Hormone levels in middle-aged and elderly men with and without erectile dysfunction in Taiwan

The change in sexual hormones with age in middle-aged and elderly Chinese men, with and without erectile dysfunction (ED), was investigated. Total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were determined from fasting serum samples by radioimmunoassay in 627 middle-aged and elderly ethnic Chinese men with and without ED. Calculated FT was derived from TT and SHBG. Patients with ED were subdivided into groups having low serum TT (<2.7 ng/ml) and normal TT (> or =2.7 ng/ml). FT and DHEAS declined and SHBG rose with age in both normal patients and in patients with ED. TT and SHBG were lower in patients with ED than in normal subjects at all ages. In contrast to findings in previous studies, levels of FT were higher in patients with ED than in normal subjects. Hormonal changes in this Chinese population generally mirrored those in previously studied ethnic populations, except for higher FT in patients with ED. This suggests that hormonal levels in patients with ED may vary in different populations. The significance and reproducibility of this finding remains to be determined.     

Testosterone levels increase in association with recovery from acute fracture in men

Summary

In this longitudinal case–control study, acute fracture was associated with low serum testosterone, which was transient in 43 % of men. While assessment of gonadal status is part of the assessment of bone fragility, measurement of testosterone in the early period after fracture may overestimate the prevalence of androgen deficiency.

Introduction

Measurement of circulating testosterone is recommended in the evaluation of bone fragility in men. Since acute illness can transiently decrease circulating testosterone, we quantified the association of acute fracture and serum testosterone levels.

Methods

A case–control study was conducted involving 240 men with a radiologically confirmed minimal trauma fracture presenting to a tertiary referral hospital and 89 age-matched men without a history of minimal trauma fracture serving as controls. Follow-up testosterone levels 6 months after baseline were available for 98 cases and 27 controls. Results were expressed as the median and interquartile (IQR) range.

Results

Compared to controls, cases had lower total testosterone [TT, 7.2 (3.5, 10.8) vs 13.6 (10.9, 17.1) nmol/L, p?<?0.001]. The 143 cases treated as inpatients had lower testosterone levels than the 97 cases treated as outpatients [TT 4.7 (2.3, 8.1) vs 10.3 (7.5, 12.7) nmol/L, p?<?0.001]. Group differences in calculated free testosterone (cFT) were comparable to the group differences in TT. At follow-up, in 98 cases, median TT increased from 6.5 nmol/L (3.2, 8.5) to 9.6 nmol/L (6.9, 12.0) p?<?0.0001, and SHBG remained unchanged. Of cases with low testosterone, 43 % with TT <10 nmol/L and/or cFT <230 pmol/L at presentation were reclassified as androgen sufficient at follow-up. TT was unchanged in the controls.

Conclusions

Low testosterone levels in men presenting with an acute fracture may, at least in part, be due to an acute, fracture-associated, stress response. To avoid over diagnosis, evaluation for testosterone deficiency should be deferred until recovery from the acute event.     

Is serum sex hormone-binding globulin a dominant risk factor for metabolic syndrome?

This multi-center, cross-sectional study investigated the association between serum testosterone (T) levels, serum sex hormone-binding globulin (SHBG) levels, and the risk of metabolic syndrome (MS) in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T (TT) and SHBG than those without MS (P < 0.001). There was no significant difference in serum free T (FT) levels between subjects with and without MS (P = 0.627). In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index (BMI), smoking and drinking status, and serum TT (odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954−0.969, P< 0.01). However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status (OR 0.981, 95% CI 0.960−1.007). Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.     

