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INTRODUCTION:   Prostate cancer has a variable natural history and, despite the existence of biochemical recurrence (BCR) predictors, they are still limited in predicting outcomes.  The role of testosterone in advanced prostate cancer is well known, however its role in localized prostate cancer is still uncertain.  In the present study, we evaluated the relationship of testosterone levels and androgen receptor (AR) expression with oncological and functional outcomes, in patients undergoing radical retropubic prostatectomy (RRP). MATERIALS AND METHODS:   Through a retrospective study, patients who underwent RRP, who had at least two preoperative total testosterone dosages, were analyzed and compared according to testosterone levels, oncological and functional outcomes.  After analyzing data, tissue samples were selected in a biorepository to carry out the AR and the AR-V7 expression. RESULTS:   After applying exclusion criteria, 212 patients were included in the analysis.  Thirty-two patients (15.1%) had low testosterone levels and, in this group, a lower rates of erectile function recovery were observed at 24 months (53.1% vs. 71.7%; p = 0.037), a higher rate of BCR (21.9% vs. 9.4%; p = 0.041) and higher International Society of Urological Pathology (ISUP) grade in biopsy products.  The AR expression was higher in patients with low testosterone, but there was no difference in relapse rates. CONCLUSIONS:   Lower levels of testosterone were related to lower rates of erectile function recovery at the end of 24 months after RRP, in addition to conferring higher rates of BCR and higher ISUP grades in biopsy.  Furthermore, patients with total testosterone < 300 ng/dL had higher expression of AR, but no difference in BCR rates.

Asunto(s)

Prostatectomía , Neoplasias de la Próstata , Receptores Androgénicos , Testosterona , Humanos , Masculino , Prostatectomía/métodos , Testosterona/sangre , Receptores Androgénicos/metabolismo , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Recurrencia Local de Neoplasia

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BACKGROUND: Premenopausal, high-risk, hormone receptor-positive breast cancer patients are often treated with ovarian suppression in combination with aromatase inhibitors (AI). This combination has important adverse effects, particularly in sexual function, such as vaginal dryness and loss of libido. There is no effective therapy for reduced sexual function in this setting. Our study aimed to determine the efficacy and safety, particularly regarding sexual function, of a low-dose, topical testosterone gel administration. METHODS: This is a pilot, single-center study, designed to evaluate the efficacy of topical testosterone gel (3 mg/day) in improving sexual function in 29 premenopausal patients on ovarian suppression in combination with an AI. The primary safety endpoint was to assess serum estradiol elevation. The primary efficacy endpoint was sexual function improvement, assessed by the Female Sexual Function Index questionnaire. RESULTS: We report the results on 29 patients. Twenty-two patients (75%) completed the 3-month treatment, and seven discontinued treatment before completion, mostly due to logistical difficulties related to the COVID-19 pandemic. All patients maintained the value of baseline mass spectrometry assay for estradiol of less than 2.7 pg/mL during the undertaken measurements. We observed a significant improvement in Female Sexual Function Index measures over the visits, with an increase from a mean of 11.7 at baseline to 19.1 in the third month (p < 0.001), with the greatest improvement observed between the second and third months. CONCLUSIONS: Our findings suggest that topical testosterone seems to be safe and may be effective in improving sexual function in patients on ovarian suppression and AI. TRIAL REGISTRATION: The project was submitted and approved through the hospital's SGPP platform in 11/26/2019 (Project No. SGPP 393819) and CAAE (Research Ethics Committee) (CAAE No 25609719.5.0000.007).

Asunto(s)

Inhibidores de la Aromatasa , Neoplasias de la Mama , Testosterona , Humanos , Femenino , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Testosterona/administración & dosificación , Testosterona/sangre , Persona de Mediana Edad , Adulto , Proyectos Piloto , Administración Tópica , Resultado del Tratamiento , Estradiol/administración & dosificación , Estradiol/efectos adversos , COVID-19 , Premenopausia , Disfunciones Sexuales Fisiológicas/etiología , Ovario/efectos de los fármacos , Ovario/metabolismo , SARS-CoV-2

