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1.
Neuroendocrinology ; 114(8): 721-732, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38697024

RESUMO

INTRODUCTION: In humans, prenatal androgen excess can lead to a broad spectrum of pathologies in adulthood, including polycystic ovary syndrome (PCOS). Women with PCOS present a variety of reproductive and metabolic disturbances and they also face increased risk to develop neuropsychiatric disorders such as depression and anxiety. Despite the high prevalence, the cause of depressive and anxiety symptoms is not fully elucidated. The use of androgenized ewe models can provide valuable insights into the pathogenesis of PCOS, as they closely mimic the reproductive, neuroendocrine, and metabolic characteristics observed in women with this condition. METHOD: We studied the impact of prenatal exposure to testosterone propionate on cognitive and behavioral performances of Ile-de-France ewes, using a plethora of behavioral tests for anxiety and cognitive performances. RESULTS: Our findings indicate that prenatal androgenized ewes exhibit markedly elevated levels of anxiety-like behavior compared to control animals, while showing no discernible differences in cognitive performance. CONCLUSION: These discoveries offer novel perspectives on how maternal androgen excess contributes to anxiogenic effects in PCOS preclinical models, underscoring the ewe's significance as a model for conducting mechanistic studies to unravel the physiological and molecular aspects of anxiety.


Assuntos
Ansiedade , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Gravidez , Ansiedade/induzido quimicamente , Ovinos , Propionato de Testosterona/farmacologia , Propionato de Testosterona/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Androgênios/farmacologia , Androgênios/efeitos adversos , Modelos Animais de Doenças , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Cognição/efeitos dos fármacos
2.
J Endocrinol Invest ; 47(3): 603-617, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37642904

RESUMO

PURPOSE: Maternal hyperandrogenism during pregnancy is associated with adverse gestational outcomes and chronic non-communicable diseases in offspring. However, few studies are reported to demonstrate the association between maternal androgen excess and cardiac health in offspring. This study aimed to explore the relation between androgen exposure in utero and cardiac health of offspring in fetal and adult period. Its underlying mechanism is also illustrated in this research. METHODS: Pregnant mice were injected with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was collected for metabolite and morphological analysis. The hearts from adult offspring were also collected for morphological and qPCR analysis. H9c2 cells were treated with 75 µM androsterone. Immunofluorescence, flow cytometry, qPCR, and western blot were performed to observe cell proliferation and explore the underlying mechanism. RESULTS: Intrauterine exposure to excessive androgen led to thinner ventricular wall, decreased number of cardiomyocytes in fetal offspring and caused cardiac hypertrophy, compromised cardiac function in adult offspring. The analysis of steroid hormone metabolites in fetal heart tissue by ultra performance liquid chromatography and tandem mass spectrometry showed that the content of androgen metabolite androsterone was significantly increased. Mechanistically, H9c2 cells treated with androsterone led to a significant decrease in phosphorylated retinoblastoma protein (pRB) and cell cycle-related protein including cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin D1 (CCND1) in cardiomyocytes. This resulted in cell cycle arrest at G1-S phase, which in turn inhibited cardiomyocyte proliferation. CONCLUSION: Taken together, our results indicate that in utero exposure to DHT, its metabolite androsterone could directly decrease cardiomyocytes proliferation through cell cycle arrest, which has a life-long-lasting effect on cardiac health. Our study highlights the importance of monitoring sex hormones in women during pregnancy and the follow-up of cardiac function in offspring with high risk of intrauterine androgen exposure.


Assuntos
Androgênios , Miócitos Cardíacos , Humanos , Adulto , Gravidez , Feminino , Animais , Camundongos , Androgênios/efeitos adversos , Androsterona , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Proteínas de Ciclo Celular , Di-Hidrotestosterona , Cardiomegalia/induzido quimicamente
3.
J Endocrinol Invest ; 47(8): 2053-2060, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38300501