Evaluation of an immunoassay kit to measure free testosterone

Introduction and objetives:The best indicators to the diagnosis of hypogonadism are free and bioavailable testosterone circulating levels. Free and bioavailable testosterone measurements are complex. However, simple kits for direct measurement of free testosterone by analog immunoassay are available. We examined the utility of an enzymoimmunoassay kit for free testosterone measurement.Material and method:One hundred thirty-three healthy males were included. Total testosterone, SHBG, albumin and free testosterone was measured. We used two different methods to free testosterone estimation: direct measurement by enzymoimmunoassay and mathematical calculation with Vermeulen’s formula, which uses albumin concentration, total testosterone and SHBG to calculate free testosterone (method recommended by the International Society for the Study of the Aging Male). We compared the two methods means values and a linear regression study was performed.Results:Mean age was 37 ± 11 years. Mean serum concentration for total testosterone was 21.43 ± 6.8 nm ol/L. The mean value for free testosterone measured by direct and mathematical method was 0.0508 ± 0.0118 nmol/L and 0.474±0.123 nmol/L respectively. In linear regression study exists a positive correlation between both methods (p< 0.05), although correlation coefficient is very low (r = 0.25).Conclusions:There are significant statistical differences between the measurements of free testosterone by direct and mathematical methods. Although certain correlation is observed, this is very low. In conclusion, free testosterone measurement by enzymoimmunoassay is not reliable.     

Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

OBJECTIVE: Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. METHODS: Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. RESULTS: There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with newly diagnosed prostate cancer had higher serum TT (P < 0.7), ADT (P < 0.2), SHBG (P < 0.2) and lower DHEAS (P < 0.008) compared to aged matched controls. CONCLUSIONS: Serum TT, SHBG, DHEAS and ADT levels are significantly lower in Arab men compared to those reported for Caucasian men, especially in early adulthood. Arab men with newly diagnosed prostate cancer have higher circulating androgens compared to healthy controls. We suggest that low circulating androgens and their adrenal precursors in Arab men when compared to Caucasians may partially account for the relatively lower risk for prostate cancer among Arab men.     

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.     

Testosterone and erectile function recovery after radiotherapy and long-term androgen deprivation with luteinizing hormone-releasing hormone agonists

OBJECTIVE: To study the recovery of testosterone levels and erectile function in men who received radiotherapy plus long-term adjuvant androgen deprivation (LTAD) with luteinizing hormone-releasing hormone (LHRH) agonists. PATIENTS AND METHODS: From April 2000 to July 2001, men who had completed prostate radiotherapy with > or = 2 years of LTAD, and had their last LHRH agonist injection at least 6 months before, were invited to participate. At study entry, the men completed the International Index of Erectile Function (IIEF), and their serum total testosterone (TT), prostate-specific antigen, LH, follicle-stimulating hormone, haemoglobin, and body mass were measured. This assessment was repeated at 1 year. RESULTS: In all, 20 men were recruited, with a mean (range) age of 70 (55-81) years. Defining a normal TT level as > or = 8.0 nmol/L, the median time to a normal level was 2.3 years (95% confidence interval (CI), 1.9-4.2). The median duration of castrate TT levels was 8 months (95% CI, 6.2-14.9). LH recovered before TT, suggesting that the rate-limiting step in the recovery of TT may be at the testicular level. The median time to recovery of normal LH levels was 3.8 months, compared to 8.0 months to reach supracastrate TT levels, and 2.3 years to reach normal TT levels. Age and the LH/TT ratio were associated with the time to recovery of both supracastrate and normal levels of TT. The IIEF was completed by 17 men; there were no significant changes in the scores in any domain of the IIEF during the study. CONCLUSIONS: Most men recover supracastrate testosterone levels after LTAD and external beam radiotherapy, but recovery of 'normal' testosterone levels is slow. Few men recover potency and sexual desire. The patients age and LH/TT ratio may be predictive of the time to recovery of both supracastrate and normal testosterone levels.     

