Recuperación de la espermatogénesis tras el abuso de esteroides anabólicos androgénicos en varones. Revisión sistemática de la literatura / Recovery of spermatogenesis after androgenic anabolic steroids abuse in men. A systematic review of the literature

Objetivo El objetivo de esta revisión sistemática es identificar el tratamiento óptimo para la infertilidad masculina derivada del abuso de esteroides anabólicos androgénicos (EAA). Métodos Se llevó a cabo una revisión sistemática según la declaración Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Se incluyeron estudios que comparaban distintos protocolos para la recuperación de la espermatogénesis tras el uso de EAA. Resultados Un total de 13 estudios que investigaban diferentes protocolos para recuperar la espermatogénesis en pacientes con abuso de EAA cumplieron los criterios de inclusión. Entre los agentes disponibles que demostraron eficacia en el reestablecimiento de la espermatogénesis se encuentran las gonadotropinas inyectables, los moduladores selectivos de los receptores de estrógenos (SERM) y los inhibidores de la aromatasa (AI), pero su uso apenas ha sido descrito en la literatura. Conclusiones Los médicos deben conocer los efectos adversos que los EAA pueden tener sobre la espermatogénesis. La infertilidad asociada a estos agentes puede ser de carácter reversible, pero la producción de espermatozoides puede tardar más de un año en normalizarse. Tanto el tratamiento conservador como el agresivo pueden estimular la espermatogénesis con resultados satisfactorios. Se requiere una mayor comprensión de la endocrinología reproductiva masculina y datos de alta calidad sobre la recuperación de la espermatogénesis tras el abuso de EAA. (AU)

Objective This systematic review aims to evaluate the optimal treatment for male infertility resulting from Anabolic Androgenic Steroids (AAS) abuse. Methods A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies that compared different protocols for the recovery of spermatogenesis in patients after AAS use were included. Results 13 studies investigating different protocols to restore spermatogenesis in patients with AAS abuse met the inclusion criteria. The available agents that showed restoration of spermatogenesis include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their use is still poorly described in the literature. Conclusions Clinicians need to be aware of the detrimental effects of AAS on spermatogenesis. AAS-associated infertility may be reversible, but sperm production may take over a year to normalize. Both conservative and aggressive treatment can boost spermatogenesis with positive results. Further understanding of male reproductive endocrinology and high-quality data on the field of restoration of spermatogenesis after AAS abuse are warranted. (AU)

Recovery of spermatogenesis after androgenic anabolic steroids abuse in men. A systematic review of the literature.

OBJECTIVE: This systematic review aims to evaluate the optimal treatment for male infertility resulting from Anabolic Androgenic Steroids (AAS) abuse. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies that compared different protocols for the recovery of spermatogenesis in patients after AAS use were included. RESULTS: 13 studies investigating different protocols to restore spermatogenesis in patients with AAS abuse met the inclusion criteria. The available agents that showed restoration of spermatogenesis include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their use is still poorly described in the literature. CONCLUSIONS: Clinicians need to be aware of the detrimental effects of AAS on spermatogenesis. AAS-associated infertility may be reversible, but sperm production may take over a year to normalize. Both conservative and aggressive treatment can boost spermatogenesis with positive results. Further understanding of male reproductive endocrinology and high-quality data on the field of restoration of spermatogenesis after AAS abuse are warranted.

Función de las hormonas sexuales en la homeostasis del hueso y su papel en el desarrollo de la osteoporosis masculina: Una revisión narrativa / Role of sex hormones in bone homeostasis and their role in the development of male osteoporosis: A narrative review

El hueso es un tejido dinámico, que se encuentra en constante adaptación durante la vida de los vertebrados con el fin de alcanzar tamaño, forma, preservar la integridad estructural del esqueleto y regular la homeostasis mineral. Su desarrollo durante la infancia es determinante para alcanzar la estatura, así como la resistencia a fracturas en edad avanzada. Las hormonas sexuales juegan un papel importante en el remodelado óseo, tanto en hombres como en mujeres y las alteraciones en los perfiles hormonales pueden conducir al desarrollo de enfermedades asociadas con el metabolismo del hueso. En mujeres, la deficiencia de estrógenos durante la menopausia es una de las principales causas de osteoporosis, mientras que en hombres los andrógenos pueden influir en la salud ósea al unirse directamente a los receptores de andrógenos o indirectamente a receptores de estrógenos. En esta revisión se explora el papel y los efectos de las hormonas sexuales sobre el metabolismo óseo, las vías de señalización implicadas y los efectos que pueden conducir al desarrollo de enfermedades como la osteoporosis. (AU)

Bone is a dynamic tissue that undergoes constant adaptation throughout the life of vertebrates to achieve size, shape, preserve the structural integrity of the skeleton, and regulate mineral homeostasis. Bone growth during childhood is crucial to achieve height and resistance to fractures later in life. Sex hormones play a key role in bone remodeling in men and women alike, and changes to hormonal profiles can trigger bone metabolism-related diseases. In women, estrogen deficiency during menopause is one of the leading causes of osteoporosis, while in men, androgens can have an impact on bone health by binding directly to androgen receptors or indirectly to estrogen receptors. This review explores the role and effects of sex hormones on bone metabolism, the signaling pathways involved, and the effects that can trigger diseases such as osteoporosis. (AU)