RESUMO

PURPOSE: While it is common for menstrual cycles to cease within the initial 6 months of treatment, there are instances where some transgender men may not experience this cessation. We analyzed transgender men undergoing gender-affirming hormone therapy (GAHT) with testosterone who experienced breakthrough bleeding in order to identify the factors associated with this condition. METHODS: In this case-control study, 24 transgender men in the case group and 48 in the control group were assessed for clinical, sociodemographic, hormonal, and body composition variables using dual-energy X-ray absorptiometry. All participants had been on GATH for at least 6 months. RESULTS: A few transgender men experienced persistent breakthrough bleeding, which was associated with decreased testosterone levels and free androgen index (FAI) compared with controls (p = 0.002 and p = 0.008, respectively). Among individuals with breakthrough bleeding, 50% had testosterone levels below the lowest tertile calculated for the sample, compared with 18.8% on controls (p = 0.007). After therapy adjustment, testosterone levels increased compared with the values obtained in the initial bleeding episode (p = 0.031). Eight transgender men required the addition of an oral progestogen to achieve amenorrhea, and these individuals had higher BMI than those in whom the adjustment of the parenteral testosterone dose was adequate (p = 0.026). A univariate prevalence ratio analysis revealed a negative association of persistent bleeding with testosterone levels (p = 0.028) and FAI levels (p = 0.019). CONCLUSION: Higher BMI and lower levels of testosterone and FAI were the main factors associated with breakthrough bleeding in transgender men.


Assuntos
Terapia de Reposição Hormonal , Testosterona , Pessoas Transgênero , Humanos , Masculino , Feminino , Adulto , Testosterona/efeitos adversos , Testosterona/administração & dosagem , Testosterona/sangue , Estudos de Casos e Controles , Terapia de Reposição Hormonal/métodos , Terapia de Reposição Hormonal/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Hemorragia Uterina/epidemiologia , Procedimentos de Readequação Sexual/efeitos adversos , Procedimentos de Readequação Sexual/métodos , Transexualidade/tratamento farmacológico , Transexualidade/sangue , Adulto Jovem , Androgênios/efeitos adversos , Androgênios/administração & dosagem , Pessoa de Meia-Idade
4.
Allergy Asthma Proc ; 45(1): 44-49, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38151740

RESUMO

Background: Hereditary angioedema (HAE) is a rare condition marked by swelling episodes in various body parts, including the extremities, upper airway, face, intestinal tract, and genitals. Long-term prophylaxis (LTP), prescribed to control recurring HAE attacks, is integral to its management. Previously, attenuated androgens (AAs) were the only oral LTP options. However, in 2020, berotralstat, an oral plasma kallikrein inhibitor, was approved in the United States. A 2018 survey of adults with HAE type I or type II showed that almost all the patients who used prophylactic HAE medication preferred oral treatment (98%) and felt that it fit their lifestyle better than injectable treatment (96%). Still, guidelines lack consensus on transitioning patients from AAs to alternative oral prophylactic therapy. Objective: This paper aims to share expert insights and patient feedback on transitioning from AAs to berotralstat, an alternative oral prophylactic therapy, from the perspective of clinicians with extensive experience in treating patients with HAE. Methods: A panel of five HAE specialists convened for a virtual half-day roundtable discussion in April 2023. Results: Discussions about transitioning from AAs to berotralstat were prompted by routine consultations, patient inquiries based on independent research, ineffective current treatment, or worsening AA-related adverse effects. For patients who switched from AAs, the physicians reported that the decision was influenced by the alternative therapy's ability to prevent HAE attacks, its safety, and the once-daily administration schedule. All expert panel members identified fewer AA-related adverse effects; better quality of life; and less severe, shorter, and less frequent HAE attacks as clinical or patient goals they hoped to achieve through the treatment switch. Conclusion: The emergence of new, highly specific LTP drugs for HAE calls for the development of comprehensive recommendations and guidelines for transitioning from AAs to alternative oral prophylactic therapy. The expert panel highlighted key factors to consider during the development of such guidelines.


