACKGROUND: Anabolic-androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general population. AAS use has been linked with increased mortality, cardiovascular disease, mental health disorders, and infertility. AAS-induced hypogonadism can persist for an uncertain time period despite cessation, during which men may report physical and neuropsychiatric symptoms. In an attempt to mitigate these symptoms and expedite testicular recovery, many men self-administer post-cycle-therapy (PCT), typically involving human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERMs), which are known to potently stimulate testicular function. However, this practice has no objective evidence of effectiveness to lessen the severity or duration of hypogonadal symptoms. METHODS: An anonymous survey of four-hundred-and-seventy men using AAS explored the symptoms they experienced when ceasing AAS use; the effect of PCT on relieving their symptoms, and their perceived role for health service support. RESULTS: The majority of respondents were white, aged 18-30 years old, and working in skilled manual work. 51.7% (n = 243) reported no issues with AAS use, but 35.3% reported increased aggression. 65.1% (n = 306) of respondents had attempted AAS cessation and 95.1% of these experienced at least one symptom upon AAS cessation. Low mood, tiredness and reduced libido were reported in 72.9%, 58.5% and 57.0% of men stopping AAS use, respectively, with only 4.9% reporting no symptoms. PCT had been used by 56.5% of respondents with AAS cessation and mitigated cravings to restart AAS use, withdrawal symptoms and suicidal thoughts by 60%, 60% and 50%, respectively. The effect of stopping AAS on body composition and recovery of testosterone or fertility was a concern in 60.5% and 52.4%, respectively. Most respondents felt PCT should be prescribed under medical supervision in the community. CONCLUSIONS: Our survey suggests that the majority of men stopping AAS use are using some form of PCT. Some self-reported symptoms of AAS-induced hypogonadism such as cravings to restart AAS use reduce by 60% and suicidal thoughts reduce by 50%. These individuals are concerned about the negative effect of AAS use and cessation. This study provides crucial information for planning future research to evaluate the effects of PCT on symptoms when men stop AAS use.


Assuntos
Anabolizantes , Hipogonadismo , Síndrome de Abstinência a Substâncias , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Esteróides Androgênicos Anabolizantes , Anabolizantes/efeitos adversos , Congêneres da Testosterona/efeitos adversos , Testosterona/efeitos adversos , Hipogonadismo/tratamento farmacológico , Hipogonadismo/induzido quimicamente , Hipogonadismo/diagnóstico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Inquéritos e Questionários
13.
Acta Oncol ; 62(12): 1898-1904, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37971326

RESUMO

BACKGROUND: Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. MATERIALS AND METHODS: The study included 78,615 men of age 55-67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995-2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. RESULTS: Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3-0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75-1.01 and HR = 0.93; 95% CI 0.87-1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. CONCLUSION: Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.


Assuntos
Doenças Cardiovasculares , Hipogonadismo , Neoplasias da Próstata , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/epidemiologia , Finlândia/epidemiologia , Hipogonadismo/tratamento farmacológico , Hipogonadismo/epidemiologia , Hipogonadismo/induzido quimicamente , Incidência , Testosterona/efeitos adversos
14.
Eur J Endocrinol ; 189(3): 297-308, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37579053

RESUMO

OBJECTIVE: Assessment of the efficacy and safety/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH). DESIGN: Placebo-controlled, double-blind, RCT, in 70 sites in Europe/USA. METHODS: Patient inclusion criteria: men with BMI of 30-50 kg/m2, morning total testosterone (TT) < 10.41 nmol/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1/0.3/1.0 mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in ≥75% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH/FSH. Safety was assessed through adverse events and laboratory monitoring. RESULTS AND CONCLUSIONS: Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1 kg/m2 and TT 7.97 nmol/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35 nmol/L, for leflutrozole 0.1 mg, 0.3 mg, and 1.0 mg groups respectively, vs 8.04 nmol/L for placebo. LH/FSH significantly increased in leflutrozole vs placebo groups. No improvements in body composition or sexual dysfunction were observed. Semen volume/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean -1.24%, -1.30%, -2.09%) and 0.66% for 0.1 mg, 0.3 mg, 1.0 mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH/LH and semen parameter changes support that leflutrozole may preserve/improve testicular function. CLINICAL TRIAL REGISTRATION NUMBER: NCT02730169.


