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1.
Endocrine ; 71(2): 281-282, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33492642
2.
BMJ Case Rep ; 14(1)2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33414114

RESUMEN

We present an unusual case of mucinous cystadenoma presenting with severe virilisation in a postmenopausal woman. A 71-year-old woman was referred to our outpatient endocrinology clinic because of rapidly progressive androgenic alopecia, clitoromegaly and male pattern pubic hair growth for 1 year. Her medical history was unremarkable. The serum testosterone level was 3.35 µg/L (normal range, <0.4 µg/L), and the dehydroepiandrosterone sulfate level was 267 µg/L (normal range, 100-800 µg/L). MRI of the abdomen revealed a 4×4 cm cystic ovarian mass. A bilateral salpingo-oophorectomy was performed, and histopathology showed a unilocular cystic structure with a yellowish content, compatible with mucinous cystadenoma. Postoperative testosterone levels quickly normalised (<0.4 µg/L).Rapidly developing postmenopausal hyperandrogenism easily turns into a diagnostic challenge for the clinician. Hormone-secreting neoplasms of the ovary are most commonly of sex cord stromal derivation, but atypical causes must be recognised as well. Cystadenomas are among the most common benign ovarian neoplasms and are classically considered 'non-functional' tumours. Most of these tumours are asymptomatic and found incidentally on pelvic examination or with ultrasound. To date and to the best of our knowledge, there are only five cases of mucinous adenoma causing virilisation in postmenopausal women identified in the literature. This sixth case adds strength to the link between ovarian mucinous cystadenoma and severe, rapidly progressive hyperandrogenism during menopause. In this case, surgical resection is the treatment of choice.


Asunto(s)
Cistoadenoma Mucinoso/complicaciones , Hiperandrogenismo/etiología , Neoplasias Ováricas/complicaciones , Posmenopausia/fisiología , Anciano , Cistoadenoma Mucinoso/cirugía , Femenino , Humanos , Neoplasias Ováricas/cirugía , Salpingooforectomía , Testosterona/sangre , Virilismo/etiología
3.
Ecotoxicol Environ Saf ; 208: 111748, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396074

RESUMEN

Microcystin-leucine arginine (MC-LR) is a kind of toxin produced by cyanobacterial, resulting in decrease of testosterone levels in serum and leading to impaired spermatogenesis. Gonadotropin-releasing hormone (GnRH) neurons play crucial roles in the regulation of testosterone release. Meanwhile, it has been demonstrated that MC-LR is capable of entering the GnRH neurons and inducing apoptosis. Nevertheless, the molecular mechanism of MC-LR induced apoptosis of GnRH neurons remains elusive. In present study, we found that MC-LR inhibited the cell viability of GT1-7 cells. In addition, we discovered apoptosis of GnRH neurons and GT1-7 cells treated with MC-LR. And increased intracellular ROS production and the release of intracellular Ca2+ were all observed following exposure to MC-LR. Furthermore, we also found the endoplasmic reticulum stress (ERs) and autophagy were activated by MC-LR. Additionally, pretreatment of the ERs inhibitor (4-Phenyl butyric acid) reduced the apoptotic rate of GT1-7 cells comparing with MC-LR exposure alone. Comparing with MC-LR treatment alone, apoptotic cell death was increased by pretreatment of GT1-7 cells with an autophagy inhibitor (3-methyladenine). Together, our data implicated that the treatment of MC-LR induced the apoptosis of GnRH neurons by activating the ERs resulting in a decrease of serum testosterone level in mice. Autophagy is a protective cellular process which was activated by ER stress and thus protected cells from apoptosis upon MC-LR exposure.


Asunto(s)
Estrés del Retículo Endoplásmico , Microcistinas/toxicidad , Testosterona/sangre , Animales , Apoptosis , Arginina/metabolismo , Bioensayo , Supervivencia Celular , Cianobacterias/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Leucina/metabolismo , Masculino , Toxinas Marinas/metabolismo , Ratones , Microcistinas/metabolismo , Neuronas/metabolismo , Testosterona/metabolismo
4.
Eur J Endocrinol ; 184(2): 337-346, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33428587

