Hormonal predictors of prostate cancer

INTRODUCTION: Androgens are necessary for the development and functioning of the prostate gland. The association of serum testosterone and pituitary hormone levels with prostate cancer development is not completely understood. In this clinical study, we evaluated the role of serum testosterone, free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in predicting prostate cancer risk in patients who had transrectal ultrasonography-guided prostate biopsy with the suspicion of prostate cancer. MATERIAL AND METHODS: A total of 211 patients who were selected to undergo prostatic biopsy due to abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level >2.5 ng/ml were included in the study. The patient characteristics of total PSA, free/total PSA ratio, serum total testosterone, free testosterone, free/total testosterone ratio, FSH and LH levels were compared according to the pathological diagnosis. RESULTS: The mean age was 63.91 years (range 44-83) and the mean PSA level was 9.23 ng/ml (range 0.13-50.41) in the whole group. Of 211 patients, 69 (32.7%) were positive for prostate cancer. The patients who were positive for prostate cancer had statistically lower levels of serum total testosterone compared with the patients who were diagnosed as having benign prostatic hyperplasia (BPH; 405 vs. 450.5 ng/dl, respectively; p = 0.013). The serum FSH level was significantly higher in men with prostatic cancer than in men with BPH (7.56 vs. 6.06 mIU/ml, respectively; p = 0.029). No significant differences between men with prostatic cancer and those with BPH were found for serum LH levels. When normal ranges for serum free and total testosterone levels were defined as 9 pg/ml and 300 ng/dl, respectively, patients who had low free testosterone and total testosterone levels had significantly higher cancer detection rates than patients with high serum androgen levels: 40.8% (40/98) versus 25.6% (29/113) (p = 0.021), and 48.6% (18/37) versus 29.3% (51/174), respectively (p = 0.023). After logistic regression analysis, none of the hormones showed a significant difference in predicting the risk of prostate cancer in patients undergoing prostate biopsy with suspicion of the disease. CONCLUSION: Our data suggest that patients diagnosed with prostate cancer have low levels of serum testosterone and high levels of serum FSH compared with the patients with BPH. No support was found for the theory that high levels of testosterone increase prostate cancer risk. Further studies are needed to clarify the relationship between hormones and prostate cancer etiology.     

Raloxifene treatment is associated with increased serum estradiol and decreased bone remodeling in healthy middle-aged men with low sex hormone levels.

In healthy middle-aged men, raloxifene treatment was associated with increased serum estradiol and decreased biochemical markers of bone turnover in subjects with estradiol levels below a threshold of 101.8 pM. INTRODUCTION: We investigated the effects of the selective estrogen receptor modulator raloxifene on bone remodeling in healthy middle-aged men. MATERIALS AND METHODS: Forty-three healthy eugonadal men (mean age, 56 years; range, 49-70 years) were enrolled in a randomized placebo-controlled, double-blind, two-sequence crossover study. The subjects received either raloxifene 120 mg/day or placebo for 6 weeks, followed by a 2-month washout period, before crossing over. To predict changes of urinary total deoxypyridinoline/creatinine on raloxifene treatment, we used a logistic regression model to determine cut-off values of sex hormones for highest sensitivity and specificity. RESULTS: In the whole group, raloxifene treatment was associated with an increase in serum sex hormones, that is, total testosterone (+13%, p < 0.01), bioavailable testosterone (+11%, p = 0.02), total estradiol (+11%, p < 0.002), and bioavailable estradiol (+11%, p = 0.035), and with a decrease in serum osteocalcin (-13%, p < 0.05) and serum total alkaline phosphatase (-6%, p < 0.05). Other biochemical markers of bone turnover remained unchanged. Using a logistic regression model to predict changes in urinary deoxypyridoline, we calculated thresholds for total (101.8 pM) and bioavailable (4.79 pM) estradiol, as well as for total (19.4 nM) and bioavailable (0.35 nM) testosterone. Raloxifene treatment was associated with an increase in serum estradiol and decrease in biochemical markers of bone turnover in men with estradiol values below these estradiol thresholds, without any significant change in subjects with values above them. Similarly, raloxifene treatment was associated with an increase in serum testosterone and a decrease in biochemical markers of bone turnover in those with baseline testosterone values below the testosterone thresholds. The association between antiresorptive effects of raloxifene and low sex hormone levels was more pronounced for estradiol than for testosterone. CONCLUSIONS: The antiresorptive effect of raloxifene was only detectable in men with low baseline estradiol levels. Unlike in postmenopausal women, the increase of estradiol may contribute to the antiresorptive effect of raloxifene in men.     