Serum total and free testosterone level of Japanese men: a population-based study

BACKGROUND: There has never been a large scale population-based study of serum levels of total testosterone (TT) and free testosterone (FT) in Japanese men. METHODS: We determined serum levels of TT and FT of 1120 Japanese men aged 40-79 years using radioimmunoassay (RIA), as a part of a population-based longitudinal study of aging. Of these, sex hormone binding protein (SHBG) was also measured by RIA in 471 men. For the latter group, the calculated free testosterone (cFT) was determined by a formula using serum level of albumin, TT and SHBG. RESULTS: The mean +/- 2 SD of TT, FT and cFT were 513 +/- 326 ng/dL (187-839 ng/dL), 13.2 +/- 7.8) pg/mL (5.4-21.0 pg/mL) and 77.0 +/- 43.4 pg/mL (33.6-120.4 pg/mL), respectively. While TT did not relate to age, FT and cFT decreased with age. FT in the 40-49 years age group was 15.1 +/- 8.4 pg/mL (6.7-23.5 pg/mL), in the 50-59 years age group was 13.9 +/- 6.8 pg/mL (7.1-20.7 pg/mL), in the 60-69 years age group was 12.0 +/- 6.6 pg/mL (5.4-18.6 pg/mL) and in the 70-79 years age group was 11.5 +/- 7.0 pg/mL (4.5-18.5 pg/mL). FT significantly correlated with cFT (Spearman's r = 0.803). The correspondence rates were 92.3% at the mean -1 SD and 98.7% at the mean -2 SD level. CONCLUSIONS: We determined the mean and standard deviation of TT, FT and cFT in Japanese men aged 40 years or older. It is supposed that FT determined by RIA would be useful for diagnosing partial androgen deficiency of aging males.     

Prostate Cancer Risk: The Significance of Differences in Age Related Changes in Serum Conjugated and Unconjugated Steroid Hormone Concentrations Between Arab and Caucasian Men

Introduction: Factors responsible for the low incidence of clinical prostate cancer (3–8/100,000 men/year) in the Arab population remain unclear, but may be related to changes in steroid hormone metabolism. We compared the levels of serum conjugated and unconjugated steroids between Arab and Caucasian populations, to determine if these can provide a rational explanation for differences in incidence of prostate cancer between the two populations. Patients/Method: Venous blood samples were obtained from 329 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15–80 years. Samples were also obtained from similar Arab men with newly diagnosed prostate cancer or benign prostatic hyperplasia (BPH). The samples were taken between 8:00 am and 12:00 noon. Serum levels of total testosterone, (TT), sex hormone binding globulin (SHBG), free androgen index (FAI); adrenal C₁₉-steroids, dehydroepiandrosterone sulphate (DHEAS) and androstenedione (ADT) were determined using Immulite kits (Diagnostic Systems Laboratories Inc, Webster Texas, USA). The results obtained in Arab men were compared with those reported for similarly aged Chinese, German and White USA men. Results: In all four ethnic groups, median TT and FAI declined with age, while SHBG increased with age. However, the mean TT and SHBG was significantly lower (p<0.01) and the FAI significantly higher in Arab men (p<0.01) compared to German men only in 21–30 years age group. In the other age groups the levels of TT and SHBG were higher in the Germans but the differences were not statistically significant. In all the racial groups serum levels of DHEAS and ADT reached a peak by about 20 years of life, and then declined progressively. The mean DHEAS in American Caucasians aged 20–29 years was 11.4 μmol/l compared to 6.22 μmol/l in the Arabs (p<0.001). The mean DHEAS in USA Caucasians aged 70–79 years was 2.5 μmol/l compared to 1.8 μmol/l (p<0.03) in the Arabs. There was no significant difference in mean serum levels of DHEAS between German and USA men. Similarly, there was no significant difference in the level of the hormones between Arab and Chinese men. Arab men with newly diagnosed prostate cancer had high serum TT, SHBG and DHEAS compared to those without the disease. Conclusions: The mean TT and SHBG was significantly lower in Arab men compared to Caucasian men especially in early adulthood. Caucasians have significantly higher serum levels of the precursor androgens DHEAS and ADT especially in early adulthood compared to Arab men. These observations of low circulating androgens and their adrenal precursors in Arab men may partially account for the decreased risk for prostate cancer among Arab men.     

Pharmacokinetics of modified slow-release oral testosterone over 9 days in normal men with experimental hypogonadism

Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 μg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P < .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency.     

