高氟对成年男性生殖内分泌功能的影响

为了探讨高氟对成年男性生殖功能的影响，对地方性氟中毒重病区的31名成年男性（20～55岁）及26名对照人群的有关生殖内分泌指标进行了检测，结果显示：高氟区人群血清黄体生成素（LH）、卵泡刺激素（FSH）较对照组明显升高（P＜0．001）；血清睾酮（T）水平则显著降低（P＜0．01），表明高氟状态能够影响成年男性的生殖内分泌功能。     

睾酮及氟他胺对雄兔动脉粥样硬化斑块稳定性与血清炎症因子的调节

目的探讨睾酮和氟他胺对动脉粥样硬化斑块稳定性与血清炎症因子的调节作用。方法主动脉病理切片行HE染色和Masson氏三色染色。血浆睾酮采用Advia Centaur免疫检测系统测定,血清肿瘤坏死因子和白细胞介素6采用放射免疫测定,血清可溶性细胞间粘附分子1和基质金属蛋白酶2应用酶联免疫吸附测定法检测。结果雄兔去睾丸后血浆睾酮水平显著降低,补充十一酸睾酮(每2周6mg/kg)使血浆睾酮恢复到正常水平,而且十一酸睾酮这一作用不受雄激素受体拮抗剂氟他胺的影响。去睾丸雄兔补充十一酸睾酮显著减小动脉粥样斑块的面积和内膜厚度,并使斑块纤维帽增厚、胶原含量增加。然而,同时补充雄激素受体拮抗剂氟他胺使去睾丸雄兔动脉粥样斑块的面积和内膜厚度增加,并使斑块纤维帽厚度减低、胶原含量下降。与假手术高脂喂养雄兔比较,去睾丸雄兔血清肿瘤坏死因子、白细胞介素6、可溶性细胞间粘附分子1和基质金属蛋白酶2显著升高;去睾丸雄兔补充十一酸睾酮后,血清肿瘤坏死因子、白细胞介素6、可溶性细胞间粘附分子1和基质金属蛋白酶2较单纯去睾丸雄兔明显降低;去睾丸雄兔同时补充氟他胺与十一酸睾酮,血清肿瘤坏死因子、白细胞介素6、可溶性细胞间粘附分子1和基质金属蛋白酶2水平再次显著升高。结论睾酮与氟他胺可以调节雄兔动脉粥样硬化斑块进展与斑块的稳定性,并影响其血清炎症因子水平。     

Reduced breast cancer incidence in women treated with subcutaneous testosterone,or testosterone with anastrozole: A prospective,observational study

Objectives

There is evidence that androgens are breast protective and that testosterone therapy treats many symptoms of hormone deficiency in both pre and postmenopausal patients. However, unlike estrogen and progestins, there is a paucity of data regarding the incidence of breast cancer in women treated with testosterone therapy. This study was designed to investigate the incidence of breast cancer in women treated with subcutaneous testosterone therapy in the absence of systemic estrogen therapy.

Study design

This is a 5-year interim analysis of a 10-year, prospective, observational, IRB approved study investigating the incidence of breast cancer in women presenting with symptoms of hormone deficiency treated with subcutaneous testosterone (T) implants or, T combined with the aromatase inhibitor anastrozole (A), i.e., T + A implants. Breast cancer incidence was compared with that of historical controls reported in the literature, age specific Surveillance Epidemiology and End Results (SEER) incidence rates, and a representative, similar age group of our patients used as a ‘control’ group. The effect of adherence to T therapy was also evaluated.

Results

Since March 2008, 1268 pre and post menopausal women have been enrolled in the study and eligible for analysis. As of March 2013, there have been 8 cases of invasive breast cancer diagnosed in 5642 person-years of follow up for an incidence of 142 cases per 100 000 person-years, substantially less than the age-specific SEER incidence rates (293/100 000), placebo arm of Women's Health Initiative Study (300/100 000), never users of hormone therapy from the Million Women Study (325/100 000) and our control group (390/100 000). Unlike adherence to estrogen therapy, adherence to T therapy further decreased the incidence of breast cancer (73/100 000).

Conclusion

T and/or T + A, delivered subcutaneously as a pellet implant, reduced the incidence of breast cancer in pre and postmenopausal women. Evidence supports that breast cancer is preventable by maintaining a T to estrogen ratio in favor of T and, in particular, by the use of continuous T or, when indicated, T + A. This hormone therapy should be further investigated for the prevention and treatment of breast cancer.     

The effects of puberty on white matter development in boys

Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD) and fractional anisotropy (FA) in 61 males aged 12.7–16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n = 22) and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n = 39). Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol) were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty × age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone.     

The effects of long-term estradiol-17beta treatment on the growth and physiology of female triploid brook trout (Salvelinus fontinalis)

Triploid female fish show impaired gonadal development, which results in the production of only a few oocytes relative to diploids. The rate of maturation of these few oocytes in much slower relative to those of diploids and is attributed to an insufficient estradiol-17beta (E(2)) stimulus. Female triploid brook trout, aged 2+, were fed E(2) for seven months (i.e., July 1998 to February 1999) in an attempt to increase plasma E(2) comparable to diploid levels and thereby accelerate rates of oocyte growth. Compared to triploids fed a normal diet (i.e., control-triploids), the administration of 30 mg E(2)/kg feed to triploids (i.e., E(2)-treated-triploids) led to the development of secondary sex characteristics, a significant reduction in hematocrit and total blood hemoglobin level, a decrease in plasma testosterone and no weight gain. Plasma vitellogenin was significantly higher in E(2)-treated-triploids than in control-triploids and diploids at every month except October 1999. Although greater than in the control-triploids, plasma E(2) for the E(2)-treated-triploids did not attain the high levels shown by the diploids during the months of peak vitellogenesis (i.e., September and October). Following maturation and spawning of diploids, sacrificed E(2)-treated and control-triploids showed no differences in ovarian development or liver size. The E(2) dose for the treated-triploids was increased to 80 mg E(2)/kg feed for approximately seven more weeks in a further attempt to increase plasma E(2), with no success. It is suggested that the low plasma E(2) of the treated-triploids was the result of a high metabolic clearance rate.     

