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.     

Influence of chronic exercise on serum cortisol levels in older adults

The circulating level of cortisol is regulated by the hypothalamic-pituitary-adrenal axis through a neuroendocrine feedback circuit. This circuit can be activated by physiological stimuli such as stress, diseases, and exercise. High levels of serum cortisol hormone normally occur as a byproduct of aging, and can cause several types of damage to the organism and exacerbate immunosenescence. There is a great deal of variability in the cortisol response with regard to type, intensity, volume, and frequency of exercise. However, these relationships have been extensively studied with respect to the acute effects of exercise. Despite the well-known effects of acute exercise on cortisol response, it is unclear how it is affected by chronic exercise and the aging process. Therefore, the aim of this study was to conduct a review of studies that attempt to analyze the influence of chronic exercise on serum cortisol hormone in older people. In order to accomplish this goal, a review from 1970 to June 2012 period was performed using the following databases: Biological Abstracts, PsycINFO, PubMed/Medline, and the Web of Science. Eight articles met the criteria used in this study. Based on the included articles, chronic exercise may influence the serum levels of cortisol levels in older people. Despite this evidence, these results may not be generalized to the entire population of older people, given the few number of studies and especially because the studies showed diversity in variables and methodologies.     

Women's perceptions of the effects of menopause and hormone replacement therapy on skin

Although women frequently associate skin issues with menopause and hormone replacement therapy (HRT), little work has been done to investigate a possible relationship. A questionnaire was given to women attending a specialist menopause clinic; 87 women responded. Skin problems generally were common, with over 64% of respondents reporting past problems. Around half felt that the menopause had resulted in skin changes; dry skin was the predominant complaint at this stage. However, use of HRT in the short term did not result in any conclusive trends in skin condition in the majority of users.     

Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity,voiding function and prostate safety parameters

Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function – erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT.     

The future of hormone replacement therapy in the aging male

This paper is based on a presentation given at the 2nd World Congress on the Aging Male, Geneva, Switzerland, February 2000     

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.     

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.     

National Osteoporosis Society's Position statement on hormone replacement therapy in the prevention and treatment of osteoporosis

Hormone replacement therapy (HRT) has been shown to increase bone density, reduce the risk of fracture and can successfully relieve menopausal symptoms. From a time when HRT was the major therapeutic option for the management of osteoporosis, women and their clinicians now have a range of treatments available. Following the publication of the Women's Health Initiative (WHI) and the Million Women Study highlighting potential side-effects, such as breast cancer, heart disease and stroke, many doctors and women are now reluctant to use HRT. The National Osteoporosis Society felt that the role of HRT in the management of osteoporosis needed to be clarified. Using the Charity's expert clinical and scientific advisers, and through public consultation with members and key stakeholders, a Position Statement has been published. We conclude that HRT has a role to play in the management of osteoporosis in postmenopausal women below the age of 60 years. The key recommendations of the Position Statement are presented in this paper.     

Effects of testosterone replacement therapy on nocturia and quality of life in men with hypogonadism: a subanalysis of a previous prospective randomized controlled study in Japan

Abstract

Objective: We investigated the effects of testosterone replacement therapy (TRT) on nocturia and general health among men with hypogonadism and nocturia.

Methods: From our previous EARTH study population, 64 patients with a clinical diagnosis of nocturia (two or more times per one night) and hypogonadism, comprising the TRT group (n?=?31) and controls (n?=?33), were included in this analysis. The TRT group was administered 250?mg of testosterone enanthate as an intramuscular injection every 4 weeks for 6 months. All patients responded to the following questionnaires: International Prostatic Symptoms Score (IPSS), Aging Male Symptoms (AMS) score and Short Form-36 health survey at baseline and 6-month visit. These categories were compared based on changes from baseline to the 6-month visit between TRT and control groups.

Results: At the 6-month visit, the TRT group had a significant decrease in IPSS question no. 7 and AMS question no. 4, whereas no significant changes were observed in the control group. Additionally, role limitation because of health program, vitality and mental health domains were significantly improved in the TRT group.