Assuntos
Angioedemas Hereditários , Adulto , Humanos , Estados Unidos , Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/prevenção & controle , Proteína Inibidora do Complemento C1/uso terapêutico , Androgênios/efeitos adversos , Qualidade de Vida
5.
J Electrocardiol ; 84: 95-99, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38579637

RESUMO

BACKGROUND: The control of the cardiovascular system depends on the autonomic nerve system. Chronic anabolic andorogenic steroids (AAS) use causes sympathovagal imbalance and increases sympathetic nerve activity. OBJECTIVE: The reduction in heart rate from the peak exercise rate following the end of the exercise stress test is known as the heart rate recovery index (HRRI). Several methods have been utilized to assess myocardial repolarization, such as QT interval (QT), corrected QT interval (QTc), and T-wave peak-to-end interval (Tp-e interval). Based on a growing number of data a higher Tp-e/QT ratio is linked to malignant ventricular arrhythmias, and an increased Tp-e interval may correlate with the transmural dispersion of repolarization. Our hypothesis is that the use of chronic AAS was decrease HRRI during maximal exercise and increased risk of cardiac arrhythmias and sudden cardiac death. METHODS: This study included 44 male bodybuilders, with an average age of 29.7 ± 8.14 years, divided into AAS abuse [AAS users (n = 21) and AAS nonuser (n = 23)]. RESULTS: The first (p = 0.001) and second minute (p = 0.001) HRRI of the subjects with AAS users were significantly lower than those of the control group. Additionally, HRRI after the third (p = 0.004) and fifth minutes (p = 0.007) of the recovery period were significantly lower in AAS group compared with the control group. Who used AAS had significantly higher QT, QTc, Tp-e, Tp-e/QT, and Tp-e/QTc values than non-users (all p = 0.001). CONCLUSIONS: Chronic AAS use has been shown to cause sympathetic dominance, which may be a pro arrhythmic state.


Assuntos
Eletrocardiografia , Frequência Cardíaca , Humanos , Masculino , Frequência Cardíaca/efeitos dos fármacos , Adulto , Levantamento de Peso , Anabolizantes/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Teste de Esforço , Androgênios/efeitos adversos , Androgênios/farmacologia , Esteróides Androgênicos Anabolizantes
6.
Subst Use Misuse ; 59(1): 10-19, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37724019

RESUMO

Background: With the online proliferation of illegal substances, the Internet offers a wide variety of information on the acquisition and intake of anabolic-androgenic steroids (AAS) and other performance and image enhancing drugs. This study focuses on investigating the characteristics of the online AAS market in Central Asia. OBJECTIVES: The primary objectives of this study were to investigate the accessibility and features of the online market for AAS in Central Asia. To achieve this, we employed a netnographic approach for a systematic exploration of websites advertising and selling AAS. The study aimed to conduct a comprehensive analysis of several key aspects, including the variety of AAS products offered, the quality of health advice provided the level of product availability, the procedures involved in making purchases, and the pricing structures within this market. RESULTS: Twenty-one websites supplying AAS in Central Asia met our inclusion criteria. Using content analysis, data were gathered on AAS offerings, quality of health advice provided, availability, purchase process, and prices. Data were synthesized using descriptive statistics. Results indicate that AAS are easily accessible for purchase without valid medical prescription in the Central Asia online market. Most websites advertised the aesthetic and ergogenic benefits of AAS use without indicating the potential complications and adverse effects. CONCLUSIONS: Public health efforts to mitigate AAS use in Central Asia should consider both the online accessibility of AAS and the lack of accompanying information on potential complications as well as adverse effects associated with their use. Efforts must be intensified to curtail the proliferation of AAS and related misleading information on the Central Asian online market.


Assuntos
Anabolizantes , Androgênios , Humanos , Androgênios/efeitos adversos , Esteróides Androgênicos Anabolizantes , Anabolizantes/efeitos adversos , Congêneres da Testosterona/efeitos adversos , Esteroides/efeitos adversos , Ásia
7.
Neuroendocrinology ; 113(12): 1193-1214, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37356425

