Serum sex steroid hormones and frailty in older American men of the Third National Health and Nutrition Examination Survey (NHANES III)

Objective: To determine whether frailty is associated with circulating total and free testosterone, total and free estradiol, and sex hormone-binding globulin (SHBG) in older men. Methods: With NHANES III data of 461 men aged 60 years and older, we used logistic regression to analyze the associations between serum concentrations of sex steroid hormones, SHBG and frailty. Participants meeting any three or more of the five frailty criteria were classified as “frail”, all others were considered as non-frail. Results: 2.5% of men were frail. Men with SHBG ≥66 nmol/L had three times the odds of frailty (OR = 2.97; 95% CI 1.28–6.86) compared to men with SHBG <66 nmol/L. Men with free testosterone levels below 243 pmol/L had an increased odds of frailty (OR = 3.92; 95% CI 1.29–11.89). None of these associations was statistically significant after additionally adjusting for body mass index, smoking and history of cardiovascular diseases (CVD). Total testosterone, and total and free estradiol serum levels were not statistically significantly associated with frailty. Conclusions: In this US nationally representative study of older men, low free testosterone and high SHBG serum levels were associated with a significantly increased odds of frailty after adjustment for age and race/ethnicity. These associations may, however, be explained by confounding due to obesity, smoking, and the higher prevalence of CVD in frail men or by low hormones or high SHBG mediating the association between obesity, smoking, CVD and frailty.     

The imbalance of sex-hormones related to depressive symptoms in obese men

Obese men may present hypogonadothrofic hypogonadism, mainly related to higher insulinemia and aromatase activity. Our objectives were to evaluate the relationship of sex-hormones profiles and frequency of depressive symptoms in 43 obese men, in a cross-sectional study. They had 19–60 years, and body mass index 30–50?kg/m². LH, total and free testosterone (TT and FT), estradiol (E₂), sex hormone binding globulin, estradiol/total testosterone ratio (E₂/T) were analyzed. Depressive symptoms were evaluated by “beck depression inventory” (BDI), and significant depression was considered if BDI?≥?16.Thirty-four (80%) presented low TT levels, but only 4 (14%) had low free testosterone and hypogonadism symptoms; 12 of 43 (28%) presented increased E₂. Forty five (56%) presented depressive symptoms, but 16 (28% of the 45) had significant depression. BDI correlated positively with E₂ (r?=?0.407; p?=?0.001) and E₂/T (r?=?0.473; p?=?0.001), but not TT or FT. Patients with significant depressive showed higher levels of estradiol (136?±?48 versus 103?±?48?pg/ml, p?=?0.02) and E₂/T (16.0?±?9.9 versus 9.8?±?4.6; p?=?0.002) (mean?±?SD).In conclusion, obese men may present relatively excess of estradiol and deficiency in testosterone, leading to an imbalance between these two hormones. The greater this imbalance, the more depressive symptoms had our patients.     

Association of bioavailable estradiol levels and testosterone levels with serum albumin levels in elderly men

Estrogens are reported to be the essential sex steroid acting on some male physiological functions, and bioavailable estrogens comprise the free and albumin-bound fractions. Moreover, most of the bioavailable sex steroid is made up of albumin-bound fraction. We examined the age-related change in serum free, albumin-bound and bioavailable estradiol levels in comparison with each fraction of testosterone and its relationship with serum albumin level in elderly men. Albumin-bound as well as bioavailable estradiol levels declined with age, and their decreases were associated much more with the decrease of albumin level than the increase of sex-hormone binding globulin (SHBG) level in sixties and seventies, and similar results were recognized in the level of each fraction of testosterone, suggesting albumin levels have an important role for maintaining bioavailable sex steroid levels in males aged over sixty. Moreover, our study showed that SHBG levels associated inversely with bioavailable sex steroid levels particularly when serum albumin level was low. It seems likely that the decrease of bioavailable estradiol as well as testosterone is induced by the decrease of albumin-bound fractions in combination with the increase of SHBG-bound fractions in males aged over sixty, and that their physical characteristics of aging could be induced by the decrease of albumin-bound fractions caused by the decrease of serum albumin regardless of total sex steroid levels.     