Association of free testosterone, glucose level and obesity among women with polycystic ovary syndrome in Soran city, Kurdistan-Iraq / Asociación de testosterona libre, nivel de glucosa y obesidad entre mujeres con síndrome de ovario poliquístico en la ciudad de Soran, Kurdistán-Irak

Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting approximately 5–10% of women of reproductive age and it is also a major cause of anovulatory infertility. PCOS is associated with obesity and conditions like hirsutism, acne, diabetes, and irregular periods. Aim: The present study aimed to evaluate the serum-free testosterone (FT) levels of women afflicted with hirsutism, one of the main physical manifestations of PCOS versus healthy women and determine whether their serum testosterone levels correlate with polycystic ovaries, glucose levels, menstrual abnormalities, and obesity. Methods: This study assessed 180 women; this included 140 females who suffered from excessive and unwanted hair growth on the chin and 40 healthy women as a control group. Free testosterone levels and fasting blood glucose levels were taken. Prior to the study, ultrasonographic (US) tests were performed for all patients to diagnose polycystic ovaries. Results: Patients with hirsutism exhibited a significant elevation in free testosterone (FT) compared to the control group. Approximately half of these women were confirmed to have a polycystic ovary, and 42.8% of them were overweight and obese. Additionally, women between 18 and 20 years old (G1) present with the highest level of FT. Conclusion: Serum FT levels were significantly increased in hirsute women, and this positively correlated with BMI and glucose levels in women with PCOS. Glucose levels may serve as a potentially effective biomarker in evaluating the severity of hirsutism in women suspected of having PCOS.(AU)

Antecedentes: El síndrome de ovario poliquístico (SOP) es la endocrinopatía más común que afecta aproximadamente al 5-10% de las mujeres en edad reproductiva y también es una de las principales causas de infertilidad anovulatoria. El SOP está asociado con la obesidad y condiciones como hirsutismo, acné, diabetes y períodos irregulares. Objetivo: El presente estudio tuvo como objetivo evaluar los niveles séricos de testosterona libre (FT, del inglés) de mujeres con hirsutismo, una de las principales manifestaciones físicas del síndrome de ovario poliquístico, en comparación con mujeres sanas y determinar si los niveles séricos de testosterona se correlacionan con ovarios poliquísticos, niveles de glucosa, anomalías menstruales y obesidad. Métodos: Este estudio evaluó a 180 mujeres; esto incluyó a 140 mujeres que sufrían de un crecimiento de vello excesivo e indeseado en la barbilla y 40 mujeres sanas como grupo de control. Se midieron el nivel de FT y el nivel de azúcar en sangre en ayunas. Antes del estudio, se realizaron pruebas ultrasonográficas a todas las pacientes para diagnosticar ovarios poliquísticos. Resultados: Los pacientes con hirsutismo exhibieron una elevación significativa en la FT en comparación con el grupo de control. Se confirmó que aproximadamente la mitad de estas mujeres tenían un ovario poliquístico y el 42,8% de ellas tenían sobrepeso y obesidad. Adicionalmente, las mujeres entre 18 y 20 años (G1) presentan el mayor nivel de FT. Conclusión: Los niveles séricos de FT aumentaron significativamente en mujeres hirsutas, y esto se correlacionó positivamente con el IMC y los niveles de glucosa en mujeres con SOP. Los niveles de glucosa pueden servir como un biomarcador potencialmente eficaz para evaluar la gravedad del hirsutismo en mujeres con sospecha de SOP.(AU)

Clinical evaluation and treatment in men with low testosterone levels and prostate cancer.

INTRODUCTION: A high prevalence of low testosterone levels has been reported in men with prostate cancer. The use of testosterone therapy in men with a history of prostate cancer is still controversial, and there is uncertainty regarding the management of these patients. METHODS: We analyzed the European and American guidelines on this topic and presented the clinical experience in the management of patients with low testosterone levels and a history of prostate cancer in one of the world's leading cancer centers. RESULTS: According to the published evidence to date, testosterone therapy in men with prostate cancer does not increase the risk of prostate cancer recurrence in the short and medium term, but there is a lack of data on the long term. Symptomatic men with low testosterone levels who are candidates for this therapy need a thorough clinical evaluation before commencing testosterone therapy. Evaluation of prostate cancer history including type of treatment administered, pathologic stage of prostate cancer and prostate specific antigen should be requested before and during testosterone treatment to assess its trend. CONCLUSION: Prostate-specific antigen should remain undetectable after radical prostatectomy or stable after radiotherapy. Otherwise, it would be a sign of uncontrolled prostate cancer, and the patient may require cessation of testosterone therapy and referral to oncology for further evaluation.

