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Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.

Neuropsychological evaluations and sex hormone assays for 188 elderly, female nursing home residents (mean age: 87.8 years; standard deviation: 7.0 years) revealed inverse relationships for dehydroepiandrosterone (DHEA) blood levels and cognition scores based on the Mini-Mental State Exam and the Test for Severe Impairment, as well as for scores of the Immediate Recall, Copy, and Recognition tests of the Visual Reproduction subtest of the Wechsler Memory Scale-Revised (WMS-R; VR). A positive correlation between estrone and depression approached significance, as did the inverse relationships between the Recognition scores of the WMS-R; VR with androstenedione. These results and findings of others suggest that sex hormone actions in elderly women may differ from those in younger populations. A possible stress-related mechanism is also posited.

Objectives: We undertook this nursing home study in order to determine the relationships between dependency in activities of daily living (ADL) and blood levels of estrone, testosterone, androstenedione, and dehydroepiandrosterone (DHEA). Little is known about this issue. Methods: cross-sectional study of 370 nursing home residents. Hormone levels in blood specimens drawn in 1997 and 1998 were correlated with degree of ADL dependency recorded in medical charts. Results: Because of multiple comparisons associations were deemed significant for P -values ≤0.017 for males and ≤0.0125 for females. In males, the following were inversely related: testosterone levels with dependency in transferring and eating; estrone with eating and a summary ADL index; and androstenedione with toileting and a summary ADL index (in all cases, r =−0.4; P =0.007–0.015). Inverse trends existed between testosterone levels and dependency in mobility and a summary ADL index; and androstenedione and eating (in all cases r =−0.3; P =0.030–0.055). Among females the following were directly related: estrone levels with dependence in mobility, toileting, transferring, and a summary ADL index; and DHEA with transferring and a summary ADL index ( r =0.2−0.3, P =0.0001–0.01). Trends existed between estrone and eating, and DHEA and toileting ( r =0.1−0.2, P =0.04). Conclusion: In male residents, higher sex hormone levels are associated with better ADL performance. Among females the opposite is true. While further studies are needed to elucidate these relationships, our results and recent findings of others suggest sex hormone actions in older women differ from those in younger populations. A possible stress-related mechanism is also presented.

Objective: To study whether a program of brief, intensive, inpatient intervention could improve glycemic control in an indigent, minority population with uncontrolled diabetes unresponsive to outpatient treatment. Methods: Patients with uncontrolled diabetes unresponsive to treatment in our outpatient Diabetes Clinic were admitted to our inpatient Diabetes Unit, where their care was directed by the Diabetes Team (an attending diabetologist, an endocrinology fellow, two nurses, and two nutritionists). Of 108 patients admitted, data were available for 96. Patients from minority populations constituted 91.7% of the group. All patients were indigent. The mean duration of stay was 4.3 days. After dismissal, patients underwent follow-up again in our Diabetes Clinic. During the 540-day follow-up period, 25 patients were electively readmitted when satisfactory improvement in glycemic control was not achieved. Hemoglobin A1c levels were averaged and plotted for the group at defined time points up to 360 days before admission and up to 540 days after admission. Results: During the year before admission, hemoglobin A1c increased slowly from 10.1 ± 0.3% (mean ± standard error) at day -360 to 10.3 ± 0.2% at day -210 (F5 = 29; P

This review pertains to gonadal function in men with human immunodeficiency virus (HIV) infection, who often exhibit clinical and biochemical evidence of hypogonadism. Hypogonadotropic hypogonadism appears to be the most commonly encountered abnormality, although complete anterior pituitary insufficiency and primary gonadal failure have been reported. Levels of sex hormone-binding globulin (SHBG) are either unchanged or increased. Plasma levels of estrogens, progesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and prolactin vary. Pathologically, except for involvement by opportunistic infections, no significant abnormality in the hypothalamic-pituitary area has been described, but evidence of orchitis is commonly present. The cause(s) of these abnormalities remains unclear. The possible factors leading to hypogonadism in HIV-infected men include HIV infection itself, opportunistic infections, chronic debilitating illness, and effects of cytokines on the hypothalamic-pituitary-gonadal axis. Further studies are needed to clarify the cause(s) of testicular dysfunction in HIV-infected men and its clinical significance, treatment, relevance to the progression of HIV infection, and influence on the immune system.

