To determine whether ethanol per se affects testosterone metabolism, alcohol was administered to normal male volunteers for periods up to four weeks, resulting in an initial dampening of the episodic bursts of testosterone secretion followed by decreases in both the mean plasma concentration and the production rate of testosterone. The volunteers received adequate nutrition and none lost weight during the study, which tended to exclude a nutritional disturbance as the cause of the decreased testosterone levels. The changes in plasma luteinizing hormone suggested both a central (hypothalamus-pituitary) and gonadal effect of alcohol. In addition, alcohol consumption increased the metabolic clearance rate of testosterone in most subjects studied, probably owing to the combined effects of a decreased plasma binding capacity for the androgen and increased hepatic testosterone A-ring reductase activity. These results indicate that alcohol markedly affects testosterone metabolism independently of cirrhosis or nutritional factors.

Context: GH replacement in Prader-Willi syndrome (PWS) children has well-defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multisite studies.Objectives: Our objective was to evaluate the effectiveness and safety of GH in GH-deficient genotype-positive PWS adults. Design:We conducted a 12-month open-label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods. Setting:The study was conducted at outpatient treatment facilities at four U.S. academic medical centers.Patients: Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements were recruited from clinical populations.Intervention: Human recombinant GH (Genotropin) was initiated at 0.2 mg/d with monthly 0.2-mg increments to a maximum 1.0 mg/d, as tolerated. Main Outcomes Measures:Lean body mass and percent fat were measured by dual-energy x-ray absorptiometry.Results: Lean body mass increased from 42.65 Ϯ 2.25 (SE) to 45.47 Ϯ 2.31 kg (P Յ 0.0001), and percent fat decreased from 42.84 Ϯ 1.12 to 39.95 Ϯ 1.34% (P ϭ 0.025) at a median final dose of 0.6 mg/d in 30 study subjects who completed 6 -12 months of GH. Mean fasting glucose of 85.3 Ϯ 3.4 mg/dl, hemoglobin A1c of 5.5 Ϯ 0.2%, fasting insulin of 5.3 Ϯ 0.6 U/ml, area under the curve for insulin of 60.4 Ϯ 7.5 U/ml, and homeostasis model assessment of insulin resistance of 1.1 Ϯ 0.2 were normal at baseline in 38 study initiators, including five diabetics, and remained in normal range. Total T 3 increased 26.7% from 127.0 Ϯ 7.8 to 150.5 Ϯ 7.8 ng/dl (P ϭ 0.021) with normalization in all subjects, including six (20%) with baseline T 3 values at least 2 SD below the mean. Mildly progressive ankle edema was the most serious treatment-emergent adverse event (five patients).Conclusions: This multicenter study demonstrates that GH improves body composition, normalizes T 3 , and is well tolerated without glucose impairment in PWS genotype adults.

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The contribution, by peripheral conversion, of androstenedione and testosterone to the circulating estrogens was determined in men with cirrhosis of the liver. The conversion ratio of androstenedione to estrone, estradiol and testosterone and the conversion ratio of testosterone to estrone (but not estradiol) and androstenedione were significantly increased. The plasma concentrations of androstenedione and testosterone were increased and decreased respectively; the mean plasma concentration of androstenedione being similar to that found in normal women. The metabolic clearance rate of androstenedione was not altered in cirrhosis although the metabolic clearance rate of testosterone was decreased. The production rate of androstenedione was elevated while that of testosterone was reduced. The instantaneous contribution of plasma androstenedione to estrone and estradiol was increased in cirrhosis as was the contribution of testosterone to estrone (but not to estradiol). Thus the increased estradiol levels in cirrhosis result, in large part, from increased peripheral conversion from the androgens. The percent contribution of plasma testosterone to plasma androstenedione was decreased although the absolute amount derived by conversion was normal. The percent contribution of plasma androstenedione to plasma testosterone was increased sevenfold in cirrhosis. The fraction of the daily androstenedione production derived from the plasma testosterone pool was not significantly altered. However, a significant fraction of the daily production rate of testosterone was derived from androstenedione. Thus, 15% of the circulating testosterone is not secreted but is derived by peripheral conversion from androstenedione. Normal levels of gonadotropins were found in cirrhosis.

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