Indices of testicular endosecretory function and of the status of the hypophyseal-gonadal system in varicocele

Testicular intrasecretory function and gonad-hypophyseal regulation were studied in 28 patients with the left-sided varicocele whose age varied from 11 to 36 years. Radioimmunoassay was used for the assessment of testosterone, estradiol, progesterone, follicle-stimulating (FS) and luteinizing (L) hormones and prolactin levels in the blood samples from femoral and internal testicular veins taken during endovascularization of varicocele. With regard to the age and manifestations of the secondary sexual signs the patients were divided into three groups. The first group (11-12-year-old) enrolled the patients with normal age-related levels of FS and L hormones in the presence of hyperprolactinemia. The positive testiculoperipheral gradient was revealed in 3 cases for estradiol and in 2 patients for testosterone and progesterone. The peripheral blood testosterone was normal in all the patients whereas estradiol and progesterone were decreased in 2 and 4 cases, respectively. All the patients of the second group (13-15-year-old) demonstrated an increase in testicular blood testosterone and estradiol as compared to their levels in the peripheral blood (1.46-1.8-fold and 1.3-7.1-fold, respectively). In 6 patients, this ratio was 1.65-2.33-fold higher. The levels of FS and L hormones were normal. In all cases hyperprolactinemia was observed. The third group (16-36-year-old) patients demonstrated a 1.4-3.1-fold gradient of testosterone in the testicular blood versus its levels in the peripheral blood. The authors defined 1.1-239-fold (mean, 8.95) estradiol gradients and 0-979-fold (mean, 2.5) progesterone gradients. In all cases but one, the levels of FS and L hormones were equal to the control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of serum sex-steroid hormones and prostate volume in African American men

BACKGROUND: Previous epidemiologic investigations of the associations of sex-steroid hormones and benign prostatic hyperplasia (BPH) have focused on predominately white populations. The objective of this study was to evaluate potential associations of body mass index (BMI), cigarette smoking, use of alcohol, and endogenous sex-steroid hormones with prostate volume in a population-based sample of African American (AA) men, ages 40-79 yr. METHODS: A total of 369 AA men without clinical evidence of prostate cancer were identified in the Flint Men's Health Study by using a population-based sampling procedure. All subjects underwent a complete urologic evaluation that included prostate volume determination by transrectal ultrasonography and serum assays for androgens and estrogens. RESULTS: After age adjustment, BMI (weight (kg)/height (m)2) was positively correlated with increasing levels of androstanediol glucuronide (AG), estradiol (E2), estrone sulfate (E1S), and the ratios of E2:total testosterone (TT) and E2:free testosterone (FT); however, increasing BMI was negatively correlated with androstenedione (AD), FT, TT, and sex hormone-binding globulin (SHBG). Multivariable regression models demonstrated that prostate volume increased with age (P < 0.001) and BMI (P = 0.02) and decreased with increasing levels of SHBG (P = 0.01). Larger prostatic volumes were also marginally associated with increasing levels of TT (P = 0.058). CONCLUSION: Circulating serum levels of SHBG and endogenous sex-steroid hormones are correlated with prostate volume and potentially impact the natural history of BPH. However, longitudinal studies are needed to demonstrate the temporal relationships of hormones and growth factors in the pathogenesis of BPH in AA men.     

Serum sex hormones and measures of benign prostatic hyperplasia

BACKGROUND: Despite biologic plausibility, the associations between sex hormones and measures of benign prostatic hyperplasia (BPH) have not been consistently reported. METHODS: Subjects were randomly selected from the Olmsted County, MN population (n, 320; median age, 60.9 years) and followed biennially since 1990. In 2002, surrogate measures of BPH were assessed from an approximation of the American Urological Association Symptom Index (AUASI), Peak urinary flow rates (Q(max)), and a transrectal ultrasound assessment of prostate volume. Serum levels of prostate specific antigen (PSA), testosterone, bioavailable testosterone, and estradiol were also measured. RESULTS: Bioavailable testosterone levels declined with increasing cross-sectional age from 53.8, 50.2, to 41.2 ng/dl (P = 0.001) in men aged <60, 60-69, and >69 years, respectively, and the estradiol/bioavailable testosterone ratio increased from 0.042, 0.044, to 0.050 (P = 0.04). Among men with bioavailable testosterone above the median, estradiol levels had a dose response relationship with prostate size. Among men with bioavailable testosterone level 相似文献   