RESUMO

Hormones are important regulators of key processes during fetal brain development. Thus, the developing brain is vulnerable to the action of chemicals that can interfere with endocrine signals. Epidemiological studies have pointed toward sexually dimorphic associations between neurodevelopmental outcomes, such as cognitive abilities, in children and prenatal exposure to endocrine-disrupting chemicals (EDCs). This points toward disruption of sex steroid signaling in the development of neural structures underlying cognitive functions, such as the hippocampus, an essential mediator of learning and memory processes. Indeed, during development, the hippocampus is subjected to the organizational effects of estrogens and androgens, which influence hippocampal cell proliferation, differentiation, dendritic growth, and synaptogenesis in the hippocampal fields of Cornu Ammonis and the dentate gyrus. These early organizational effects correlate with a sexual dimorphism in spatial cognition and are subject to exogenous chemical perturbations. This review summarizes the current knowledge about the organizational effects of estrogens and androgens on the developing hippocampus and the evidence for hippocampal-dependent learning and memory perturbations induced by developmental exposure to EDCs. We conclude that, while it is clear that sex hormone signaling plays a significant role during hippocampal development, a complete picture at the molecular and cellular levels would be needed to establish causative links between the endocrine modes of action exerted by EDCs and the adverse outcomes these chemicals can induce at the organism level.


Assuntos
Androgênios , Disruptores Endócrinos , Criança , Humanos , Androgênios/efeitos adversos , Disruptores Endócrinos/toxicidade , Estrogênios/farmacologia , Transdução de Sinais , Encéfalo
8.
Clin J Sport Med ; 33(5): e115-e122, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35533133

RESUMO

OBJECTIVE: It remains unknown whether myonuclei remain elevated post anabolic-androgenic steroid (AAS) usage in humans. Limited data exist on AAS-induced changes in gene expression. DESIGN: Cross-sectional/longitudinal. SETTING: University. PARTICIPANTS: Fifty-six men aged 20 to 42 years. INDEPENDENT VARIABLES: Non-resistance-trained (C) or resistance-trained (RT), RT currently using AAS (RT-AS), of which if AAS usage ceased for ≥18 weeks resampled as Returning Participants (RP) or RT previously using AAS (PREV). MAIN OUTCOME MEASURES: Myonuclei per fiber and cross-sectional area (CSA) of trapezius muscle fibers. RESULTS: There were no significant differences between C (n = 5), RT (n = 15), RT-AS (n = 17), and PREV (n = 6) for myonuclei per fiber. Three of 5 returning participants (RP1-3) were biopsied twice. Before visit 1, RP1 ceased AAS usage 34 weeks before, RP2 and RP3 ceased AAS usage ≤2 weeks before, and all had 28 weeks between visits. Fiber CSA decreased for RP1 and RP2 between visits (7566 vs 6629 µm 2 ; 7854 vs 5677 µm 2 ) while myonuclei per fiber remained similar (3.5 vs 3.4; 2.5 vs 2.6). Respectively, these values increased for RP3 between visits (7167 vs 7889 µm 2 ; 2.6 vs 3.3). CONCLUSIONS: This cohort of past AAS users did not have elevated myonuclei per fiber values, unlike previous research, but reported AAS usage was much lower. Training and AAS usage history also varied widely among participants. Comparable myonuclei per fiber numbers despite decrements in fiber CSA postexposure adheres with the muscle memory mechanism, but there is variation in usage relative to sampling date and low numbers of returning participants.


Assuntos
Anabolizantes , Esteróides Androgênicos Anabolizantes , Masculino , Humanos , Androgênios/efeitos adversos , Anabolizantes/efeitos adversos , Músculos , Expressão Gênica
9.
Phytother Res ; 37(9): 4018-4041, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37165686

RESUMO

Polycystic ovary syndrome (PCOS) is most common in women of reproductive age, giving rise to androgen excess and anovulation, leading to infertility and non-reproductive complications. We explored the ameliorating effect of naringenin in PCOS using the Sprague Dawley (SD) rat model and human granulosa cells. Letrozole-induced PCOS rats were given either naringenin (50 mg/kg/day) alone or in combination with metformin (300 mg/kg/day), followed by the estrous cycle, hormonal analysis, and glucose sensitivity test. To evaluate the effect of naringenin on granulosa cell (hGC) steroidogenesis, we treated cells with naringenin (2.5 µM) alone or in combination with metformin (1 mM) in the presence of forskolin (10 µM). To determine the steroidogenesis of CYP-17A1, -19A1, and 3ßHSD2, the protein expression levels were examined. Treatment with naringenin in the PCOS animal groups increased ovulation potential and decreased cystic follicles and levels of androgens. The expression levels of CYP-17A1, -19A1, and 3ßHSD2, were seen restored in the ovary of PCOS SD rats' model and in the human ovarian cells in response to the naringenin. We found an increased expression level of phosphorylated-AKT in the ovary and hGCs by naringenin. Naringenin improves ovulation and suppress androgens and cystic follicles, involving AKT activation.


