Effects of Low-to-Moderate Doses of Anabolic Steroids on Lipid Profile and Muscle Hypertrophy in Resistance Training Practitioners: A Systematic Review with Meta-Analysis

Abstract Background: The use of androgenic anabolic steroids (AAS) is prevalent among young bodybuilders, motivated by aesthetic results. Although the medical community condemns this practice for its potential deleterious effect, we must recognize the need for more scientific research on the likelihood and magnitude of the adverse events. Objective: To evaluate whether high-quality, scientific evidence supports that AAS negatively affect lipid profile and promote muscle hypertrophy in resistance training practitioners. Methods: A systematic review of the literature of randomized clinical trials was conducted in the PubMed / Medline, Scielo and Science direct databases. The searches were conducted by two independent researchers by June 2018. A significance level of 5% was considered in the analysis. Results: Six clinical trials involving 170 resistance training practitioners were included. A significant heterogeneity was found in studies evaluating the effects of AAS on lipid profile and muscle hypertrophy (I² = 97, 95 and 91%, respectively), with no significant effects on HDL-cholesterol (-5.62mg/dL, 95%CI −12.10, 0.86, p= 0.09), LDL-cholesterol (7.76 mg/dL, 95%CI −9.70, 25.23, p= 0.57) and muscle hypertrophy (2.44kg 95%CI 0.02, 4.86, p=0.05). Conclusion: Current evidence does not support that low-to-moderate doses of AAS cause serious negative effects on lipid profile or promote muscle hypertrophy in resistance training practitioners.

ANDROGEN RECEPTOR EXPRESSION IN TRIPLE NEGATIVE BREAST CANCER AND ITS RELATIONSHIP TO PROGNOSTIC FACTORS / Expressão de receptor de androgênio em câncer de mama triplo negativo e sua relação com fatores prognósticos

Objective: Triple negative breast cancer (TNBC) is a subset of tumors with an aggressive intrinsic biology, resulting in poor prognosis. Androgen receptor (AR) is currently one of the most studied biomarkers in TNBC, playing a role in the genesis and development of breast cancer. Methods: In this cross-sectional study, we retrospectively reviewed the medical records of all patients with TNBC who received care from 2012 to 2014 at a single health center in southern Brazil. Histological material from breast tumors was analyzed by immunohistochemistry for AR expression and related to age, histological grade, tumor-infiltrating lymphocytes (TILs), and Ki-67. Results: Of 34 TNBC cases identified, 23 (67.6%) were AR negative and 11 (32.4%) were AR positive. The average age of the patients was 51.9 years (range: 30­82 years). Among positive cases, AR was weakly expressed in 6 and strongly expressed in 5 cases. Most patients (n=28; 82.0%) had poorly differentiated tumors. Mean Ki-67 expression was 65.0% in AR-negative and 43.6% in AR-positive cases (p<0.05). There was a significant association between age and AR expression (p<0.005), which was associated with mean age 70.8 years in the strongly AR-positive group and 42.3 years in the weakly AR-positive group. The mean percentage of TILs was 38.6% in AR-positive and 39.1% in AR-negative cases (p=0.391). Conclusion: There was no significant association between AR expression and histological grade or TILs. AR positivity in TNBC was associated with older age and tumors with lower Ki-67 expression, indicating two subgroups with distinct phenotypes in patients with TNBC.

Objetivo: O câncer de mama negativo triplo (triple negative breast cancer ­ TNBC) é um subtipo de tumores com biologia intrínseca agressiva, resultando em pior prognóstico. O receptor de andrógeno (androgen receptor ­ AR) é atualmente um dos biomarcadores mais estudados em TNBC, desempenhando papel na gênese e no desenvolvimento do câncer de mama. Métodos: Neste estudo transversal, revisamos retrospectivamente os registros médicos de todos os pacientes com TNBC que receberam atendimento de 2012 a 2014 em um único centro no sul do Brasil. O material histológico dos tumores de mama foi analisado por imuno-histoquímica para a expressão de AR e relacionado a idade, grau histológico, linfócitos infiltrantes de tumores (TILs) e Ki-67. Resultados: Dos 34 casos identificados de TNBC, 23 (67,6%) eram AR negativos e 11 (32,4%), AR positivos. A idade média foi de 51,9 anos (30­82 anos). Entre os casos positivos, AR foi fracamente expresso em 6 e fortemente expresso em 5 casos. A maioria dos pacientes (n=28, 82,0%) apresentou tumores pouco diferenciados. A expressão média de Ki-67 foi de 65,0% em AR-negativo e 43,6% em AR-positivo (p<0,05). Houve associação significativa entre a idade e a expressão de AR (p<0,005), associada à idade média de 70,8 anos no grupo com AR fortemente positivo e de 42,3 anos no grupo com AR fracamente positivo. A porcentagem média de TILs foi de 38,6% em AR-positivo e de 39,1% em AR-negativo (p=0,391). Não houve associação significativa entre expressão AR e grau histológico ou TILs. Conclusão: A positividade de AR em TNBC foi associada com idade mais avançada e tumores com menor expressão de Ki-67, indicando dois subgrupos com fenótipos distintos em pacientes com TNBC.