RESUMEN

Objective: Staphylococcus aureus is a major human pathogen, and nasal carriers have an increased risk for infection and disease. The exploration of host determinants for nasal carriage is relevant to decrease infection burden. Former studies demonstrate lower carriage prevalence in women and among users of progestin-only contraceptives. The aim of this study was to investigate the possible associations between circulating sex-steroid hormones and nasal carriage of Staphylococcus aureus in a general population. Methods: In the population-based sixth Tromsø study (2007-2008) nurses collected nasal swab samples from 724 women aged 30-87 not using any exogenous hormones, and 700 of the women had a repeated nasal swab taken (median interval 28 days). We analysed a panel of serum sex-steroids by liquid chromatography tandem mass spectrometry, and collected information about lifestyle, health and anthropometric measures. Multivariable logistic regression was used to study the association between circulating sex-steroids and Staphylococcus aureus carriage (one swab) and persistent carriage (two swabs), while adjusting for potential confounding factors. Women in luteal phase were excluded in the analysis of androgens. Results: Staphylococcus aureus persistent nasal carriage prevalence was 22%. One standard deviation increase in testosterone and bioavailable testosterone was associated with lower odds of persistent nasal carriage, (OR = 0.57; 95% CI = 0.35-0.92 and OR = 0.52, 95% CI = 0.30-0.92) respectively. Analysis stratified by menopause gave similar findings. Persistent carriers had lower average levels of androstenedione and DHEA, however, not statistically significant. Conclusion: This large population-based study supports that women with lower levels of circulating testosterone may have increased probability of Staphylococcus aureus persistent carriage.


Asunto(s)
Portador Sano/microbiología , Hormonas Esteroides Gonadales/sangre , Cavidad Nasal/microbiología , Staphylococcus aureus , Adulto , Anciano , Anciano de 80 o más Años , Androstenodiona/sangre , Portador Sano/epidemiología , Deshidroepiandrosterona/sangre , Femenino , Humanos , Menopausia , Persona de Mediana Edad , Posmenopausia , Prevalencia , Infecciones Estafilocócicas/epidemiología , Testosterona/sangre
5.
Cochrane Database Syst Rev ; 1: CD013211, 2021 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482034

RESUMEN

BACKGROUND: Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial. OBJECTIVES: Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work. SELECTION CRITERIA: RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 µmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels. AUTHORS' CONCLUSIONS: We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.


Asunto(s)
Atorvastatina/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Síndrome del Ovario Poliquístico/sangre , Testosterona/sangre , Anciano , Andrógenos/sangre , Androstenodiona/sangre , Atorvastatina/efectos adversos , Sesgo , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Placebos/farmacología , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores Sexuales , Globulina de Unión a Hormona Sexual/análisis , Globulina de Unión a Hormona Sexual/efectos de los fármacos
6.
J Ethnopharmacol ; 264: 113382, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32918991

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Crassostrea gigas Thunberg and other oysters have been traditionally used in China as folk remedies to invigorate the kidney and as natural aphrodisiacs to combat male impotence. AIM OF THE STUDY: Erectile dysfunction (ED) has become a major health problem for the global ageing population. The aim of this study is therefore to evaluate the effect of peptide-rich preparations from C. gigas oysters on ED and related conditions as increasing evidence suggests that peptides are important bioactive components of marine remedies and seafood. MATERIALS AND METHODS: Crassostrea oyster peptide (COP) preparations COP1, COP2 and COP3 were obtained from C. gigas oysters by trypsin, papain or sequential trypsin-papain digestion, respectively. The contents of testosterone, cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in mice and/or cells were measured by enzyme-linked immunosorbent assays. Real-time PCR was used to assess the expression of genes associated with sex hormone secretion pathways. The model animal Caenorhabditis elegans was also used to analyze the gene expression of a conserved steroidogenic enzyme. In silico analysis of constituent peptides was performed using bioinformatic tools based on public databases. RESULTS: The peptide-rich preparation COP3, in which >95% peptides were <3000 Da, was found to increase the contents of male mouse serum testosterone and cAMP, both of which are known to play important roles in erectile function, and to increase the activity of mouse penile NOS, which is closely associated with ED. Further investigation using mouse Leydig-derived TM3 cells demonstrates that COP3 was able to stimulate the production of testosterone as well as NO, a pivotal mediator of penile erection. Real-time PCR analysis reveals that COP3 up-regulated the expression of Areg and Acvr2b, the genes known to promote sex hormone secretion, but not Fst, a gene involved in suppressing follicle-stimulating hormone release. Furthermore, COP3 was also shown to up-regulate the expression of let-767, a well-conserved C. elegans gene encoding a protein homologous to human 17-ß-hydroxysteroid dehydrogenases. Preliminary bioinformatic analysis using the peptide sequences in COP3 cryptome identified 19 prospective motifs, each of which occurred in more than 10 peptides. CONCLUSIONS: In this paper, Crassostrea oyster peptides were prepared by enzymatic hydrolysis and were found for the first time to increase ED-associated biochemical as well as molecular biology parameters. These results may help to explain the ethnopharmacological use of oysters and provide an important insight into the potentials of oyster peptides in overcoming ED-related health issues.


