Human aging is generally accompanied by a gradual decline in various physiological functions, which in some people results in physical impairments, and ultimately may cause disabilities which worsen the quality of life and limit independence. Normal aging is also frequently associated with reduced circulating levels of growth hormone (GH), insulin-like growth factor-I (IGF-I), and sex steroid hormones; decreased muscle mass and strength; and increased total and intra-abdominal fat. Treatment with recombinant human GH (rhGH) or sex steroids can improve body composition in some older persons, yet the effects of such hormonal treatment (singly or in combination) on various physiological functions remain to be defined. We hypothesize that age-related decreases in GH, IGF-I and sex steroids separately and interactively contribute to diminished skeletal muscle mass and strength, increased body fat, and reduced aerobic capacity in elderly women and men; and that restitution of normal GH, IGF-I and sex steroid status by combined hormone therapy wil exert additive or synergistic effects to increase muscle mass and strength, decrease body fat, and increase aerobic capacity. Thus, we are now conducting a placebo-controlled, double-masked study in a group of healthy, ambulatory, community- dwelling women and men beyond 65 years of age, with low IGF-I and sex steroid levels, to determine whether 6-months of administration of rhGH alone, sex steroid hormones alone (estrogen/progestin in women and testosterone in men), or combined rhGH plus sex steroids will increase or improve skeletal muscle mass, strength, and total body protein synthesis; decrease total and intra-abdominal fat; and improve aerobic capacity and cardiovascular function, as well as selected endocrine, metabolic, immunological, dermatological, and psychobehavioral functions. In the screening/recruitment portion of this study, we have evaluated interested volunteers by way of health screening interviews, providing a two-hour study information and informed consent, screening serum for testosterone, IGF-I, and PSA in men, while women are screened by a routine CBC, blood chemistries, liver and kidney function tests, thyroid function test, cholesterol, IGF-I, and urinalysis. Results were evaluated and eligible subjects underwent a complete history and physical, mini-mental exam and an exercise stress test. Blood work was collected on men at the time of their physical in order to complete their evaluation. Women were scheduled for a mammogram if they had not had one within one year, and gynecological evaluation and endometrial biopsy. This screening process afforded the researcher team key information regarding the suitability of volunteer patients, afforded potential participants personal familiarity with the study team, and, for all, promoted efforts to reduce possible risks. Recruitment and screening for the Growth Hormone and Sex Steroid Study ended in mid-June, 1998. In the final year, more than 200 men and women were excluded due to health problems and/or medication use; 10 men and 7 women were screened of whom 4 men and 5 women were enrolled. There were no adverse events resulting from the active screening process, although a number of individuals were newly found to have health-related issues to exclusion from the study and referral to private physicians for further evaluation. Should the current study reveal beneficial effects of hormone replacement then we plan to conduct certain targeted, longer-term investigations to examine the interactions of similar hormone treatments with other interventions (e.g., exercise conditioning), and their effects on functional status measurements in selected elderly populations.
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