Serum osteoprotegerin and sex steroid levels in patients with prostate cancer

The relationship between sex steroids and osteoprotegerin (OPG) in patients with prostate cancer is not well established. Our aim was to evaluate serum OPG levels in patients with prostate cancer and its relationship with sex steroids, bone mineral density, bone turnover markers, and fractures. We performed a cross-sectional study including 91 patients with prostate cancer. We determined: bone mineral density by dual-energy x-ray absorptiometry, bone turnover markers, serum levels of sex steroids and osteoprotegerin, and prevalent radiographic vertebral fractures. Serum OPG levels were higher in patients with vertebral fractures (8.02 ± 2.0 vs 4.91 ± 0.28 pmol/L; P < .05). OPG level and the duration of hormonal therapy were related (r = 0.299, P = .004), but this association did not persist after adjustment for age. In patients without androgen deprivation therapy, serum OPG levels were correlated with the levels of total testosterone (r = 0.508, P = .001) and bioavailable testosterone (r = 0.311, P = .037). In patients receiving androgen deprivation therapy, serum OPG levels were correlated with levels of total estradiol (r = 0.199, P = .18), bioavailable estradiol (r = 0.37, P = .009), and free estradiol (r = 0.349, P = .016). In conclusion, in patients with prostate cancer treated with androgen deprivation therapy, serum OPG levels were correlated with the levels of total estradiol, bioavailable estradiol, and free estradiol. Our hypothesis is that in patients with androgen deprivation therapy, the higher relative estrogen levels could stimulate OPG production in response to the higher resorption state. Future prospective studies are needed to clarify the role of OPG in androgen deprivation therapy-mediated bone loss.     

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   

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.     

Osteoporosis in men: a potential role for the sex hormone binding globulin

The exact mechanism of bone loss remains unknown in primary male osteoporosis. It has been suggested that estrogen and sex hormone binding globulin (SHBG) play a role in regulating bone turnover and bone mass in healthy men > 65 years of age. In the present study, 80 men (mean age 49.7 years) with bone mineral density >2.5 SD below the young adult value and 40 age-matched controls were recruited to evaluate the relationships between sex hormone levels, bone biochemical markers levels, and bone mineral density. Fasting serum samples were assayed for total and free testosterone total estradiol, and SHBG. The free androgen index, was calculated as: [total testosterone/SHBG * 100]. Bone remodeling was evaluated by measurement of urinary levels of the C-telopeptide of type I collagen (CTx) and free deoxypyridinoline (D-Pyr), serum osteocalcin, and bone-specific alkaline phosphatase (bSAP). There was no significant difference between controls and osteoporotic men according to age, body mass index (BMI), total testosterone, and estradiol. In contrast, serum SHBG level was significantly higher (+42.2%), whereas free androgen index was lower (-24.8%) in patients with primary or secondary osteoporosis. Testosterone and estradiol levels did not correlate with any bone resorption or bone formation markers. In contrast, stepwise linear regression analysis showed that SHBG was significantly correlated with D-Pyr (r = 0.45, p < 0.05) and CTx (r = 0.34, p < 0.05) in primary osteoporosis. In secondary osteoporosis, SHBG was correlated with D-Pyr (r = 0.48, p < 0.05) and bSAP (r = 0.55, p < 0.01). After adjustment for age and BMI, hip bone mineral density (BMD) was not associated with testosterone or estradiol but only with serum SHBG (r = -0.33, p < 0.01) in primary osteoporosis. The same relationship was observed in men with secondary osteoporosis (r = -0.34, p < 0.01). Among osteoporotic patients, spinal radiography showed at least one vertebral crush fracture in 36 men and none in 44. Serum SHBG concentration was significantly associated with the presence of vertebral fracture: the odds ratio was 2.0 (95% confidence interval [CI] 1.2-3.5) for an increase of one standard deviation of SHBG. In conclusion, the present study showed that serum SHBG concentration is increased in middle-aged men with primary or secondary osteoporosis and is correlated with bone remodeling markers, hip bone mineral density, and vertebral fracture risk.     