Conclusions: Six-month TRT may improve nocturia, sleep conditions and quality of life among men with hypogonadism and nocturia.     

Association between serum levels of testosterone and biomarkers of subclinical atherosclerosis

Objective: To investigate the association between serum levels of testosterone and biomarkers of subclinical atherosclerosis based on data from 119 middle-aged men of the general population.

Methods: Testosterone, Apolipoprotein A-1 (ApoA-1), Apolipoprotein B (ApoB), Apolipoprotein B-to-Apolipoprotein A-1 ratio (ApoB-to-ApoA-1), high-sensitive C-reactive protein (hsCRP), and fibrinogen levels were measured. Data were also gathered based on age, BMI, waist circumference, smoking, alcohol consumption, and family history of cardiovascular diseases. Men were classified into two groups based on testosterone levels: hypogonadal (testosterone ≤12?nmol/L) and eugonadal men (testosterone >12?nmol/L).

Results: When compared to eugonadal, the hypogonadal men were significantly older (56?years vs. 55?years, p?=?.03), had greater BMI (28?kg/cm² vs. 26?kg/cm², p?=?.01), and higher waist circumference (104?cm vs. 100?cm, p?=?.01). Moreover, ApoB, ApoB-to-ApoA-1 ratio, and hsCRP were significantly higher in hypogonadal men compared to eugonadal men (1.1?g/L vs. 1.0?g/L, p?=?.03), (0.8 vs. 0.7, p?=?.03), (3.3?mg/L vs. 2.0?mg/L, p?=?.01), respectively. On the other hand, ApoA-1 and fibrinogen levels did not differ significantly between groups (p?>?.05). In an adjusted multivariate regression analysis model, only ApoB showed a significant negative association with testosterone levels (β?=??0.01; 95% CI?=??0.02, ?1.50; p?=?.04).

Conclusion: Testosterone levels showed an inverse relation to ApoB, a biomarker implicated in subclinical atherosclerosis. These findings support the hypothesis that low testosterone levels play a role in atherosclerosis.     

Effects of acute androstenedione supplementation on testosterone levels in older men

The purpose of the study was to examine the effects of acute androstenedione supplementation on hormone levels in older men at rest and during exercise. Men (n?=?11) between the ages of 58 and 69 were divided into an experimental (n?=?6; 62.33?±?2.57 y) and control (n?=?5; 60.2?±?1.02 y) groups. Each participant received an oral 300?mg dose of either androstenedione (experimental) or a cellulose placebo (control) for 7 d. Pre- and post-supplementation participants completed two separate, 20-min strength tasks consisting of leg extension and leg curls at different percentages of their 10-RM. Researchers collected blood samples pre-, during, and post-exercise. Blood samples were analyzed for testosterone, androstenedione, and estradiol levels. The researchers found a significant difference between pre- (4.36?±?56?ng/mL) and post- (5.51?±?0.35?ng/mL) testosterone levels, as well as pre- (0.88?±?0.20) and post- (7.46?±?1.25) androstenedione levels, but no significant differences between pre- and post-estradiol levels for either group. It appears that short-term androstenedione supplementation augmented acute testosterone responses to resistance exercise in older men. However, further study of this supplement is needed to determine any potential it may have in mitigating andropause.     

Effects of testosterone administration on liver structure and function in aging rats

Aging males have a decrease in testosterone levels, by which the testosterone treatment may influence in a negatively fashion the liver.

Aim: This study aimed to analyze the effects of aging with or without testosterone administration on the liver components of animals.

Methods: Wistar rats were divided into three groups: 20 months’ group (G20), 24 months’ group (G24), group treated with testosterone for 16 weeks (GT). All groups were sacrificed at 24 months except for G20 that was sacrificed at 20 months.