Testosterone level and mortality in elderly men with systolic chronic heart failure

Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure (CHF) have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. A total of 175 elderly men (age≥60 years) with CHF were recruited. Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured, and estimated free testosterone (eFT) was calculated. The median follow-up time was 3.46 years. Of these patients, 17 had a TT level below 8 nmol l⁻¹ (230 ng dl⁻¹), 27 had an eFT level below 0.225 nmol l⁻¹ (65 pg ml⁻¹) and 12 had both. Using the age-specific tenth percentiles of TT and eFT in healthy men in our laboratory as cutoff points, the prevalences of TT and eFT deficiency was 21.7% (38/175) and 27.4% (48/175), respectively. Both TT and eFT were inversely associated with left ventricular ejection fraction (LVEF) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (all P<0.01). Kaplan–Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate (both P<0.01 by log-rank test). However, after adjustment for clinical variables, there were no significant associations of either TT or eFT levels with survival time (OR=0.97, 95% CI: 0.84–1.12, P=0.28 and OR=0.92, 95% CI: 0.82–1.06, P=0.14, respectively). Our study showed that levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, but they are not independent predictors for mortality.     

男性不育患者精子形态学分析与生殖激素关系的研究

目的:研究男性不育患者精子形态与生殖激素的关系,探讨畸形精子症的发病机制。方法:研究对象为90例男性不育患者,年龄25～40岁,利用Prader睾丸计评估患者睾丸容积,根据世界卫生标准进行精液常规分析,利用化学发光法测定血清生殖激素和性激素结合球蛋白(SHBG)浓度,计算得出游离睾酮和生物活性睾酮的浓度。结果:90例男性不育患者精子浓度均在正常范围,根据精子形态分析结果分为3个研究组,即组1(正常形态精子<4%)、组2(正常形态精子≥4%且<10%)和组3(正常形态精子≥10%),每组30例。3组之间年龄没有统计学差异(P>0.05);左侧睾丸容积分别为(14.27±3.65)ml,(16.90±3.57)ml和(14.57±3.57)ml,P组1,2=0.006,P组1,3=0.741和P组2,3=0.014;右侧睾丸容积分别为(14.60±3.70)ml,(16.60±3.35)ml和(14.67±3.54)ml,P=0.05;血清泌乳素(PRL)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、总睾酮(TT)和SH-BG在3组之间均没有统计学差异(P>0.05);血清游离睾酮(FT)水平分别为(0.25±0.07)nmol/L,(0.29±0.07)nmol/L和(0.31±0.13)nmol/L,P组1,2=0.086,P组1,3=0.010和P组2,3=0.364;生物活性睾酮(Bio-T)水平分别为(5.81±1.58)nmol/L,(6.78±1.55)nmol/L和(7.29±3.02)nmol/L,P组1,2=0.086,P组1,3=0.010和P组2,3=0.364。另外,正常形态精子百分率与血清FT、Bio-T水平之间均存在正相关(P<0.05)。结论:男性不育患者血清FT和Bio-T水平越高,则正常形态精子百分率越高,提示FT和Bio-T可能参与畸形精子症发病过程。     

The clinical relevance of sex hormone levels and sexual activity in the ageing male

OBJECTIVES: To assess the changes in sex hormone levels with age and the relationship of sexual functioning to testosterone levels, evaluating serum testosterone levels and erectile function in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: The study included 213 men with LUTS (age range 31-78 years) who had no confirmed erectile dysfunction. Their serum total and free testosterone, and sex-hormone binding globulin (SHBG) levels were measured, and they completed the International Index of Erectile Function (IIEF) questionnaire. RESULTS: The total and free testosterone levels decreased and SHBG increased with age, but only the change in free testosterone and SHBG were statistically significant. The correlation with age was closer for free testosterone (r = - 0.356, P < 0.001) than for SHBG (r = 0.177, P = 0.010). Regression analysis of the five domain scores of the IIEF and three hormonal levels, after correcting for age, showed that free testosterone level was significantly correlated with erectile function (r = 0.2136, P = 0.005) and orgasmic function (r = 0.179, P = 0.020), but SHBG levels were significantly correlated only with orgasmic function (r = - 0.154, P = 0.046). Total testosterone levels showed no significant correlation with any of the five domains of the IIEF. CONCLUSIONS: Of the sex hormone levels, the change in free testosterone correlated most closely with ageing and had the closest correlation with sexual activity. Contrary to previous reports, free testosterone and SHBG levels were significantly correlated with orgasmic function and/or erectile function rather than sexual desire. A complete study of sex hormone levels is needed to evaluate patients with erectile dysfunction.     

Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men

The circadian pattern in levels of serum total testosterone (T) in men becomes blunted with normal aging. However, because T not bound to sex hormone-binding globulin (non-SHBG-T) is felt to be a better representative of biologically available T than is total T, the possibility of a 24-h variation in non-SHBG-T in young men and the possibility that aging is associated with a blunting of that rhythm were investigated. Hourly blood samples were drawn on 10 normal young men (mean age 27.3 years) and 10 normal elderly men (mean age 70.7 years) over a 24-h period and the serum was assayed for total T, sex hormone-binding globulin (SHBG), and total protein; non-SHBG-T was calculated. SHBG was determined by radioimmunoassay as well as by a steroid-binding assay. Young men had a significantly higher (p less than 0.05) mean 24-h level of non-SHBG-T (1.91 +/- 0.62 nm/l) than did the elderly men (0.86 +/- 0.01 nM/l). Also, each young man showed a significant circadian rhythm in non-SHBG-T, with a group mean daily variation of 1.42 +/- 0.38 nM/l. In contrast, only 60% of the elderly men demonstrated a significant circadian rhythm in non-SHBG-T, and the group mean rhythm was blunted (maximum excursion 0.38 +/- 0.07 nM/l) compared with that of the young men. SHBG and total protein levels demonstrated similar 24-h variations in the two age groups. It was concluded that non-SHBG-T serum levels, similar to serum total T levels, demonstrate a circadian pattern in young men and this circadian rhythmicity becomes blunted with normal aging.     

Transdermal testosterone gel increases serum testosterone levels in hypogonadal men in Taiwan with improvements in sexual function

A randomized, double-blind, placebo-controlled trial was conducted to (1) evaluate efficacy and safety of transdermal testosterone gel (AndroGel) for hypogonadal men in Taiwan, and (2) observe improvements in sexual function through international index of erectile function (IIEF) scores. Eligible hypogonadal men were randomized to receive 50 mg/day transdermal testosterone gel (TTG) or placebo for 3 months. Primary end point was change from baseline in total testosterone (TT) and free testosterone (FT). Secondary end points were change from baseline in serum hormone levels (such as dihydrotestosterone (DHT), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex-hormone-binding globulin (SHBG)) and changes in IIEF scores. Safety evaluations included adverse events (AEs) and skin irritation assessment. Compared with baseline, the TTG group (n=20) had statistically significant increases in mean TT levels at month 1 (P=0.024) and month 2 (P=0.025), but no significant changes at month 3. TT levels in the placebo group (n=18) showed no statistically significant change at any visit. Changes in FT levels paralleled changes in TT levels in both groups. TTG group IIEF scores were significantly increased at month 3 (P=0.01), compared with a decline in placebo scores. No drug-related AEs occurred in the TTG group; the placebo group had 2 AEs (mild skin rash). In conclusion, TTG effectively restores serum TT and FT levels to a normal physiological range for hypogonadal men in Taiwan and improves sexual function.     