Asunto(s)
Factores Biológicos/aislamiento & purificación , Factores Biológicos/farmacología , Crassostrea/enzimología , Fragmentos de Péptidos/aislamiento & purificación , Fragmentos de Péptidos/farmacología , Testosterona/sangre , Animales , Caenorhabditis elegans , Células Cultivadas , Biología Computacional/métodos , Relación Dosis-Respuesta a Droga , Pruebas de Enzimas/métodos , Hidrólisis , Masculino , Ratones
7.
Biomed Pharmacother ; 133: 111085, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33378981

RESUMEN

Obesity is a significant global health and socio-economic challenge, and considered an important risk factor for poor health outcomes including male reproductive dysfunction and infertility. As excess adiposity causes testicular dysfunction and infertility, novel therapeutic strategies require investigation. Nigella sativa (Ns) seed oil and metformin have both demonstrated a potential positive effect on obesity, although both remain poorly investigated in male fertility. Therefore, this study aimed to determine the effect of Ns oil and metformin on total body weight (TBW), mitochondrial membrane potential (MMP), serum testosterone and semen parameters in an obese animal model. Wistar rats (n = 54) were divided into six groups: normal chow (NC), high sugar diet (HSD) only, HSD and saline, HSD and metformin (75 mg/Kg/day), HSD and Ns (200 mg/Kg/day) (NS200), HSD and Ns (400 mg/Kg/day) (NS400). Intervention was force fed for the last 8 weeks of the 14 weeks dietary exposures. Results showed that the HSD increased TBW (P = 0.001) and reduced sperm concentration (P = 0.013) and progressive motility (P = 0.009) compared to the NC group. Metformin, NS200 and NS400 improved TBW (P = 0.035, P = 0.006 and P = 0.005, respectively) and testosterone (P < 0.001) compared to the HSD saline group, where metformin and NS400 improved sperm concentration (P < 0.001 and P = 0.049, respectively) and MMP (P < 0.001). There were no changes in sperm motility and viability for all experimental exposures, although NS400 (P = 0.047) negatively affected sperm viability. Metformin and Ns may be novel treatment options in obesity-induced infertility, although a potential negative impact on viability is cautioned for high dose Ns. These results warrant further investigation of Ns and Metformin for the management of obese infertile males.


Asunto(s)
Fármacos Antiobesidad/farmacología , Fármacos para la Fertilidad Masculina/farmacología , Fertilidad/efectos de los fármacos , Infertilidad Masculina/prevención & control , Metformina/farmacología , Obesidad/tratamiento farmacológico , Aceites Vegetales/farmacología , Espermatozoides/efectos de los fármacos , Testosterona/sangre , Animales , Biomarcadores/sangre , Modelos Animales de Enfermedad , Infertilidad Masculina/sangre , Infertilidad Masculina/patología , Infertilidad Masculina/fisiopatología , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Obesidad/sangre , Obesidad/patología , Ratas Wistar , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/metabolismo , Espermatozoides/patología
8.
Ecotoxicol Environ Saf ; 207: 111563, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33254417

RESUMEN

Exposure to endocrine-disrupting chemicals (EDCs) has been hypothesized as a cause of declining sheep reproductive efficiency. Understanding the long-term effects of EDCs such as heavy metals on reproductive health requires investigation in 'real life' of sheep that are reared in industrial areas. The aim of this study was to evaluate the effect of long-term exposure of Kermani rams to high levels of environmental heavy metals probably emitted from a copper smelter at KhatoonAbad in ShahreBabak, Kerman province. Testicular characteristics were determined in randomly-selected rams (3-4 years old) at 4 directions (south, north, east, and west) and 4 distances (10, 20, 30, and 40 km) from the smelter. Testicular trace element contents, size, serum testosterone, histological attributes and seminal characteristics, except semen volume, were affected by both the direction and the distance from the smelter (P < 0.05). Testicular contents of Pb, Cd, Cr, and Ni, and sperm abnormalities were higher at 10 km south from the smelter and lower at 40 km west. Other parameters were higher at 40 km west and lower at 10 km south. Interestingly, the testicular contents of Cu at 10 km south were lower and associated with higher sperm abnormalities in the rams reared closer to the smelter. The highest weight, length and circumference of the testis were found at 40 km west. The lowest concentration of testosterone was observed at 10 km south, being 92.6% lower than the highest values obtained at 40 km west. The diameter of seminiferous tubules and epithelial height at 10 km south were 8.9% and 27.5% lower than the highest values obtained at 40 km west. A positive correlation between Pb, Cd, Cr and Ni contents in the testis with sperm abnormalities, and a negative correlation between these elements with the other parameters were found. It was concluded that long-term exposure to heavy metals might have been a cause of decreased fertility in rams and probably other living species in this region.