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Background: Testosterone (T) therapy increases lean mass and reduces total body and truncal fat mass in hypogonadal men. However, the underlying molecular mechanisms for the reciprocal changes in fat and lean mass in humans are not entirely clear. Methods: Secondary analysis of specimens obtained from a single-arm, open-label clinical trial on pharmacogenetics of response to T therapy in men with late-onset hypogonadism, conducted between 2011 and 2016 involving 105 men (40-74 years old), who were given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subcutaneous fat (SCF), peripheral blood mononuclear cells (PBMC) and serum were obtained from the participants at different time points of the study. We measured transcription factors for adipogenesis and myogenesis in the SCF, and PBMC, respectively, by real-time quantitative PCR at baseline and 6 months. Serum levels of FOLLISTATIN, PAX7, MYOSTATIN, ADIPSIN, and PRDM16 were measured by ELISA. Results: As expected, there was a significant increase in T and estradiol levels after 6 months of T therapy. There was also a reduction in fat mass and an increase in lean mass after 6 months of T therapy. Gene-protein studies showed a significant reduction in the expression of the adipogenic markers PPARγ in SCF and ADIPSIN levels in the serum, together with a concomitant significant increase in the expression of myogenic markers, MYOD in PBMC and PAX7 and FOLLISTATIN levels in the serum after 6 months of T therapy compared to baseline. Interestingly, there was a significant increase in the adipo-myogenic switch, PRDM16, expression in SCF and PBMC, and in circulating protein levels in the serum after 6 months of T therapy, which is likely from increased estradiol. Conclusion: Our study supports that molecular shift from the adipogenic to the myogenic pathway in men with hypogonadism treated with T could be mediated directly or indirectly by enhanced PRDM16 activity, in turn a result from increased estradiol level. This might have led to the reduction in body fat and increase in lean mass commonly seen in hypogonadal men treated with T.

Asunto(s)

Composición Corporal , Proteínas de Unión al ADN , Hipogonadismo , Testosterona , Factores de Transcripción , Humanos , Masculino , Testosterona/sangre , Persona de Mediana Edad , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/metabolismo , Hipogonadismo/sangre , Adulto , Anciano , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Composición Corporal/efectos de los fármacos , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Transducción de Señal/efectos de los fármacos , Terapia de Reemplazo de Hormonas

RESUMEN

OBJECTIVE: Aim: To determine the relationship between body composition and hormonal levels in young men with metabolic syndrome. PATIENTS AND METHODS: Materials and Methods: 123 males with a mean age of 24.1 ± 4.3 years (33 with metabolic syndrome (MS group) and 90 healthy physically active men (control group) were recruited at the study of body composition and hormone status. The total testosterone, cortisol, and insulin in blood serum by ELISA, the body weight (kg), lean body mass (kg) and fat mass (kg, %) by bioimpedance analysis method were investigated. RESULTS: Results: It was establish the significand difference the mean value of body composition (body weight, lean body weight, fat body mass (kg, %), testosterone, cortisol insulin, and glucose concentration between MS group and control group. CONCLUSION: Conclusions: A present study established the significant correlation of testosterone, insulin, and glucose concentration with fat body mass in all participants (MS and control groups). The negativee effect of overweight (BMI > 25; FBM > 18 %) and obesity (BMI > 30; FBM > 25 %) for testosterone concentration was determined due to an increase of FBM > 20 % and insulin increasing > 9,0 µlU/l.

Asunto(s)

Composición Corporal , Hidrocortisona , Insulina , Síndrome Metabólico , Testosterona , Humanos , Masculino , Síndrome Metabólico/sangre , Testosterona/sangre , Adulto , Adulto Joven , Insulina/sangre , Hidrocortisona/sangre , Glucemia/metabolismo , Glucemia/análisis , Índice de Masa Corporal

