Plasma sex hormone levels and mortality in disabled older men and women.

AIM: To investigate the relationship between circulating sex hormone levels and subsequent mortality in disabled elderly. METHODS: This prospective observational study was comprised of 214 elderly subjects aged 70-96 years (117 men and 97 women; mean ± standard deviation age, 83 ± 7 years), receiving services at long-term care facilities in Nagano, Japan. All-cause mortality by baseline plasma sex hormone levels was measured. RESULTS: After excluding deaths during the first 6 months, 27 deaths in men and 28 deaths in women occurred during a mean follow up of 32 months and 45 months (up to 52 months), respectively. Mortality rates differed significantly between high and low testosterone tertiles in men, but did not differ significantly between middle and low tertiles. Compared with subjects in the middle and high tertiles, men with testosterone levels in the low tertile (<300 ng/dL) were more likely to die, independent of age, nutritional status, functional status and chronic disease (hazard ratio [HR] = 3.27, 95% confidence interval [CI] = 1.24-12.91). In contrast, the low dehydroepiandrosterone sulfate (DHEA-S) tertile was associated with higher mortality risk in women (multivariate adjusted HR = 4.42, 95% CI = 1.51-12.90). Exclusion of deaths during the first year and cancer deaths had minimal effects on these results. DHEA-S level in men and testosterone and estradiol levels in women were not related to mortality. CONCLUSION: Low testosterone in men and low DHEA-S in women receiving care at facilities are associated with increased mortality risk, independent of other risk factors and pre-existing health conditions.

Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment.

AIM: There is little evidence that dehydroepiandrosterone (DHEA) has beneficial effects on physical and psychological functions in older women. We investigated the effect of DHEA supplementation on cognitive function and ADL in older women with cognitive impairment. METHODS: A total of 27 women aged 65-90 years (mean ± standard deviation, 83 ± 6) with mild to moderate cognitive impairment (Mini-Mental State Examination, MMSE; 10-28/30 points), receiving long-term care at a facility in Japan were enrolled. Twelve women were assigned to receive DHEA 25 mg/day p.o. for 6 months. The control group (n = 15) matched for age and cognitive function was followed without hormone replacement. Cognitive function was assessed by MMSE and Hasegawa Dementia Scale-Revised (HDS-R), and basic activities of daily living (ADL) by Barthel Index at baseline, 3 and 6 months. Plasma hormone levels including testosterone, DHEA, DHEA-sulfate and estradiol were also followed up. RESULTS: After 6 months, DHEA treatment significantly increased plasma testosterone, DHEA and DHEA-sulfate levels by 2-3-fold but not estradiol level compared to baseline. DHEA administration increased cognitive scores and maintained basic ADL score, while cognition and basic ADL deteriorated in the control group (6-month change in DHEA group vs control group; MMSE, +0.6 ± 3.2 vs -2.1 ± 2.2, P < 0.05; HDS-R, +2.8 ± 2.8 vs -0.3 ± 4.1, P < 0.05; Barthel Index, +3.7 ± 7.1 vs -2.7 ± 4.6, P = 0.05). Among the cognitive domains, DHEA treatment improved verbal fluency (P < 0.05). CONCLUSION: DHEA supplementation in older women with cognitive impairment may have beneficial effects on cognitive function and ADL.

Association of low testosterone with metabolic syndrome and its components in middle-aged Japanese men.

Epidemiological studies have shown that low testosterone is associated with metabolic syndrome (MetS) in Caucasian men. We investigated whether testosterone level is related to the prevalence of MetS in middle-aged Japanese men. A cross-sectional survey was conducted in 194 men aged 30-64 years (49+/-9). Blood sampling was performed in the morning after a 12-h fast, and the relationship between plasma hormone and MetS was analyzed. Low total testosterone was associated with MetS according to the Japanese criteria (HRs of 2.02 by quartile of testosterone; 95% CI=1.43-2.87) and the International Diabetes Federation criteria (HRs of 1.68 by quartile of testosterone; 95% CI=1.25-2.25). Age-adjusted regression analyses revealed that testosterone was significantly related to the MetS parameters of obesity (beta=-0.365 and -0.343 for waist circumference and body mass index, respectively), hypertension (beta=-0.278 and -0.157 for systolic and diastolic blood pressure, respectively), dyslipidemia (beta=-0.242 and 0.228 for triglycerides and high-density lipoprotein cholesterol, respectively), insulin resistance (beta=-0.253 and -0.333 for fasting plasma glucose and homeostasis model assessment of insulin resistance, respectively) and adiponectin (beta=0.216). Inclusion of waist circumference into the model largely weakened the association of testosterone with other metabolic risk factors. In contrast, high estradiol was associated with MetS and its parameters, mostly attributing to the positive correlation between estradiol and obesity. Dehydroepiandrosterone sulfate was not associated with MetS or its parameters. These results suggest that low testosterone is associated with MetS and its parameters in middle-aged Japanese men. The association between estradiol and MetS needs further investigation.