Mission Statement

Aim.?To investigate sex hormone and androgen receptor (AR) levels and to evaluate their relationship with diabetes mellitus (DM) in senile men.

Methods.?The cross-sectional study included 492 elderly men comprising 104 healthy subjects (mean age 71.4 ± 5.2 years), 259 subjects without DM (71.5 ± 5.0 years) and 129 DM patients (73.0 ± 6.3 years). Plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG), estradiol (E₂), luteinising hormone) and follicle-stimulating hormone (FSH) were determined. AR-positive cells were measured by flow cytometry.

Results.?TT concentrations were significantly lower in the DM group (13.8 ± 4.7 nmol/l) than in the healthy (17.1 ± 6.1 nmol/l) and non-diabetes groups (15.8 ± 6.0 nmol/l; all P < 0.01). FT, SHBG, AR-positive proportion (AR%) and AR fluorescence intensity showed a decreasing trend among the healthy, non-DM and DM groups, but the differences were not significant. TT, E₂, E₂/testosterone and SHBG were negatively correlated with blood glucose. SHBG was positively correlated and TT and AR% were negatively correlated with the course of DM. Logistic multiple regression analysis revealed that age, waist/hip ratio, FSH, SHBG and AR% are potential risk factors for DM.

Conclusions.?Low levels of TT, SHBG and AR may be potential risk factors for DM in elderly men.     

Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis

Background Because of the great controversy over the role of androgens in the pathogenesis of atherosclerosis, we investigated the relationship between serum sex hormone levels and angiographically confirmed coronary artery disease in men.

Material and methods We investigated 86 men aged 40–60 years, 56 with coronary artery disease and 30 healthy men, matched by age, as a control group. Body mass index and waist to hip ratio were calculated and total body fat mass and percentage of abdominal deposit were investigated by dual-energy X-ray absorptiometry (Dpx (?+?) Lunar, USA). The serum levels of sex hormones and insulin were measured using commercial radioimmunoassay and IRMA (by SHBG) kits (DPC, USA). The serum levels of lipids and glucose were assessed by means of enzymatic methods.

Results Men with coronary artery disease had lower total testosterone levels (17.01?±?6.42 vs. 19.37?±?6.58?nmol/l; p?<?0.05), testosterone/estradiol ratio (228.5?±?88.5 vs. 289.8?±?120.1; p?<?0.05) and free androgen index (FAI) (59.49?±?14.79 vs. 83.03?±?25.81; p?<?0.0001), and higher levels of estrone (49.5?±?27.7 vs. 36.6?±?12.7?pg/ml) than men in the control group. Moreover, men with coronary artery disease were more insulin-resistant than controls and had an atherogenic lipid profile. There was an inverse correlation (p?<?0.05) between testosterone level and serum level of glucose (r?=??0.29), triglycerides (r?=??0.37), body mass index (r?=??0.55), waist (r?=??0.43), total body fat mass (r?=??0.3) and fasting insulin resistance index. A significant positive association (p?<?0.05) was found between testosterone and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol level in serum (r?=?0.26).

Conclusions Low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.     

Correlation between sex hormone levels and obesity in the elderly male

Objective: To investigate the levels of sex hormones and androgen receptor (AR) in elderly male patients and to explore a possible correlation with obesity. Methods: The cross-sectional study included 314 Elderly males (age ≥ 65 year). Of these subjects, 104 were healthy (age range 65–92 year; mean 71.38 ± 5.154 year), 74 were obese (65–87 year; 71.32 ± 4.74 year), and 111 were overweight (65–85 year; 71.43 ± 5.03 year). The following parameters were measured: total testosterone (TT), free testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), estradiol (E2), luteinizing hormone, follicle-stimulating hormone and AR. Results: (i) The levels of TT and SHBG in the obesity group were significantly lower than those in non-obese subjects. (ii) Body mass index (BMI) negatively correlated with TT and SHBG. (iii) Multiple regression analysis revealed that TT (β: ?0.230; p = 0.045) and SHBG (β: ?0.163; p = 0.02) were statistically correlated with BMI. Conclusion: Testosterone levels in the obese population were significantly lower than in the non-obese population and there is a significant association between testosterone levels and the extent of obesity.     