RESUMEN

BACKGROUND: The causal relationships between testosterone, estradiol, estrogen sulfotransferase, and idiopathic pulmonary fibrosis (IPF) are not well understood. This study employs a bidirectional two-sample Mendelian Randomization (MR) approach to explore these associations. METHODS: All genetic data utilized in our study were obtained from the IEU Open GWAS project. For the MR analysis, we employed the inverse variance weighted (IVW), MR-Egger, and weighted median methods to assess the causal relationships. We also conducted a multivariate MR (MVMR) analysis, with adjustments made for smoking. To ensure the robustness of our findings, sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression, the MR-PRESSO global test, and the leave-one-out method. RESULTS: Genetically predicted increases in serum testosterone levels by one standard deviation were associated with a 58.7% decrease in the risk of developing IPF (OR = 0.413, PIVW=0.029, 95% CI = 0.187 ∼ 0.912), while an increase in serum estrogen sulfotransferase by one standard deviation was associated with a 32.4% increase in risk (OR = 1.324, PIVW=0.006, 95% CI = 1.083 ∼ 1.618). No causal relationship was found between estradiol (OR = 1.094, PIVW=0.735, 95% CI = 0.650 ∼ 1.841) and the risk of IPF. Reverse MR analysis did not reveal any causal relationship between IPF and testosterone (OR = 1.001, PIVW=0.51, 95% CI = 0.998 ∼ 1.004), estradiol (OR = 1.001, PIVW=0.958, 95% CI = 0.982 ∼ 1.019), or estrogen sulfotransferase (OR = 0.975, PIVW=0.251, 95% CI = 0.933 ∼ 1.018). The MVMR analysis demonstrated that the association between testosterone (OR = 0.442, P = 0.037, 95% CI = 0.205 ∼ 0.953) and estrogen sulfotransferase (OR = 1.314, P = 0.001, 95% CI = 1.118 ∼ 1.545) and the risk of IPF persisted even after adjusting for smoking. CONCLUSIONS: Increased serum levels of testosterone are associated with a reduced risk of IPF, while increased levels of serum estrogen sulfotransferase are associated with an increased risk. No causal relationship was found between estradiol and the development of IPF. No causal relationship was identified between IPF and testosterone, estradiol, or estrogen sulfotransferase.

Asunto(s)

Estradiol , Fibrosis Pulmonar Idiopática , Análisis de la Aleatorización Mendeliana , Sulfotransferasas , Testosterona , Humanos , Estradiol/sangre , Sulfotransferasas/genética , Testosterona/sangre , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/sangre , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Femenino , Masculino , Factores de Riesgo

RESUMEN

Heat stress due to climate warming can significantly affect the synthesis of sex hormones in male adolescents, which can impair the ability of the hypothalamus to secrete gonadotropin-releasing hormone on the hypothalamic-pituitary-gonadal axis, which leads to a decrease in luteinizing hormone and follicle-stimulating hormone, which ultimately negatively affects spermatogenesis and testosterone synthesis. For optimal spermatogenesis, the testicular temperature should be 2-6 °C lower than body temperature. Heat stress directly affects the testes, damaging them and reducing testosterone synthesis. Additionally, chronic heat stress abnormally increases the level of aromatase in Leydig cells, which increases estradiol synthesis while decreasing testosterone, leading to an imbalance of sex hormones and spermatogenesis failure. Low levels of testosterone in male adolescents lead to delayed puberty and incomplete sexual maturation, negatively affect height growth and bone mineral density, and can lead to a decrease in lean body mass and an increase in fat mass. In order for male adolescents to acquire healthy reproductive capacity, it is recommended to provide sufficient nutrition and energy, avoid exposure to heat stress, and provide foods and supplements to prevent or repair testosterone reduction, germ cell damage, and sperm count reduction caused by heat stress so that they can enter a healthy adulthood.

Asunto(s)

Hormonas Esteroides Gonadales , Respuesta al Choque Térmico , Reproducción , Masculino , Adolescente , Humanos , Reproducción/fisiología , Hormonas Esteroides Gonadales/metabolismo , Respuesta al Choque Térmico/fisiología , Testosterona/sangre , Espermatogénesis , Testículo/crecimiento & desarrollo , Maduración Sexual/fisiología

RESUMEN

OBJECTIVES: To evaluate the possible association between androgenic alopecia (AGA) and lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: A total of 148 patients aged over 45 with LUTS secondary to BPH were prospectively enrolled in this study. According to the Norwood-Hamilton classification, the patients were divided into two groups: AGA (n = 69) and non-AGA (n = 79). In addition, the cases of AGA were categorized as vertex (n = 39) and frontal baldness (n = 30). The International Prostate Symptom Score (IPSS), uroflowmetry parameters, prostate volume, serum total testosterone (TT), and free and total prostate-specific antigen concentrations of all patients were assessed and compared between the groups. Correlations between the AGA grade and other variables were also investigated. RESULTS: The serum TT level (354 ± 97.1 vs. 308.6 ± 73.1 ng/dL, p = 0.01), total IPSS (16.1 ± 8.1 vs. 13.4 ± 7.7, p = 0.04), IPSS storage subscore (IPSS-S) (7.1 ± 3.5 vs. 5.8 ± 3.6, p = 0.03), and number of nocturia episodes (2.5 ± 1.4 vs. 1.8 ± 1.4, p < 0.01) were significantly higher in the AGA group than in the non-AGA group. There were no significant differences in any of the parameters between the patients with vertex and frontal baldness. The AGA grade showed a significant positive correlation with the TT level (r = 0.407, p = 0.003), IPSS-S (r = 0.164, p = 0.04), and number of nocturia episodes (r = 0.203, p = 0.015). CONCLUSIONS: This study demonstrated that among patients with LUTS, those with AGA had worse symptoms and higher TT levels compared with those without AGA of similar age. Furthermore, the AGA grade was positively correlated with the TT level and storage symptoms.