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling

Introduction In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age. Patients and measurements In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5–20 years) and 55 adult women (age: 20–37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 β estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D₃]. Results Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567±895 vs. 8976±805 pmol/l, p<0.05). sALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 β estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both age subgroups of the AN patients. Other hormones or nutritional parameters displayed age-related correlations with bone markers, leading to different stepwise regression models for each age interval. In mature adolescent AN patients, up to 54% of the osteocalcin variance was due to BMI, cortisol and 17 β estradiol, while 54% of the sCTX variance was determined by GH. In adult subjects, freeT3 and IGF-I accounted for 64% of osteocalcin variance, while 65% of the sCTX variance was due to GH, FTI and methoxyamines. Conclusions We suggest a more complex mechanism of AN bone uncoupling that includes not only “classical” influence elements like cortisol, IGF-I, GH or 17 β estradiol but also freeT3, catecholamines and a “direct” hormone-independent impact of denutrition. Continuous changes of these influences with age should be considered within the therapeutic approach to AN bone loss.     

Relationship between lower urinary tract symptoms and serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia

Study Type – Aetiology (case series)
Level of Evidence 4

OBJECTIVES

To investigate a possible association between the severity of lower urinary tract symptoms (LUTS) and the serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia (BPH) that underwent surgery for severe benign prostatic obstruction.

PATIENTS AND METHODS

In all, 127 selected men with symptomatic BPH attending our urology clinic were recruited. The clinical conditions of BPH were assessed by digital rectal examination, serum prostate‐specific antigen (PSA) determination, International Prostate Symptom Score (IPSS), transrectal ultrasonography and maximum urinary flow rate (Q_max) value at uroflussimetry. Before surgery, we measured the serum concentrations of total testosterone (TT) and free testosterone (FT), oestradiol, prolactin, luteinizing hormone and follicle‐stimulating hormone. We excluded men with endocrine diseases, those with prostate disease who were receiving antiandrogen therapy and those with psychological diseases. The relationships between the IPSS score and serum sex hormone levels were determined.

RESULTS

The final study population consisted of 122 men (mean age of 70.66 years), as five were excluded (three due to incomplete evaluation and two who were diagnosed with prostate cancer). On statistical analysis, the total IPSS was significantly associated with age (r= 0.405, P < 0.001) and TT (r= 0.298, P= 0.020) but not with FT or the serum levels of the other sex hormones. The serum levels of testosterone and IPSS did not correlate with prostate volume and Q_max. PSA level and age correlated with prostate volume (r= 0.394, P < 0.001; r = 0.374, P < 0.001, respectively). We distinguished two subgroups of patients: the first group of 40 men with an IPSS of <19 and the second group of 82 with an IPSS of >19, and we evaluated the median levels of TT in each group. There was an increased risk of LUTS in men with a greater serum concentration of TT (P= 0.042), although the mean TT level was in the normal range.

CONCLUSIONS

In the present study, the severity of LUTS was associated with age and serum levels of TT but only age correlated with the measures of BPH, especially prostate volume. The potential effects of testosterone on LUTS may well be indirect. Additional large studies are needed to confirm these preliminary results.     

