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Los esteroides anabólicos y los moduladores selectivos de receptores de andrógenos (SARMs) se han utilizado durante décadas con el fin de incrementar la masa muscular y mejorar el rendimiento atlético, por lo que su uso sin supervisión médica y sin autorización regulatoria va en aumento, y esto plantea serias preocupaciones de salud pública. Este reporte de caso presenta a un paciente masculino que desarrolló hepatotoxicidad con patrón colestásico secundario al uso de Ligandrol, un SARM. Aunque los SARMs se promocionan como alternativas más seguras a los esteroides anabólicos, este caso destaca los riesgos potenciales asociados con su uso, específicamente, la lesión hepática. Diversas agencias regulatorias han emitido alertas sobre la asociación de los SARMs con cáncer, osteoporosis e injuria hepática. El Ligandrol, también conocido como LGD-4033, es popular entre atletas y fisicoculturistas, pero no está aprobado para consumo humano y es una sustancia prohibida en el deporte. En Colombia, se han publicado casos en los que se reportan efectos adversos de esteroides anabólicos, pero no se encuentran reportes que asocien el Ligandrol con una falla hepática. Este caso es, por tanto, relevante para la literatura médica nacional. El objetivo de este reporte es sensibilizar a los médicos sobre el riesgo de compromiso hepático con Ligandrol y contribuir a la creciente evidencia sobre los peligros de los SARMs. Es crucial aumentar la conciencia sobre estos riesgos, tanto entre profesionales de la salud como en el público general, dada la falta de regulación y estudios a largo plazo sobre la seguridad de estos compuestos.

Anabolic steroids and selective androgen receptor modulators (SARMs) have been used for decades to increase muscle mass and enhance athletic performance, and their use without medical supervision and regulatory approval is increasing, raising serious public health concerns. This case report presents a male patient who developed cholestatic hepatotoxicity secondary to the use of Ligandrol, a SARM. Although SARMs are promoted as safer alternatives to anabolic steroids, this case highlights the potential risks associated with their use, specifically, liver injury. Several regulatory agencies have issued warnings about the association of SARMs with cancer, osteoporosis, and liver injury. Ligandrol, also known as LGD-4033, is popular among athletes and bodybuilders, but it is not ap-proved for human consumption and is a banned substance in sport. In Colombia, there have been published cases reporting adverse effects of anabolic steroids, but no reports associating Ligandrol with liver failure. This case is therefore relevant to the national medical literature. The aim of this report is to raise awareness among physicians about the risk of liver compromise with Ligandrol and to contribute to the growing evidence on the dangers of SARMs. It is crucial to raise awareness of these risks, both among health professionals and the general public, given the lack of regulation and long-term studies on the safety of these compounds.

Os esteróides anabolizantes e os moduladores seletivos dos receptores androgênicos (SARMs) têm sido utilizados há décadas para aumentar a massa muscular e melhorar o desempenho atlético, pelo que a sua utilização sem supervisão médica e sem autorização regulamentar está a aumentar, o que levanta sérias preocupações de saúde pública. Este relato de caso apresenta um paciente do sexo masculino que desenvolveu hepatotoxi-cidade com padrão colestático secundário ao uso de Ligandrol, um SARM. Embora os SARMs sejam promovidos como alternativas mais seguras aos esteróides anabolizantes, este caso destaca os riscos potenciais associados ao seu uso, especificamente, lesões hepáticas. Várias agências reguladoras emitiram alertas sobre a associação de SARMs com cancro, osteoporose e lesões hepáticas. O ligandrol, também conhecido como LGD-4033, é popular entre atletas e fisiculturistas, mas não está aprovado para consu-mo humano e é uma substância proibida nos esportes. Na Colômbia, foram publicados casos em que são relatados efeitos adversos de esteróides anabolizantes, mas não há relatos que associem Ligandrol à insuficiência hepática. Este caso é, portanto, relevante para a literatura médica nacional. O objetivo deste relatório é conscientizar os médicos sobre o risco de envolvimento hepático com o Ligandrol e contribuir para a crescente evidência sobre os perigos dos SARMs . É crucial aumentar a sensibilização para estes riscos, tanto entre os profissionais de saúde como entre o público em geral, dada a falta de regulamentação e de estudos de longo prazo sobre a segurança destes compostos.