Asunto(s)

Alopecia , Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Testosterona , Humanos , Masculino , Hiperplasia Prostática/complicaciones , Alopecia/complicaciones , Alopecia/etiología , Síntomas del Sistema Urinario Inferior/etiología , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Testosterona/sangre , Índice de Severidad de la Enfermedad , Antígeno Prostático Específico/sangre

RESUMEN

BACKGROUND: Since the discovery of COVID-19 in December 2019, the novel virus has spread globally causing significant medical and socio-economic burden. Although the pandemic has been curtailed, the virus and its attendant complication live on. A major global concern is its adverse impact on male fertility. AIM: This study was aimed to give an up to date and robust data regarding the effect of COVID-19 on semen variables and male reproductive hormones. MATERIALS AND METHODS: Literature search was performed according to the recommendations of PRISMA. Out of the 852 studies collected, only 40 were eligible for inclusion in assessing the effect SARS-CoV-2 exerts on semen quality and androgens. More so, a SWOT analysis was conducted. RESULTS: The present study demonstrated that SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio. CONCLUSIONS: The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels.

Asunto(s)

COVID-19 , SARS-CoV-2 , Análisis de Semen , Testosterona , Humanos , Masculino , Testosterona/sangre , SARS-CoV-2/aislamiento & purificación , Fertilidad , Infertilidad Masculina/virología , Infertilidad Masculina/sangre , Hormona Luteinizante/sangre , Recuento de Espermatozoides , Semen/virología , Semen/metabolismo , Motilidad Espermática

RESUMEN

OBJECTIVE: Female sexual dysfunction (FSD) is highly prevalent and can result from hypovitaminosis D. Besides the role of vitamin D in normal bone development, studies showed it could reduce oxidative stress and lipid peroxidation. This prospective study aims to evaluate the relationship between serum vitamin D, testosterone, and oxidative stress levels in women with FSD. MATERIALS AND METHODS: In this cross-sectional study, a total of 40 women with FSD (age range: 18-45 years) were randomly assigned into two groups of intervention and control. In the intervention group, patients received vitamin D 300,000 IU intramuscularly (IM) and then 50,000 IU orally once a week for four weeks. We measured the serum vitamin D, testosterone, and oxidative stress levels, as well as the Female Sexual Function Index (FSFI) at baseline and monthly for three months. RESULTS: Serum testosterone levels significantly increased in the intervention group at the end of the third month (P = 0.014). Also, FSFI scores significantly improved (P < 0.01) in the intervention group compared to the control group. While there was positive a correlation between serum vitamin D levels with glutathione, total antioxidant capacity (TAC), testosterone, and FSFI score, there was a negative correlation between serum vitamin D levels with malondialdehyde (MDA), protein carbonyl, and nitric oxide. CONCLUSION: We witnessed that women with FSD had low serum vitamin D levels. So, modifying serum vitamin D levels must be considered as a treatment option. Moreover, vitamin D supplementation improved testosterone, serum oxidative stress, and sexual function.

Asunto(s)

Estrés Oxidativo , Disfunciones Sexuales Fisiológicas , Testosterona , Vitamina D , Humanos , Femenino , Testosterona/sangre , Estrés Oxidativo/efectos de los fármacos , Adulto , Vitamina D/sangre , Estudios Transversales , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven , Estudios de Casos y Controles , Disfunciones Sexuales Fisiológicas/sangre , Disfunciones Sexuales Fisiológicas/etiología , Adolescente , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/complicaciones , Vitaminas/administración & dosificación , Vitaminas/sangre

