Testosterone alters iron metabolism and stimulates red blood cell production independently of dihydrotestosterone.

Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis. However, it remains unknown whether the (type II) 5α-reduction of T to dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some other tissues. Our purpose was to determine whether inhibition of type II 5α-reductase (via finasteride) alters red blood cell (RBC) production and serum markers of iron homeostasis subsequent to testosterone-enanthate (TE) administration in older hypogonadal men. Sixty men aged ≥60 yr with serum T <300 ng/dl or bioavailable T <70 ng/dl received treatment with TE (125 mg/wk) vs. vehicle paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased RBC count 9%, hematocrit 4%, and hemoglobin 8% while suppressing serum hepcidin 57% (P < 0.001 for all measurements). Most of the aforementioned changes occurred in the first 3 mo of treatment, and finasteride coadministration did not significantly alter any of these effects. TE also reduced serum ferritin 32% (P = 0.002) within 3 mo of treatment initiation without altering iron, transferrin, or transferrin saturation. We conclude that TE stimulates erythropoiesis and alters iron homeostasis independently of the type II 5α-reductase enzyme. These results demonstrate that elevated DHT is not required for androgen-mediated erythropoiesis or for alterations in iron homeostasis that would appear to support iron incorporation into RBCs.

Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial.

Testosterone acts directly at androgen receptors and also exerts potent actions following 5α-reduction to dihydrotestosterone (DHT). Finasteride (type II 5α-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men could produce musculoskeletal benefits without prostate enlargement. Sixty men aged ≥60 yr with a serum testosterone concentration of ≤300 ng/dl or bioavailable testosterone ≤70 ng/dl received 52 wk of treatment with testosterone enanthate (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8-14% (P = 0.015 to <0.001), fat-free mass 4.04 kg (P = 0.032), lumbar spine bone mineral density (BMD) 4.19% (P < 0.001), and total hip BMD 1.96% (P = 0.024) while reducing total body fat -3.87 kg (P < 0.001) and trunk fat -1.88 kg (P = 0.0051). In the first 3 mo, testosterone increased hematocrit 4.13% (P < 0.001). Coadministration of finasteride did not alter any of these effects. Over 12 mo, testosterone also increased prostate volume 11.4 cm(3) (P = 0.0051), an effect that was completely prevented by finasteride (P = 0.0027). We conclude that a higher-than-replacement TE combined with finasteride significantly increases muscle strength and BMD and reduces body fat without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement but is not required for benefits in musculoskeletal or adipose tissue.

Cognitive effects of testosterone and finasteride administration in older hypogonadal men.

Serum concentrations of neuroactive androgens decline in older men and, in some studies, low testosterone is associated with decreased cognitive function and incidence of depression. Existing studies evaluating the effect of testosterone administration on cognition in older men have been largely inconclusive, with some studies reporting minor to moderate cognitive benefit, while others indicate no cognitive effect. Our objective was to assess the cognitive effects of treating older hypogonadal men for 1 year with a supraphysiological dose of testosterone, either alone or in combination with finasteride (a type II 5α-reductase inhibitor), in order to determine whether testosterone produces cognitive benefit and whether suppressed dihydrotestosterone influences cognition. Sixty men aged ≥ 60 years with a serum testosterone concentration of ≤ 300 ng/dL or bioavailable testosterone ≤ 70 ng/dL and no evidence of cognitive impairment received testosterone-enanthate (125 mg/week) versus vehicle, paired with finasteride (5 mg/day) versus placebo using a 2×2 factorial design. Testosterone caused a small decrease in depressive symptoms as assessed by the Geriatric Depression Scale and a moderate increase in visuospatial memory as assessed by performance on a recall trial of the Rey-Osterrieth Complex Figure Test. Finasteride caused a small increase in performance on the Benton Judgment of Line Orientation test. In total, major improvements in cognition were not observed either with testosterone or finasteride. Further studies are warranted to determine if testosterone replacement may improve cognition in other domains.

Description and students' perceptions of a required geriatric clerkship in postacute rehabilitative care.

This article describes medical students' evaluation of a geriatric clerkship in postacute rehabilitative care settings. This was a cross-sectional study of fourth-year medical students who completed a mandatory 2-week rotation at a postacute care facility. Students were provided with three instructional methods: Web-based interactive learning modules; small-group sessions with geriatric faculty; and Geriatric Interdisciplinary Care Summary (GICS), a grid that students used to formulate comprehensive interdisciplinary care plans for their own patients. After the rotation, students evaluated the overall clerkship, patient care activities, and usefulness of the three instructional methods using a 5-point Likert scale (1=poor to 5=excellent) and listed their area of future specialty. Of 156 students who completed the rotation, 117 (75%) completed the evaluation. Thirty (26%) chose specialties providing chronic disease management such as family, internal medicine, and psychiatry; 34 (29%) chose specialties providing primarily procedural services such as surgery, radiology, anesthesiology, pathology, and radiation oncology. Students rated the usefulness of the GICS as good to very good (mean+/-standard deviation 3.3+/-1.0). Similarly, they rated overall clerkship as good to excellent (3.8+/-1.0). Analysis of variance revealed no significant group difference in any of the responses from students with the overall clerkship (F(112, 4)=1.7, P=.20). Students rated the geriatric clerkship favorably and found the multimodal instruction to be useful. Even for students whose career choice was not primary care, geriatrics was a good model for interdisciplinary care training and could serve as a model for other disciplines.

The Effects of Aging and Endurance Exercise on Cardiovascular Performance in Healthy Elderly: A Review of the Literature.

CV performance declines over time in healthy elderly subjects due to aging, as well as declining physical activity. Recent studies with older, often sedentary individuals, demonstrate that aerobic endurance exercise may improve several measures of CV function. Although further research is needed to characterize the CV effects of exercise, particularly in elderly women and the oldest old population, aerobic endurance exercise should be advocated in the healthy elderly.