Aromatization of androgens is important for skeletal maintenance of aged male rats

A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6–10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9–14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance. Received: 13 October 1995 / Accepted: 23 February 1996     

Inhibition of human adrenal androgen secretion by ketoconazole

Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.Abbreviations CV coefficient of variation - MV mean value - SEM standard error of the mean - f female - m male - K ketoconazole - ACTH adrenocorticotropic hormone - DHEA dehydroepiandrosterone - DHEAS dehydroepiandrosterone sulfate - A androstenedione - T testosterone - F cortisol - P progesterone - H hirsutism - C Cushing's disease - EAS ectopic ACTH syndrome - ATU adrenal tumor     

睾酮对雄性家兔血管损伤后内皮功能及内膜增生的影响

目的:探讨睾酮对雄性家兔腹主动脉球囊损伤后内皮功能及内膜增生的影响。方法:选择健康雄性新西兰白兔24只随机分成3组:对照组(假去势)、低睾酮血症组(去势)及睾酮替代组(去势1周后加用长效十一酸睾酮单次肌注,14mg/kg),每组8只。去势10d后对所有动物行腹主动脉球囊损伤术。损伤后两周测血浆睾酮、血脂、一氧化氮代谢产物(NO₂^-/NO₃^-)、超氧化物歧化酶(SOD)及丙二醛(MDA)水平,并截取腹主动脉进行图像分析。结果:睾酮替代组和对照组的血浆总胆固醇、甘油三酯、低密度脂蛋白及MDA水平和新生内膜面积明显低于低睾酮血症组(P＜0.01或P＜0.05),睾酮替代组和对照组的NO₂^-/NO₃^-及对照组的SOD水平高于低睾酮血症组(P均＜0.05),替代组和对照组两组间比较各数据无差异。结论:生理水平的睾酮(内源性或外源性替代)具有保护雄性家兔血管内皮,抑制动脉损伤后内膜增生的作用。     

Treatment of keratoconjunctivitis sicca with topical androgen

Objective: Androgens have been reported to influence lipid production of sebaceous glands and even many ocular tissues. The effect of topical androgen therapy on a 54-year-old patient with keratoconjunctivitis sicca (KCS) and decreased lipid phase of the tear film is reported. Methods: For assessment of the lipid phase of the tear film, break up time (BUT) and lipid layer thickness (LLT) were monitored during 6 months before treatment as well as 3 months while using a daily topical androgen therapy. Results: During the topical androgen therapy the pathological lipid phase of the tear film was completely restored indicated by the normalisation of the values of BUT and LLT. Conclusion: These findings are consistent with animal experiments indicating that topical administered androgen can restore the decreased lipid phase of the tear film. This may open up new therapeutic strategies for KCS.     

Effects of hormonal replacement with androgens and estrogens on male sexual behavior and plasma levels of these steroids in gonadectomized golden hamsters (Mesocricetus auratus)

Because the endocrine control of sexual behavior in male hamsters remains controversial, this study analyzed the influence of different androgens and estrogens in the regulation of masculine, sexual behavior (MBS). Aromatizable androgens: androstenedione (A) and testosterone (T), a non-aromatizable androgen: 5α-dihydrotestosterone (DHT), as well as estrogens (E₂ and E₁) alone or in combination with DHT, were administered in gonadectomized, sexually experienced males, for 3 weeks. In addition, plasma levels of these steroids were determined. Gonadectomy completely suppressed masculine sexual behavior (MSB) after 4 weeks. Both A and T replacements restored all the sexual behavior parameters in castrated hamsters by the 3rd week of treatment, with A being more potent in restoring all copulatory series and maintaining all MSB parameters, including long intromissions. Castrated males treated with DHT showed little interest in the female and did not display any copulatory behavior. Gonadectomized males treated with estrogens alone showed active anogenital investigation and displayed some mounts, but did not ejaculate. Males treated with estrogens combined with DHT had longer latencies and less number of ejaculations than males treated with aromatizable androgens. Long intromissions were observed only in males treated with T or A. Plasma levels of A were significantly higher than T levels in intact males. In males treated with A both androgens and estrogens were present in plasma. These results support the notion that aromatizable androgens, mainly A, but not non-aromatizable androgens or even estrogens in combination with DHT, play a relevant role in the endocrine regulation of MSB in the golden hamster.     