Trends in sex hormone concentrations in US males: 1988-1991 to 1999-2004

Previous studies suggest that male testosterone concentrations have declined over time. To explore this in a large US population, we examined testosterone and free testosterone concentrations in National Health and Nutrition Examination Surveys (NHANES) from 1988-1991 and 1999-2004. We also examined sex hormone-binding globulin (SHBG), estradiol, and androstanediol glucuronide (3α-diol-G) over the same period. Non-Hispanic white, non-Hispanic black, and Mexican-American men from 1988-1991 and 1999-2004 NHANES surveys who were ≥20 years old and had serum from morning blood draws were included in this analysis (1988-1991: N = 1,413; 1999-2004: N = 902). Testosterone, estradiol and SHBG were measured by competitive electrochemiluminescence immunoassays and 3α-diol-G was measured by enzyme immunoassay. Free testosterone was calculated using testosterone and SHBG values. Adjusted mean hormone concentrations were estimated using linear regression, accounting for NHANES sampling weights and design, age, race/ethnicity, body mass index, waist circumference, alcohol use and smoking. Differences in adjusted mean concentrations (Δ) and two-sided p-values were calculated; p < 0.05 was statistically significant. Overall, 3α-diol-G and estradiol declined between 1988-1991 and 1999-2004, but there was little change in testosterone, free testosterone, or SHBG (Δ: 3α-diol-G = -1.83 ng/mL, p < 0.01; estradiol = -6.07 pg/mL, p < 0.01; testosterone = -0.03 ng/mL, p = 0.75; free testosterone = -0.001 ng/mL, p = 0.67; SHBG = -1.17 nmol/L, p = 0.19). Stratification by age and race revealed that SHBG and 3α-diol-G declined among whites 20-44 years old (Δ: SHBG = -5.14 nmol/L, p < 0.01; 3α-diol-G = -2.89 ng/mL, p < 0.01) and free testosterone increased among blacks 20-44 years old (Δ: 0.014 ng/mL, p = 0.03). Estradiol declined among all ages of whites and Mexican-Americans. In conclusion, there was no evidence for testosterone decline between 1988-1991 and 1999-2004 in the US general population. Subgroup analyses suggest that SHBG and 3α-diol-G declined in young white men, estradiol declined in white and Mexican-American men, and free testosterone increased in young black men. These changes may be related to the increasing prevalence of reproductive disorders in young men.     

Prospective inverse associations of sex hormone concentrations in men with biomarkers of inflammation and oxidative stress

The suggested associations between sex hormone concentrations and inflammatory biomarkers in men originate from cross-sectional studies and small-scale clinical trials. But prior studies have not investigated longitudinal associations. Overall, 1344 men aged 20-79 years from the population-based cohort Study of Health in Pomerania were followed up for 5.0 (median) years. We used multivariable regression models to analyze cross-sectional and longitudinal associations of serum sex hormone concentrations (total testosterone [TT], sex hormone-binding globulin [SHBG], calculated free testosterone [free T], and dehydroepiandrosterone sulfate [DHEAS]) with biomarkers of inflammation (fibrinogen, high-sensitive C-reactive protein [hsCRP], and white blood cell count [WBC]) and oxidative stress (γ-glutamyl transferase [GGT]) using ordinary least square regression and generalized estimating equation models, respectively. Cross-sectional models revealed borderline associations of sex hormone concentrations with hsCRP, WBC, and GGT levels that were not retained after multivariable adjustment. Longitudinal multivariable analyses revealed an inverse association of baseline TT, free T, and DHEAS concentrations with change in fibrinogen levels (per SD decrement in TT, 0.25 [95% confidence interval, 0.04-0.45]; in free T, 0.30 [0.09-0.51]; and in DHEAS, 0.23 [0.11-0.36]). Furthermore, baseline DHEAS concentrations were inversely associated with change in WBC levels (per SD decrement, 0.53 [0.24-0.82]). Baseline TT, SHBG, free T, and DHEAS concentrations were also inversely associated with change in GGT after multivariable adjustment. The present study is the first to demonstrate prospective inverse associations between sex hormone concentrations and markers of inflammation and oxidative stress in men. Additional studies are warranted to elucidate potential mechanisms underlying the revealed associations.     