Assuntos
Cisto Folicular , Metformina , Síndrome do Ovário Policístico , Humanos , Feminino , Ratos , Animais , Androgênios/efeitos adversos , Ratos Sprague-Dawley , Letrozol/efeitos adversos , Proteínas Proto-Oncogênicas c-akt , Cisto Folicular/complicações , Modelos Animais de Doenças
10.
Harm Reduct J ; 20(1): 56, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37098574

RESUMO

BACKGROUND: The masculinizing effects from anabolic-androgenic steroid (AAS) appear to be different between men and women, leading to calls for more gender-specific information regarding women and AAS use. This study sought to gather perspectives from both men and women on the unique challenges surrounding women's use of AAS, irrespective of their personal use. Secondly, the study interrogated how women's AAS practices differ from those of men specifically. METHODS: The data presented in this paper come from a subsample of participants who participated in a larger study investigating women and performance and image enhancing drug (PIED) use in Australia. Participants were included in the current analysis if they were: (i) males or females who competed with or coached female strength athletes using AAS and (ii) female and male strength athletes who used AAS. The final sample comprised 21 participants of which there was a proportion of males (n = 7) and females (n = 7) using AAS. RESULTS: Women's choices in AAS selection were predominantly around oral compounds (e.g. Oxandrolone) as well as other PIEDs (e.g. Clenbuterol). Some women report the use of injectable AAS represents a change in the profile of the typical female user as it reportedly comes alongside drastic physical and psychological changes. CONCLUSIONS: The unique challenges facing women who use AAS are largely isolation and stigma, with little evidence-based practice or education being available to them online or through peer-groups. Future work may consider piloting harm reduction strategies that may be co-designed with this group.


Assuntos
Anabolizantes , Substâncias para Melhoria do Desempenho , Humanos , Masculino , Feminino , Androgênios/efeitos adversos , Esteroides , Esteróides Androgênicos Anabolizantes , Anabolizantes/efeitos adversos , Congêneres da Testosterona/efeitos adversos , Substâncias para Melhoria do Desempenho/efeitos adversos
11.
Mod Pathol ; 34(1): 85-94, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32939016

RESUMO

Testosterone therapy (TT) is administered to enhance masculinization in transgender individuals. The long-term effect of exogenous testosterone on breast tissues remains unclear. Our study evaluated the modulation of breast morphology by TT in transgender individuals with special attention to duration of TT. We reviewed 447 breast surgical specimens from gender affirming chest-contouring surgery, and compared histopathological findings including degree of lobular atrophy, and atypical and non-atypical proliferations between subjects who did (n = 367) and did not (n = 79) receive TT. TT for one patient was unknown. TT for >12 months was associated with seven histopathological features. Longer duration of TT was significantly associated with higher degrees of lobular atrophy (p < 0.001). This relationship remained significant after accounting for age at surgery, ethnicity, body mass index, and presurgical oophorectomy (adjusted p < 0.001). Four types of lesions were more likely to be absent in breast tissues exposed to longer durations of TT: cysts (median = 16.2 months; p < 0.01; adjusted p = 0.01), fibroadenoma (median = 14.8 months; p = 0.02; adjusted p = 0.07), pseudoangiomatous stromal hyperplasia (median = 17.0 months; p < 0.001; adjusted p < 0.001), and papillomas (median = 14.7 months; p = 0.04; adjusted p = 0.20). Columnar cell change and mild inflammation were also less likely to occur in subjects receiving TT (p < 0.05), but were not linked to the duration of TT. Atypia and ductal carcinoma in situ were detected in 11 subjects (2.5%) all of whom received TT ranging from 10.1 to 64.1 months. The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.