Klinefelter syndrome: The characterization of the clinical and sociological features of 51 patients / Síndrome de Klinefelter: caracterización de los rasgos clínicos y sociológicos de 51 pacientes

Introduction: Klinefelter syndrome is the most frequently found aneuploidy among male patients. Its clinical presentation is very heterogeneous, and thus poses a challenge for a timely diagnosis. Methods: A retrospective study was carried out with 51 consecutively selected patients diagnosed with Klinefelter Syndrome from Jan/2010 to Dec/2019. The karyotypes were identified using high resolution GTL banding at the Genetics Department. Multiple clinical and sociological parameters were studied by collecting data from the clinical records. Results: 44 (86%) of the 51 patients presented a classical karyotype (47,XXY) and 7 (14%) showed evidence of mosaicism. The mean age at diagnosis was 30.2±14.3 years old. Regarding the level of education (N=44), 26 patients (59.1%) had no secondary education, with 5 (11.4%) patients having concluded university studies. Almost two thirds of the sample revealed learning difficulties (25/38) and some degree of intellectual disability was present in 13.6% (6/44). Half of the patients were either non-qualified workers (19.6%) or workers in industry, construction, and trades (30.4%), which are jobs that characteristically require a low level of education. The proportion of unemployed patients was 6.5%. The main complaints were infertility (54.2%), followed by hypogonadism-related issues (18.7%) and gynecomastia (8.3%). 10 patients (23.8%, N=42) were biological parents. With regards the question of fertility, assisted reproductive techniques were used in 39.6% of the studied subjects (N=48), with a success rate (a take home baby) of 57.9% (11/19), 2 with donor sperm and 9 with the patients’ own gametes. Only 41% of the patients (17/41) were treated with testosterone. (AU)

Introducción: El síndrome de Klinefelter es la aneuploidía más frecuente entre los pacientes varones. Su presentación clínica es muy heterogénea, por lo que supone un reto para su diagnóstico oportuno. Métodos: Se realizó un estudio retrospectivo con 51 pacientes seleccionados consecutivamente con diagnóstico de Síndrome de Klinefelter desde enero de 2010 hasta diciembre de 2019. Los cariotipos se identificaron mediante bandeo GTL de alta resolución en el Departamento de Genética. Se estudiaron múltiples parámetros clínicos y sociológicos mediante la recogida de datos de las historias clínicas. Resultados: De los 51 pacientes, 44 (86%) presentaron un cariotipo clásico (47,XXY) y siete (14%) evidenciaron mosaicismo. La edad media al diagnóstico fue de 30,2 ± 14,3 años. En cuanto al nivel de estudios (n = 44), 26 pacientes (59,1%) no tenían estudios secundarios, y cinco (11,4%) habían concluido estudios universitarios. Casi dos tercios de la muestra revelaban dificultades de aprendizaje (25/38) y algún grado de discapacidad intelectual estaba presente en 13,6% (6/44). La mitad de los pacientes eran trabajadores no cualificados (19,6%) o trabajadores de la industria, la construcción y los oficios (30,4%), que son empleos que característicamente requieren un bajo nivel educativo. La proporción de pacientes en paro era de 6,5%. Las principales quejas eran la infertilidad (54,2%), seguida de problemas relacionados con el hipogonadismo (18,7%) y la ginecomastia (8,3%); 10 pacientes (23,8%, n = 42) eran padres biológicos. En cuanto a la cuestión de la fertilidad, se utilizaron técnicas de reproducción asistida en 39,6% de los sujetos estudiados (n = 48), con una tasa de éxito (un bebé para llevar a casa) de 57,9% (11/19), dos con semen de donante y nueve con gametos propios de los pacientes. Solo 41% de los pacientes (17/41) fueron tratadas con testosterona. (AU)

Therapeutic potential of testosterone on sperm parameters and chromatin status in fresh and thawed normo and asthenozoospermic samples / Potencial terapéutico de la testosterona sobre los parámetros espermáticos y el estado de la cromatina en muestras frescas y descongeladas de normo y astenozoospermia

Background: Hormonal changes alter the physiological level of ROS and cause oxidative stress in the cell. As estimated, hormonal deficiencies, environmental and ideological factors make up about 25% of male infertility. Pathogenic reactive oxygen species (ROS) is a chief cause of unexplained infertility. Limited studies exist on the effects of testosterone on human sperm culture. Therefore, in the current study, the effect of different doses of testosterone on sperm parameters and chromatin quality was investigated. Materials and methods: Semen samples from 15 normospermic and 15 asthenospermic patients were prepared by swim up method, and then were divided into four groups by exposing to different concentrations of testosterone (1, 10, and 100nM) for 45min. Samples without any intervention were considered as control group. All samples were washed twice. Sperm parameters and chromatin protamination were assessed in each group and the remains were frozen. After two weeks, all tests were repeated for sperm thawed. Also, the MSOM technique was used to determine the sperm morphology of class 1. Results: Although sperm parameters were not show any significant differences in normospermic and asthenospermic samples exposed to different concentrations of testosterone before and after freezing, chromatin protamination was significantly decreased in the normospermic samples exposed to 10nM of testosterone before freezing (p<0.006), as well as 1 and 10nM of testosterone after freezing compared to control samples (p=0.001 and p=0.0009, respectively). (AU)