Studies from this laboratory have shown that obese men have elevated serum estrogen levels and diminished levels of follicle-stimulating hormone (FSH) and free and total testosterone, all in proportion to their degree of obesity. The decreases in testosterone and FSH constitute a state of hypogonadotropic hypogonadism (HHG), and we have hypothesized that it results from feedback suppression of the pituitary by the elevated estrogen levels. We tested this hypothesis by lowering the serum estrogens of 6 health obese men (body mass index [BMI], 38 to 73) by administering the aromatase inhibitor testolactone (1 g daily for 6 weeks). Twenty-four-hour mean serum testosterone rose in every subject, from a mean of 290 +/- 165 ng/dL to a mean of 403 +/- 170 (P

The androgen-excess theory posits a central role of androgens in promoting breast cancer development. At first glance, this appears to contradict the currently accepted central role of estrogens in this process, but as we will show, the apparent contradiction is not a real one. In the present article, we review the mechanisms by which androgen excess may stimulate cancer growth in different subsets of estrogen receptor-positive and estrogen receptor-negative tumors. We also propose an endocrine classification of postmenopausal breast cancer based on the simultaneous evaluation of a patient's serum testosterone levels and the estrogen receptor status of the tumor. This classification identifies several different subsets of tumors and may have important clinical implications.

The literature findings on endogenous hormonal profiles in women with breast cancer are reviewed in detail. It is concluded that four sets of findings are valid: (1) diminished adrenal androgen production, probably genetic, in women with premenopausal breast cancer; (2) ovarian dysfunction (luteal inadequacy plus increased testosterone production) in breast cancer at all ages; (3) increased 16 alpha-hydroxylation of estradiol in breast cancer at all ages; and (4) evidence that prolactin is a permissive risk factor for breast cancer, and that the pregnancy-induced decrease in prolactin levels may account for the protective effect of early pregnancy against breast cancer.

The measurement called desirable body weight (DBW) was derived by actuaries to indicate that weight which is associated with the lowest mortality. Percent deviation from DBW has become a standard measure of fatness. A different obesity index, body mass index (BMI), is weight in kilograms divided by the square of height in meters. Many workers consider both measures inferior to the measurement of body fat content (BFC). We compared the three measures of fatness in 40 men aged 18-50 and 48 women aged 21-47, ranging from nonobese to extremely obese. Total BFC was determined by isotope dilution of 3H-labeled water. DBWs used were those listed in the US Air Force Examination Manual of 1971; these approximate the midpoint of the range of medium-frame values in the 1959 Metropolitan Life Insurance Tables, but have the advantage of providing a single value for each height. We found nearly perfect correlation (r = 0.99, p0.001) between BMI and percent deviation from DBW in both men and women ranging from 14% below to 305% above DBW. Correlations between percent deviation from DBW and total BFC were extremely high: 0.95 (p0.001) for the men and 0.94 (p0.001) for the women, essentially the same as correlations between BMI and BFC, which were 0.96 (p0.001) for the men and 0.95 (p0.001) for the women. It appears that the two technically simple weight-height indices, BMI and percent deviation from DBW, give just as accurate a measurement of fatness as the technically complex measurement of total BFC.(ABSTRACT TRUNCATED AT 250 WORDS)

To document the caloric intake of very obese persons and investigate the food choices and dietary composition that maintain severe obesity, we studied the self-selected food intake required to maintain stable weight in two groups of very obese subjects: 11 inpatients with a mean weight 181% above desirable body weight and 35 outpatients with a mean weight 125% above desirable body weight. Qualitative and quantitative food intake were evaluated using records obtained on the hospital metabolic ward for the inpatients and using self-recorded food records for the outpatients. Absolute caloric intake in both groups was greater in proportion to the degree of obesity (deviation from desirable body weight); caloric intake per unit of lean body mass (kilocalories per gram urinary creatinine) was constant regardless of the degree of obesity and was essentially the same as that of normal nonobese persons. Food records indicated that the obese subjects maintained their high caloric intake by consuming mostly foods of high caloric density, with occasional binge eating. They largely avoided foods of low intrinsic energy density and modified-calorie foods, ie, foods with decreased fat, nonnutritive sweeteners, or fillers. By substituting foods of lower caloric density for usual food choices from the same food group, obese persons could decrease caloric intake by 20% and increase potential for notable weight loss.