RESUMEN

OBJECTIVE: In this study, we aimed to explore the potential association between COVID-19 infection, hospitalization, severe COVID-19, and erection dysfunction (ED) using the two-sample Mendelian randomization (MR) method. METHODS: Data pertaining to COVID-19 were extracted from the latest version of the COVID-19 Host Genetics Initiative genome-wide association study (GWAS) meta-analyses (Round 7, April 2022), and outcome data were obtained from the Open GWAS database. We applied various MR analysis methods, including the inverse variance weighted method, weighted median method, and MR-Egger regression. RESULTS: Our investigation revealed a negative causal association between COVID-19 hospitalization and ED (total testosterone levels: beta = -0.026; 95% confidence interval: -0.049 to -0.001). However, no evidence supported causal relationships between COVID-19 infection, hospitalization for COVID-19, or severe COVID-19 and other ED risk factors. CONCLUSION: The results of this comprehensive MR analysis suggest a negative causal link between COVID-19 hospitalization and total testosterone levels. Nonetheless, COVID-19 (comprising infection, hospitalization, and severe illness) may not directly correlate with an increased risk of ED. These findings imply that COVID-19 may exert a distinct impact on ED through indirect pathways.

Asunto(s)

COVID-19 , Disfunción Eréctil , Estudio de Asociación del Genoma Completo , Hospitalización , Análisis de la Aleatorización Mendeliana , SARS-CoV-2 , Testosterona , Humanos , COVID-19/genética , COVID-19/complicaciones , COVID-19/virología , Masculino , Disfunción Eréctil/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , Testosterona/sangre , Factores de Riesgo , Polimorfismo de Nucleótido Simple

RESUMEN

This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.

Asunto(s)

Hipotálamo , Subunidad alfa del Factor 1 Inducible por Hipoxia , Síndrome del Ovario Poliquístico , Piroptosis , Ratas Wistar , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/patología , Femenino , Animales , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/patología , Piroptosis/efectos de los fármacos , Ratas , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Resistencia a la Insulina , Factor 2 Relacionado con NF-E2/metabolismo , Modelos Animales de Enfermedad , Letrozol/farmacología , Triglicéridos/sangre , Triglicéridos/metabolismo , Hormona Luteinizante/sangre , Hormona Folículo Estimulante/sangre , Adiponectina/metabolismo , Adiponectina/sangre , Testosterona/sangre , Leptina/sangre , Leptina/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Ácido gamma-Aminobutírico/metabolismo

Asunto(s)

Neoplasias de la Próstata , Testosterona , Humanos , Neoplasias de la Próstata/cirugía , Masculino , Testosterona/sangre , Testosterona/uso terapéutico

RESUMEN

OBJECTIVE: Transgender women who underwent gonadectomy have lower serum testosterone concentrations than cisgender women. There is uncertainty regarding the dosing and side effects of supplementation of testosterone in transgender women. This study aimed to assess the feasibility of dosing testosterone to the cisgender female physiological range in transgender women. In addition, we explored changes in cardiovascular parameters, virilizing side effects, and clinical symptoms. DESIGN: This is an open-label, single-arm feasibility study. Participants initially went through a dose-titration phase with 2-week intervals of 0.07-0.09-0.13 mL (277-318-403 µg bioavailable testosterone) testosterone 2% gel to establish a dose leading to serum testosterone concentrations between 1.5 and 2.5 nmol/L. This dose was then continued for 8 weeks. METHODS: Participants applied daily transdermal testosterone 2% gel (Tostran®) at the prescribed dosage. Testosterone was measured every 2-4 weeks. Laboratory analyses, side effects, and clinical symptoms were evaluated. RESULTS: In total, 12 participants were included. Most participants required a dose of 0.07 mL (277 µg bioavailable testosterone) or 0.09 mL (318 µg bioavailable testosterone) to reach serum testosterone concentrations of 1.5-2.5 nmol/L. Continuing this dose, testosterone concentrations remained stable throughout the study. Changes in clinical outcomes were in the desired direction, and side effects were mild. CONCLUSIONS: The use of testosterone supplementation in transgender women seems feasible and safe in the short term. Although dosing requires personalized titration, stable testosterone levels can be established. A blinded, placebo-controlled, randomized clinical trial is needed to study the clinical benefit.