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BACKGROUND@#Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.@*METHODS@#Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR.@*RESULTS@#Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter -42 bp to -28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial-mesenchymal transition in tumor progression.@*CONCLUSIONS@#This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

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El síndrome de ovario poliquístico (SOP) es un trastorno frecuente en mujeres en edad fértil que se caracteriza por el exceso de andrógenos, oligo/anovulación y/o la presencia de morfología de ovarios poliquísticos. La patogénesis del SOP no se ha dilucidado y se ha propuesto que la microbiota intestinal puede desempeñar un rol clave en este síndrome, debido al impacto de la microbiota en el metabolismo de los lípidos, la glucosa y los esteroides. El principal objetivo de esta revisión es dilucidar la función de la microbiota intestinal y sus metabolitos derivados en la patogénesis del síndrome, así como también, aportar con nuevas ideas para su tratamiento.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in childbearing age women characterized by androgen excess, oligo/anovulation, and polycystic ovarian morphology. The specific pathogenesis of PCOS has not been elucidated and it has been proposed that gut microbiota may play a key role in PCOS, due to its role on lipid, glucose, and steroid metabolism. The main objective of this review is to elucidate the function of gut microbiota and derived metabolites in the pathogenesis and provide new ideas for treatment.

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Abstract Objective This study aimed to translate and validate the Estro-Androgenic-Symptom Questionnaire in Women (EASQ-W) into Brazilian Portuguese language, as we hypothesized that this tool would be consistent for addressing the specific context of hormonal symptoms in menopause. Methods In a cross-sectional study, a total of 119 women with Genitourinary Syndrome of Menopause (GSM) and 119 climacteric women without GSM were included. The EASQ-W was translated, and its psychometric properties were rigorously examined. Participants completed questionnaires covering sociodemographic details, the EASQ-W, and the Menopause Rating Scale (MRS). A subgroup of 173 women was re-invited after 4 weeks for test-retest analysis of the EASQ-W. Additionally, the responsiveness of the questionnaire was evaluated in 30 women who underwent oral hormonal treatment. Results The internal consistency of the EASQ-W was found to be satisfactory in both GSM and control groups (Cronbach's alpha ≥ 0.70). Notably, a floor effect was observed in both groups; however, a ceiling effect was only evident in the sexual domain of the GSM group. Construct validity was established by comparing the EASQ-W with the MRS, yielding statistically significant correlations (0.33831-0.64580, p < 0.001). The test-retest reliability over a 4-week period was demonstrated to be satisfactory in both the GSM and control groups (ICC 0.787-0.977). Furthermore, the EASQ-W exhibited appropriate responsiveness to oral hormonal treatment (p < 0.001). Conclusion This study successfully translated and validated the Estro-Androgenic-Symptom Questionnaire in Women (EASQ-W) into Brazilian Portuguese, with satisfactory internal consistency, test-retest reliability, and construct validity.