The impact of age,BMI and sex hormone on aging males’ symptoms and the international index of erectile function scores

Objective: To analyze the impact of age, BMI and sex hormone on aging males’ symptoms (AMS) and the 5-item version of the international index of erectile function (IIEF-5) scores in middle-aged and elderly Chinese men.

Methods: A population-based cross-sectional study was conducted in Jiashan County. A total of 969 men, aged between 40 and 80 years old, were admitted. Physical examination and the sex hormones were measured, and AMS and IIEF-5 scores were assessed.

Results: The oneway ANOVA analysis indicated older age groups had higher AMS total-scores, somatic and sexual sub-scores, and lower IIEF5 scores (all p?r_pairwise) analyses showed the significant associations between AMS and age or sex hormone (cFT, Bio-T, SHBG, and LH) levels, and similar for IIEF5. However, when age was adjusted, the correlation coefficients (r_partial) weakened, and correlation significance disappeared, except LH (for AMS: r_partial?=?0.096, p?=?.009; for IIEF-5: r_partial?= ?0.140, p?=?.001). Multiple linear regressions confirmed the influence of increased age and LH on the AMS and IIEF5 scores.

Conclusion: CFT, Bio-T and SHBG failed to yield any additional predicting information when age was adjusted. To improve the male reproductive health, future research should pay more attention on aging-related comorbidities and how to improve general wellness.     

Decline of serum levels of free testosterone in aging healthy Chinese men

Objective.?To investigate the age-related change of serum androgen levels in healthy men and to define a cut-off value of serum testosterone for the diagnosis of androgen deficiency in the aging male.

Method.?1080 healthy men aged 20 to ?70 years old were enrolled in Beijing, Shanghai, Xian and Chongqing. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), calculated free testosterone (cFT), sex hormone binding globulin (SHBG), 17beta-oestradiol (E2), the T/LH ratio, and T/SHBG as a free testosterone index (FTI) were all determined.

Results.?Serum total T did not significantly decline, but the cFT, T/LH and FTI progressively decreased with aging. To determine androgen deficiency, the 10th percentile value of men <40 years was defined as the lower cut-off value for cFT, T/LH or FTI, which were 0.3 nmol/L, 2.8 nmol/IU, and 0.4 nmol/IU respectively. With the median value of cFT of men aged between 20 and 49 years as the criterion, the level of cFT was lower in 2.82% of men from 40 to 49 years, in 19.53% from 50 to 59 years, in 22.57% from 60 to 69 years, and in 33.19% of men ?70 years. Taking the above value of cFT as the cut-off point, the prevalence of androgen deficiency in men 40–49 years was 13.0%, 31.8% in men 50–59 years, 30.1% in men 60 to 69 years, and 46.7% in men >70 years.

Conclusions.?(i). While serum total T values do not decline with aging, the levels of cFT gradually decline with aging; (ii) when using the value of cFT of the 10th percentile of men aged 20 to 39 years as the cut-off point, the prevalence of androgen deficiency was <15% before the age of 50 years, and about 30% thereafter, approaching 45% after the age of 70 years; and (iii) in this study the values of T/LH paralleled those of cFT closely; therefore, T/LH could serve as a surrogate for cFT.     

Circulating testosterone and estradiol,autonomic balance and baroreflex sensitivity in middle-aged and elderly men with heart failure

Abstract

Background: Heart failure (HF) is considered as a cardiogeriatric syndrome. Its fundamental pathophysiological feature is autonomic imbalance (and associated abnormalities within cardiovascular reflex control), but recent evidence suggests the involvement of deranged hormone metabolism. Both these neural and endocrine pathologies have serious clinical and prognostic consequences in patients with HF. We investigated the relations between autonomic status, baroreflex sensitivity (BRS) and hormone status in men with mild systolic HF.