Age-related changes in plasma androgen levels and their association with cardiovascular risk factors in male Japanese office workers.

AIM: To assess the age-related change in plasma androgen levels in healthy middle-aged men and whether any clinical parameters are associated with the hormonal change. METHODS: The study was comprised of male Japanese office-workers aged 40-64 years, who had undergone an annual health check-up in 2002 and 2007 (96 and 76 men, respectively). Body mass index and blood pressure were measured, and serum concentration of lipids, glucose and uric acid in addition to plasma total testosterone, free testosterone and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in the morning after an overnight fast. The 5-year hormonal changes and their associations with clinical parameters were analyzed in 33 men who repeated the examination at both check-ups. The cross-sectional associations of hormonal levels with clinical parameters were also investigated. RESULTS: Age was negatively associated with free testosterone (r = -0.399, P < 0.001 in 2002; r = -0.458, P < 0.001 in 2007) and DHEA-S (r = -0.233, P = 0.02 in 2002; r = -0.336, P < 0.01 in 2007) but not with total testosterone, while the 5-year changes of free testosterone and DHEA-S levels were not significant and showed no associations with major cardiovascular risk factors. Cross-sectionally, after adjustment for age, linear regression analysis showed a positive association between free testosterone and blood hemoglobin and a negative association between total testosterone and serum uric acid. CONCLUSION: In Japanese middle-aged men, 5-year androgen decline is too subtle to detect, and endogenous androgen levels seem to have relatively weak association with cardiovascular risk profiles.

Association of plasma sex hormone levels with functional decline in elderly men and women.

AIM: We aimed to determine whether plasma sex hormone levels are associated with activities of daily living (ADL), cognition, depression and vitality in elderly individuals with functional decline. METHODS: Two hundred and eight consecutive persons 70 years or older (108 men and 100 women; mean +/- standard deviation, 81 +/- 7 years) with a chronic stable condition, receiving long-term care at a long-term care facilities located in Nagano Prefecture, Japan, were enrolled. Plasma total testosterone, free testosterone (only in men), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S) and estradiol levels were determined in the morning after an overnight fast. Comprehensive geriatric assessment was performed including basic ADL by Barthel Index, instrumental ADL, cognitive function by Hasegawa Dementia Scale--Revised, mood by Geriatric Depression Scale and ADL-related vitality by Vitality Index. RESULTS: Simple regression analysis showed that, in men, plasma total and free testosterone levels were associated with basic ADL (R = 0.292 and R = 0.282), instrumental ADL (R = 0.261 and R = 0.408), cognitive function (R = 0.393 and R = 0.553) and vitality (R = 0.246 and R = 0.396), while DHEA(-S) was associated with cognitive function, and estradiol with cognitive function as well as vitality. In women, the only significant correlation was between DHEA(-S) and basic ADL. Adjustment for age and nutritional markers did not influence the associations of plasma sex hormone levels with functional scores except for that of free testosterone with Barthel Index. CONCLUSION: These results suggest that sex hormones have sex-specific associations with physical and neuropsychiatric functions in elderly individuals, and that endogenous testosterone is related to global function in elderly men.

[Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

[Effects of antiosteoporotic agents on glucose and lipid metabolism and cardiovascular system].

Cardiovascular disease is the main contributor of mortality among postmenopausal women. Hormone Replacement Therapy (HRT) has been reported to have a beneficial effect on metabolic and vascular factors. Although, randomized clinical trials have questioned the efficacy of HRT in primary and secondary coronary artery disease (CAD) prevention despite confirming the lipid-lowering effect of HRT. As for selective estrogen receptor modulators (SERMs) , the available information suggests a neutral balance on CAD and stroke, and an increase in risk similar to estrogens for venous thromboembolic diseases. Evidence from both basic science and clinical studies supports the protective role of vitamin D beyond its effect on mineral metabolism. Recent studies suggest that Vitamin D improves vascular compliance, and reduces pro-inflammatory cytokines which may contribute to the improved survival observed in retrospective studies examining the outcome of patients treated with activated Vitamin D compared to those who were not.