Antecedentes: Los cambios hormonales alteran el nivel fisiológico de las especies reactivas de oxígeno (reactive oxygen species [ROS]) patógenas y provocan estrés oxidativo en la célula. Según estimaciones, las deficiencias hormonales, los factores ambientales y los ideológicos constituyen alrededor del 25% de la infertilidad masculina. Las ROS son una causa principal de infertilidad inexplicable. Existen estudios limitados sobre los efectos de la testosterona en el cultivo de esperma humano. Por lo tanto, en el estudio actual se ha investigado el efecto de diferentes dosis de testosterona sobre los parámetros del esperma y la calidad de la cromatina. Materiales y métodos: Se prepararon muestras de semen de 15 pacientes normospérmicos y 15 astenospérmicos mediante el método swim up, y luego se dividieron en cuatro grupos exponiéndolos a diferentes concentraciones de testosterona (1, 10 y 100nM) durante 45min. Las muestras sin ninguna intervención se consideraron como grupo control. Todas las muestras se lavaron dos veces. En cada grupo se evaluaron los parámetros espermáticos y la protaminación de la cromatina, y los restos se congelaron. Dos semanas después se repitieron todas las pruebas de esperma descongelado. Asimismo, se utilizó la técnica MSOM para determinar la morfología espermática de clase 1. Resultados: Aunque los parámetros espermáticos no mostraron diferencias significativas en las muestras normospérmicas y astenospérmicas expuestas a diferentes concentraciones de testosterona antes y después de la congelación, la protaminación de la cromatina disminuyó significativamente en las muestras normospérmicas expuestas a 10nM de testosterona antes de la congelación (p<0,006), así como a 1 y 10nM de testosterona después de la congelación, en comparación con las muestras de control (p=0,001 y p=0,0009, respectivamente). (AU)

Chronic minocycline administration improves spermatogenesis in rats / La administración crónica de minociclina mejora la espermatogénesis en ratas

Introduction: Minocycline is a tetracycline with promising protective effects on different organs which are completely distinct from its antibacterial effects. Methods: To evaluate the effects of chronic administration of this agent on histological structure and sperm parameters of testes, forty adult male rats were randomly allocated into 2 equal groups I: control animals and II: treated animal that received 25mg/kg/day minocycline, orally. After 90 days of treatment, serum level of testosterone was assessed as well as sperm count, motility and morphology. Moreover, histological and histomorphometric evaluation of testes was performed including determination of height of the seminiferous germinal epithelium and perpendicular diameter of seminiferous tubules. Numbers of spermatogonia, primary spermatocytes, spermatids, Sertoli and Leydig cells were counted. Johnsen's scoring method was also performed. Results: Sperm parameters significantly improved in minocycline-treated animals. Moreover, number of germ cells in different stages of development significantly increased in treatment group as compared to control. This finding was associated with better Johnsen's score and thicker epithelium in seminiferous tubules. However, serum testosterone levels, Leydig and Sertoli cell count as well as tubular diameter did not show significant changes (p>0.05). Discussion: Chronic administration of minocycline is associated with improved spermatogenesis and sperm characteristics without affecting steroidogenesis in rats. (AU)

Introducción: La minociclina es una tetraciclina con efectos protectores prometedores en diferentes órganos que son completamente distintos de sus efectos antibacterianos. Métodos: Para evaluar los efectos de la administración crónica de este agente sobre la estructura histológica y los parámetros espermáticos de los testículos, se asignaron al azar 40 ratas macho adultas en 2 grupos iguales: I, animales control; y II, animal tratado que recibió 25mg/kg/día de minociclina, por vía oral. Después de 90 días de tratamiento, se evaluó el nivel sérico de testosterona, así como el recuento, la motilidad y la morfología de los espermatozoides. Además, se realizó una evaluación histológica e histomorfométrica de los testículos, incluida la determinación de la altura del epitelio germinal seminífero y el diámetro perpendicular de los túbulos seminíferos. Se contó el número de espermatogonias, espermatocitos primarios, espermátidas, células de Sertoli y Leydig. También se realizó el método de puntuación de Johnsen. Resultados: Los parámetros de los espermatozoides mejoraron significativamente en los animales tratados con minociclina. Además, el número de células germinales en diferentes etapas de desarrollo aumentó significativamente en el grupo de tratamiento en comparación con el control. Este hallazgo se asoció con una mejor puntuación de Johnsen y un epitelio más grueso en los túbulos seminíferos. Sin embargo, los niveles séricos de testosterona, el recuento de células de Leydig y Sertoli y el diámetro tubular no mostraron cambios significativos (p>0,05). Discusión: La administración crónica de minociclina se asocia con una mejor espermatogénesis y características de los espermatozoides sin afectar la esteroidogénesis en ratas. (AU)

Therapeutic potential of testosterone on sperm parameters and chromatin status in fresh and thawed normo and asthenozoospermic samples.