Methods: We examined 46 men with stable systolic HF (age: 62?±?10 years, NYHA class I/II: 10/36 [22%/78%], ischemic aetiology: 72%, left ventricular ejection fraction: 32?±?8%). Serum hormone levels (i.e. total testosterone [TT], dehydroepiandrosterone sulphate [DHEAS], oestradiol [E2], insulin-like growth factor type 1 [IGF-1] and cortisol) were assessed using immunoassays. Estimated free testosterone (eFT) was estimated using the Vermeulen’s equation. Heart rate variability (HRV) was assessed in time and frequency domains, based on 10-min resting recordings. BRS was estimated using the sequence method (BRS-Seq) and the phenylephrine test (BRS-Phe).

Results: Deficiencies in circulating TT, eFT, DHEAS and IGF-1 (defined as a serum hormone ≤the 10th percentile calculated for the adequate age category in the cohort of healthy men) were found in respectively 13%, 30%, 55% and 93% of men with systolic HF. Serum SHBG ≥50?nmol/L and cortisol ≥700?nmol/L characterised, respectively 44% and 29% of men with HF. In multivariable models after the adjustment for clinical variables, the following relationships were found in examined men: DHEAS and SDNN (time domain of HRV defined as a standard deviation of average R–R intervals) (β?=?0.29, p?=?0.03); E2 and: HRV-LF (ms²) (β?=?0.37, p?=?0.01), HRV-HF (ms²) (β?=?0.44, p?=?0.02) and BRS-Phe (β?=?0.51, p?=?0.008); TT and: HRV-HF (%) (β?=?0.35, p?=?0.02), HRV-LF/HF ratio (β?=??0.35, p?=?0.02) and BRS-Seq (β?=?0.33, p?=?0.04).

Conclusions: The observed associations between reduced circulating androgens, oestrogens and lower HRV and depleted BRS, irrespectively of HF severity suggest the pathophysiological links between these two mechanisms. These results constitute the premises to investigate whether the pharmacological supplementation of depleted hormones would enable to restore the autonomic balance and improve the efficacy of reflex control within the cardiovascular system in men with systolic HF.     

Cross-sectional analysis between prostate volumes and serum sex hormones in Japanese men attending a urological clinic

Aim: To evaluate epidemiologically the association between measured prostate volume and sex hormones.

Methods: Between December 2012 and September 2014, 226 patients attending the urological clinic were assessed for the relationship between prostate volume (PV) and, serum sex hormones, physical size, personal habits, etc. Prostate volume was measured by using transabdominal ultrasonography. Statistically, the Pearson correlation coefficients test was used.

Results: Total cases, the cases of PV?≤?25?ml, and the cases of PV?>?25?ml were evaluated respectively. Total cases and the cases of PV?>?25?ml showed a positive significant correlation with testosterone (T), but the cases of PV?≤?25?ml showed no such correlation. The cases of PV?>?25?ml had a positive significant correlation with estradiol (E2), but total cases and cases of PV?≤?25?ml did not. Dehydroepiandrosterone sulfate (DHEAS) showed no correlation with any case of PV, however it decreased significantly with age and had a correlation with alopecia. The E2/T ratio had no correlation with any case of PV, but on the other hand, the T/DHEAS and E2/DHEAS ratios had significant positive correlation with PV?>?25?ml.

Conclusions: Serum T and E2 had significant positive correlation with measured PV especially in larger prostates. This result seems to correspond with the conventional theory that T and E2 have an etiological effect on benign prostatic hyperplasia. DHEAS did not show direct correlation with PV, however it appeared to suppress the role of T and E2 on benign prostatic hyperplasia growth. DHEAS might be a key to understanding the etiology of benign prostatic hyperplasia with aging.     

Relationship between testosterone serum levels and lifestyle in aging men

Objective.?The aim of this study was to evaluate the association between serum levels of testosterone and free testosterone to lifestyle in aging males.

Methods.?Men between 45 and 85 years were assessed regarding body mass index (BMI), nicotine and alcohol consumption, stress level, physical and social activity, and sleeping quality by a self-administered questionnaire. In parallel, serum levels of testosterone (T), free testosterone (fT), LH, FSH, DHEA-S, E2 and SHBG were obtained.

