Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.

Uncertainty is a common experience for women living with breast cancer, particularly when treatment cannot assure disease cure. The study described in this article sought to provide insight into uncertainty experiences for women living with breast cancer. Hermeneutic phenomenology and photographic hermeneutics were used to describe and interpret uncertainty for nine women between 2 and 6 years posttreatment for breast cancer. Data were collected using interviews and interpretations of photographs. Five themes of uncertainty among women were uncovered. Major study findings included support for a reconceptualization of Mishel's Uncertainty in Illness Theory and the explication of growth-producing aspects of uncertainty.

Abstract-Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify age-and gender-related alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60°head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (Ϫ10.2Ϯ2 versus Ϫ1.2Ϯ3 mm Hg; Pϭ0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (Pϭ0.02). Upright plasma norepinephrine was lower in women (Pϭ0.02). Women had greater supine high-frequency R-R interval power than men (Pϭ0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (Pϭ0.01), despite higher supine (Pϭ0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness. (Hypertension. 1999;33:1195-1200.)Key Words: sympathetic nervous system Ⅲ norepinephrine Ⅲ spectral analysis Ⅲ hypotension A nalyses of the beat-to-beat variability of cardiac R-R intervals have been used to quantify alterations in autonomic function and predict adverse clinical events. 1,2 Since both age and gender have a profound influence on the risk of cardiovascular disease and death, it is important to understand the effects of healthy aging and gender on autonomic control of cardiovascular function. Previous studies have shown reductions in heart rate (HR) variability with aging 3,4 and increases in high-frequency HR variability in women compared with men. [5][6][7] Since many studies did not rigorously screen subjects to exclude occult cardiovascular disease, it is not known whether abnormalities in short-term autonomic control of HR reflect subclinical cardiovascular disease or whether they represent "normal" age-or gender-related alterations in autonomic function.The effects of age and gender on beat-to-beat blood pressure (BP) dynamics have been less well studied, and it is not known whether changes in the autonomic regulation of beat-to-beat BP are associated with hemodynamic impairment. Therefore, we asked the following questions: (1) Are there specific age-and gender-related alterations in the autonomic control of beat-tobeat BP dynamics in healthy individuals free of cardiovascular disease? (2) If so, what are the hemodynamic consequences of these changes during orthostatic stress?We u...

OBJECTIVE—Autoimmune thyroid disease (AIT), celiac disease, and Addison’s disease are characterized by the presence of autoantibodies: thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in AIT, tissue transglutaminase antibody (TTGAb) in celiac disease, and 21-hydroxylase antibody (21-OHAb) in Addison’s disease. The objective of this study was to define the prevalence of these autoantibodies and clinical disease in a population with type 1 diabetes. RESEARCH DESIGN AND METHODS—We screened 814 individuals with type 1 diabetes for TPOAb, TGAb, TTGAb, and 21-OHAb. Clinical disease was defined by chart review. Factors related to the presence of autoimmunity and clinical disease including age at onset of type 1 diabetes, duration of diabetes, age at screening, sex, and the presence of autoantibodies were reviewed. RESULTS—The most common autoantibodies expressed were TPOAb and/or TGAb (29%), followed by TTGAb (10.1%) and 21-OHAb (1.6%). Specific HLA DR/DQ genotypes were associated with the highest risk for expression of 21-OHAb (DRB1*0404-DQ8, DR3-DQ2) and TTGAb (DR3-DQ2- DR3-DQ2). The expression of thyroid autoantibodies was related to 21-OHAb but not to TTGAb. The presence of autoantibodies was associated with and predictive of disease. CONCLUSIONS—In this large cohort of individuals with type 1 diabetes, the expression of organ-specific autoantibodies was very high. The grouping of autoantibody expression suggests common factors contributing to the clustering.