Asunto(s)
Contaminantes Ambientales/toxicidad , Metales Pesados/toxicidad , Testículo/efectos de los fármacos , Animales , Cobre/toxicidad , Masculino , Reproducción , Análisis de Semen/veterinaria , Ovinos , Espermatozoides/efectos de los fármacos , Espermatozoides/fisiología , Testículo/fisiología , Testosterona/sangre , Pruebas de Toxicidad Crónica , Oligoelementos/metabolismo
9.
Metabolism ; 114: 154399, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33058848

RESUMEN

BACKGROUND: Little is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM). METHODS: We evaluated 1128 older men free of cardiovascular disease in a prospective cohort study using data from the Cardiovascular Health Study. T and DHT were measured by liquid chromatography-tandem mass spectrometry and SHBG by fluoroimmunoassay. Our outcomes included incident hip fracture (n = 106) over a median of 10.2 years and BMD and LBM by dual-energy x-ray absorptiometry (n = 439). RESULTS: In Cox regression models mutually adjusted for T, SHBG, and covariates, each standard deviation increment in DHT (0.23 ng/ml) was associated with a 26% lower risk of hip fracture (adjusted hazard ratio [aHR] 0.74, 95% confidence interval (CI) 0.55-1.00, p = 0.049). Similarly, SHBG was associated with fracture in mutually adjusted models (aHR HR 1.26, 95% CI, 1.01-1.58, p = 0.045). In contrast, T (aHR, 1.16, 95% CI, 0.86-1.56, p = 0.324) was not significantly associated with fracture in mutually adjusted models. T, DHT and SHBG were not associated with BMD. T and DHT were both positively associated with LBM in individual models. CONCLUSIONS: In older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not. Future studies should elucidate the mechanisms by which DHT affects bone health.


Asunto(s)
Envejecimiento/fisiología , Densidad Ósea/fisiología , Dihidrotestosterona/sangre , Fracturas de Cadera/epidemiología , Testosterona/sangre , Absorciometría de Fotón , Anciano , Anciano de 80 o más Años , Composición Corporal/fisiología , Fémur/diagnóstico por imagen , Fracturas de Cadera/metabolismo , Articulación de la Cadera/diagnóstico por imagen , Humanos , Incidencia , Masculino , Estudios Prospectivos , Riesgo , Globulina de Unión a Hormona Sexual/metabolismo , Espectrometría de Masas en Tándem
10.
Chemosphere ; 262: 127792, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32805656

RESUMEN

Tebuconazole is a triazole fungicide, used in agriculture to treat phytopathogenic fungi, and as a biocide, has been reported to be related to reproductive and developmental toxicity. The purpose of this study was to investigate the effect of tebuconazole exposure on rat fetal Leydig cells and fetal testis during pregnancy. Pregnant Sprague-Dawley rats were randomly divided into 4 groups, daily gavaged with corn oil (as a control), 25, 50, and 100 mg/kg body weight tebuconazole for 10 days (from the 12th day of pregnancy). Tebuconazole increased fetal serum testosterone and progesterone levels at a dose of 100 mg/kg. Exposure to 100 mg/kg tebuconazole significantly caused an increase in the number of fetal Leydig cells per testis without inducing cell aggregation. Tebuconazole up-regulated the expression of Star, Cyp11a1, Hsd17b3, and Fshr and their proteins. Further investigation found that tebuconazole caused increased phosphorylation of AKT1, ERK1/2, and mTOR, the level of BCL2, as well as the decrease of Beclin1, LC3B, and BAX, which may contribute to the fetal Leydig cell autophagy and proliferation. In conclusion, in utero exposure of tebuconazole causes the proliferation of fetal Leydig cells.