Results.?In total, 375 men with a mean age of 59.9 years (9.2 ± SD) entered this study; 25.4% and 27.4% had hypogonadal testosterone or free testosterone serum levels, respectively. Nicotine consumption (smokers had higher levels of T and fT; p < 0.01), BMI (negative correlation to T; p < 0.01) and age (negative correlation to fT; p < 0.001) correlated with serum levels of testosterone or free testosterone. Physical and social activity, nicotine and alcohol consumption, stress level and sleep quality did not show a significant association with serum androgen levels.

Conclusion.?This prospective study of 375 men aged 45 to 85 years confirms the correlation between age, BMI and smoking with serum levels of testosterone and free testosterone, whereas the investigated variety of lifestyle factors did not show a significant association to serum androgen levels.     

Significant association between serum dihydrotestosterone level and prostate volume among Taiwanese men aged 40–79 years

Introduction.?We evaluated the association between serum sex hormone levels and prostate volume in Taiwanese men.

Methods.?A cross-sectional study was conducted in 505 men (aged 40–79 years, mean age 58 years). Serum total testosterone (TT), free testosterone (FT), dihydrotestosterone (DHT) and estradiol (E2) levels were measured. Total prostate volume (TPV) and transition zone volume (TZV) were measured by transrectal ultrasonography. Body mass index (BMI), DHT/TT and E2/TT were calculated. Correlations were determined using univariate and multivariate regression analyses.

Results.?Apart from DHT, an age-dependent change of sex hormone levels were observed. On univariate analyses, age, BMI, serum DHT level and DHT/TT ratio, as well as serum E2 level and E2/TT ratio, but not serum TT and FT levels showed a significant association with prostate volume. On multivariate analysis, however, only serum DHT level and DHT/TT ratio remained significant. Logistic regression analysis showed that the odds ratios (95% confidence interval) of the second, third, and fourth quartiles of serum DHT levels for benign prostatic hyperplasia (defined as TPV?≥20?ml) risk were 2.06 (1.21–3.51), 2.66(1.56–4.53) and 7.15(4.0–12.6), respectively (p?<?0.001).

Conclusions.?Higher serum DHT level and DHT/TT ratio were associated with larger prostate volume and higher prevalence of BPH in Taiwanese men.     

The impact of metabolic syndrome on serum total testosterone level in patients with erectile dysfunction

Abstract

Objectives: To determine the association between metabolic syndrome (MetS) and serum testosterone levels (TT) in patients with erectile dysfunction (ED).

Methods: This study included 280 ED patients above 40-years-of-age. Participants were divided into two groups according to 2005 criteria of International Diabetes Federation. The severity of ED was determined according to the International Index of Erectile Function-EF (IIEF-EF score; 0–10 severe ED, 11–25 mild to moderate ED). The severity of ED, serum TT levels and other MetS components were compared between the groups.

Results: The mean age of the patients was 55.7?±?8.2 years. One hundred eighteen patients (%42.1) had MetS. Sixty-eight patients with MetS (57.6%) and 71 patients without MetS (43.8%) had severe ED (p?=?0.031). A total of 46 (16.4%) patients had hypogonadism. Hypogonadism was seen more prevalent in patients with MetS (22.9% vs. 11.7%, p?=?0.013). Logistic regression analyses for ED risk factors demonstrated that abnormal FBG increased the relative risk of severe ED up to 10.7-fold (p?<?0.001) but not presence of hypogonadism (p?=?0.706).

Conclusion: Metabolic syndrome was seen in almost half of the patients with ED. ED was more severe among MetS patients. Hypogonadism alone is a not risk factor for severe ED.     

Are the Aging Male’s Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire suitable for the screening of late-onset hypogonadism in aging Chinese men?