Results: Aging and testosterone treatment alters the body weight (BW), liver weight (LW) and relative liver weight. Besides, testosterone increased the mitogen capacity of hepatocytes. Nonetheless, we reinforce the negative effects of testosterone on old animals’ liver as chronic hepatic congestion and/or cholestasis. In addition, we observed that testosterone plays an important role on hepatic glycogen stores.

Conclusions: Our study showed many implications for the knowledge about the effects of aging with or without testosterone administration on old animals’ liver.     

Comprehensive evaluation of androgen replacement therapy in aging Japanese men with late-onset hypogonadism

Abstract

Objective: This study assessed the efficacy and safety of testosterone replacement therapy (TRT) in aging Japanese men with late-onset hypogonadism (LOH).

Methods: This study included 50 (median age: 57.7 years) Japanese men with LOH, who were consecutively enrolled and treated with TRT for at least six months at our institution. We evaluated the following measurements before and after six months of treatment with TRT as follows: blood tests, prostate volume, residual urine volume, self-ratings for International Index of Erectile Function 5 (IIEF-5), International Prostate Symptom Score (IPSS), Self-Rating Depression Scale (SDS), Aging Male Symptom (AMS) and the Medical Outcomes Study 8-item Short-Form health survey (SF-8).

Results: Following six months of TRT, the levels of testosterone, red blood cells, hemoglobin and hematocrit were significantly increased from baseline, while total cholesterol level was significantly decreased from baseline. Furthermore, TRT led to a significant increase in IIEF-5 score and a significant decrease in IPSS score. Of 30 men who were diagnosed with depression at baseline, only 11 men (36.7%) were still suffering from depression after TRT, and SDS scores were significantly decreased from baseline at month six. Treatment with TRT led to a significant decrease in all scores of the AMS scale as well as a significant improvement in all scores of the SF-8 survey, with the exception of the bodily pain score.

Conclusion: These findings suggest that TRT is an effective and safe treatment for aging Japanese men with LOH. TRT improved depressive symptoms as well as health-related quality of life.     

Effects of testosterone replacement therapy on hypogonadal men with osteopenia or osteoporosis: a subanalysis of a prospective randomized controlled study in Japan (EARTH study)

Objective: We investigated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) among hypogonadal men with osteopenia/osteoporosis.

Methods: From our previous EARTH study population, 74 patients with a clinical diagnosis of osteopenia or osteoporosis and hypogonadism were included in this study, as the TRT (n?=?35) and control (n?=?34) groups. The TRT group was administered 250?mg of testosterone enanthate injection every 4 weeks for 12 months. The BMD, waist circumference, body mass index, body fat percentage, and muscle volume were measured at baseline and at 12 months. Blood biochemical data, including total cholesterol, triglycerides, HDL-cholesterol, hemoglobin A1c, and adiponectin values were also evaluated.

Results: At the 12-month visit, BMD significantly increased in both groups. However, comparisons on changes of parameter values from baseline to the 12-month visit between the TRT and control groups were significantly different in BMD (5.0?±?5.0 vs. 3.0?±?3.2; p?=?.0434) and in adiponectin value (?0.90?±?3.33 vs. 0.10?±?2.04; p?=?.0192). There were no significant changes in other parameters.

Conclusions: TRT for 12 months could improve BMD with a decrease in adiponectin levels among hypogonadal men with osteopenia/osteoporosis.     

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.     

Use of unopposed systemic estrogen therapy in non-hysterectomized women: a population-based study in the UK

A population study of 28 general practices in Oxfordshire, UK found that 0.028% of 17,712 non-hysterectomized women aged 45-60 years were using systemic unopposed estrogen. This is significantly lower than that reported in the Million Women Study.     

Association of DHEA-S and estradiol serum levels to symptoms of aging men

Objectives A number of interactions between agerelated changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations. Methods In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays. Results A total of 375 men with a mean age of 59.9 ± 9.2 years (mean ± standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 ± 90.9 μg/dl and 29.7 ± 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels. Conclusion This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impact of DHEA-S on sexual function.