Relationship between serum sex hormones levels and degree of benign prostate hyperplasia in Chinese aging men

Benign prostatic hyperplasia (BPH) is one of the most common medical conditions in middle aged and older men. This study investigated the relationship between serum levels of sex hormones and measures of BPH in the aging male population of China. Prostate symptoms were assessed as part of a free health screening program for men ≥40 years of age. The examination included digital rectal examination, determination of serum prostate-specific antigen levels, International Prostate Symptom Score (IPSS) and transrectal ultrasonography. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and estradiol (E₂) were evaluated. The men also completed a health and demographics questionnaire and received a detailed physical examination. The final study population consisted of 949 men with a mean age of 58.9 years. Pearson correlation analysis indicated that there were significant correlations between age and levels of all sex hormones except TT, and between age and prostate volume (PV; r=0.243; P<0.01) or IPSS (r=0.263; P<0.01). Additional significant correlations were found between IPSS and serum levels of LH (r=0.112; P<0.01) and FSH (r=0.074; P<0.05), but there were no significant correlations between sex hormone levels and PV. Multivariate linear regression analysis showed significant correlations between age and body mass index (BMI) with PV (P<0.0001). In addition, there was a significant correlation between age and PV with IPSS (P<0.0001). Serum sex hormone levels did not correlate with PV or IPSS. The effects of endocrine changes on measures of BPH in aging men require further investigation in longitudinal and multicenter studies that include patients with all severities of BPH.     

Prostate-specific antigen and prostate volume in Korean men with spinal cord injury: a case-control study

STUDY DESIGN: Prospective, cross-sectional, case-control study. SETTING: Outpatient department in Seoul, Korea. OBJECTIVES: To assess prostate volume and serum prostate-specific antigen (PSA) levels in Korean men with spinal cord injury (SCI). METHODS: A total of 31 SCI patients with ages ranging between 45 and 81 years old (median age, 58 years) were studied. Thirty-one age-matched individuals without SCI were enrolled in the study as controls. We tested PSA levels and performed transrectal ultrasonographies on all enrolled patients. Of the patients with SCI, 20 were evaluated for testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. RESULTS: Serum PSA levels and prostate volume parameters in the two groups had similar values: the median (5th-95th percentiles) serum PSA level was 1.56 ng/ml (0.12-9.77) for SCI patients and 1.04 ng/ml (0.50-2.98) for controls (P=0.481), whereas the median (5th-95th percentiles) prostate volume was 18.33 ml (10.16-76.78) for SCI patients and 20.80 ml (14.23-41.22) for controls (P=0.072). No significant differences were found when serum PSA levels and prostate volumes were compared according to SCI patient injury characteristics. Testosterone levels were lower than the normal range in 7 SCI patients (35%), LH was higher than the normal range in 10 SCI patients (20%), and FSH was higher than the normal range in eight SCI patients (40%). We observed an age-related increase in FSH levels (r=0.634, P=0.004), although hormone levels did not correlate with serum PSA levels and prostate volume parameters. CONCLUSIONS: According to our results, serum PSA levels and prostate volume in Korean SCI patients are not different from those in uninjured men and are not affected by injury characteristics.     

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.     

Alterations in the pulsatile properties of gonadotropin secretion in alcoholic men