Abstract

The Aging Male’s Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire have been widely used for screening men suspected of late-onset hypogonadism (LOH). We evaluated the consistency of the two questionnaires with sex hormone levels. A total of 985 men completed the two questionnaires, as well as an analysis of the serum levels of total testosterone (TT), bioavailable testosterone (BT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL) and sex hormone-binding globulin (SHBG). No correlation was observed between any hormone level and the psychological or somatic section of the AMS score, whereas the sexual section was correlated with the levels of FT, LH, FSH, SHBG and BT. Significant correlations were observed between the result of the two questionnaires and these hormone levels. When LOH was defined as TT?<?300?ng/dl and FT?<?5?ng/dl, the sensitivity and specificity of the AMS scale were 54.0% and 41.2% compared with 78.7% and 14.8% for the ADAM questionnaire. Several sex hormone levels correlated with the two questionnaires, but neither of these questionnaires had sufficient sensitivity and specificity. It is necessary to provide a new questionnaire applicable to the Chinese population to screening LOH.     

The age-testosterone relationship in black,white, and Mexican-American men,and reasons for ethnic differences

Recent studies give contradictory findings regarding testosterone levels in white, black, and Hispanic men. Here, I present a cross-sectional reanalysis of serum testosterone and sex hormone-binding globulin (SHBG) in 1637 males, aged 12–90, who participated in the morning examination of the Third National Health and Nutrition Examination Survey (NHANES III) during the year 1988–1991. Testosterone and SHBG in males are described precisely over the age range 12 to 90 years. Testosterone and SHBG are not notably different in white and Mexican-American (MA) males. In the age range 20–69 years, black men average 0.39 ng/ml higher testosterone than white and MA men (p < 0.001). The higher testosterone in black men is partly explained by low marriage rate and low adiposity.     

The relationship between serum total testosterone and free testosterone levels with serum hemoglobin and hematocrit levels: a study in 1221 men

Objective: To investigate the relationship between serum total testosterone (TT) and free testosterone (FT) levels in men with anemia.

Methods: We reviewed the records of 1221 subjects between March 2009 and December 2014. All the subjects’ blood samples were drawn for TT and FT assays. Their serum hemoglobin (Hb) and serum hematocrit (Hct) levels were measured. The primary objective of our study was to investigate the association between TT and FT levels with Hb and Hct levels.

Results: The mean age was 59.82?±?12.71 years. The mean TT and FT levels were 4.54?±?2.02?ng/mL and 10.63?±?3.69?pg/mL, respectively. The mean Hb and Hct levels were 14.72?±?1.34?g/dL and 43.11?±?3.75%, respectively. Subjects with low TT (<2.35?ng/mL) had low Hb and Hct levels (p?p?Conclusions: Subjects with low TT and FT levels had low Hb and Hct levels. This suggests that TT and FT play a significant role in erythropoiesis. Testosterone replacement therapy may be effective in men with hypogonadism to reduce the incidence of anemia.     

Complex relationship between sex hormones,insulin resistance and leptin in men with and without prostatic disease

Objectives: To assess sex hormones, leptin and insulin-resistance in men with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and to study associations between androgens and histologic score of prostate tissue in PCa.

Subjects and methods: Two hundred ten men older than 45 years selected from 2906 participants of a population screening for PCa were studied: 70 with PCa, 70 with BPH and 70 controls (CG), matched by body mass index and age. Insulin, IGF-1, PSA, leptin, total, free (fT) and bioavailable testosterone (bT) and estradiol were measured. Each group was subdivided into two subgroups considering the presence of metabolic syndrome (MS); androgens and leptin levels were analyzed in the subgroups.

Results: Prostate cancer and BPH patients presented higher total, fT and bT levels than CG. IGF-1, insulin and HOMA index were higher in BPH than in the other two groups. PCa presented higher leptin [median (range) 6.5 (1.3–28.0) versus 4.8 (1.1–12.3) ng/ml; p?p?=?0.025] levels than CG. After dividing men considering the presence of MS, leptin was higher and total testosterone was lower in MS patients in all the groups.

Conclusions: It was observed a coexistence of an altered hormone profile with increased sex hormones and leptin in PCa patients, in accordance with the new perspective of PCa pathogenesis.