Reproductive hormonal dynamics were assessed in 10 massively obese men, 200-380% of ideal body weight (percentage ideal body weight) and 11 similarly-aged controls who were 85-135% of ideal body weight. The mean serum testosterone of the obese group was significantly lower than normal (223.1 ± 26.9 (SEM) ng/dl vs. 599.2 ± 58.1 ng/dl, P < 0.001). Despite their reduced serum testosterone levels, the obese subjects had normal secondary sexual characteristics except for slightly decreased facial hair and normal sized testes. The mean sex-hormone-binding-globulin level of the obese group was also lower than normal (0.247 ± 0.037 (SEM) /i,g dihydrotestosterone bound/dl vs. 0.672 ±0.125 /Ag/dl, P < 0.01), while their mean per cent free testosterone, determined by equilibrium dialysis, was higher than normal (4.19 ± 0.29 (SEM) % vs. 2.04 ± 0.08%, P < 0.001). Though the mean free testosterone was not significantly different in the 2 groups (obese 9.5 ± 1.3 (SEM) ng/dl, normal 12.1 ± 1.1 ng/dl), within the obese group there were significant negative correlations between total serum testosterone and percentage ideal body weight (r = -0.85, P < 0.01), as well as between free testosterone and percentage ideal body weight (r = -0.70, P < 0.05). Two of the most obese subjects (wt > 220 kg) had free testosterone concentrations more than two standard deviations below the normal mean. Within the obese group, there was no significant correlation of sex-hormone-bindingglobulin with total serum testosterone, free testosterone, or percentage ideal body weight. Baseline serum LH and FSH were normal in 9 obese subjects, including the 2 with low free testosterone, and elevated in one whose free testosterone was normal. The increases in serum LH after LHRH were not subnormal in the obese group, and the 2 subjects with low free testosterone did not have supranormal responses. Increases in serum LH and FSH after clomiphene were normal in the obese group. The serum testosterone of the obese group increased by a mean of 190% after clomiphene and by a further 120% (mean) after HCG, with all subjects attaining a serum testosterone over 600 ng/dl, thus indicating substantial testicular reserve. We conclude that, in massively obese men, 1) serum testosterone and sex-hormone-binding-globulin are low, 2) total serum testosterone and free testosterone correlate negatively with weight but do not correlate significantly with sex-hormone-binding-globulin, 3) responses to LHRH, HCG, and clomiphene indicate substantial reproductive hormonal axis reserve, and 4) a subpopulation (2/10) of the most massively obese subjects may have a defect in the hypothalamic-pituitary axis as suggested by its low free testosterone in the absence of elevated gonadotropins or hyper-response to LRH. (J Clin Endocrinol Metab 45: 1211, 1977 O BESITY is associated with abnormalities in many endocrine systems, including hyperinsulinemia, hypersecretion of cortisol, suppressed release of growth hormone, and abnormal thyroid function (1). In addition, obese women have an increase...

No other potential causes of TSH suppression, including medication changes or interference in the TSH assay, could be identified. The mechanism of the fall in serum TSH in these four patients is unclear at this time. Should these findings be confirmed in larger prospective studies, metformin's ability to suppress TSH without causing clinical or chemical hyperthyroidism might render this drug a useful adjunct to the treatment of patients with thyroid cancer.

Data are presented from 1,166 patients with Dukes B and C carcinoma of the colon who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-01 between November 1977 and February 1983. Patients were randomized to one of three therapeutic categories: 1) no further treatment following curative resection (394 patients); 2) postoperative chemotherapy consisting of 5-fluorouracil, semustine, and vincristine (379 patients); or 3) postoperative BCG (393 patients). The average time on study was 77.3 months. A comparison between patients receiving postoperative adjuvant chemotherapy and those treated with surgery alone indicated that there was an overall improvement in disease-free survival (P = .02) and survival (P = .05) in favor of the chemotherapy-treated group. At 5 years of follow-up, patients treated with surgery alone were at 1.29 times the risk of developing a treatment failure and at 1.31 times the likelihood of dying as were similar patients treated with combination adjuvant chemotherapy. Comparison of the BCG-treated group with the group treated with surgery alone indicated that there was no statistically significant difference in disease-free survival (P = .09). There was, however, a survival advantage in favor of the BCG-treated group (P = .03). At 5 years of follow-up, patients randomized to the surgery-alone arm were at 1.28 times the risk of dying as were similar patients treated with BCG. Further investigation disclosed that this survival advantage in favor of BCG was a result of a diminution in deaths that were non-cancer related. When analyses were conducted on which events not related to cancer recurrence were eliminated, the survival difference between the BCG and control groups became nonsignificant (P = .40); the cumulative odds at 5 years decreased from 1.28 to 1.10. The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection.

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