BACKGROUND: Hormonal changes alter the physiological level of ROS and cause oxidative stress in the cell. As estimated, hormonal deficiencies, environmental and ideological factors make up about 25% of male infertility. Pathogenic reactive oxygen species (ROS) is a chief cause of unexplained infertility. Limited studies exist on the effects of testosterone on human sperm culture. Therefore, in the current study, the effect of different doses of testosterone on sperm parameters and chromatin quality was investigated. MATERIALS AND METHODS: Semen samples from 15 normospermic and 15 asthenospermic patients were prepared by swim up method, and then were divided into four groups by exposing to different concentrations of testosterone (1, 10, and 100nM) for 45min. Samples without any intervention were considered as control group. All samples were washed twice. Sperm parameters and chromatin protamination were assessed in each group and the remains were frozen. After two weeks, all tests were repeated for sperm thawed. Also, the MSOM technique was used to determine the sperm morphology of class 1. RESULTS: Although sperm parameters were not show any significant differences in normospermic and asthenospermic samples exposed to different concentrations of testosterone before and after freezing, chromatin protamination was significantly decreased in the normospermic samples exposed to 10nM of testosterone before freezing (p<0.006), as well as 1 and 10nM of testosterone after freezing compared to control samples (p=0.001 and p=0.0009, respectively). Similarly, chromatin protamination in the asthenospermic samples was significantly decreased at concentration of 1nM of testosterone before and after freezing (p=0.0014 and p=0.0004, respectively), and at concentration of 10nM of testosterone before and after freezing (p=0.0009, p=0.0007) compared to control samples. CONCLUSION: Using a low dose of testosterone in the sperm culture medium, has positive effects on chromatin quality.

Klinefelter syndrome: The characterization of the clinical and sociological features of 51 patients.

INTRODUCTION: Klinefelter syndrome is the most frequently found aneuploidy among male patients. Its clinical presentation is very heterogeneous, and thus poses a challenge for a timely diagnosis. METHODS: A retrospective study was carried out with 51 consecutively selected patients diagnosed with Klinefelter Syndrome from Jan/2010 to Dec/2019. The karyotypes were identified using high resolution GTL banding at the Genetics Department. Multiple clinical and sociological parameters were studied by collecting data from the clinical records. RESULTS: 44 (86%) of the 51 patients presented a classical karyotype (47,XXY) and 7 (14%) showed evidence of mosaicism. The mean age at diagnosis was 30.2±14.3 years old. Regarding the level of education (N=44), 26 patients (59.1%) had no secondary education, with 5 (11.4%) patients having concluded university studies. Almost two thirds of the sample revealed learning difficulties (25/38) and some degree of intellectual disability was present in 13.6% (6/44). Half of the patients were either non-qualified workers (19.6%) or workers in industry, construction, and trades (30.4%), which are jobs that characteristically require a low level of education. The proportion of unemployed patients was 6.5%. The main complaints were infertility (54.2%), followed by hypogonadism-related issues (18.7%) and gynecomastia (8.3%). 10 patients (23.8%, N=42) were biological parents. With regards the question of fertility, assisted reproductive techniques were used in 39.6% of the studied subjects (N=48), with a success rate (a take home baby) of 57.9% (11/19), 2 with donor sperm and 9 with the patients' own gametes. Only 41% of the patients (17/41) were treated with testosterone. CONCLUSION: This study identifies the most important clinical and sociological findings of Klinefelter syndrome patients that should be considered when deciding workout and disease management.

Executive summary of the position statement of the Spanish Societies SEQCML/SEEN/SEEP. Recommendations for the measurement of sex steroids in clinical practice.

Accurate measurement of sex steroids, particularly testosterone and estradiol, is relevant for the diagnosis and treatment of a wide range of conditions. Unfortunately, current chemiluminescent immunoassays have analytical limitations with important clinical consequences. This document reviews the current state of clinical assays for estradiol and testosterone measurements and their potential impact in different clinical situations. It also includes a series of recommendations and necessary steps to introduce steroid analysis by mass spectrometry into national health systems, a methodology recommended for more than a decade by international societies.

Eficacia y seguridad de la testosterona en el tratamiento del deseo sexual hipoactivo en mujeres: ¿qué dice la evidencia? / Efficacy and safety of testosterone in the treatment of hypoactive sexual desire in women: what does the evidence say?

Objetivo: Determinar la eficacia y seguridad de la testosterona, en el tratamiento del deseo sexual hipoactivo en mujeres. Materiales y métodos: Se hizo una revisión sistemática de la literatura en diferentes bases de datos electrónicas (CINAHL, DynaMed, EMBASE, Lilacs, Medline, Scopus, entre otras), entre enero de 1990 y mayo de 2021; a través de términos de búsqueda estandarizados. Los desenlaces evaluados incluyeron la eficacia y seguridad de la testosterona en el incremento del deseo sexual, el número total de actividad sexual satisfactoria, el número de orgasmos y el nivel de angustia en pacientes con deseo sexual hipoactivo y proporción de reacciones adversas. Resultados: Se incluyeron 72 artículos. El uso de testosterona, en mujeres posmenopáusicas con deseo sexual hipoactivo reporta un positivo efecto sobre la función sexual, con aumentos significativos en la actividad sexual satisfactoria, así como mejoría en todos los dominios de la función sexual (deseo, excitación y respuesta orgásmica) y una disminución de la angustia personal, con incremento en la puntuación del Índice de Función Sexual Femenino. En las mujeres en edad fértil, la testosterona se formula para uso «off-label», de tal manera que se utilizan compuestos y dosis ideadas para tratamientos en hombres o fórmulas magistrales (las cuales no están aprobadas por los grupos de consenso ni avalados por investigaciones), pero no ha demostrado ningún efecto sobre la función sexual. Las reacciones adversas más frecuentes suelen ser el hirsutismo y el acné, aunque en general la testosterona, a dosis fisiológicas, tiene un perfil de seguridad favorable. Conclusiones: La testosterona es una terapia eficaz y segura en el tratamiento del trastorno del deseo sexual hipoactivo en mujeres después de la menopausia. En la actualidad no hay disponibilidad de estudios que avalen el uso de la terapia con testosterona en mujeres en edad reproductiva, por lo tanto, no está aprobado su uso. (AU)