Asunto(s)

Estudios de Factibilidad , Testosterona , Personas Transgénero , Humanos , Testosterona/administración & dosificación , Testosterona/sangre , Femenino , Adulto , Masculino , Persona de Mediana Edad , Adulto Joven , Relación Dosis-Respuesta a Droga , Administración Cutánea , Andrógenos/administración & dosificación , Andrógenos/sangre , Andrógenos/efectos adversos , Terapia de Reemplazo de Hormonas/métodos

RESUMEN

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.

Asunto(s)

Quimiocinas , Obesidad , Hormonas Peptídicas , Síndrome del Ovario Poliquístico , Fumar , Humanos , Femenino , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Obesidad/sangre , Obesidad/metabolismo , Adulto , Hormonas Peptídicas/sangre , Quimiocinas/sangre , Fumar/efectos adversos , Fumar/sangre , Índice de Masa Corporal , Péptidos y Proteínas de Señalización Intercelular/sangre , Lipocalina 2/sangre , Apelina/sangre , Adulto Joven , Testosterona/sangre , Insulina/sangre

RESUMEN

HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical trial, conducted at two sites in South Africa from 2018-2019, randomized HIV-negative women aged 18-40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214-218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p < 0.0001); NET-EN D0 0.551, 25W 0.253 nmol/L, -54.1%, (p < 0.0001)], SHBG [DMPA-IM D0 45.0, 25W 32.7 nmol/L, -29.8% (p < 0.0001); NET-EN D0 50.2, 25W 17.6 nmol/L, -65.1% (p < 0.0001)], and calculated free testosterone levels [DMPA-IM D0 6.87, 25W 5.38 pmol/L, -17.2% (p = 0.0371); NET-EN D0 6.00, 25W 3.70, -40.0% (p < 0.0001)]. After adjusting for change from D0, the total testosterone, SHBG and calculated free testosterone levels were significantly higher for DMPA-IM than NET-EN (64.9%, p < 0.0001; 101.2%, p < 0.0001; and 38.0%, p = 0.0120, respectively). The substantial and differential decrease in testosterone and SHBG levels does not explain our previous finding of no detected decrease in risky sexual behavior or sexual function for DMPA-IM or NET-EN users from D0 to 25W. Medroxyprogesterone (MPA) and NET are androgenic and are both present in molar excess over testosterone and SHBG concentrations at 25W. Any within or between contraceptive group androgenic effects on behavior in the brain are likely dominated by the androgenic activities of MPA and NET and not by the decreased endogenous testosterone levels. The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).

Asunto(s)

Anticonceptivos Femeninos , Acetato de Medroxiprogesterona , Noretindrona , Globulina de Unión a Hormona Sexual , Testosterona , Humanos , Femenino , Noretindrona/administración & dosificación , Noretindrona/análogos & derivados , Acetato de Medroxiprogesterona/administración & dosificación , Testosterona/sangre , Adulto , Globulina de Unión a Hormona Sexual/metabolismo , Globulina de Unión a Hormona Sexual/análisis , Adolescente , Adulto Joven , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/farmacología , Inyecciones Intramusculares

RESUMEN

Paradoxical sleep deprivation (PSD) presents different effects on metabolism and neurological functions. In addition, over long duration, sleep restriction (SR) can promote permanent changes. The prostate is an endocrine-dependent organ with homeostatic regulation directly related to hormone levels. Our study proposed to demonstrate the experimental prostatic effects of PSD (96 h), PSD with recovery (PSR - 96/96 h), and sleep restriction (SR - 30 PSD cycles/recovery). PSD and SR promoted decrease in serum testosterone and significant increase in serum and intraprostatic corticosterone. In agreement, androgen receptors (AR) were less expressed and glucocorticoid receptors (GR) were enhanced in PSR and SR. Thus, the prostate, especially under SR, demonstrates a castration-like effect due to loss of responsiveness and sensitization by androgens. SR triggered an important inflammatory response through enhancement of serum and intraprostatic pro- (IL-1α, IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines. Furthermore, the respective receptors of anti-inflammatory cytokines (IL-1RI and TNF-R) were highly expressed in the prostatic epithelium and stroma. PSR can partially restore prostate homeostasis, as it restores testosterone and the prostate proliferation index, in addition to promoting balance in the inflammatory response that is considered protective. PSD and SR are key factors in the endocrine axis that coordinate prostatic homeostasis, and significant changes in these factors have consequences on prostate functionality.