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Objective: The objective of the study is to determine through a historical cohort, the characteristics, treatment patterns, and outcomes of a population with hormone-sensitive metastatic cancer at a referral center in Bogota. Method: This was a historical cohort observational study. All patients with metastatic hormone-sensitive prostate cancer from 2018 to May 2022 who received androgen deprivation therapy with or without treatment intensification were included through convenience sampling. The distribution of the epidemiological variables of interest, treatment of choice, and survival analysis was performed, as well as the distribution by years of the therapies of choice. Statistical significance was set at p < 0.05. Results: We included 125 hormone-sensitive metastatic prostate cancer (mHSPC) patients with a median age of 73.5 years (confidence interval: 71.48-75.31), a median PSA of 209 ng/mL, and 90% of patients with synchronous mHSPC. The distribution of high-volume mHSPC was 92% and M1b was 91%. The distribution of castration methods over time revealed that 21% of the patients underwent surgical castration and 79% received pharmacological castration. Since 2018, 40% of patients received androgen deprivation therapies (ADT) exclusively, 30% received treatment with taxanes, and 30% received androgen receptor axis-directed therapies. Trends in treatment distribution from 2018 to 2022 indicated a decline in exclusive ADT use from 41% in 2019 to 16% in 2022. 9% of the patients abandoned treatment. Conclusion: A description of the population of a national reference center for the treatment of hormone-sensitive prostate cancer with demographic characteristics according to global trends was provided

Objetivo: Caracterizar a la población y el tratamiento recibido de pacientes con cáncer metastásico hormonosensible (mHSPC) en un centro de referencia en Bogotá. Método: Cohorte histórica, observacional. Se incluyeron todos los pacientes con mHSPC que recibieron terapia de supresión androgénica, con o sin intensificación, desde el 2018 hasta mayo del 2022. Muestreo por conveniencia. Se describe la distribución de las variables epidemiológicas de interés, el tratamiento de elección, se realiza un análisis de supervivencia, así como de distribución por años de las terapias de elección. Se consideró significación estadística con un grado de significación (p) < 0,05. Resultados: Se incluyeron 125 pacientes con mHSPC, con una mediana de edad de 73,5 años (IC: 71,48-75,31), con una mediana de antigeno porstático específico (PSA) de 209 ng/mL, el 90% de los pacientes con mHSPC sincrónicos. La distribución de mHSPC de alto volumen fue del 92%, M1b 91%. La distribución global en el tiempo de castración quirúrgica fue del 21% y farmacológica del 79%. El 40% de los pacientes recibieron desde el 2018 terapia de deprivación de andrógenos (ADT) exclusiva, tratamiento con taxanos el 30% y terapias dirigidas al eje del receptor de andrógenos el 30% de los pacientes. Se describen las tendencias de distribución por años desde 2018 hasta 2022, pasando de ADT exclusiva en un 41% para el 2019 a un 16% para el 2022. El 9% de los pacientes abandonaron el tratamiento. Conclusión: Se realiza una descripción de la población de un centro de referencia nacional en el tratamiento de cáncer de próstata hormonosensible con características demográficas acorde a las tendencias globales

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We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

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Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.

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Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of childbearing age, which seriously affects women's reproductive health. In recent years, more and more studies have found that serum anti-Müllerian hormone (AMH) has certain significance in the diagnosis and treatment evaluation of PCOS. In addition, with the improvement of detection methods, more attention has been paid to the significance of female androgens and AMH in the evaluation of PCOS. This article reviews the recent research progress of serum AMH and androgens in the evaluation of PCOS.

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Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

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Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

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El síndrome de insensibilidad a los andrógenos (SIA), conocido también como un síndrome de feminización testicular, incluye un grupo variado de mutaciones que se relacionan con la disfunción de los receptores de andrógenos y la resistencia de los tejidos diana a la acción de las hormonas masculinas. Es causado por alteraciones genéticas localizadas en la secuencia de codificación de los receptores de andrógenos ligada al cromosoma Xq11 - 12, el gen que codifica al receptor de los andrógenos, de un individuo genéticamente masculino (46 XY). Las formas clínicas moderada, parcial o completa, dependen del grado de insensibilidad androgénica. Los avances en las causas genéticas han permitido que estas condiciones congénitas de desarrollo del sexo cromosómico, gonadal o anatómico atípico sean denominados trastornos de diferenciación sexual