Effect of Rehabilitation Program on Endocrinological Parameters in Patients with COPD and in Healthy Subjects

Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation and endocrinological disturbance. The aim of this study is to analyze the effect of rehabilitation program on the balance of anabolic versus catabolic hormone in patients with COPD and in healthy subjects. Methods: Nineteen patients with COPD and 16 age-matched healthy subjects undertooked exercise training 3 days/week for 8 weeks. Before and after the training program the concentration of growth hormone (GH), Insulin-Like Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 3 (IGF-BP3), testosterone and cortisol in serum were determined. The exercise measurements included a 6-Minute Walking Test (6MWT). Results: After 8 weeks, there was no significant change in lung function in patients with COPD and healthy subjects. Growth hormone, Insulin-like Growth Factor-1 and Insulin-like Growth Factor-Binding Protein 3 increased significantly after rehabilitation training (p < 0.01). The rehabilitation program improves the testosterone/cortisol ratio (T/C ratio) in both groups. There is a significant improvement in the 6-Minute Walking distance (6MWD) in both groups (p < 0.01). Dyspnea and heart rate at rest and at the peak of the 6-Minute Walking Test (6MWT) decreased significantly after training program (p < 0.01). Conclusion: Pulmonary rehabilitation induces an improvement of the anabolic process and reduces proteine distruction by the modifications in endocrinological factors regulating skeletal muscle in patients with COPD.     

The effect of vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and testosterone deficiency

BackgroundAutoimmune (Hashimoto’s thyroiditis) is characterized by a strong female preponderance, which may suggest that sex hormones have an impact on thyroid autoimmunity. The aim of this study was to investigate whether testosterone determines vitamin D action on thyroid antibody titers and thyroid function tests in men with autoimmune thyroiditis and low testosterone levels.MethodsThe study included 36 men with testosterone deficiency, 17 of whom had been treated for at least 26 weeks with oral testosterone undecanoate (120 mg daily). Because of coexistent euthyroid Hashimoto’s thyroiditis, all participants were then treated with vitamin D (100 μg daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin, free thyroid hormones, testosterone and 25-hydroxyvitamin D, as well as Jostel’s thyrotropin index, SPINA-GT and SPINA-GD were assessed before vitamin D treatment and 26 weeks later.ResultsWith the exception of testosterone levels, there were no significant differences between both study groups in serum hormone levels, antibody titers and thyroid function tests. All participants completed the study. In addition to increasing 25-hydroxyvitamin D levels, vitamin D increased SPINA-GT and reduced thyroid peroxidase and thyroglobulin antibody titers. In testosterone-treated men, vitamin D increased testosterone levels. Vitamin D did not affect serum levels of thyrotropin, free thyroid hormones, Jostel’s thyrotropin index and SPINA-GD. Treatment-induced changes in thyroid antibody titers and SPINA-GT were more pronounced in testosterone-treated than testosterone-naïve men.ConclusionsThe obtained results suggest that the beneficial effect on thyroid autoimmunity and thyroid secretory function is stronger in men receiving testosterone therapy.     

Pharmacodynamic effects of intravenous alcohol on hepatic and gonadal hormones: influence of age and sex

Background: Growth hormone (GH)–insulin‐like growth factor‐1 (IGF‐1) axis and gonadal hormones demonstrate extensively associated regulation; however, little is known about the effects of acute alcohol exposure on these hormones. This study examined the effects of intravenous alcohol on the GH–IGF‐1 axis and gonadal hormone concentrations, and the influence of age and sex on their regulation. Methods: Forty‐eight healthy volunteers (24 men and 24 women each in the 21 to 25 and 55 to 65 year age groups) underwent a 2‐session single‐blinded study. Subjects received in randomized counter‐balanced order, alcohol infusions, individually computed based on a physiologically based pharmacokinetic model, to maintain a steady‐state (“clamped”) exposure of 50 mg% or saline for 3 hours in separate sessions. Blood samples collected at baseline and postinfusion in each session were assayed for levels of GH, IGF‐1, free testosterone, and estradiol. Results: Acute alcohol administration resulted in changes in gonadal hormones that differed by sex. Change in free testosterone showed a significant treatment × baseline interaction (p < 0.001), indicating that alcohol‐induced suppression of testosterone occurred predominantly in men. On the other hand, change in estradiol showed a significant treatment × sex interaction (p = 0.028), indicating that alcohol‐induced increases in estradiol occurred predominantly in women. There was a trend for alcohol‐induced decreases in IGF‐1 levels. Change in GH showed a significant main effect of baseline (p < 0.001) and a trend for treatment by baseline interaction, suggesting an alcohol‐induced decrease in individuals with high baseline GH values. There was also a significant main effect of sex (p = 0.046) indicating that men had greater changes in GH across treatment compared with women. Conclusions: Alcohol induced a complex pattern of hormonal responses that varied between younger and older men and women. Some of the observed sex‐based differences may help improve our understanding of the greater susceptibility to alcohol‐related hepatic damage seen in women.