The functional characteristics of the hypothalamic-pituitary-testicular axis were examined quantitatively in 10 chronic alcoholic men without hepatic dysfunction or clinical nutritional deficiencies. Spontaneous gonadotropin pulsatility was analyzed in blood sampled every 20 minutes over a 24-hour period 3 to 16 days after abstinence from alcohol and again 29 to 39 days later. The numbers of LH and FSH pulses per 24 hours were normal in these alcoholic men compared with controls. However, we found increased mean 24-hour concentrations of immunoactive LH (P = 0.012) and FSH (P = 0.018), increased peak heights for LH (P = 0.035) and FSH (P = 0.004), decreased fractional LH (P = 0.002) and FSH (P = 0.044) pulse amplitudes and increased interpulse valley mean LH (P = 0.010) and FSH (P = 0.018) concentrations. Serum levels of total testosterone, total estradiol and estrone were normal, whereas concentrations of free testosterone and free estradiol were increased. Pituitary release of LH and FSH was normal in response to low (5-micrograms) and high (95-micrograms) doses of GnRH given intravenously. The present observations indicate that in chronically alcoholic men, acute abstinence from ethanol is associated with elevated circulating concentrations of immunoactive gonadotropins in the presence of intact spontaneous gonadotropin pulsatility, preserved pituitary responsiveness to exogenous GnRH, and increased concentrations of free testosterone and free estradiol. Such findings are consistent with alterations in the endogenous feedback actions of sex steroid hormones in this setting.     

Hormonal markers of aging in men with laryngeal carcinoma

BACKGROUND: Cancer of the larynx, a frequent neoplasm in older people, occurs several times more often in men than in women. Surprisingly, the highest incidence of the disease is observed in the period in which concentrations of a number of hormones (eg, androgens, growth hormone) decrease. Our objective was to look for differences in hormonal markers of aging between men with laryngeal carcinoma and healthy control subjects. METHODS: Seventy-eight men with cancer of the larynx and 51 healthy age-matched controls were recruited for the study. In each of the examined men, serum concentrations of total testosterone, free testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, steroid-hormone binding globulin, estradiol, and insulin-like growth factor type 1 (IGF-1) were determined. RESULTS: Men with laryngeal carcinoma had lower serum concentrations of IGF-1 (136 +/- 75 vs 318 +/- 141 ng/mL, p < .000001), lower free testosterone (11.95 +/- 5.38 vs 15.48 +/- 4.96 pg/mL, p < .001), and lower dihydrotestosterone/total testosterone ratio (0.07 +/- 0.06 vs 0.09 +/- 0.04, p < .05) than healthy controls had. CONCLUSIONS: Somatopause seems to be more evident in men with laryngeal carcinoma than in age-matched controls. In our observation, low concentration of IGF-1 predicted the presence of laryngeal carcinoma more than low concentration of free testosterone did.     

Influence of ageing and some lifestyle factors on male gonadal function: a study in Bulgaria

There are few systematic studies on the relationship between blood testosterone concentrations and the symptoms of androgen deficiency in ageing males. To assess the changes in sex hormone levels with age in relation with some lifestyle factors, the serum levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured in 33 men, age range 40-89 years. In addition, free testosterone (FT) and the free androgen index (FAI) were calculated. Seventeen healthy men under 40 years were involved as controls. The men over 40 years revealed significantly decreased TT, FT and FAI, and in the subgroup of men over 60 years, FSH and SHBG were significantly increased. Pearson's analysis showed that TT levels were significantly correlated with body mass index (BMI) (r = -0.464, P < 0.01) and body weight (r = -0.413, P < 0.05). SHBG levels were significantly correlated not only with age (r = +0.407, P < 0.05), but also with LH (r = +0.605, P < 0.001) and alcohol consumption (r = +0.382, P < 0.05). In conclusion, the TT, FT and FAI decreased in males over 40 years, but the alterations in hormone levels with age are more pronounced in men over 60 years. The important determinants of sex hormones are age, BMI and some lifestyle factors.     

EFFECT OF EXOGENOUS TESTOSTERONE ON PROSTATE VOLUME, SERUM AND SEMEN PROSTATE SPECIFIC ANTIGEN LEVELS IN HEALTHY YOUNG MEN

Purpose

We investigate and define the effects of exogenous testosterone on the normal prostate.