Although androgens are believed to influence the distribution of human adipose tissue and have been detected in human fat, receptors for these sex hormones have yet to be identified. These studies demonstrate that a high-affinity, limited-capacity binding component for the synthetic androgen methyltrienolone (R1881) exists in ammonium sulfate precipitates of human adipose tissue cytosols. The equilibrium dissociation constant (Kd = 0.1 to 0.4 nmol/L, n = 6) and the number of binding sites (2 to 26 fmol/mg protein, n = 22) are consistent with those reported for androgen receptors in rat prostate, human prostatic carcinoma, MCF-7 cells, and baboon myocardium. The relative steroid-binding specificities of the human adipose tissue androphile (R1881 approximately 5 alpha-dihydrotestosterone greater than testosterone greater than estradiol approximately progesterone much greater than dexamethasone) are similar, but not identical, to those reported for androgen receptors in rat prostate (R1881 greater than 5 alpha-dihydrotestosterone approximately testosterone greater than estradiol greater than progesterone much greater than cortisol) and baboon myocardium (R1881 greater than 5 alpha-dihydrotestosterone greater than testosterone greater than progesterone greater than estradiol much greater than cortisol). The function of the androgen-binding component in human adipose tissue is not known.

A male to female ration of coronary disease of 2:1 has been a consistent finding. This differential persists event when the classic risk factors for coronary disease--hypertension, smoking, obesity, diabetes, and hyperlipidemia--are controlled for gender. The most likely ultimate cause of this phenomenon is male-female differences in sex hormone patterns. Clinical studies in this area have either compared the sex hormone profiles of men and women with and without coronary disease or computed the relative prevalence of disease in populations that differ in their sex hormone patterns. In general, research findings have disputed the hypothesis that persons with coronary disease have low levels of a protective factor such as estrogen or progesterone and high levels of testosterone. Coronary disease patients actually have elevated estrogen levels and low testosterone levels; endogenous progesterone levels are normal before infarction but show a stress-mediated increase in the immediate postinfarction period. Findings of a low prevalence of coronary disease in premenopausal women, a loss of protection after menopause, and a low prevalence of coronary disease in men with cirrhosis-related hyperestrogenemia suggest that natural estrogens are antiatherogenic. The protective effect of pregnancy against myocardial infarction, despite concomitant potentially thrombogenic levels of estrogen at the time, seems to indicate that progesterone, whose levels are also extremely high during pregnancy, plays a major anti-infarction protective effect distinct from that of estrogen. Studies of women oral contraceptive (OC) users and men taking estrogens for brief periods have found that these exogenous hormones produce coronary thrombosis but not atherosclerosis. Finally, the finding of increased coronary disease risk in long-term OC users indicates that synthetic estrogens favor coronary atherosclerosis by suppressing natural estrogen and progesterone production.

To determine the effect of obesity on serum gonadotropin levels and any possible sex difference in the effect, we measured the 24-hour mean serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations in 62 healthy men with Body Mass Index (BMI) ranging from 20 - 94 and 61 healthy, regularly cycling women with BMIs ranging from 19 - 76. We also measured free testosterone (T) and estradiol (E2) in these subjects. There was a significant negative correlation between serum FSH and BMI in men: FSH(IU/L) = 49.9 x BMI -0.567; r = - 0.376, p = 0.0026; but a significant positive correlation between serum FSH and BMI in women: FSH(IU/L) =7.66 +/- 0.071 x BMI; r = 0.302, p = 0.018. Serum LH was weight-invariant in both sexes. In men, free T was negatively correlated with BMI: Free T (nmol/L) = 0.74 - 0.0068 x BMI; r = 0.585, p = 0.0381; and free E2 was positively correlated with BMI: Free E2 (pmol/L) = - 1.03 +/- 0.057 x BMI; r = 0.50, p = 0.0014. In obese women as a group, free T was higher than in lean women (33 +/- 6.8 S.E.M. vs. 17.4 +/- 2.0 pmol/L; p < 0.0001), and free E2 was also higher than in lean women: (6.90 +/- 0.80 vs. 4.84 +/- 0.55 pmol/L; p = 0.046). Of the many cases of hypothalamic-pituitary hormonal dysregulation that have been reported in obesity, none has been studied for sex differences. Our results mandate that possible sex differences be investigated in all cases of dysregulation.