Assuntos
Hipogonadismo , Síndrome de Klinefelter , Humanos , Masculino , Sêmen , Hipogonadismo/etiologia , Hipogonadismo/induzido quimicamente , Testosterona/efeitos adversos , Obesidade/complicações , Obesidade/tratamento farmacológico , Hormônio Foliculoestimulante , Método Duplo-Cego , Resultado do Tratamento
15.
Ann Vasc Surg ; 97: 113-120, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37453467

RESUMO

BACKGROUND: Vascular graft infections (VGIs) are a major source of morbidity following vascular bypass surgery. Hypogonadal men may be at increased risk for impaired wound healing and infections, but it is unclear if testosterone replacement therapy (TRT) mitigates this risk. We designed this study to evaluate the relationship between hypogonadism and the use of testosterone replacement therapy (TRT) with subsequent risk for developing a VGI. METHODS: We performed a retrospective analysis of claims in the MarketScan database identifying men greater than 18 years of age who underwent placement of a prosthetic graft in the peripheral arterial circulation from January 2009 to December 2020. Patients were stratified based on diagnosis of hypogonadism and use of TRT within 180 days before surgery. The primary outcome was VGI and the need for surgical excision. The association between hypogonadism and TRT use on risk of VGI was analyzed using Kaplan-Meier plots and multivariate Cox proportional hazards models. RESULTS: We identified 18,312 men who underwent a prosthetic bypass graft procedure in the upper and lower extremity during the study period, of which 802 (5%) had diagnosis of hypogonadism. Among men with hypogonadism, 251 (31%) were receiving TRT. Patients on TRT were younger, more likely to be diabetic, and more likely develop a VGI during follow-up (14% vs. 8%; P < 0.001) that was in the lower extremity. At 5 years, freedom from VGI was significantly lower for hypogonadal men on TRT than patients not on TRT or without hypogonadism (Log rank P < 0.001). In Cox regression models adjusted for age, diabetes, obesity, smoking, corticosteroid use, and procedure type, hypogonadal men on TRT were at a significantly increased risk of graft infection (hazard ratio (HR):1.94, 95% confidence interval (CI):1.4-2.7; P < 0.001) compared to controls. CONCLUSIONS: This study demonstrates TRT among hypogonadal men is associated with an increased risk of prosthetic VGIs. Temporary cessation of TRT should be considered for men undergoing prosthetic graft implants, particularly those in the lower extremity.


Assuntos
Hipogonadismo , Doenças Vasculares , Masculino , Humanos , Testosterona/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Hipogonadismo/diagnóstico , Hipogonadismo/induzido quimicamente , Hipogonadismo/complicações , Doenças Vasculares/complicações
16.
Reprod Fertil ; 4(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36757334

RESUMO

Lay summary: Anabolic steroids (also known as 'steroids') are banned drugs like testosterone, which make muscles bigger in men. These drugs are dangerous because they stop the testes from making natural testosterone and can cause heart attacks. Men stopping steroids have very low testosterone, which makes them feel weak, depressed, suicidal, infertile, and unable to have erections. We surveyed over 100 doctors to find out how they treat men giving up steroids. We report that doctors differ widely in the way they treat these men. Most doctors simply advise men to wait for the natural recovery of testosterone levels to happen. But 20% of doctors give men drugs to boost testosterone and make men feel better. Unfortunately, many patients had not recovered by the time of our survey. In summary, our survey highlights differences and limitations in the treatment of men giving up steroids. The use of steroids is increasing rapidly among young men, so we recommend further work to improve the treatment of men who are motivated to give up steroids.


Assuntos
Anabolizantes , Hipogonadismo , Animais , Humanos , Esteróides Androgênicos Anabolizantes , Androgênios/efeitos adversos , Endocrinologistas , Anabolizantes/efeitos adversos , Congêneres da Testosterona/efeitos adversos , Testosterona/efeitos adversos , Hipogonadismo/induzido quimicamente , Hipogonadismo/veterinária , Esteroides/efeitos adversos
18.
Reprod Sci ; 30(4): 1291-1305, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36097247

RESUMO

The purpose of this study is to investigate the effect of aerobic exercise (AE) training and/or oyster peptide (OP) supplementation on the formation of late-onset hypogonadism (LOH). AE training and/or OP supplement was performed during Cytoxan (CTX)-induced LOH formation in male SD rats for 6 consecutive weeks. Low dose of CTX could decrease mating times, the levels of luteinizing hormone (LH), total testosterone (TT), free testosterone (FT) in serum and TT, androgen receptor (AR), androgen binding protein (ABP), and glutathione peroxidase (GSH-Px) in testicle, but increase capture latency, mating latency, and malondialdehyde, and downregulate the mRNA expression of steroidogenic acute regulatory (StAR), P450 cholesterol side chain cleavage enzyme (P450scc), and StAR-related lipid transfer domain 7 (StARD7) in testicle. Every change was altered by AE training combined with OP supplement significantly, except for serum LH. Moreover, the effect of AE training combined with OP supplement was better than that of AE training on serum TT, FSH, testicular TT, mating latency, capture times, and mating times. AE training combined with OP supplement during CTX-induced LOH formation can prevent the LOH development by enhancing pituitary-gonads axis's function and reducing testicular oxidative stress to promote testosterone synthesis and spermatogenesis.


