Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy

The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown.To address this knowledge gap,we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment.Puberty was suppressed by orchidectomy in male mice at 5 weeks of age.At 3 weeks post-surgery,male-to-female mice were treated with a high dose of estradiol(~0.85 mg)by intraperitoneal silastic implantation for 12 weeks.Controls included intact and orchidectomized males at 3 weeks post-surgery,vehicle-treated intact males,intact females and orchidectomized males at 12 weeks post-treatment.Compared to male controls,orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture.Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis,while the periosteal circumference increased to a level that was intermediate between intact male and female controls,resulting in increased maximal force and stiffness.In trabecular bone,estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate,consistent with the anabolic action of estradiol on osteoblast proliferation.These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT.Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.

【特刊综述】男性雄激素缺乏：一种多系统综合征

雄性激素对于多器官系统有重要影响，而这些器官系统对男性一生的健康比如调节性功能、身体功能和行为学功能起着决定性作用。雄激素缺乏是一种多系统综合征，表现出与明显的血清睾酮低水平相关的典型临床特征。雄激素缺乏的临床表现因年龄和其它诸如并存病、遗传因素、环境因素及社会文化因素等患者个体特性而不同。

Diagnosis and treatment of hypogonadism in older men： proceed with caution

Male hypogonadism, defined as clinical features of androgen deficiency combined with confirmed unequivocally low testosterone levels [1], is a straightforward diagnosis in younger men with tmderlying testicular and pituitary pathology. The diagnosis ofhypogonadism in older men is challenging, because of the non-specificity of symptoms and the age-related decline in testosterone levels which is accelerated by chronic disease and obesity.

Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.

Testicular volume and clinical correlates of hypothalamic–pituitary–testicular function:A cross-sectional study in obese men

The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic–pituitary–testicular(HPT)axis function.This was a cross-sectional substudy of a larger randomized controlled trial including obese men,body mass index(BMI)≥30 kg m−2,with a total testosterone level<12 nmol l−1.Testicular volume was measured by orchidometer,testosterone by liquid chromatography/tandem mass spectrometry,and body composition by dual-energy X-ray absorptiometry.Men completed the Aging Males'Symptoms(AMS)score,International Index of Erectile Function-5(IIEF-5),physical function,and handgrip dynamometer testing.Eighty-nine men participated with a median(interquartile range[IQR])age of 53.1(47.6,59.2)years,BMI of 37.0(34.6,40.5)kg m−2,and a total testosterone of 7.0(6.1,7.9)nmol l−1.Median testicular volume was 18(IQR:10,20)ml.Testicular volume was negatively correlated with BMI(τ=−0.1952,P=0.010)and total fat mass(τ=−0.2115,P=0.005)independent of age and testosterone.When BMI,testosterone,sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were present in a multivariable model,only BMI(-0.38 ml change in testicular volume per 1 kg m-2BMI;95%CI:−0.74,−0.02;P=0.04)and LH(-0.92 ml change in testicular volume per 1 IU l-1 LH;95%CI:−1.75,−0.095;P=0.03)remained independent significant predictors of testicular volume.Testicular volume was positively correlated with IIEF-5(τ=0.2092,P=0.021),but not related to handgrip strength,physical function tests,or AMS.In obese men,testicular volume is inversely and independently associated with measures of adiposity,but not with most clinical or biochemical markers of HPT axis action.From a clinical perspective,this suggests that obesity might compromise the reliability of reduced testicular volume as a sign of androgen deficiency in men.

Testosterone treatment in older men： glass half empty or half full？

在在 JAMA 和 JAMA 实习生 Med 出版的一系列使随机化的控制试用，美国研究人员与睾丸激素层次在老人检验了睾丸激素治疗的效果<冠的动脉匾体积上的 275 ng dl 1， 1 认知功能， 2 贫血症， 3 并且容量的骨头 density.4 当试用在贫血症和骨头密度关于改进显示出积极结果时，长术语的研究被要求描出在这张人口的长期的风险和好处。

Plasma miRNA expression profile in the diagnosis o＇ late-onset hypogonadism

在自然杂志报导科学 Reports1 的研究人员使用了定序的下一代和量的反向的 transcriptase PCR (RT-PCR ) 技术介绍血浆 microRNA (miRNA ) 在有或没有迟了发作的性腺机能减退(LOH ) 的人的队的表示。学习作为新奇 biomarkers 建议三 miRNAs 的一块面板帮助 LOH 的诊断。