Asunto(s)

Gerbillinae , Próstata , Receptores Androgénicos , Privación de Sueño , Testosterona , Animales , Masculino , Privación de Sueño/metabolismo , Privación de Sueño/patología , Próstata/metabolismo , Próstata/patología , Testosterona/sangre , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Corticosterona/sangre , Citocinas/metabolismo , Inflamación/metabolismo , Inflamación/patología , Castración , Andrógenos/metabolismo

RESUMEN

Social behavior is sexually dimorphic, which is regulated by gonadal hormones in the brain. Our recent study found that exposure to low doses of bisphenol-A (BPA) during adolescence, permanently alters social behavior in adult male mice, but the underlying mechanisms remain unclear. Using adolescent gonadectomy (GDX) male mice with testosterone propionate (TP, 0.5 mg/kg) supplement (TP-GDX), this study showed that BPA antagonized promoting effects of TP on social interaction, sexual behavior, and aggression in GDX mice. BPA eliminated the reversal effects of TP on GDX-induced decrease in the number of immunoreactive to arginine vasopressin (AVP-ir) neurons in the medial amygdala (MeA) and the levels of AVP receptor 1a (V1aR) in the MeA and the nucleus accumbens (NAc). In addition, BPA removed down-regulation in the levels of dopamine (DA) transporter (DAT) and DA receptor 1 (DR1) in the NAc of TP-GDX mice. BPA exposure reduced testosterone (T) levels in the brain and serum and the expression of androgen receptor (AR) protein in the amygdala and striatum of sham-operated and TP-GDX males. These results suggest that adolescent exposure to BPA inhibits regulation of androgen in AVP and DA systems of the brain regions associated with social behavior, and thus alters social behaviors of adult male mice.

Asunto(s)

Compuestos de Bencidrilo , Fenoles , Receptores Androgénicos , Conducta Social , Animales , Masculino , Fenoles/toxicidad , Compuestos de Bencidrilo/toxicidad , Compuestos de Bencidrilo/farmacología , Ratones , Receptores Androgénicos/metabolismo , Receptores Androgénicos/efectos de los fármacos , Testosterona/sangre , Testosterona/metabolismo , Receptores de Dopamina D1/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/efectos de los fármacos , Agresión/efectos de los fármacos , Conducta Sexual Animal/efectos de los fármacos , Andrógenos/farmacología , Propionato de Testosterona/farmacología , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Arginina Vasopresina/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo

RESUMEN

The timing of exposure to the steroid hormone, testosterone, produces activational and organizational effects in vertebrates. These activational and organizational effects are hypothesized to relate with the number of female mating partners and reproductive success in males. We tested this hypothesis by examining 151 wild degu (Octodon degus) males across a 10-year study. We quantified the association between adult serum testosterone levels (i.e., an indirect index of adult activational effects) and anogenital distance (AGD) length (i.e., a direct index of fetal organizational effects), and their interaction on the number of female mating partners and reproductive success. We found no evidence of an association between adult male serum testosterone levels and the number of female mating partners, or between adult male serum testosterone levels and reproductive success. However, male AGD was positively associated with reproductive success, but not so with the number of female mating partners. Additionally, the positive association between male AGD and male reproductive success was mediated by the number of mates. Our findings do not support major roles of activational or organizational effects of testosterone on the number of female mating partners and its consequences on male reproductive success. Instead, our results suggest that compared with individual male attributes, the female social environment plays a more important role in driving male reproductive success.

Asunto(s)

Reproducción , Conducta Sexual Animal , Testosterona , Masculino , Animales , Testosterona/farmacología , Testosterona/sangre , Femenino , Conducta Sexual Animal/efectos de los fármacos , Conducta Sexual Animal/fisiología , Reproducción/fisiología , Reproducción/efectos de los fármacos , Octodon/fisiología , Parejas Sexuales , Conducta Social