Objective: To determine the efficacy and safety of testosterone in the treatment of hypoactive sexual desire in women. Materials and methods: A systematic review of the literature was carried out in different electronic databases (CINAHL, DynaMed, EMBASE, Lilacs, Medline, Scopus, among others), between January 1990 and May 2021; through standardized search terms. The outcomes evaluated included the efficacy and safety of testosterone in increasing sexual desire, the total number of satisfactory sexual activity, the number of orgasms and the level of distress in patients with hypoactive sexual desire and the proportion of adverse reactions. Results: 72 articles were included. The use of testosterone, in postmenopausal women, with hypoactive sexual desire, reports a positive effect on sexual function, with significant increases in satisfactory sexual activity, as well as improvement in all domains of sexual function (desire, arousal and orgasmic response) and a decrease in personal anguish, with an increase in the Female Sexual Function Index score. In women of childbearing age, testosterone is formulated for “off-label” use, in such a way that compounds and doses designed for treatments in men or magisterial formulas are used (which are not approved by consensus groups or endorsed by research), but has not shown any effect on sexual function. The most frequent adverse reactions are usually hirsutism and acne, although in general testosterone, at physiological doses, has a favorable safety profile. Conclusions: Testosterone is an effective and safe therapy in the treatment of hypoactive sexual desire disorder in women after menopause. Currently there are no studies available to support the use of testosterone therapy in women of reproductive age, therefore, its use is not approved. (AU)

Low testosterone levels as an independent risk factor for mortality in male patients with COVID-19: Report of a Single-Center Cohort Study in Mexico / Niveles bajos de testosterona como factor de riesgo independiente de mortalidad en pacientes masculinos con COVID-19: Informe de un estudio de cohorte de un solo centro en México

Introduction and objectives: Throughout the coronavirus disease 2019 (COVID-19) pandemic, a greater severity and lethality of the disease has been highlighted in male patients, so we set out to evaluate the prognostic role of serum testosterone levels in the clinical results of this population. Methods: In this single-center and cross-sectional design, we included male patients admitted to our hospital with COVID-19 confirmed diagnosis. The biochemical analysis included lymphocytes, lactate dehydrogenase (LDH), total testosterone (TT), dehydroepiandrosterone, follicle-stimulating hormone, and luteinizing hormone. Receiver operating characteristic curves, univariate and bivariate analysis, and binary logistic regression for multivariate analysis were performed. A p value<0.05 was consider significant. Results: From 86 men included, 48.8% died. TT levels were lower in non-survivor patients than in survivor patients (4.01nmol/L [0.29–14.93] vs 5.41 (0.55–25.08) nmol/L, p=0.021). The independent risk factors that increased the relative risk (RR) of dying from COVID-19 were: age>59 years (RR 3.5 [95% IC 1.0–11.6], p=0.045), TT levels<4.89nmol/L (RR 4.0 [95% IC 1.2–13.5], p=0.027) and LDH levels>597IU/L (RR 3.9 [95% IC 1.2–13.1], p=0.024). Patients who required mechanical ventilation (p=0.025), had lymphopenia (p=0.013) and LDH levels>597IU/L (p=0.034), had significantly lower TT levels compared to those who did not present these conditions. There were no differences in TT levels between patients who had or did not have comorbidities. Conclusions: A TT level<4.89nmol/L increase four times the RR of death from COVID-19 in men, regardless of age or presence of comorbidities. (AU)

Introducción y objetivos: A lo largo de la pandemia de la enfermedad por coronavirus de 2019 (COVID-19), se ha destacado una mayor gravedad y letalidad de la enfermedad en pacientes del sexo masculino, por lo que nos propusimos evaluar el papel pronóstico de los niveles séricos de testosterona en los resultados clínicos de esta población. Métodos: En este diseño transversal de un único centro, incluimos a pacientes masculinos ingresados en nuestro hospital con diagnóstico confirmado de COVID-19. El análisis bioquímico incluyó linfocitos, lactato deshidrogenasa (LDH), testosterona total (TT), dehidroepiandrosterona, hormona estimulante del folículo y hormona luteinizante. Se elaboraron curvas «característica operativa del receptor», análisis univariado y bivariado y regresión logística binaria para análisis multivariado. Se consideró significativo un valor de p<0,05. Resultados: De los 86 hombres incluidos, el 48,8% falleció. El nivel de TT fue más bajo en los pacientes no supervivientes que en los supervivientes (4,01 [0,29-14,93] nmol/L vs. 5,41 [0,55-25,08] nmol/L; p=0,021). Los factores de riesgo independientes que aumentaron el riesgo relativo (RR) de muerte por COVID-19 fueron: edad>59 años (RR 3,5: IC 95% 1,0-11,6; p=0,045), cifra de TT<4,89 nmol/L (RR 4,0; IC 95%: 1,2-13,5; p=0,027) y de LDH>597 UI/L (RR 3,9; IC 95%: 1,2-13,1; p=0,024). Los pacientes que requirieron ventilación mecánica (p=0,025), tenían linfopenia (p=0,013), un nivel de LDH>597 UI/L (p=0,034) y de TT significativamente más bajos que aquellos que no presentaban estas condiciones. No hubo diferencias en los niveles de TT entre los pacientes que tenían o no comorbilidades. Conclusiones: Un nivel de TT<4,89 nmol/L aumenta 4 veces el RR de muerte por COVID-19 en hombres, independientemente de la edad o la presencia de comorbilidades. (AU)

