David A. Gruenewald

Testosterone supplementation therapy for older men: potential benefits and risks

Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo‐controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality‐of‐life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded.

Low Testosterone Is Associated with Decreased Function and Increased Mortality Risk: A Preliminary Study of Men in a Geriatric Rehabilitation Unit

Objectives: To evaluate whether low testosterone levels are associated with greater depression or poorer function in a geriatric rehabilitation unit.

Age-related decrease in proopiomelanocortin gene expression in the arcuate nucleus of the male rat brain

The decline in reproductive function with aging is due in part to decreased gonadotropin-releasing hormone (GnRH) secretion. beta-Endorphin (beta E), an endogenous opioid peptide derived from proopiomelanocortin (POMC), is thought to exert a tonic inhibitory effect upon hypothalamic GnRH secretion. We tested the hypothesis that the age-related decrease in GnRH secretion in male rats is due to increased beta E synthesis, by comparing POMC mRNA levels in the arcuate nucleus (ARC) of intact young, middle-aged and old male rats. In an initial study (Study 1), sixteen 20-microns coronal sections each from the ARC of 3- (n = 5) and 23-month-old (n = 4) male Fischer 344 rats were anatomically matched and analyzed. In a second study (Study 2), four anatomically matched sections of caudal arcuate nucleus from 3- (n = 4), 11- (n = 7) and 23-month-old (n = 5) male rats were compared. POMC mRNA levels were quantitated by in situ hybridization histochemistry, using a 35S-labeled oligodeoxynucleotide probe complementary to a portion of rat POMC cDNA and computerized image analysis. The number of grains per cell and cells per section were used as indices of cellular POMC mRNA content and the number of neurons expressing the POMC gene, respectively. Cellular POMC mRNA content was significantly lower in old compared to young animals (Study 1: 54 +/- 3 vs. 74 +/- 2 grains/cell, p less than 0.01; Study 2: 59 +/- 2 vs. 71 +/- 2 grains/cell, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging and the neuroendocrine regulation of reproduction and body weight

Aging in men is associated with a decline in trophic factors such as testosterone (T), alterations in body composition and impaired energy and body weight regulation. We performed studies to investigate the mechanisms underlying age-related changes in the neuroendocrine control of testis function, body composition, food intake and body weight in the Brown Norway (BN) rat. We found that similar to aging men, male BN rats demonstrate both primary and secondary testicular failure with aging without confounding age-related tumors, hormonal changes and systemic illnesses. With aging, these animals have blunted circadian variations in luteinizing hormone (LH) and T, and decreased hypothalamic gonadotropin-releasing hormone (GnRH) synthetic capacity with preserved pituitary gonadotropin responses to GnRH. We found that aging male BN rats have increased peripheral and visceral adiposity associated with increased insulin and leptin levels, and decreased relative lean body mass and muscle mass. We found that these rats exhibit reduced food intake and body weight gain associated with decreased hypothalamic neuropeptide Y (NPY) gene expression in the arcuate nucleus (ARC), both during ad-libitum feeding and after a 72-h fast. Recently, we found that old male BN rats treated chronically with troglitazone, an insulin sensitizer, lowered high insulin and leptin levels, decreased body fat, and corrected the blunted food intake and body weight gain response to fasting without affecting basal ARC NPY gene expression. These findings suggested that hyperinsulinemia and/or hyperleptinemia associated with aging may contribute to the age-related impairment in energy and weight regulation. Our studies suggest that the aging male BN rat is an excellent model to investigate the mechanisms underlying the age-associated changes in the neuroendocrine control of body composition, energy intake and body weight.

“Meet Me Where I Am”: Removing Barriers to End-of-Life Care for Homeless Veterans and Veterans Without Stable Housing

Objective: To describe the barriers and facilitators of end-of-life (EOL) care for Veterans without stable housing (VWSH) as perceived by Veterans at 1 VA medical center and EOL care staff. Design: Qualitative descriptive study. Secondary applied content analysis of data from interviews and focus groups in our parent study. Setting/Participants: VA Puget Sound Health Care System and VWSH. Results: The core emergent theme in the words of Veterans and health-care workers was “meet me where I am,” a statement of what many Veterans want most from their health care. Barriers and facilitators often reflected the presence or absence of important factors such as relationship and trust building, care coordination and flexibility, key individuals and services, and assistance in navigating change. Conclusions: These findings suggest that to improve health care for VWSH, interventions must be multifaceted, including a suite of support services, flexibility and creative problem-solving, and adaptations in communication approaches. The authors offer specific recommendations for improving EOL care for VWSH based on these findings.

Low testosterone is associated with decreased function and increased mortality risk

Objectives: To evaluate whether low testosterone levels are associated with greater depression or poorer function in a geriatric rehabilitation unit.

Aging and the Male Reproductive System

Compared to women, men experience a more variable, gradual, and progressive decline in reproductive function as they age. Male reproductive system aging is notable for reductions in testicular secretion of testosterone; alterations in hypothalamic/pituitary regulation of testicular function; structural changes in the testis, penis, and accessory sexual glands; and alterations in sexual function, spermatogenesis, and fertility. The significance of most of these age-related changes in male reproductive physiology is unclear, although erectile dysfunction and some consequences of the age-related decline in testosterone levels may have a major negative impact on quality of life in aging men.