Androgen insensitivity syndrome (AIS), also known as testicular feminization syndrome, includes a diverse group of mutations that are related to androgen receptor dysfunction and resistance of target tissues to the action of hormones masculine. It is caused by localized genetic alterations in the androgen receptor coding sequence linked to chromosome Xq11-12, the gene encoding the androgen receptor, of a genetically male (46 XY) individual. Moderate, partial, or complete clinical forms depend on the degree of androgen insensitivity. Advances in genetic causes have allowed these congenital conditions of atypical chromosomal, gonadal, or anatomical sex development to be called disorders of sexual differentiation

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ABSTRACT Adrenal steroid biosynthesis and its related pathology are constant evolving disciplines. In this paper, we review classic and current concepts of adrenal steroidogenesis, plus control mechanisms of steroid pathways, distribution of unique enzymes and cofactors, and major steroid families. We highlight the presence of a "mineralocorticoid (MC) pathway of zona fasciculata (ZF)", where most circulating corticosterone and deoxycorticosterone (DOC) originate together with 18OHDOC, under ACTH control, a claim based on functional studies in normal subjects and in patients with 11β-, and 17α-hydroxylase deficiencies. We emphasize key differences between CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) and the onset of a hybrid enzyme - CYP11B1/CYP11B2 -, responsible for aldosterone formation in ZF under ACTH control, in "type I familial hyperaldosteronism" (dexamethasone suppressible). In "apparent MC excess syndrome", peripheral conversion of cortisol to cortisone is impaired by lack of 11β-hydroxysteroid dehydrogenase type 2, permitting free cortisol access to MC receptors resulting in severe hypertension. We discuss two novel conditions involving the synthesis of adrenal androgens: the "backdoor pathway", through which dihydrotestosterone is formed directly from androsterone, being relevant for the fetoplacental setting and sexual differentiation of male fetuses, and the rediscovery of C19 11-oxygenated steroids (11-hydroxyandrostenedione and 11-ketotestosterone), active androgens and important markers of virilization in 21-hydroxylase deficiency and polycystic ovaries syndrome. Finally, we underline two enzyme cofactor deficiencies: cytochrome P450 oxidoreductase which partially affects 21- and 17α-hydroxylation, producing a combined clinical/hormonal picture and causing typical skeletal malformations (Antley-Bixler syndrome), and PAPSS2, coupled to SULT2A1, that promotes sulfation of DHEA to DHEAS, preventing active androgens to accumulate. Its deficiency results in reduced DHEAS and elevated DHEA and androgens with virilization. Future and necessary studies will shed light on remaining issues and questions on adrenal steroidogenesis.

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BACKGROUND@#Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP).@*METHODS@#Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses.@*RESULTS@#A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR] = 1.07, 95% confidence intervals [95% CI] = 0.60-1.90, P = 0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction = 0.0247, HR = 0.37, 95% CI = 0.14-1.00, P = 0.0497).@*CONCLUSION@#Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

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OBJECTIVE@#To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA).@*METHODS@#A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol.@*RESULTS@#The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case.@*CONCLUSION@#The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