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients / Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal

Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.

Low testosterone levels as an independent risk factor for mortality in male patients with COVID-19: Report of a Single-Center Cohort Study in Mexico.

INTRODUCTION AND OBJECTIVES: Throughout the coronavirus disease 2019 (COVID-19) pandemic, a greater severity and lethality of the disease has been highlighted in male patients, so we set out to evaluate the prognostic role of serum testosterone levels in the clinical results of this population. METHODS: In this single-center and cross-sectional design, we included male patients admitted to our hospital with COVID-19 confirmed diagnosis. The biochemical analysis included lymphocytes, lactate dehydrogenase (LDH), total testosterone (TT), dehydroepiandrosterone, follicle-stimulating hormone, and luteinizing hormone. Receiver operating characteristic curves, univariate and bivariate analysis, and binary logistic regression for multivariate analysis were performed. A p value<0.05 was consider significant. RESULTS: From 86 men included, 48.8% died. TT levels were lower in non-survivor patients than in survivor patients (4.01nmol/L [0.29-14.93] vs 5.41 (0.55-25.08) nmol/L, p=0.021). The independent risk factors that increased the relative risk (RR) of dying from COVID-19 were: age>59 years (RR 3.5 [95% IC 1.0-11.6], p=0.045), TT levels<4.89nmol/L (RR 4.0 [95% IC 1.2-13.5], p=0.027) and LDH levels>597IU/L (RR 3.9 [95% IC 1.2-13.1], p=0.024). Patients who required mechanical ventilation (p=0.025), had lymphopenia (p=0.013) and LDH levels>597IU/L (p=0.034), had significantly lower TT levels compared to those who did not present these conditions. There were no differences in TT levels between patients who had or did not have comorbidities. CONCLUSIONS: A TT level<4.89nmol/L increase four times the RR of death from COVID-19 in men, regardless of age or presence of comorbidities.

Chronic minocycline administration improves spermatogenesis in rats.

INTRODUCTION: Minocycline is a tetracycline with promising protective effects on different organs which are completely distinct from its antibacterial effects. METHODS: To evaluate the effects of chronic administration of this agent on histological structure and sperm parameters of testes, forty adult male rats were randomly allocated into 2 equal groups I: control animals and II: treated animal that received 25mg/kg/day minocycline, orally. After 90 days of treatment, serum level of testosterone was assessed as well as sperm count, motility and morphology. Moreover, histological and histomorphometric evaluation of testes was performed including determination of height of the seminiferous germinal epithelium and perpendicular diameter of seminiferous tubules. Numbers of spermatogonia, primary spermatocytes, spermatids, Sertoli and Leydig cells were counted. Johnsen's scoring method was also performed. RESULTS: Sperm parameters significantly improved in minocycline-treated animals. Moreover, number of germ cells in different stages of development significantly increased in treatment group as compared to control. This finding was associated with better Johnsen's score and thicker epithelium in seminiferous tubules. However, serum testosterone levels, Leydig and Sertoli cell count as well as tubular diameter did not show significant changes (p>0.05). DISCUSSION: Chronic administration of minocycline is associated with improved spermatogenesis and sperm characteristics without affecting steroidogenesis in rats.

Prevalence of men's health history in male breast cancer patients.

INTRODUCTION: Male breast carcinoma (MBC) is an uncommon disease, accounting for less than 0.5% of cancer diagnoses in men. Data on the prevalence thereof in Argentina are unknown. PRIMARY OBJECTIVE: To estimate the prevalence of a men's health history associated with MBC as well as the anthropometric and clinical characteristics of the study population. METHODS: This cross-sectional study included all men according to original biological sex over 18 years of age with a history of breast cancer who sought care at the Hospital Italiano de Buenos Aires [Italian Hospital of Buenos Aires] between January 2010 and December 2018. RESULTS: We included 57 men with breast cancer. Their median age was 71 years. Of them, 53.06% had obesity and 24.53% had diabetes. With respect to men's health history, 5.56% (2/36) had infertility, 29.17% (14/48) had gynaecomastia and 60.71% (17/28) had sexual dysfunction. Some 63% (7/11) had androgen deficiency based on laboratory diagnosis; of them, 45.45% (5/11) had high gonadotropins. CONCLUSION: We identified similarities with the literature as to the prevalence of obesity, diabetes and infertility in patients with MBC. The prevalence of testosterone deficiency was higher than reported for men of the same age. Many of these factors support the need to examine the role of endogenous hormones. Further research is required to help physicians care for and counsel men at higher risk of this disease.