3'-大豆苷元磺酸钠抗实验性小鼠良性前列腺增生的作用观察

目的:研究3'-大豆苷元磺酸钠(DSS)对实验性小鼠BPH及性激素平衡的影响。方法:40只雄性小鼠随机分为5组:正常对照组、BPH模型组、前列康组(阳性对照)、20mg/(kg.d)DSS组及40mg/(kg.d)DSS组,每组8只。皮下注射丙酸睾酮建立小鼠BPH模型。正常对照组给予橄榄油0.1ml/只,前列康组给予前列康5g/(kg.d),DSS组给予DSS20mg、40mg/(kg.d)灌胃。观察每组处理12d后小鼠前列腺湿重、前列腺指数、前列腺组织形态学变化和性激素水平。结果:DSS治疗12d后,与模型组相比,DSS组小鼠前列腺湿重及前列腺指数出现剂量依赖性的降低(P(0.05或P(0.01),光镜下见增生的腺上皮乳头减少或消失,腺体上皮细胞呈低立方或扁平状;血清T、E2含量和T/E2比值明显降低(P(0.05或P(0.01),40mg/(kg.d)DSS组的结果与前列康组相似。结论:DSS对丙酸睾酮所致小鼠BPH具有显著的拮抗作用,其作用机制在一定程度上与降低小鼠血清T、E2含量及T/E2比值有关。     

The effect of testicular irradiation on established BPH in the dog: evidence of a non-steroidal testicular factor for BPH maintenance

Irradiation of the testes of four to 13-year-old male beagles with benign prostatic hyperplasia (BPH) was undertaken to attempt to evaluate the possibility that the testes secrete a non-androgenic accessory sex gland-stimulating substance that may have a critical role in the development of BPH. Available evidence indicates that development of prostatic hyperplasia in dog and man is dependent on testicular secretions and that testes irradiation is unlikely to alter testosterone secretion appreciably but does produce profound effects on the seminiferous tubules. Thirteen non-irradiated and shoulder irradiated control and 16 beagles subjected to 1500 to 2200 rads single dose testis irradiation had pre-irradiation, interval post-irradiation and terminal caliper measurements of prostatic length, width and depth, prostatic and testicular biopsies, and determination of serum testosterone and estradiol levels. Four beagles survived in a group observed for 109 weeks post testis irradiation, 12 in a group observed for 51 and 10 in a group observed for 59 weeks. The wet weight of the prostate was determined at sacrifice. Ratios of the final/initial length and width and final actual/initial calculated weight of the prostate were significantly decreased in testis-irradiated as compared to control beagles. Histologic evaluation also demonstrated a significant difference in degree of prostatic stimulation in control and testis-irradiated groups. The serum testosterone and estradiol levels were not significantly different in the testis-irradiated and control beagles. These observations indicate that irradiation of the testes of beagles with BPH alters the size, weight and histology to suggest decreased stimulation of the prostate without producing an identifiable change in the serum levels of the steroid hormones studied. The data support the hypothesis that the testis of the aging beagle secretes a non-androgenic and probably non-steroidal prostatic stimulating substance which is affected by irradiation of the testis.     

Low serum testosterone levels are predictive of prostate cancer

Purpose

Although hormones play fundamental roles in prostate growth, their clinical significance is not completely clear. Aims of present study were to assess whether testosterone and serum sex hormone levels are predictors of benign prostatic hyperplasia (BPH) or prostate cancer (PC) and to verify whether prostate cancer is associated with low testosterone levels, and to test association between testosterone levels and known prognostic factors in prostate cancer.

Methods

In 206 consecutive patients with benign prostatic hyperplasia or prostate cancer testosterone, follicle-stimulating hormone, luteinizing hormone and prolactin levels were tested and correlated with disease. In patients with prostate cancer, hormone levels were also correlated with known prognostic factors. Predictive value was assessed for age, prostate-specific antigen (PSA), PSA ratio, PSA density, prostate volume and serum sex hormone levels using multiple logistic regression analysis and receiver operating characteristic curves.

Results

Considering sex hormones, only testosterone levels were significantly lower in patients with prostate cancer than those with BPH; testosterone levels appear to be independent predictor of prostate cancer, enhancing predictive accuracy for BPH and PC. Testosterone levels do not seem to be associated with known clinical prognostic factors.

Conclusions

This study supports experimental findings that testosterone levels are predictor of prostate cancer and that prostate cancer is frequently associated with low testosterone levels. In the diagnostic work-up for prostate cancer, adding testosterone determination to PSA test may improve predictive accuracy.     

Influence of age and endocrine factors on the volume of benign prostatic hyperplasia.