Challenges in the Diagnosis of the Right Patient for Testosterone Replacement Therapy

Diagnosis of testosterone deficiency is important to identify patients who might benefit from testosterone replacement therapy. Unfortunately, the diagnosis of hypogonadism may be a challenge for many practicing physicians, including endocrinologists and urologists. Signs and symptoms, such as sexual dysfunction, change in body composition, lethargy, and mood changes, are nonspecific and the available questionnaires are generally not useful in clinical practice. The diagnosis of testosterone deficiency is ultimately based on measurement of serum testosterone levels. However, marked variations in the reference ranges of serum testosterone levels among laboratories pose a challenge for physicians when interpreting the results. In addition, initial laboratory assessments usually determine total testosterone levels. About 1–2% of total testosterone is free and a further 30–50% is bound with low affinity to albumin; only these two components are bioavailable to the target tissues. In general, assuming the normal reference range for serum total testosterone in adult men is 300–1000 ng/dl (10–35 nmol/l), levels of < 250 ng/dl (8.7 nmol/l) suggest the patient is likely to be hypogonadal, whereas levels of > 350 ng/dl (12.7 nmol/l) suggest the symptoms may not be due to androgen deficiency. Values between 250 to 350 ng/dl warrant a repeat morning serum testosterone determination with assessment of free or bioavailable testosterone. In men with symptoms suggestive of androgen deficiency and borderline serum testosterone levels, where there are no contraindications to androgen therapy, a short therapeutic trial of testosterone may be justified.     

Age-related prevalence of low testosterone in men with spinal cord injury

Objective

To describe the relationship of advancing age in persons with chronic spinal cord injury (SCI) on the prevalence of low testosterone in men with SCI compared to historical normative data from able-bodied men in the general population.

Design

Retrospective, cross-sectional study. Two hundred forty-three healthy, non-ambulatory outpatient men with chronic SCI from age of 21 to 78 years were included in this retrospective analysis.

Results

Forty-six percent of men with SCI were identified as having low serum total testosterone concentrations (total testosterone <11.3 nmol/l). The age-related decline in SCI for total serum testosterone concentration was 0.6%/year compared to 0.4%/year in the Massachusetts Male Aging Study. Between the third and eighth decade of life, men with SCI had a 15, 39, 50, 53, 58, and 57% prevalence rate of low serum total testosterone, which is higher than values reported for each decade of life for able-bodied men in the Baltimore Longitudinal Study on Aging.

Conclusion

Compared with the general population, low serum total testosterone concentration occurs earlier in life in men with SCI, at a higher prevalence by decade of life, and their age-related decline in circulating total testosterone concentration is greater. Studies of T replacement therapy in men with SCI should assist in determining the possible functional and clinical benefits from reversing low serum total testosterone concentration.     

Age as a Predictive Factor of Testosterone Improvement in Male Patients After Bariatric Surgery: Preliminary Results of a Monocentric Prospective Study

Background

Male obesity can be associated with symptomatic alterations in sex hormones resulting in hypogonadism and impaired fertility. Surgical-induced weight loss can improve the sex hormone profile in men. The aim of the present study is to evaluate the levels of sex hormones in obese males before and after 6 months from bariatric surgery. Possible mechanisms and clinical implications are also discussed.

Methods

We evaluated levels of serum total testosterone (TT), sex hormone-binding globulin (SHBG), calculated free testosterone (cFT), follicular-stimulating hormone (FSH), luteinizing hormone (LH), and total estradiol (E2) in 20 male patients at the baseline and 6 months after bariatric surgery.

Results

Median [interquartile range] age at the time of surgery was 40.5 [27.2–46.7] years with a median [interquartile range] BMI of 43.6 [40.9–48.7] kg/m². The median baseline levels of TT, SHBG, cFT, LH, and FSH were reduced; levels of E2 were elevated. At 6 months from surgery, the median BMI dropped to 34.8 [31.7–40.5]?kg/m², TT, SHBG, cFT, LH, and FSH increased, while levels of E2 decreased. The improvement in the sex hormone profile was more evident in younger patients, with a statistically significant difference in cFT following surgery and in the raise of TT and cFT between the groups of patients below and above 35 years. At multivariate analysis, the age was the best predictive factor of the postoperative variations of TT.

Conclusions

These preliminary results confirm the general improvement in sex hormone profile in obese men after bariatric surgery and introduce the age as a possible contributing factor to this improvement.