Materials and Methods

A total of 31 healthy volunteers 21 to 39 years old were randomized to receive either 100, 250 or 500 mg. testosterone via intramuscular injection once a week for 15 weeks. Baseline measurements of serum testosterone, free testosterone and prostate specific antigen (PSA) were taken at week 1. Semen samples were also collected for PSA content and prostate volumes were determined by transrectal ultrasound before testosterone injection. Blood was then drawn every other week before each testosterone injection for the 15 weeks, every other week thereafter until week 28 and again at week 40. After the first 15 weeks semen samples were again collected, and prostate volumes were determined by repeat transrectal ultrasound.

Results

Free and total serum testosterone levels increased significantly in the 250 and 500 mg. dose groups. No significant change occurred in the prostate volume or serum PSA levels at any dose of exogenous testosterone. Total semen PSA levels decreased following administration of testosterone but did not reach statistical significance.

Conclusions

Despite significant elevations in serum total and free testosterone, healthy young men do not demonstrate increased serum or semen PSA levels, or increased prostate volume in response to exogenous testosterone injections.     

Effect of soluble and insoluble fiber diets on serum prostate specific antigen in men

PURPOSE: We assess whether high fiber diets influence serum prostate specific antigen (PSA) related to effects on serum sex hormone levels and fecal steroid excretion. MATERIALS AND METHODS: A randomized crossover controlled trial was performed on 14 healthy men with hyperlipidemia on 2 metabolic diets 4 months in duration with each containing foods high in soluble or insoluble fiber and approximately 25 to 30 gm. dietary fiber per 1,000 kilocalories. Serum PSA, free testosterone and estradiol, and fecal bile acid and neutral sterol excretion were evaluated. RESULTS: Mean serum PSA was lower with the soluble than the insoluble fiber diet (0.07+/-0.03 ng./ml., p = 0.035). No treatment difference was seen in free testosterone or estradiol, although the latter decreased significantly with the insoluble fiber diet (9+/-3 pmol./l., p = 0.004). After 16 weeks total fecal bile acid output was greater with the soluble (341+/-56 mg. daily) compared to the insoluble (203+/-35, p = 0.001) fiber diet but no differences were seen in fecal neutral sterol elimination. The treatment difference in fecal lithocholic acid output related to the difference in serum PSA (r = 0.57, p = 0.035). CONCLUSIONS: A small but statistically significantly lower serum PSA was seen in healthy men consuming soluble fiber, which was not related to changes in serum sex hormones but was related to the increased lithocholic acid output as a possible marker of increased fecal steroid elimination. The effect of soluble fiber on prostatic disease may warrant further investigation.     

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.     

前列腺移行区体积与年龄及性激素的相关性研究

目的:探讨前列腺总体积(TV)和移行区体积(TZV)与年龄和性激素之间的关系。　方法:82例男性分为 两组,A组31例,年龄≤59岁,B组51例,年龄≥60岁,采用经直肠前列腺超声测定前列腺TV、TZV,采用放射免疫 法测定血清中总睾酮(T)、游离睾酮(fT)、雌二醇(E2)浓度。应用指数回归分析法和单因素方差分析法(ANOVA) 进行统计学分析。　结果:年龄与前列腺TV、TZV,TZV/TV比值差异有显著性(P<0.01);fT浓度与TZV呈显著 正相关性,E2浓度与TZV呈负相关性(P均<0.01),而T的浓度变化与TZV大小无明显的相关性(P>0.05)。　 结论:TZV在60岁后有明显加速增长趋势,与血清中性激素浓度有关。     

Testicular function in hyperthyroidism.