Assuntos
Hipogonadismo , Testículo , Ratos , Masculino , Animais , Ciclofosfamida/farmacologia , Ratos Sprague-Dawley , Testículo/metabolismo , Testosterona , Hipogonadismo/induzido quimicamente , Hipogonadismo/prevenção & controle , Hormônio Luteinizante , Suplementos Nutricionais
19.
Medicina (B Aires) ; 82(6): 873-880, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-36571526

RESUMO

INTRODUCTION: Our objective was to assess whether physicians who care for people with type 2 diabetes address andrological symptoms such as erectile sexual dysfunction, decreased libido, and symptoms and/or signs of hypogonadism. METHODS: An anonymous survey was carried out with 171 doctors, 113 were females (66.1%), the mean age was 46 ± 10 years (females: 45 ± 10 and males: 49 ± 10, p = 0.006). RESULTS: There were no differences in responses according to gender. Regarding the presence of erectile sexual dysfunction and/or decreased libido, 44.4% (n = 76) and 55.6% (n = 95) did not ask about them, respectively. In patients with symptoms of hypogonadism, 50.9% (n = 87) did not request a testosterone measurement. Regarding the improvement of the metabolic profile of type 2 diabetes mellitus and sexual symptoms after replacement with testosterone, 65.8% of the respondents answered that both conditions could improve after treatment. In the presence of symptoms compatible with hypogonadism, 74.7% of those surveyed stated that the measurement of testosterone should be performed. A total of 108 (63.2%) showed interest in being trained on topics related to type 2 diabetes and disorders of the sexual sphere. CONCLUSION: A large percentage of physicians who take care of men with type 2 diabetes do not inquire about andrological disorders. It is necessary to raise awareness and train doctors to detect, treat and/or refer these frequent health problems, not only to improve the quality of life of patients but also to effectively respond and prevent a major health problem.


Introducción: Los trastornos andrológicos son frecuentes en varones con diabetes tipo 2. El objetivo fue evaluar si los médicos que atienden a personas con diabetes tipo 2 abordan problemas andrológicos como disfunción sexual eréctil, disminución de libido y síntomas de hipogonadismo. Métodos: Se llevó a cabo una encuesta anónima a 171 médicos, de ellos 113 fueron mujeres (66.1%) con una edad media de 46 ± 10 años (mujeres: 45 ± 10 y varones: 49 ± 10, p = 0.006). Resultados: No hubo diferencias en las respuestas según el género. El 44.4% (n = 76) y el 55.6% (n = 95) no preguntan sobre la presencia de disfunción sexual eréctil y/o disminución de libido, respectivamente. El 50.9% (n = 87) no solicitó medición de testosterona en pacientes con síntomas de hipogonadismo. El 65.8% de los participantes respondió que el reemplazo con testosterona puede mejorar el perfil metabólico de la diabetes mellitus tipo 2 y los síntomas sexuales. El 74.7% de los encuestados afirmó que la medición de testosterona debería realizarse ante la presencia de síntomas compatibles con hipogonadismo. El 63.2% (n = 108) mostró interés en formación sobre temas relacionados a diabetes tipo 2 y trastornos de la esfera sexual. Conclusión: Un gran porcentaje de médicos que asisten a varones con diabetes tipo 2 no indaga sobre trastornos andrológicos. Es necesario concientizar y entrenar a los médicos, para detectar, tratar y/o derivar estos problemas de salud tan frecuentes, no solo para mejorar la calidad de vida de los pacientes sino para responder y prevenir efectivamente a un problema mayor de salud.


Assuntos
Diabetes Mellitus Tipo 2 , Disfunção Erétil , Hipogonadismo , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Qualidade de Vida , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/diagnóstico , Testosterona , Hipogonadismo/etiologia , Hipogonadismo/induzido quimicamente
20.
Rev Clin Esp (Barc) ; 222(10): 612-620, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36400345

RESUMO

The use of anabolic steroids affects not only professional athletes but also the general population (bodybuilders, gym clients, and adolescents). In the first case, its use is prohibited and sanctioned by the World Anti-Doping Agency and Olympic committees. For the other users, it is difficult to establish its prevalence since many obtain the products via the internet. The reasons for its use are varied and different forms of use and other types of users have been described. Among the side effects of steroid use, hypogonadism is the most frequent cause for endocrinological consultation. After a general introduction to doping, this review describes the historical background of anabolic-androgenic steroids, their classification, forms of use, physiological effects, adverse effects on different organs and systems, treatment of hypogonadism, as well as detection methods.


Assuntos
Anabolizantes , Hipogonadismo , Esportes , Adolescente , Humanos , Anabolizantes/efeitos adversos , Esteróides Androgênicos Anabolizantes , Congêneres da Testosterona/efeitos adversos , Atletas , Hipogonadismo/induzido quimicamente
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