Asunto(s)
Fungicidas Industriales/toxicidad , Células Intersticiales del Testículo/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Reproducción/efectos de los fármacos , Triazoles/toxicidad , Animales , Femenino , Células Intersticiales del Testículo/metabolismo , Masculino , Fosfoproteínas/genética , Fosforilación , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Testículo/efectos de los fármacos , Testículo/embriología , Testículo/patología , Testosterona/sangre , Regulación hacia Arriba
11.
Eur J Endocrinol ; 184(1): 107-122, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33112262

RESUMEN

Objective: Hypogonadism is common in HIV-infected men. The relationship between health status, sex steroids and body composition is poorly known in HIV. The aim was to investigate the association between health status (comorbidities/frailty), body composition, and gonadal function in young-to-middle-aged HIV-infected men. Design: Prospective, cross-sectional, observational study. Methods: HIV-infected men aged <50 years and ongoing Highly Active Antiretroviral Therapy were enrolled. Serum total testosterone (TT), estradiol (E2), estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, LH and FSH by immunoassay. Free testosterone (cFT) was calculated by Vermeulen equation. Body composition was assessed by dual-energy X-ray absorptiometry and abdominal CT scan. Multimorbidity (MM) and frailty were defined as ≥3 comorbidities and by a 37-item index, respectively. Results: A total of 316 HIV-infected men aged 45.3 ± 5.3 years were enrolled. Body fat parameters were inversely related to cFT and TT, and directly related to E1 and E2/testosterone (TS) ratio. Patients with MM had lower cFT (P < 0.0001) and TT (P = 0.036), and higher E1 (P < 0.0001) and E2/TS ratio (P = 0.002). Frailty was inversely related to cFT (R2 = 0.057, P < 0.0001) and TT (R2 = 0.013, P = 0.043), and directly related to E1 (R2 = 0.171, P < 0.0001), E2 (R2 = 0.041, P = 0.004) and E2/TS ratio (R2 = 0.104, P < 0.0001). Conclusions: Lower TT and cFT, higher E1, E2/TS ratio and visceral fat were independently associated to poor health status and frailty, being possible hallmarks of unhealthy conditions in adult HIV-infected men. Overall, MM, frailty and body fat mass are strictly associated to each other and to sex steroids, concurring together to functional male hypogonadism in HIV.


Asunto(s)
Tejido Adiposo , Estrona/sangre , Infecciones por VIH/fisiopatología , Hipogonadismo/fisiopatología , Testosterona/sangre , Absorciometría de Fotón , Adulto , Terapia Antirretroviral Altamente Activa , Composición Corporal , Estudios Transversales , Fragilidad/fisiopatología , Fragilidad/virología , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estado de Salud , Indicadores de Salud , Humanos , Hipogonadismo/virología , Masculino , Persona de Mediana Edad , Multimorbilidad , Estudios Prospectivos
12.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-33370966

RESUMEN

A 64-year-old postmenopausal female patient presented with approximately 5 years of intermittent spotting, progressive hirsutism and significantly increased libido and clitoral hypersensitivity with spontaneous orgasms multiple times a day beginning a few months prior. Initial hormone work-up revealed elevated total serum testosterone, androstenedione and 17-hydroxyprogesterone. Luteinising hormone, follicle stimulating hormone, estradiol, dehydroepiandrosterone-sulfate, thyroid stimulating hormone and prolactin were all within normal limits. Initial suspicions suggested an androgen-secreting tumour, likely in the ovary. The lesion was undetectable on transvaginal ultrasound and abdominal-pelvic CT scan. Laparoscopic bilateral salpingo-oophorectomy was performed to remove the likely source of excess androgens. Visible gross lesions were not observed intraoperatively; however, bilateral Leydig (hilus cell) tumours were confirmed by histopathology. Serum testosterone, androstenedione and 17-hydroxyprogesterone levels were normalised postoperatively within 2 weeks and 1 month, respectively.


Asunto(s)
Hirsutismo/etiología , Tumor de Células de Leydig/diagnóstico , Neoplasias Ováricas/diagnóstico , Ovario/patología , 17-alfa-Hidroxiprogesterona/sangre , Androstenodiona/sangre , Femenino , Humanos , Tumor de Células de Leydig/sangre , Tumor de Células de Leydig/complicaciones , Tumor de Células de Leydig/cirugía , Persona de Mediana Edad , Neoplasias Ováricas/sangre , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/cirugía , Ovario/cirugía , Posmenopausia , Salpingooforectomía , Testosterona/sangre , Resultado del Tratamiento
13.
Zhonghua Nan Ke Xue ; 26(3): 237-241, 2020 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33346963