Assuntos
Androgênios/efeitos adversos , Doenças Mamárias/induzido quimicamente , Mama/efeitos dos fármacos , Testosterona/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Cirurgia de Readequação Sexual , Pessoas Transgênero
12.
Gynecol Oncol ; 161(2): 342-346, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33663874
13.
Scand J Med Sci Sports ; 31(2): 427-438, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33038020

RESUMO

An estimated 4-6% of fitness center visitors uses anabolic-androgenic steroids (AAS). Reliable data about adverse reactions of AAS are scarce. The HAARLEM study aimed to provide insight into the positive and negative effects of AAS use. One hundred men (≥18 years) who intended to start an AAS cycle on short notice were included for follow-up. Clinic visits took place before (T0 ), at the end (T1 ), and three months after the end of the AAS cycle (T2 ), and one year after the start of the cycle (T3 ), and comprised a medical history, physical examination, laboratory analysis, and psychological questionnaires. During the follow-up period, four subjects reported a serious adverse event, that is, congestive heart failure, acute pancreatitis, suicidal ideation, and exacerbation of ulcerative colitis. All subjects reported positive side effects during AAS use, mainly increased strength (100%), and every subject reported at least one negative health effect. Most common were fluid retention (56%) and agitation (36%) during the cycle, and decreased libido (58%) after the cycle. Acne and gynecomastia were observed in 28% and 19%. Mean alanine transaminase (ALT) and creatinine increased 18.7 U/l and 4.7 µmol/L, respectively. AAS dose and cycle duration were not associated with the type and severity of side effects. After one-year follow-up (T3 ), the prevalence of observed effects had returned to baseline. There was no significant change in total scores of questionnaires investigating wellbeing, quality of life, and depression. In conclusion, all subjects experienced positive effects during AAS use. Four subjects experienced a serious adverse event. Other side effects were mostly anticipated, mild, and transient.


Assuntos
Anabolizantes/farmacologia , Androgênios/farmacologia , Acne Vulgar/induzido quimicamente , Adulto , Idoso , Acatisia Induzida por Medicamentos/etiologia , Anabolizantes/efeitos adversos , Androgênios/efeitos adversos , Biomarcadores/sangue , Colite Ulcerativa/induzido quimicamente , Depressão/induzido quimicamente , Progressão da Doença , Ginecomastia/induzido quimicamente , Insuficiência Cardíaca/induzido quimicamente , Humanos , Libido/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Países Baixos , Pancreatite/induzido quimicamente , Estudos Prospectivos , Ideação Suicida , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
14.
Andrologia ; 53(7): e14062, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33887077

RESUMO

The anabolic-androgenic steroids (AAS) are clinically used as an androgen replacement, in hypogonadism treatment, to induce puberty, and also in the treatment of chronic degenerative diseases. The AAS use out of clinical context is becoming massively, being used merely for aesthetic reasons. AAS abuse may cause severe disarrangement on the HPG axis and generate a significant decrease in testosterone synthesis and secretion by the testes. This review aims to evaluate whether the hypogonadism induced by AAS abuse is reversible and under what circumstances the reversibility is possible. For this, PRISMA guidelines and several databases are used between July and September 2020. Altogether, this systematic review identified and analysed 179 cases of AAS users. Of these, 168 cases had the hypogonadism clearly diagnosed and proven to be linked exclusively to AAS abuse. However, between these 168 cases, only 38 cases presented fully known outcomes and among these, merely in 4, the hypogonadism was completely reversible (2 based on drug therapy) with HPG axis recovery. In conclusion, this review presents evidences that AAS-induced hypogonadism is a seriously underestimated problem, and in the majority of cases, full recovery is very difficult to succeed.


Assuntos
Anabolizantes , Hipogonadismo , Transtornos Relacionados ao Uso de Substâncias , Anabolizantes/efeitos adversos , Androgênios/efeitos adversos , Humanos , Hipogonadismo/induzido quimicamente , Masculino , Esteroides , Transtornos Relacionados ao Uso de Substâncias/complicações , Congêneres da Testosterona/efeitos adversos
15.
Gan To Kagaku Ryoho ; 48(1): 77-79, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33468728