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OBJECTIVE@#Androgen deficiency is common in aging males and may have unfavourable health consequences. Large-scale studies suggested low testosterone level might increse mortality and morbidity in ageing males. However, young men with low testosterone level might be neglected. Recent studies reported young men with infertility may have reduced testosterone level. To investigate the incidence of androgen deficiency in males with infertility and possible factors affecting the low testosterone level.@*METHODS@#Between January 2011 and December 2012, 407 men with infertility caused by varicocele (VC), obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) in our center were included. The number of men in each group of OA, NOA and VC was 141, 97 and 169, respectively. All the eligible patients underwent a serum testosterone assessment by a single morning blood draw (between 8:00 to noon) to test for concentration of the total testosterone. All serum samples were determined by radioimmunoassay in our andrology laboratory. Androgen deficiency was defined as having a total testosterone level less than 300 ng/dL.@*RESULTS@#The mean age was (30.4±5.8) years. The mean testosterone level was (4.18±1.64) ng/dL (range 0.30 to 11.32 ng/dL). The overall incidence of androgen deficiency was 26.5% (108/407). The incidences of androgen deficiency in NOA, OA and VC groups were 40.2% (39/97), 19.1% (27/141) and 24.9% (42/169), respectively, which were significantly higher in the NOA than in the VC and OA groups (P < 0.001). The incidences had no difference between the VC and OA groups (P=0.229). Univariate analysis revealed the cause of infertility, FSH and the mean testis volume as possible affecting factors for androgen deficiency. However, on multivariate analysis the only cause of infertility was an independent predictor. The incidence of androgen deficiency was the highest in the NOA group [OR 0.492 (95% confidence interval 0.288-0.840)].@*CONCLUSION@#NOA and varicocele might be risk factors of androgen deficiency. Young men with NOA may have a higher possibility of low testosterone level. Testosterone level should be followed up after NOA and varicocele treatment. Androgen deficiency should be assessed in males with infertility in clinical practice.

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INTRODUCCIÓN Y OBJETIVO: El rol de la testosterona exógena en la función sexual femenina ha sido estudiado durante muchos años, con resultados contradictorios. En el último tiempo se ha promovido el uso de pellets de testosterona como una solución para mejorar la libido femenina, la cognición, la fuerza muscular y los sistemas cardiovascular y óseo, e incluso evitar el envejecimiento. Por ello, revisamos las publicaciones para tratar de responder si esto es una moda o el tratamiento más innovador del último tiempo. MÉTODO: Se analizaron las bases de datos PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct y ResearchGate. RESULTADOS: De acuerdo con la evidencia, la mejor testosterona disponible es la transdérmica y debe ser usada solo en el trastorno del deseo sexual hipoactivo (TDSH). Los trabajos que evalúan los pellets de testosterona tienen sesgos metodológicos importantes. Si bien son útiles para mejorar la función sexual femenina, producen concentraciones plasmáticas suprafisiológicas de testosterona, por lo que no se puede establecer su seguridad a largo plazo. Tampoco hay datos suficientes que avalen su uso para mejorar el rendimiento cognitivo y el bienestar general, en el tratamiento de enfermedades cardiovasculares o en la prevención de enfermedad ósea. CONCLUSIONES: La testosterona solo se recomienda en el tratamiento del TDSH por vía transdérmica. No recomendamos el uso de pellets de testosterona para el tratamiento de la disfunción sexual ni como hormona antienvejecimiento, ya que no hay estudios consistentes sobre su seguridad, eficacia y efectos adversos a largo plazo.

INTRODUCTION AND OBJECTIVE: The role of exogenous testosterone in female sexual function has been studied for many years with contradictory results. In recent times, the use of testosterone pellets has been promoted as a solution to improve female libido, cognition, muscle strength, cardiovascular system, bone and even prevent aging. Therefore, we will review the publications in order to answer whether this is a fad or the most innovative treatment of recent times. METHOD: The databases PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct and ResearchGate were analyzed. RESULTS: So far, the evidence best testosterone available is transdermal testosterone and that it should be used only in hypoactive sexual desire disorder (HSDD). Papers evaluating testosterone pellets have significant methodological biases. While they are useful in improving female sexual function, they produce supra-physiological plasma levels of testosterone, so their long-term safety cannot be established. There is also insufficient data to support their use in improving cognitive performance and general well-being, treatment of cardiovascular disease or prevention of bone disease. CONCLUSIONS: Testosterone is only recommended for the tratment of HSDD via the transdermal route. We do not recommended the use of testosterone pellets for the treatment of sexual dysfunction or as an anti aging hormone, as there are no consistent studies on its safety, efficacy, and long-term adverse effects.

ABSTRACT

Abstract To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.

Resumo Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.