To determine whether endocrine factors influence the volume of benign prostatic hyperplasia (BPH), 23 hormonal factors were measured in the serum of 64 men ages 42 to 71 years with low volume prostatic cancer and these levels were correlated with the volume of benign hyperplastic tissue in their radical prostatectomy specimens. With age there was a significant increase in the volume of BPH. Also with age there was a significant decrease in the serum levels of free testosterone, androstenedione, dehydroepiandronsterone (DHA), dehydroepiandronsterone sulphate (DHA-S), delta 5-androstenediol, and 17-hydroxypregnenolone, and a significant increase in sex hormone-binding globulin (SHBG), LH, and FSH. When BPH volume and hormone levels were corrected for age, BPH volume correlated positively with free testosterone, estradiol, and estriol. These data indicate that with age patients with larger volumes of BPH have higher serum androgen and estrogen levels suggesting that serum androgen and estrogen levels may be factors in the persistent stimulation of BPH with age. If so, therapeutic attempts at lowering plasma testosterone levels, reducing estrogen levels, or blocking androgenic stimulation through other mechanisms may interfere with the progression of BPH with age. Conversely, the fact that androgen production declines gradually with age may explain the observation that only 20 to 30% of men who live to age 80 require surgical treatment for urinary obstruction from BPH.     

Endocrine environment of benign prostatic hyperplasia--relationships of sex steroid hormone levels with age and the size of the prostate]

To determine the influence of endocrine factors on benign prostatic hyperplasia (BHP), the levels of three sex steroid hormones i.e., total testosterone (Total-T), free testosterone (Free-T) and estradiol (E2), were measured in serum of healthy 154 men. Their ages ranged from 18 to 91 years old. In 59 men, prostatic size was estimated by digital examination and was subdivided into three groups: smaller than or equal to walnut size, small hen's egg size and equal to or larger than hen's egg size. Firstly, relationships of sex hormone levels with age were studied. There was a slight decrease in Total-T over 60 years old, a significant decrease in Free-T, and no change in E2 with age. Thus, E2/Total-T and E2/Free-T ratio increased significantly after middle-age. Secondly, relationships of hormone levels with prostatic size were studied. In the larger prostate group, a significantly lower level of Total-T and significantly higher level of E2 were detected. But there was no difference in Free-T. Thus, the prostatic size was correlated positively with E2 level, E2/Total-T and E2/Free-T ratio. These suggest that the endocrine environment tended to be estrogens-dominant with age, in particular, after middle-age, and that patients with large prostates have more estrogens-dominant environments. We conclude that estrogens are key hormones for the induction and the development of BPH.     

健康人群肾小球滤过率的增龄变化及其与营养、炎症和性激素的关联性研究

目的分析估算肾小球滤过率(eGFR)的增龄变化及其与营养、炎症和性激素的关联，为深入研究和临床防治增龄性eGFR减退提供线索。 方法多中心、横断面的大样本流行病学调查，共纳入健康研究对象520名(男224名，女296名)，依年龄分为成年组(年龄<65岁)和老年组(年龄≥65岁)，回顾性膳食调查计算热量和营养素摄入量，利用CKD-EPI公式计算eGFR；同时检测炎症、性激素及生化指标，多元线性回归分析总体人群、成人组和老年组的各项指标与eGFR的关联性。 结果①无论男性还是女性，eGFR均伴随增龄下降(P<0.05)，男女之间无明显差别(P>0.05)；②成人女性eGFR与睾酮、雌二醇、黄体酮均呈正相关(P<0.05)；③eGFR的独立影响因素，总体人群为体质量指数、平均动脉压、血清白蛋白、血清转铁蛋白、白细胞介素-6(IL-6)、雌二醇、黄体酮、纤维摄入量、硫胺素摄入量及尼克酸摄入量；成人组为平均动脉压、血清白蛋白、高敏C反应蛋白、雌二醇及镁摄入量；老年组仅为IL-6。 结论伴随增龄eGFR进行性降低，炎症状态是健康人群、特别是老年人eGFR的重要影响因素，成年女性eGFR与性激素明显相关。     

前列腺增生症证型与体内性激素水平的临床研究

目的:研究前列腺增生症中医证型与体内性激素水平的相关性.方法:选择500例患者,中医辨证分为血瘀下焦、膀胱湿热、肾阴亏虚、肾阳不足、肺热气闭,均在就诊次日上午抽空腹血4 mL,进行血清性激素测定.结果:T值以血瘀下焦、肾阴亏虚证较高,肾阳不足证明显偏低,两者比较差别有显著性(P＜0.01);膀胱湿热证和肺热气闭证居中,与血瘀下焦、肾阴亏虚证比较差别也具有显著性(P＜0.05).E2值以肾阳不足证明显偏高,血瘀下焦和膀胱湿热证次之,肾阴亏虚和肺热气闭证较低.各组间比较差别具有显著性(P＜0.01).结论:前列腺增生症各证型与血清性激素水平变化有一定规律可循,同时也为证型客观化、微观化提供了相应证据.     