Testicular function was assessed in nine men aged 17 to 35 years and seven men aged 36 to 46 years with Graves' disease. Levels of total testosterone, estradiol, sex hormone binding globulin, luteinizing hormone, and follicle stimulating hormone, and gonadotropin responses to gonadotropin releasing hormone were significantly greater than these levels and responses in age-matched controls. Although the percentage of free testosterone was lower than control values in the hyperthyroid men, calculated levels of free testosterone were not different from normal. Lower than normal percentages of free estradiol values resulted in higher than normal calculated free estradiol levels. As a result, the free testosterone/free estradiol ratio in the men with Graves' disease was lower than normal. Although mean sperm densities in the hyperthyroid men were not different from control values, the percent forward progressive motility of sperm from these men was significantly lower than control values. The hormonal and seminal abnormalities corrected when the patients became euthyroid after radioiodine therapy. The results of this study indicate that hyperthyroid men may have abnormalities in their hypothalamic-pituitary-testicular axes.     

Declining testicular function in aging men

Age-related decline in male sex hormones, particularly testosterone, is referred to as andropause. Like menopause, andropause is associated with physical and emotional changes that may be alleviated by hormone replacement therapy. Hypogonadism in aging men, as defined by a low free testosterone index, is due to declining testosterone production and increased sex hormone-binding globulin levels. About 30% of men in their 60s and more than 80% of men over 80 y may have a low free testosterone index. Diagnosis of hypogonadism is based on clinical symptoms (eg, decreased muscle mass, fractures, loss of libido) and laboratory determinations of serum testosterone-usually total testosterone levels. Measuring bioavailable testosterone, or free testosterone, is expensive and time-consuming, but may more accurately detect hypogonadism. Testosterone replacement therapy is generally safe in aging men and may improve libido, cognition, bone mineral density, body mass composition, and serum lipoproteins. Although contraindicated in men with prostate or breast cancer, testosterone replacement therapy in aging men warrants examination. Any of the available testosterone formulations can be used, but injectable forms have certain advantages, including excellent dose adjustability, lack of skin irritation, and low cost.     

Androgen receptor gene polymorphism and prostate zonal volumes in Australian and Chinese men

Prostate diseases are age and androgen dependent. The evolution of clinically overt pathology requires decades of exposure to adult male levels of circulating testosterone, but the precise relationship between age and androgen circulation remains poorly understood. A marker of integrated androgen action over prolonged periods would therefore be a valuable tool for clinical and epidemiologic research into the origins of prostate disease. In order to evaluate these 2 factors, we have studied the CAG-repeat length polymorphism of the androgen receptor gene and the size of the total, central, and peripheral zones of the prostate, estimated by planimetric ultrasound in 2 populations with widely different susceptibility to death from invasive prostate cancer. From a larger epidemiologic study of the effects of ethnicity and migration on the origins of prostate disease, a nested-case control study was undertaken with 50 Chinese men living in Yue Yang, China and 50 non-Chinese men living in Sydney, Australia. All men had undergone planimetric transrectal prostate ultrasound together with blood sampling to determine CAG-repeat length by polymerase chain reaction and immunoassay of plasma testosterone, estradiol, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), and prostate-specific antigen (PSA). Australian men had larger central (7.9 +/- 0.4 vs 3.3 +/- 0.3 mL) and total (29.8 +/- 1.2 vs 25.5 +/- 1.1 mL) but not peripheral (22.0 +/- 0.9 vs 22.2 +/- 0.8 mL) prostate volumes compared with Chinese men. Even after adjustment for differences in body size (the Australian men were taller and heavier), the central-zone volume remained lower by approximately 50% in Chinese men (P < 0.001), whereas testis and total-prostate volumes were no longer significantly different. The length of CAG repeats was no different between Australian men (22.5 +/- 0.5 repeats) and Chinese men (22.5 +/- 0.5 repeats), and there was no correlation within or between populations in CAG repeats or any measure of prostate volume or hormones. DHT concentration was 20% lower in Chinese men compared with Australian men (1.6 +/- 0.1 vs 2.0 +/- 0.1 nmol/L, P = 0.005), a difference that persisted after age adjustment (P = 0.039) but that was removed by adjustment for differences in total-prostate size (P = 0.12). Blood testosterone, estradiol, SHBG, and PSA concentrations were not different between the 2 populations. Hence, the hypothesis is refuted that the CAG repeat polymorphism in the androgen receptor gene (within the nonpathologic range) and the central-prostate zone volume might be markers of long-term androgen sensitivity. Whether either factor alone may constitute a marker of androgen sensitivity remains to be established by other means, and a long-term marker of integrated androgen action suitable for clinical and epidemiologic research is still lacking.     