RESUMO

Gender identity disorder is defined as a condition in which physical and mental sexuality do not match. A female-to-male (FTM)has the mental sexuality of males and the physical sexuality of females. FTM transsexuals generally receive androgen therapy, mastectomy, and sex reassignment surgery to live as their desired sex. The risk of breast cancer in FTM transsexual patients remains unclear. We report a case of breast cancer in an FTM transsexual. A 44-year-old man who underwent mastectomy and sex reassignment surgery and received androgen as hormone therapy developed breast cancer. At first glance, mastectomy and sex reassignment surgery may reduce the risk of breast cancer by suppressing estrogen. However, there are reports of breast cancer in FTM transsexuals. It is important to provide sufficient information that patients may develop breast cancer from residual breast tissue and that they should therefore start hormone therapy even if they have undergone mastectomy and sex reassignment surgery. In order to decide whether to restart androgen therapy after breast surgery, it is necessary to consider not only the risk of recurrence of breast cancer but also their gender identity.


Assuntos
Neoplasias da Mama , Disforia de Gênero , Adulto , Androgênios/efeitos adversos , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Identidade de Gênero , Humanos , Masculino , Mastectomia , Recidiva Local de Neoplasia
16.
Br J Haematol ; 189(5): 976-981, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32128787

RESUMO

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.


Assuntos
Androgênios/uso terapêutico , Transtornos da Insuficiência da Medula Óssea/tratamento farmacológico , Adolescente , Adulto , Androgênios/efeitos adversos , Transtornos da Insuficiência da Medula Óssea/sangue , Transtornos da Insuficiência da Medula Óssea/genética , Transtornos da Insuficiência da Medula Óssea/terapia , Canadá/epidemiologia , Linhagem da Célula , Criança , Pré-Escolar , Terapia Combinada , Danazol/efeitos adversos , Danazol/uso terapêutico , Progressão da Doença , Substituição de Medicamentos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Oximetolona/efeitos adversos , Oximetolona/uso terapêutico , Pancitopenia/tratamento farmacológico , Pancitopenia/etiologia , Sistema de Registros , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Resultado do Tratamento , Virilismo/induzido quimicamente
17.
Biol Reprod ; 102(6): 1225-1233, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32068232

RESUMO

Androgens are essential for penile development and for maintaining penile structural and functional integrity. Loss of androgen levels or function results in a decrease in smooth muscle content, accumulation of adipocytes in the corpora cavernosa, and inhibition of erectile function. Our previous studies with a mouse model (KiLHRD582G) of constitutive luteinizing hormone receptor activity also showed structural abnormalities in the penis caused by a decrease in smooth muscle content, accumulation of chondrocytes, and sexual dysfunction. As KiLHRD582G mice exhibit very high levels of testosterone at all postnatal ages, the goal of this study was to determine if the elevated androgen levels were responsible for the morphological changes in the penis. Implantation of testosterone capsules in wild-type mice at neonatal (2 weeks) and postpubertal (5 weeks) ages resulted in the accumulation of chondrocytes in the corpora cavernosa of the adult animals. Mice implanted with testosterone capsules at 2 weeks of age exhibited a 4-fold increase in serum testosterone with a 1.5-fold loss of smooth muscle at 24 weeks of age. Collagen content was unchanged. Only 57% of testosterone implanted mice were fertile at 24 weeks of age. Mice implanted with testosterone capsules at 5 weeks of age showed no decrease in smooth muscle content at 24 weeks, although serum testosterone levels were elevated 5-fold. Implantation with dihydrotestosterone also resulted in chondrocyte accumulation and a 2-fold loss in smooth muscle content. Together, these studies demonstrate that supraphysiological levels of androgens cause structural changes in the penile corpora cavernosa and impair fertility.


Assuntos
Músculo Liso/efeitos dos fármacos , Músculo Liso/crescimento & desenvolvimento , Pênis/efeitos dos fármacos , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Envelhecimento , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Animais , Animais Recém-Nascidos , Condrócitos/efeitos dos fármacos , Condrócitos/fisiologia , Implantes de Medicamento , Fertilidade , Masculino , Camundongos , Maturidade Sexual
18.
Psychooncology ; 29(8): 1338-1346, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32539186