RESUMEN

Objective: To investigate the effect of Jiarong Tablets (JRT) on the testicular morphology and function of rats with late-onset hypogonadism (LOH). METHODS: LOH models were established in 8 eighteen-month-old male SD rats, treated intragastrically with distilled water (the model control group, n = 4) or JRT at 0.375 g/kg/d, qd (the JRT group, n = 4), and another 5 two-month-old normal male SD rats were also given distilled water by gavage (normal control group), all for 28 days. Then all the rats were weighed and sacrificed for measurement of the serum T level and pathological and electron microscopic examination of the testis tissue. RESULTS: Compared with the normal controls, the LOH models showed significantly decreased testis coefficient (P < 0.05) and serum T level (ï¼»3.40 ± 0.06ï¼½ vs ï¼»5.88 ± 0.46ï¼½ ng /ml, P < 0.05). No statistically significant differences were observed in the model control and JRT groups in the body weight and testis coefficient (P > 0.05), but the serum T level (ï¼»4.50 ± 0.78ï¼½ ng/ml) was remarkably decreased in the latter (P < 0.05). In comparison with the model controls, the rats treated with JRT exhibited increases in the sperm count in the seminiferous tubules and the amount of testicular interstitial cells. Electron microscopy revealed a markedly increased number of mitochondria in the JRT-treated animals, with some mitochondrial sheaths and cristae but no obvious mitochondrial edema. CONCLUSIONS: Jiarong Tablets can elevate the serum T level and improve the testicular morphology and ultrastructure of LOH rats.


Asunto(s)
Medicamentos Herbarios Chinos , Hipogonadismo , Testículo/efectos de los fármacos , Animales , Medicamentos Herbarios Chinos/farmacología , Hipogonadismo/tratamiento farmacológico , Masculino , Ratas , Ratas Sprague-Dawley , Recuento de Espermatozoides , Comprimidos , Testículo/anatomía & histología , Testosterona/sangre
14.
J Vis Exp ; (166)2020 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-33369605

RESUMEN

Sex steroids, produced by the gonads, play an essential role in brain and pituitary tissue plasticity and in the neuroendocrine control of reproduction in all vertebrates by providing feedback to the brain and pituitary. Teleost fishes possess a higher degree of tissue plasticity and variation in reproductive strategies compared to mammals and appear to be useful models to investigate the role of sex steroids and the mechanisms by which they act. The removal of the main source of sex steroid production using gonadectomy together with blood sampling to measure steroid levels has been well-established and fairly feasible in bigger fish and is a powerful technique to investigate the role and effects of sex steroids. However, these techniques raise challenges when implemented in small size teleost models. Here, we describe the step-by-step procedures of gonadectomy in both males and female Japanese medaka followed by blood sampling. These protocols are shown to be highly feasible in medaka indicated by a high survival rate, safety for the life span and phenotype of the fish, and reproducibility in terms of sex steroid clearance. The use of these procedures combined with the other advantages of using this small teleost model will greatly improve the understanding of feedback mechanisms in the neuroendocrine control of reproduction and tissue plasticity provided by sex steroids in vertebrates.


Asunto(s)
Recolección de Muestras de Sangre/métodos , Tamaño Corporal , Castración , Oryzias/anatomía & histología , Oryzias/sangre , Animales , Castración/instrumentación , Estradiol/sangre , Femenino , Gónadas/cirugía , Masculino , Modelos Animales , Oviposición , Reproducibilidad de los Resultados , Suturas , Testosterona/análogos & derivados , Testosterona/sangre
15.
PLoS One ; 15(12): e0243732, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33332460

RESUMEN

BACKGROUND: Chronic rhinosinusitis may be associated with nasal polyposis. Recurrence of disease is often observed and may be due to an intolerance of acetylsalicylic acid. Sex hormones are known to modulate allergic reactions and inflammation. Whether they may be involved in the development and progression of nasal polyposis has not been investigated yet. AIM: Examine the relationship between levels of sex hormones and nasal polyposis. METHODS: Hormonal levels (estradiol, testosterone and progesterone) in patients with nasal polyposis (n = 26) with or without acetylsalicylic acid-intolerance were determined and compared to hormonal levels in patients with septal deviation (n = 35). Cone-beam computed tomography scans were analysed by using scores as defined by Lund and Mackay and by Kennedy. RESULTS: Our results show a 5 times greater odds (p = 0.01) for developing nasal polyposis in the presence of lowered estradiol plasma levels than in the presence of normal / elevated levels. When analyzing females and males separately, a 6 times greater odds for females to develop nasal polyposis in the presence of lowered estradiol plasma levels was calculated (p = 0.02). Thus, females are more likely to develop nasal polyposis when they have lowered estradiol levels than males. In addition, female patients showed an increased risk for developing ASA intolerance (p = 0.01). CONCLUSION: Variation of sex hormones may be involved in nasal polyposis. Further studies including more patients to validate the presented results are required. SIGNIFICANCE: Retrospective clinical investigation suggesting a correlation between varying sex hormones and nasal polyposis.