Endocrine patterns in patients with benign and malignant prostatic diseases

BACKGROUND: The known importance of the endocrine system, particularly of steroid hormones, for development of the prostate gland and the fact that steroid hormones act as immunmodulators prompted us to compare hypophyseal, adrenal, and gonadal hormones, including cortisol, in patients with benign and malignant prostatic diseases. METHODS: Patients with newly diagnosed, untreated prostate cancer (PC) (n = 75) and, as a control population, those with untreated lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) (n = 159) entered this prospective study. In all patients, the following parameters were obtained by serum analysis: prostate-specific antigen (PSA), human luteinizing hormone (hLH), human follicle-stimulating hormone (hFSH), testosterone, estradiol (E2), cortisol, and dehydroepiandrosterone-sulphate (DHEA-S). Serum samples were collected of fasting patients between 7. 30-10.00 AM. RESULTS: Age was comparable in both groups (PC: 65.6 +/- 7.6 years (mean +/- standard deviation) vs. controls: 64.9 +/- 8. 1 years; P = 0.56). HFSH (PC: 6.6 +/- 3.9 mIU/ml; controls: 8.4 +/- 6.4 mIU/ml; P = 0.04), hLH (PC: 5.3 +/- 4.8mIU/ml; controls: 7.6 +/- 6.2 mIU/ml; P = 0.009), and estradiol (PC: 25.8 +/- 12.7 pg/ml; controls: 32.6 +/- 12.6 pg/ml; P = 0.0003) were significantly lower in PC patients than controls. Cortisol (PC: 16.7 +/- 4.2 microg/dl; controls: 13.5 +/- 4.3 microg/dl; P < 0.0001) was significantly higher in cases. The difference for cortisol and estradiol concentrations between PC patients and controls held true in all life-decades. Serum concentrations for DHEA-S and testosterone were comparable between PC and control patients. In PC patients, none of the endocrine parameters correlated to serum PSA or clinical/pathological stage. CONCLUSIONS: Patients with newly diagnosed, untreated PC yielded significantly higher cortisol and lower estradiol serum concentrations than controls. The known effect of cortisol on the immune status warrants further studies.     

Influence of sex hormones on prostate volume in men on hemodialysis

The relationship between sex hormones and prostate volume in 90 men on hemodialysis and 91 healthy men was investigated. In men on hemodialysis, serum levels of total and free testosterone were significantly reduced compared with the controls (P < .001), whereas the serum estradiol level was significantly elevated in men on hemodialysis (P < .001). However, prostate volumes were not different between the 2 groups. Serum estradiol level correlated with the prostate volume in controls (P < .001), whereas total and free testosterone levels did not correlate with the prostate volume. In men on hemodialysis, serum levels of total and free testosterone and estradiol did not correlate with the prostate volume. The present study suggests that sex hormones do not play important roles in the prostate growth in men on hemodialysis.     

Comparative study of plasma steroid and steroid glucuronide levels in normal men and in men with benign prostatic hyperplasia