Bone Mineral Density and Androgen Levels in Elderly Males

To clarify the relationship of sex male hormones and bone in men, we studied in 140 healthy elderly men (aged 55–90 years) the relation between serum levels of androgens and related sex hormones, bone mineral density (BMD) at different sites, and other parameters related to bone metabolism. Our results show a slight decrease of serum-free testosterone with age, with an increase of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in a third of the elderly subjects studied. BMD decreased significantly with age in all regions studied, except in the lumbar spine. We found a positive correlation between body mass index (BMI) and BMD at the lumbar spine and femoral neck (P < 0.001). No relationship was found (uni- and multivariate regression analysis) between serum androgens or sex hormone-binding globulin (SHBG) and BMD. We found a positive correlation of vitamin D binding protein (DBP) and osteocalcin with lumbar spine BMD and with BMI, DBP, IGF-1, and PTH with femoral neck BMD. In conclusion, there is a slight decline in free testosterone and BMD in the healthy elderly males. However, sex male hormones are not correlated to the decrease in hip BMD. Other age-related factors must be associated with bone loss in elderly males. Received: 29 April 1997 / Accepted: 9 November 1997     

HRT加用雄激素对绝经后妇女骨代谢影响的探讨

探讨雌孕激素替代治疗加用雄激素类药对绝经后妇女骨密度和骨代谢指标的影响及其治疗安全性。方法 :85例绝经后健康妇女随机分为两组 :试验组 4 5例 ,每日口服倍美安 (含天然结合型雌激素 0 .6 2 5 mg+醋酸甲羟孕酮 2 .5 mg) 1粒 +去氢甲基睾丸素 2 mg;对照组 4 0例 ,每日口服倍美安 1粒 ,两组均服药 8w,观察两组妇女用药前及用药 4 w末、8w末、用药后 1月、2月各观察点的骨密度值、血清碱性磷酸酶、尿羟脯氨酸 /肌酐、尿钙 /肌酐比值及血脂、副反应等。结果 :1两组治疗过程骨密度值均逐渐升高 ,尿羟脯氨酸 /肌酐、尿钙 /肌酐比值逐渐降低 ,用药 4 w末、8w末、用药后 1月两组间比较有显著性差异。2两组治疗过程血胆固醇、血甘油三酯、低密度脂蛋白逐渐下降 ,试验组改善脂质代谢的特点未受影响。3两组在治疗副反应上比较差异无显著性。结论 :绝经后妇女雌孕激素替代治疗中加入雄激素类药可以提高骨量 ,减少骨丢失。对血脂代谢无不利影响。是一种防治绝经后骨质疏松的安全有效的方法     

Endogenous urinary steroids in premenopausal women with uterine leiomyomas.

OBJECTIVES: To study the effect of endogenous steroids on the presence of uterine leiomyomas. METHODS: Urine samples of 27 premenopausal women with leiomyomas and 25 age-matched healthy premenopausal women were collected. The concentration of estrogens and androgens in the urine samples of the two groups were determined using a gas chromatography mass spectrometer and the two groups were compared. To study metabolic changes in patients indirectly, the concentration ratios of precursor metabolite to product metabolite of the two groups were also compared. RESULTS: Urinary concentrations of 17beta-estradiol, 5-androstene-3beta, 16beta, 17beta, triol, 11-keto-ethiocholanolone, 11beta-hydroxy-androsterone, 11beta-hydroxy-etiocholanolone, THS, THA, THE, alpha-cortol and beta-cortol were significantly higher in patients than in controls. The concentration ratios of 17beta-estradiol/estrone and 11/beta-hydroxy-ethiocholanolone/11beta-hydroxy-androsterone increased in patients. CONCLUSIONS: The presence of uterine leiomyomas correlates with an increase in urinary concentrations of estrogens and androgens, and it appears to be caused by a decrease in patients' metabolism of steroids.