RESUMO

OBJECTIVE: Androgen deprivation therapy (ADT) enhances survival of advanced prostate cancer patients and is therefore used as a concomitant therapy. However, ADT has been reported to cause negative side effects on cognition and emotional processing. So far, research referred to the effects of short-term treatment. Since the brain may adapt to androgen deprivation, we were especially interested in the long-term effects of ADT on cognitive and socioeconomic decision making. METHODS: Participants underwent a battery of tests that have been associated with testosterone. We compared the results of three matched test groups: (1) prostate cancer patients with ADT up to 20 years, (2) prostate cancer controls without treatment and (3) healthy controls. We further measured the morning testosterone content in participants' saliva. RESULTS: Testosterone concentration was positively associated with visuospatial performance across and within the test groups. Patients with long-term ADT showed an overall decline in cognitive performance. Compared with untreated patients, ADT was also associated with a reduced intergroup bias during socioeconomic decision making, which was in line with previous observations in young men suggesting that testosterone may promote ingroup favoritism. Finally, depression scores were increased in ADT, while quality of life was negatively associated with the treatment. CONCLUSION: These findings conform to results made after short-term treatment. ADT promotes negative side effects on cognitive function. We also show for the first time that testosterone deprivation may affect socioeconomic decision making. Nevertheless, it should be emphasized that these effects cannot outweigh the previously described advantages of ADT in the treatment of prostate cancer.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Androgênios/efeitos adversos , Transtornos Cognitivos/induzido quimicamente , Neoplasias da Próstata/psicologia , Adaptação Fisiológica , Idoso , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Cognição/efeitos dos fármacos , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Fatores Socioeconômicos
19.
Curr Opin Urol ; 30(3): 309-316, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32205812

RESUMO

PURPOSE OF REVIEW: Recently in October 2019 a Global Consensus Position on the use of Testosterone Therapy for Women was published. The use of testosterone and other agents for female sexual dysfunction (FSD) is an important topic for the urologist focusing on sexual health. This review describes the known causes for FSD, and discusses the role of androgens in this disorder, the evidence for using testosterone treatment, and other current and emerging therapies. RECENT FINDINGS: A recent meta-analysis, published in The Lancet Diabetes & Endocrinology evaluated a total of 36 randomized control trials spanning 1990-2018 and includes a total of 8480 patients. The primary findings were that testosterone therapy (TTh) increased sexual function including satisfactory sexual event frequency, sexual desire, pleasure, arousal, orgasm, responsiveness, and self-image when compared with either a placebo or drug-control (e.g., estrogen ±â€Šprogestogen). In addition, TTh reduced sexual concerns and distress in postmenopausal women. Side effects included an increase in weight, acne, and hair growth, but there was no increase in serious adverse events. Importantly, TTh duration was greater than 12 weeks in all randomized control trials included in this meta-analysis. SUMMARY: TTh is effective to treat FSD in postmenopausal women. More data is required to evaluate the long-term safety data on the effects of TTh on cardiovascular health, breast health, cognitive function, and the musculoskeletal system in women.


Assuntos
Androgênios , Terapia de Reposição Hormonal/métodos , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Testosterona/uso terapêutico , Androgênios/efeitos adversos , Androgênios/uso terapêutico , Nível de Alerta/efeitos dos fármacos , Feminino , Humanos , Libido/efeitos dos fármacos , Orgasmo/efeitos dos fármacos , Testosterona/efeitos adversos
20.
J Pediatr Hematol Oncol ; 42(5): e352-e354, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32079984

RESUMO

The incidence of pediatric venous thromboembolism (VTE) has been increasing in the past few decades and can be associated with significant mortality and morbidity. There are known risk factors associated with VTE, including estrogen therapy. However, the relationship between testosterone and VTE remains unclear. Here, we present a 17-year-old female-to-male transgender patient without a history of inherited thrombophilia, who developed pulmonary embolism while receiving testosterone injections for gender dysphoria. Despite the limited data on testosterone and the risk of VTE, health care providers should counsel patients and family about the possible increased risk of VTE when starting testosterone.


Assuntos
Androgênios/efeitos adversos , Testosterona/efeitos adversos , Tromboembolia Venosa/patologia , Adolescente , Feminino , Humanos , Masculino , Prognóstico , Pessoas Transgênero , Tromboembolia Venosa/induzido quimicamente
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