[Efficacy and safety of testosterone in the treatment of hypoactive sexual desire in women: what does the evidence say?] / Eficacia y seguridad de la testosterona en el tratamiento del deseo sexual hipoactivo en mujeres: ¿qué dice la evidencia?

OBJECTIVE: To determine the efficacy and safety of testosterone in the treatment of hypoactive sexual desire in women. MATERIALS AND METHODS: A systematic review of the literature was carried out in different electronic databases (CINAHL, DynaMed, EMBASE, Lilacs, Medline, Scopus, among others), between January 1990 and May 2021; through standardized search terms. The outcomes evaluated included the efficacy and safety of testosterone in increasing sexual desire, the total number of satisfactory sexual activity, the number of orgasms and the level of distress in patients with hypoactive sexual desire and the proportion of adverse reactions. RESULTS: 72 articles were included. The use of testosterone, in postmenopausal women, with hypoactive sexual desire, reports a positive effect on sexual function, with significant increases in satisfactory sexual activity, as well as improvement in all domains of sexual function (desire, arousal and orgasmic response) and a decrease in personal anguish, with an increase in the Female Sexual Function Index score. In women of childbearing age, testosterone is formulated for "off-label" use, in such a way that compounds and doses designed for treatments in men or magisterial formulas are used (which are not approved by consensus groups or endorsed by research), but has not shown any effect on sexual function. The most frequent adverse reactions are usually hirsutism and acne, although in general testosterone, at physiological doses, has a favorable safety profile. CONCLUSIONS: Testosterone is an effective and safe therapy in the treatment of hypoactive sexual desire disorder in women after menopause. Currently there are no studies available to support the use of testosterone therapy in women of reproductive age, therefore, its use is not approved.

Effects of resistance training on consecutive and non-consecutive days on hormonal, neuromuscular and morphological responses in recreationally trained men / Efeitos do treinamento de força em dias consecutivos e não consecutivos nas respostas hormonal, neuromuscular e morfológica em homens treinados recreacionalmente

abstract The purpose of the present study was to investigate the effect of two recovery periods between consecutive and non-consecutive days in strength training sessions on hormonal, neuromuscular and morphological variables in recreationally trained men. Nineteen young men completed the study and were randomly divided into two groups: 24R, 24-hour recovery group (n = nine) and 72R, 72-hour recovery group (n = ten). The strength training program (RT) lasted six weeks with two serial routines, with a weekly frequency of four times. The saliva sample was collected once a week in the morning to determine salivary testosterone. The 1RM, jump against movement and body composition tests were performed in the pre- and post-training periods. As for salivary testosterone, there was no significant effect with respect to time and between groups. Both groups improved maximal strength in terms of intervention time in the barbell bench press and in the leg press 45º, not differing between groups and body composition showed significant interaction in time to body fat percentage ∆% = -14.6 ± 10.0 (24R) and -17.2 ± 10.9 (72R); p = 0.00, fat mass ∆% = -13, 7 ± 9.2 (24R) and -18.2 ± 13.0 (72R); p = 0.00 and fat-free mass ∆% = 3.5 ± 2.7 (24R) and 2.5 ± 2 .8 (72R), p = 0.00. The recovery periods 24 and 72 hours between sessions induced similar responses in the parameters investigated in recreationally strength-trained men.

resumo O objetivo do presente estudo foi investigar o efeito de dois períodos de recuperação entre dias consecutivos e não consecutivos em sessões de treinamento de força sobre variáveis hormonais, neuromusculares e morfológicas em homens treinados recreacionalmente. Dezenove homens jovens completaram o estudo e foram divididos aleatoriamente em dois grupos: 24R, grupo de recuperação de 24 horas (n = nove) e 72R, grupo de recuperação de 72 horas (n = dez). O programa de treinamento de força (TF) durou seis semanas com duas rotinas seriadas, com frequência semanal de quatro vezes. A amostra de saliva foi coletada uma vez por semana no período da manhã para determinação da testosterona salivar. Os testes de 1RM, salto contra movimento e composição corporal foram realizados nos períodos pré e pós-treinamento. Quanto à testosterona salivar, não houve efeito significativo em relação ao tempo e entre os grupos. Ambos os grupos melhoraram a força máxima em termos de tempo de intervenção no supino reto com barra e no leg press 45º, não diferindo entre os grupos e composição corporal apresentaram interação significativa no tempo para percentual de gordura corporal ∆% = -14,6 ± 10,0 (24R) e -17,2 ± 10,9 (72R); p = 0,00, massa gorda ∆% = -13, 7 ± 9,2 (24R) e -18,2 ± 13,0 (72R); p = 0,00 e massa isenta de gordura ∆% = 3,5 ± 2,7 (24R) e 2,5 ± 2,8 (72R), p = 0,00. Os períodos de recuperação de 24 e 72 horas entre as sessões induziram respostas semelhantes nos parâmetros investigados em homens treinados de força recreacionalmente.