Asunto(s)
Aspirina/efectos adversos , Hipersensibilidad a las Drogas/epidemiología , Estradiol/sangre , Pólipos Nasales/inmunología , Progesterona/sangre , Testosterona/sangre , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Tomografía Computarizada de Haz Cónico , Hipersensibilidad a las Drogas/sangre , Hipersensibilidad a las Drogas/inmunología , Estradiol/inmunología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mucosa Nasal/diagnóstico por imagen , Pólipos Nasales/sangre , Pólipos Nasales/diagnóstico , Progesterona/inmunología , Recurrencia , Estudios Retrospectivos , Rinitis/sangre , Rinitis/inducido químicamente , Rinitis/epidemiología , Rinitis/inmunología , Sinusitis/sangre , Sinusitis/inducido químicamente , Sinusitis/epidemiología , Sinusitis/inmunología , Testosterona/inmunología , Adulto Joven
16.
Artículo en Inglés | MEDLINE | ID: mdl-33322590

RESUMEN

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, infertility, obesity, and insulin resistance, which results in increased concentrations of testosterone (T), which disturbs follicular growth and ovulation. This study aimed to assess PCOS women's clinical, endocrinological, and metabolic parameters concerning hyperandrogenism severity. RESULTS: 314 women (mean age 27.3 ± 4.6; mean body mass index (BMI) 25.7 ± 5.6) with PCOS, were divided into terciles according to T concentrations: <0.64 ng/mL (group 1), 0.64 to 0.84 ng/mL (Group 2) and >0.84 ng/mL (group 3). The mean concentration of T in all women was 0.59 ng/mL and correlated negatively with the number of menstrual cycles per year (MPY) (r = -0.36; p < 0.0001) and positively with Ferriman-Gallway score (FG) (r = 0.33; p < 0.0001), luteinizing hormone (LH) (r = 0.19; p < 0.0001) and dehydroepiandrosterone sulfate (DHEAS) (r = 0.52; p < 0.0001). Positive correlation between BMI and hirsutism (r = 0.16; p < 0.0001), total cholesterol (TC) (r = 0.18; p < 0.0001), low-density lipoprotein (LDL) (r = 0.29; p < 0.0001), and triglycerides (TG) (r = 0.40; p < 0.0001) was demonstrated. The division into subgroups confirmed the lowest MPY, highest LH, and hirsutism in group 3. BMI, insulin sensitivity indices, and lipid profile parameters were not different between the three T subgroups. CONCLUSIONS: We found no correlation between testosterone levels and insulin sensitivity or dyslipidemia in women with PCOS. Metabolic abnormalities may contribute more significantly than hyperandrogenemia to PCOS development.


Asunto(s)
Hormona Luteinizante/sangre , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Índice de Masa Corporal , Sulfato de Deshidroepiandrosterona/sangre , Dislipidemias , Femenino , Hirsutismo , Humanos , Resistencia a la Insulina , Testosterona/sangre , Adulto Joven
17.
Eur J Endocrinol ; 183(6): R167-R183, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33105105

RESUMEN

Overt hypogonadism in men adversely affects body composition and metabolic health, which generally improve upon testosterone (TS) therapy. As obese men often display lower serum TS levels, in particular when they present with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), there have been claims that androgen therapy prevents or reverses obesity and improves metabolic health. This has contributed to the increase in TS prescriptions during the past two decades. In this narrative review, based on findings from larger observational studies and randomized controlled intervention trials, we evaluate whether low TS predicts or predisposes to obesity and its metabolic consequences, and whether obese men with low TS are truly hypogonadal. We further describe the mechanisms underlying the bi-directional relationships of TS levels with obesity and metabolic health, and finally assess the evidence for TS therapy in men with obesity, MetS and/or T2DM, considering efficacy, safety concerns and possible alternative approaches. It is concluded that low serum sex hormone-binding globulin and total TS levels are highly prevalent in obese men, but that only those with low free TS levels and signs or symptoms of hypogonadism should be considered androgen deficient. These alterations are reversible upon weight loss. Whether low TS is a biomarker rather than a true risk factor for metabolic disturbances remains unclear. Considering the limited number of sound TS therapy trials have shown beneficial effects, the modest amplitude of these effects, and unresolved safety issues, one cannot in the present state-of-the-art advocate TS therapy to prevent or reverse obesity-associated metabolic disturbances. Instead, the focus should remain on lifestyle measures and management of obesity-related consequences.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/métodos , Hipogonadismo/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Testosterona/uso terapéutico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Hipogonadismo/sangre , Hipogonadismo/complicaciones , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Obesidad/sangre , Obesidad/complicaciones , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre , Resultado del Tratamiento
18.
Eur J Endocrinol ; 183(5): 529-536, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33071222