Are 2D: 4D finger-length ratios an indicator of androgenetic alopecia in males?

Abstract BACKGROUND: Although the pathogenesis of androgenetic alopecia is not completely understood, the roles of genetic susceptibility and androgens are well-known. A lower ratio of the second digit (index finger = 2D) to the fourth digit (ring finger = 4D) length has been hypothesized to reflect prenatal androgen exposure and/or higher sensitivity to androgens. OBJECTIVES: To determine the relationship between the second to fourth digit length ratio and androgenetic alopecia. METHODS: Finger length measurements were made by a digital vernier calliper. Androgenetic alopecia severity was assessed using the Hamilton-Norwood scale. Subjects with an androgenetic alopecia score of grade III or more were included in the study. RESULTS: A total of 189 males with androgenetic alopecia and 171 healthy controls were enrolled in the study. The age range of participants was 19-65 years. The 2D:4D ratios in patients with androgenetic alopecia were significantly lower than those of healthy controls for the right hand; however, no significant difference was found for the left hand. Average 2D:4D ratios in androgenetic alopecia patients were also lower than in controls. No significant relationship was observed between androgenetic alopecia severity and 2D:4D ratios. CONCLUSION: Our data support the anatomical evidence of in utero androgen exposure and/or an individual’s sensitivity to androgens in patients with androgenetic alopecia. Furthermore, the right hand 2D:4D ratio might be an indicator of androgenetic alopecia development.

Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

Objectives Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway. .

Enfermedad de Kennedy en el Perú: Primeros casos con diagnóstico molecular / Kennedy disease in Peru: First cases with molecular diagnosis

La enfermedad de Kennedy es un trastorno neurodegenerativo de herencia recesiva ligada al cromosoma X, de inicio en la adultez, caracterizado por degeneración progresiva de las neuronas motoras espinales, debido a una mutación dinámica del gen del receptor de andrógeno. Se presentan tres familias (cinco casos) con temblor, calambres, debilidad muscular generalizada lentamente progresiva con atrofia, afectación de músculos bulbares y alteraciones endocrinas. El estudio neurofisiológico demostró compromiso de segunda motoneurona. El análisis molecular mostró una expansión anormal de tripletes citosina-adenina-guanina en el gen de receptor de andrógeno en todos los casos. Todos los pacientes cursaron con una presentación clínica típica de la enfermedad siendo los primeros casos de enfermedad de Kennedy con diagnóstico molecular realizado en el Perú.

Kennedy’s disease is an X-linked recessive disorder with onset in adulthood, characterized by progressive degeneration of spinal motor neurons due to a dynamic mutation in the androgen receptor gene. We report three families (five cases) characterized by progressive weakness involving both limbs and bulbar muscles, atrophy, tremor, cramps and endocrinologic disturbances; the neurophysiological studies demonstrated second motor neuron impairment. The molecular analysis identified abnormal CAG repeats expansion in the androgen receptor gene (AR) in all cases. Clinical features were consistent with other previous reports. These are the first Peruvian cases of Kennedy´s disease with confirmed molecular diagnosis.

Você conhece esta síndrome? / Do you know this syndrome?

A síndrome do Nevo de Becker consiste na associação do nevo de Becker com hipoplasia mamária e outras alterações ósseas ou musculares ipsilaterais a lesão. È considerada desordem hormônio dependente causada pelo distúrbio na atividade do receptor de androgênios que parece estar aumentado no nevo de Becker podendo influenciar no desenvolvimento das lesões associadas. Apresentamos um caso relevante desta síndrome pela raridade da sistematização das lesões, além do exuberante acometimento extracutâneo neste caso.

Becker nevus syndrome is the association of Becker's nevus with breast hypoplasia and other ipsilateral bone or muscle changes. It is considered to be a hormone-dependent disorder caused by a disturbance in the activity of the androgen receptor that appears to be increased in Becker's nevus, which may influence the development of associated lesions. We present a relevant case of this syndrome due to the rare systematization of the lesions in addition to the exuberant extracutaneous involvement in this case.

Immunohistochemical study of androgen, estrogen and progesterone receptors in salivary gland tumors

The aim of this work was to study the immunohistochemical expression of androgen receptor, estrogen receptor and progesterone receptor in pleomorphic adenomas, Warthin's tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas of salivary glands. A total of 41 pleomorphic adenomas, 30 Warthin's tumors, 30 mucoepidermoid carcinomas and 30 adenoid cystic carcinomas were analyzed, and the immunohistochemical expression of these hormone receptors were assessed. It was observed that all cases were negative for estrogen and progesterone receptors. Androgen receptor was positive in 2 cases each of pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma. In conclusion, the results do not support a role of estrogen and progesterone in the tumorigenesis of pleomorphic adenomas, Warthin's tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas. However, androgen receptors can play a role in a small set of salivary gland tumors, and this would deserve further studies.