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      Bioavailable Testosterone Linearly Declines Over A Wide Age Spectrum in Men and Women From The Baltimore Longitudinal Study of Aging

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          Abstract

          <div class="section"> <a class="named-anchor" id="d6324272e259"> <!-- named anchor --> </a> <h5 class="section-title" id="d6324272e260">Background:</h5> <p id="d6324272e262">Age-related changes in testosterone levels in older persons and especially in women have not been fully explored. The objective of this study was to describe age-related trajectories of total testosterone (TT), ammonium sulfate precipitation–measured bioavailable testosterone (mBT), and sex hormone–binding glycoprotein (SHBG) in men and women from the Baltimore Longitudinal Study of Aging, with special focus on the oldest adults. </p> </div><div class="section"> <a class="named-anchor" id="d6324272e264"> <!-- named anchor --> </a> <h5 class="section-title" id="d6324272e265">Methods:</h5> <p id="d6324272e267">Participants included 788 White men and women aged 30–96 years with excellent representation of old and oldest old, who reported not taking medications known to interfere with testosterone. Longitudinal data were included when available. TT, mBT, and SHBG were assayed. Age-related trajectories of mBT were compared with those obtained using calculated bioavailable testosterone (cBT). Generalized least square models were performed to describe age-related trajectories of TT, mBT, and SHBG in men and women. </p> </div><div class="section"> <a class="named-anchor" id="d6324272e269"> <!-- named anchor --> </a> <h5 class="section-title" id="d6324272e270">Results:</h5> <p id="d6324272e272">mBT linearly declines over the life span and even at older ages in both sexes. In men, TT remains quite stable until the age of 70 years and then declines at older ages, whereas in women TT progressively declines in premenopausal years and slightly increases at older ages. Differences in age-related trajectories between total and bioavailable testosterone are only partially explained by age changes in SHBG, whose levels increases at accelerated rates in old persons. Noteworthy, although mBT and cBT highly correlated with one another, mBT is a much stronger correlate of chronological age than cBT. </p> </div><div class="section"> <a class="named-anchor" id="d6324272e274"> <!-- named anchor --> </a> <h5 class="section-title" id="d6324272e275">Conclusion:</h5> <p id="d6324272e277">In both men and women, mBT linearly declines over the life span and even at old ages. Its relationship with age-related phenotypes should be further investigated. </p> </div>

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          Most cited references53

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          Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study.

          Health and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men. A longitudinal survey of 2736 community-dwelling men aged 40-79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (±S.D.) 4.4±0.3 years later. Paired testosterone results were available for 2395 men. Mean (±S.D.) annualised hormone changes were as follows: testosterone -0.1±0.95  nmol/l; free testosterone (FT) -3.83±16.8  pmol/l; sex hormone-binding globulin (SHBG) 0.56±2.5  nmol/l and LH 0.08±0.57  U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost ≥15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic-pituitary-testicular (HPT) axis function. Body weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction.
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            Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen.

            Estrogen (E) deficiency associated with the menopause is the major cause of bone loss in aging women. However, men also lose significant amounts of bone with age, but they do not have the equivalent of menopause, and serum total testosterone (T) and E levels decline only marginally with age in men. Thus, it has been difficult to attribute bone loss in aging men to either T or E deficiency. Here, we show in a population-based, age-stratified sample of 346 men, aged 23-90 yr, that serum total T and E (estradiol plus estrone) levels decreased over the life span by 30% and 12%, respectively, but bioavailable (or nonsex hormone-binding globulin-bound) T and E levels decreased by 64% and 47%, respectively. In these men and in a parallel cohort of 304 women, aged 21-94 yr, serum PTH increased 84% and 64% over the life span, and urinary N-telopeptide of type I collagen (NTx) excretion, a bone resorption marker, increased 77% and 80% between age 50-85 yr in the men and women, respectively. By univariate analyses, serum bioavailable T and E levels correlated positively with bone mineral density (BMD) at the total body, spine, proximal femur, and distal radius and negatively with urinary NTx excretion in men and women. Urinary NTx excretion was also negatively associated with BMD in both sexes. By multivariate analyses, however, serum bioavailable E level was the consistent independent predictor of BMD in both men and postmenopausal women. Thus, bioavailable E levels decline significantly with age and are important predictors of BMD in men as well as women. These studies suggest that in contrast to traditional belief, age-related bone loss may be the result of E deficiency not just in postmenopausal women, but also in men.
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              The role of androgens and estrogens on healthy aging and longevity.

              Aging is associated with a loss of sex hormone in both men (andropause) and women (menopause). In men, reductions in testosterone can trigger declines in muscle mass, bone mass, and in physical function. In women, the impact of the loss of sex hormones, such as estradiol, on bone is well elucidated, but evidence is limited on whether the loss of estradiol negatively affects muscle mass and physical function. However, deficiencies in multiple anabolic hormones have been shown to predict health status and longevity in older persons. Thus, consideration should be given as to whether targeted hormone replacement therapies may prove effective at treating clinical conditions, such as age-related sarcopenia, cancer cachexia, and/or acute or chronic illnesses. If initiated carefully in the appropriate clinical population, hormone replacement therapies in men and women may prevent and reverse muscle and bone loss and functional declines and perhaps promote healthy aging and longevity.
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                Author and article information

                Journal
                The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
                GERONA
                Oxford University Press (OUP)
                1079-5006
                1758-535X
                August 09 2016
                September 2016
                September 2016
                February 27 2016
                : 71
                : 9
                : 1202-1209
                Article
                10.1093/gerona/glw021
                4978359
                26921861
                404a9379-1c26-4247-81d2-fcc593b00546
                © 2016
                History

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