RESUMEN

Maternal behavior experienced in early life provides essential scaffolding to infant psychobiology with life-long effects on neurobiological and behavioral outcomes. However, infants are not passive recipients of caregiving. Evidence in rodents suggests that pups actively contribute to dam-pup interactions by soliciting maternal care with auditory, tactile, and hormonal cues. The limited bedding and nesting material (LBN) rearing manipulation induces changes in maternal care that have been attributed to maternal stress caused by the low-resource environment. The goal of the current study was to determine whether LBN also alters pup cues for maternal behavior, with implications for the mechanism of LBN-induced effects. Rat dams and pups were randomly assigned to LBN or Control rearing conditions on postnatal day (P) 0-6 and pups were fostered to the same or different condition on P6-13. LBN increased pup-directed maternal behaviors measured through 24 h monitoring using machine learning based automated analysis. LBN altered several pup cues known to affect maternal behavior including reducing pup core body temperature, reducing body weight, and altering pup vocalizations on P6 and P12. P6-13 LBN-exposed pups had elevated serum testosterone, which positively correlated with maternal licking and grooming. LBN reduced pup movement between nest attendance onset and the start of nursing, which was negatively related to dam nursing latency and contributed to longer nursing latency in LBN dams. P0-6 pup exposure to LBN also led to longer nest attendance bouts and shorter licking and grooming bouts on P7 and P9, suggesting lasting effects of LBN on pups. These data demonstrate that LBN changes pup behavioral and hormonal signals consistent with eliciting more maternal care, contributing to augmented pup-directed behaviors. This bidirectional interplay may be a critical mechanism involved in the lasting effects of early life environments.

Asunto(s)

Animales Recién Nacidos , Señales (Psicología) , Conducta Materna , Animales , Conducta Materna/fisiología , Femenino , Ratas , Masculino , Conducta Animal/fisiología , Testosterona/sangre , Ratas Long-Evans , Ambiente , Ratas Sprague-Dawley , Vocalización Animal/fisiología

RESUMEN

BACKGROUND: The efficacy of GLP1 receptor agonists (GLP1-RAs) in treating polycystic ovarian syndrome (PCOS) remains unclear. While GLP1-RAs are known to promote weight loss in patients with diabetes and living with obesity, their impact on weight reduction and hormonal regulation in women with PCOS is understudied. Therefore, we aimed to assess the efficacy of GLP1-RAs in PCOS women living with obesity through a meta-analysis, comparing their effects to placebo. HYPOTHESIS: The use of GLP1-RAs in PCOS women living with obesity can reduce body mass index and waist circumference as well as improve hyperinsulinism, and hyperandrogenism as well as normalize total testosterone, total cholesterol and HOMA-IR markers in PCOS women living with obesity. METHODS: We systematically searched the PubMed, Cochrane Central, Scopus and Embase databases to identify randomized controlled trials (RCT) comparing GLP1-RAs versus placebo among women diagnosed with PCOS based on the Rotterdam Criteria. Our primary outcomes of interest included body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. We performed data extraction and quality assessment for studies that met the inclusion criteria. We pooled mean difference (MD) and 95 % confidence intervals (CI) with a random-effect model for continuous endpoints. RESULTS: We included 176 participants from four RCTs. Semaglutide and Liraglutide were used in 23 (13 %) and 103 (58 %) participants, respectively. GLP1-RAs use was associated with a significant reduction in waist circumference (MD: -5.16 cm; 95 % CI: -6.11 to -4.21; p ˂ 0.00001), body mass index (BMI) (MD: -2.42; 95 % CI: -3.10 to -1.74; p ˂ 0.00001), serum triglycerides (MD: -0.20; 95 % CI: -0.30 to -0.11; p ˂ 0.00001) and total testosterone levels (MD: -1.33; 95 % CI: -2.55 to -0.12; p = 0.03) when compared to placebo. There was no significant difference in total cholesterol (MD: -0.04; 95 % CI: -0.10 to 0.01; p = 0.15) and HOMA-IR (MD: -0.30; 95 % CI: -0.92 to 0.32; p = 0.35) levels. Adverse events information was available for 112 patients, where 49 had light side effects such as nausea and abdominal pain. CONCLUSION: The use of GLP1-RAs demonstrates efficacy in reducing BMI, triglycerides, waist circumference and total testosterone. There was no significant difference in total cholesterol and HOMA-IR levels. These results signify its viability as a favourable treatment option for managing PCOS symptoms in women living with obesity.

Asunto(s)

Obesidad , Síndrome del Ovario Poliquístico , Ensayos Clínicos Controlados Aleatorios como Asunto , Pérdida de Peso , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/sangre , Femenino , Pérdida de Peso/efectos de los fármacos , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/sangre , Receptor del Péptido 1 Similar al Glucagón/agonistas , Liraglutida/uso terapéutico , Resultado del Tratamiento , Testosterona/sangre , Índice de Masa Corporal , Hipoglucemiantes/uso terapéutico , Adulto , Circunferencia de la Cintura/efectos de los fármacos , Resistencia a la Insulina