Plasma steroids were analyzed in 16 normal men and in 10 men with prostatic benign hyperplasia (BPH). The steroids measured by radioimmunoassay include pregnenolone, 17-OH-pregnenolone, dehydroepiandrosterone, androst-5-ene-3 beta, 17 beta-diol, testosterone, dihydrotestosterone, androstane-3 alpha, 17 beta-diol, androstane-3 beta, 17 beta-diol, estrone, and estradiol as well as their glucuronide derivatives. In addition, cortisol and the sulphoconjugated form of dehydroepiandrosterone were determined. Whereas the levels of pregnenolone, pregnenolone glucuronide and 17-OH-pregnenolone glucuronide are not different in the two groups, the levels of 17-OH-pregnenolone in the BPH group (0.87 +/- 0.07 ng/ml) exceed by two-fold (p less than 0.01) those observed in normal men. Plasma dehydroepiandrosterone and androst-5-ene-3 beta, 17 beta-diol concentrations are markedly elevated in the BPH group (1.49 +/- 0.23 and 0.55 +/- 0.08 ng/ml vs the control groups 0.43 +/- 0.11 and 0.31 +/- 0.05 ng/ml, respectively). Since the plasma cortisol and pregnenolone levels are comparable in these two groups, our data suggest that the elevation of plasma 17-OH-pregnenolone, dehydroepiandrosterone, and androst-5-ene-3 beta, 17 beta-diol reflects an increase of adrenal 17-hydroxylase activity in patients with BPH. A slight increase of the plasma dihydrotestosterone and androsterone glucuronide concentration is also observed in men with BPH, indicating an increase of 5 alpha-reduced androgen formation. We have also observed, in the BPH group, a 50% decrease (p less than 0.01) of plasma glucuronidated androst-5-ene-3 beta, 17 beta-diol, estrone, and estradiol levels, suggesting that the transformation of unconjugated estrogenic steroids into glucuronide derivative is inhibited in BPH patients. In summary, our data indicate that adrenal C-19 steroids might be involved in the process of BPH. Furthermore, whereas the estrogen glucuronide formation is diminished in men with BPH, the prostatic androgen metabolism as reflected by plasma dihydrotestosterone and androsterone glucuronide concentrations seems to be increased.     

Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury

Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for both men and women. These findings represent a paradigm shift when thinking about the role of sex steroids in neuroprotection clinically after TBI.     

Association between endogenous hormones and sex hormone-binding globulin and bone turnover in older women: study of osteoporotic fractures

Estrogen therapy decreases bone remodeling, but the association between endogenous estradiol (E2), estrone (E1), testosterone (T), and bone turnover in older women is not clear. To test the association of serum E2, E1, free T, and sex hormone-binding globulin (SHBG) with bone turnover, we analyzed cross-sectional relationships among E2, E1, T, SHBG, and biochemical markers of bone turnover serum osteocalcin [OC], serum bone-specific alkaline phosphatase [bAP], and serum breakdown products of C telopeptide of type I collagen [CTx] in 704 women enrolled in the Study of Osteoporotic Fractures. Women with lower estradiol levels tended to have higher levels of bone turnover, but the association was weak (R(2) = 0.01 for the association E2-OC, p = 0.03; and R(2) = 0.024 for E2-CTx, p = 0.001). Relationships between SHBG and turnover were also weak (R(2) for the association SHBG-OC was 0.07, p < 0.001, and 0.03 for SHBG-sCTx, p = 0.03), or not significant (R(2) < 0.01 for the association SHBG-bAP). Associations of E1 and T with these markers were of the same magnitude. These results were not modified after adjustment for age, weight, and smoking status. We conclude that older women with low endogenous hormones have somewhat higher bone turnover, but these associations are weak. Bone turnover is determined mainly by factors other than endogenous concentrations of sex hormones.     

Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls

This study sought to identify differences in serum hormone levels between prostatic cancer (CaP) patients, benign prostatic hyperplasia (BPH) patients, and clinic controls (CC). Serum testosterone, estradiol, and prolactin values were obtained from 35 CaP, 42 BPH, and 161 CC patients attending a single medical center between January 1984 and April 1985. Relative risk estimates adjusted for age and race were calculated to compare hormone values between each case group and the CC. The distributions of hormone values and the testosterone to estradiol (T/E) ratios were grouped into thirds with the lowest third forming the reference category. The relative risk estimates for BPH in the middle and high thirds of testosterone were greater than unity (1.26 and 2.10, respectively), whereas the relative risk estimates in the middle and high thirds of estradiol were less than unity (0.63 and 0.35, respectively). For the middle and high thirds of the T/E ratio, the relative risk estimates for BPH showed statistically significant three- to fourfold increases. Modest depression of serum testosterone and estradiol was noted for CaP patients compared to CC, although the differences were not statistically significant. This depression was interpreted to be a likely result of the malignant process rather than a cause of it, whereas the development of clinically evident BPH was felt to be a biologically plausible response to an elevated T/E ratio.