Serum concentrations of sex hormones in men with severe lower urinary tract symptoms and benign prostatic hyperplasia

OBJECTIVE: To find out the impact of age-related changes in serum concentrations of sex hormones on the development of severe lower urinary tract symptoms and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study group consisted of 61 consecutive patients subjected to prostatectomy for BPH between 2000-2001 in our clinic. Forty-five randomly assigned, age and socioeconomically matched cases without any lower urinary tract symptoms were taken as the control group. Both clinical BPH and control groups were divided to 3 age groups (namely 50-59, 60-69 and > or = 70 years) and age-related changes in serum concentrations of sex hormones were investigated. RESULTS: Prostate adenoma weight was found to be increased significantly (p = 0.02) with advancing age in clinical BPH group. There was no difference between serum concentrations of measured sex hormones between small and large prostates except for serum estradiol levels, which were found to be significantly higher in patients who had an adenoma weight of > 50 g (p = 0.047). Similar results were obtained in both clinical BPH and control groups with respect to age-related changes in serum concentrations of sex hormones. Briefly there was an age-related decrease in serum free testosterone levels and increase in serum estradiol, prolactin and gonadotropin levels. Serum free testosterone concentration was significantly higher in the control group for ages 60-69 (p = 0.015) while total testosterone was higher in BPH patients for patients older than 70 years of age (p = 0.027). No other significant change was documented between 2 groups. An age-dependent increase in serum E/freeT ratio was documented in both clinical BPH and control patients whereas serum freeT/T ratio was decreased in the BPH group with advancing age (p = 0.008). CONCLUSION: The decrease in serum free testosterone concentrations with a relative rise in serum estradiol levels with advancing age might be an important factor in the development of BPH. However it is likely that serum concentrations of sex hormones play little impact on the clinical severity of BPH.     

High-grade prostate cancer is associated with low serum testosterone levels

BACKGROUND: The aim of this study was to assess whether low serum testosterone levels in men with newly diagnosed prostate cancer have an association to the endocrine status, prostate-specific antigen (PSA) levels, Gleason score, and androgen receptor expression. METHODS: Besides a full clinical work-up, the following hormones were quantified in men with newly diagnosed prostate cancer by serum analysis: total testosterone, human luteinising hormone (hLH), human follicle stimulating hormone (hFSH), estradiol, and dehydroepiandrostendione (DHEA). In a subgroup of men, androgen receptor expression was determined immunohistochemically. RESULTS: One hundred and fifty six patients (65.7 +/- 8.5 yrs) with a mean PSA of 29.8 ng/ml (median: 7.4 ng/ml) were analysed. Fifty-two patients (33%) had a partial androgen deficiency (serum testosterone < 3.0 ng/ml). These men had lower hLH (3.3 vs. 5.9 mIU/ml), hFSH (6.2 vs. 8.4 mIU/ml), and estradiol (18.8 vs. 29.1 pg/ml) serum levels. Mean Gleason score was higher (7.4 vs. 6.2) in men with a low serum testosterone, PSA-levels were lower (25.3 vs. 31.9 ng/ml). Mean testosterone levels decreased from 4.1 +/- 1.7 ng/ml in patients with Gleason scores < or = 5 to 2.8 +/- 2.7 ng/ml with Gleason scores > or = 8. Androgen receptor expression was higher in patients with low serum testosterone. CONCLUSIONS: Patients with high Gleason score prostate cancer have lower testosterone and estradiol serum levels. The fact that gonadotropins were lower in parallel suggests a tumor-mediated suppression of the hypothalamic-pituitary-gonadal hormone axis particularly in men with high Gleason score tumours.