RESUMEN

Objective: Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step toward individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change. Design and methods: Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from the start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage. Results: A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR: 0.67, 95% CI: 0.48-0.94 per SD increase in testosterone and OR: 1.36, 95% CI: 1.01-1.83 per SD increase in LH). Conclusions: There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individual effects rather than solely relying on a standardized dosage of hormone therapy.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Andrógenos/uso terapéutico , Composición Corporal , Estradiol/uso terapéutico , Estrógenos/uso terapéutico , Testosterona/uso terapéutico , Personas Transgénero , Adulto , Distribución de la Grasa Corporal , Acetato de Ciproterona/uso terapéutico , Relación Dosis-Respuesta a Droga , Impedancia Eléctrica , Estradiol/sangre , Femenino , Humanos , Hormona Luteinizante/sangre , Masculino , Medicina de Precisión , Procedimientos de Reasignación de Sexo/métodos , Testosterona/análogos & derivados , Testosterona/sangre , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
19.
Science ; 370(6513): 208-214, 2020 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-33033216

RESUMEN

Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.


Asunto(s)
Adaptación Fisiológica/genética , Factor 9 de Crecimiento de Fibroblastos/genética , Topos/genética , Elementos Reguladores de la Transcripción , Diferenciación Sexual/genética , Esteroide 17-alfa-Hidroxilasa/genética , Animales , Inversión Cromosómica , Conjuntos de Datos como Asunto , Femenino , Regulación de la Expresión Génica , Genoma , Ratones , Ratones Transgénicos , Secuencias Repetidas en Tándem , Testosterona/sangre , Testosterona/genética
20.
Eur J Endocrinol ; 183(6): 561-569, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33055297

RESUMEN

Objective: The impact of different combinations of long-term gender-affirming hormone therapy (GAHT) in transwomen (TW) is largely unknown. To assess the effects of 5-year administration of cyproterone acetate (CPA) or leuprolide acetate (Leu) plus transdermal or oral estradiol (E). Design: Cohort study based on prospectively collected data. Fifty TW received 50 mg CPA daily orally (n = 25; CPA+E group) or 3.75 mg Leu i.m. monthly (n = 25; Leu+E group) with 1 or 2 mg E daily for 5 years. Reproductive hormones, biochemical and anthropometric parameters, body composition and bone mineral density (BMD) were assessed. Results: LH, FSH and total testosterone levels were similarly and significantly suppressed in both groups. Prolactin increased only in the CPA+E group (P = 0.002). Fasting insulin resistance and glucose progressively increased in the CPA+E group only (treatment × time effect P = 0.002 and P = 0.043, respectively). Total cholesterol increased more in the Leu+E group than in the CPA+E group and HDL-cholesterol decreased in the CPA+E group (time × treatment interaction effect, P = 0.007). Lumbar and total body BMD increased in both groups after 3 years. No serious adverse events were recorded. Conclusions: Both regimens were effective in suppression of T production. CPA+E worsened the metabolic profile with a slight increase in PRL levels. All subjects presented an increase in BMD regardless of treatment. These preliminary data could have clinical implications in the choice of GAHT, in particular for those TW not requiring gender-affirming surgery.


Asunto(s)
Acetato de Ciproterona/administración & dosificación , Estradiol/administración & dosificación , Leuprolida/administración & dosificación , Testosterona/sangre , Transexualidad/sangre , Transexualidad/tratamiento farmacológico , Adulto , Antagonistas de Andrógenos/administración & dosificación , Estudios de Cohortes , Esquema de Medicación , Quimioterapia Combinada , Estrógenos/administración & dosificación , Femenino , Fármacos para la Fertilidad Femenina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Testosterona/antagonistas & inhibidores , Personas Transgénero
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