Despite nearly six decades of epidemiological studies, meta-analyses, and reviews, there is still considerable controversy in the literature about the question, does postmenopausal estrogen administration increase the risk of breast cancer? In an effort to resolve the controversy, a number of animal, biochemical, and clinical investigative studies in this field have been reviewed. The following summary formulation is proposed: 1. Administration of estrogen is inherently capable of promoting the growth of breast cancer, and therefore of increasing the incidence of clinical breast cancer. 2. Human response to estrogen is like that of the low-cancer-incidence strains of mice studied by Lacassagne, in that large doses and prolonged administration are required to induce clinical breast cancer. 3. The blood levels of estradiol produced by the usual doses of postmenopausal estrogen are relatively low, equivalent to those of the follicular phase of the menstrual cycle. These levels may be near the threshold for producing breast-cancer-promoting effects; therefore, the tumor response will vary greatly in different populations, depending on genetic susceptibility factors: a. The prevalence of a family history of premenopausal breast cancer in a first-degree relative. b. The prevalence of abnormal BRCA1, BRCA2, and p53 genes. c. The prevalence of increased 16 alpha-hydroxylation of estradiol. d. The prevalence of smokers who are slow acetylators. 4. Consumption of alcohol (5 grams or more daily) along with the postmenopausal estrogen administration results in elevation of blood estradiol levels to values equivalent to those of the periovulatory peak of the menstrual cycle, which may be well above the threshold for producing breast-cancer-promoting effects in all women. The risk for cancer will therefore be uniformly increased in women who use alcohol and take estrogen. 5. Increased risk of breast cancer from postmenopausal estrogen administration can be eliminated by taking two synergistic steps: a. Eliminating alcohol consumption, or at least keeping it well below an average of 5 grams daily (equivalent to 2/3 ounce of whiskey or 3 ounces of wine). b. Diminishing the capacity to 16 alpha-hydroxylate estradiol, either through pharmacological agents such as indole-3-carbinol or through increased consumption of cruciferous vegetables. It is concluded that despite the inherent ability of postmenopausal estrogen therapy to increase the risk of breast cancer in theory, the increased risk can be eliminated in practice by minimizing or eliminating consumption of alcohol and ingesting pharmacological or dietary agents that reduce the 16 alpha-hydroxylation of estradiol.

Study objectives To determine whether bone imaging with 99m Tc methylene diphosphonate is a specific method of making the diagnosis of costochondritis in patients with chest pain who rule out for myocardial infarction. Design Nonblinded prospective controlled study in 20 patients and 10 control subjects. Setting Inpatient medical service of a tertiary teaching hospital. Patients Two hundred consenting patients admitted to the hospital with chest pain and suspected myocardial infarction were examined. Those in whom acute myocardial infarction was ruled out were evaluated for the clinical signs of costochondritis, ie , tenderness over one or more costochondral junctions. Twenty patients who met the clinical criterion gave informed consent and were subjected to bone imaging. Ten control subjects with cancer who did not have clinical signs of costochondritis underwent bone imaging to rule out metastatic disease (normal in all cases). Interventions Bone imaging with IV 99m Tc methylene diphosphonate. Measurements Bone scans of the investigative patients and the control subjects were read by two independent nuclear medicine specialists. Results Sixteen of the 20 patients with clinically diagnosed costochondritis showed increased technetium uptake at all costochondral junctions bilaterally; six of them also had increased uptake elsewhere on the chest wall (sternum, manubrium, or first rib). All 10 of the control patients likewise showed increased technetium uptake at all costochondral junctions bilaterally. Conclusions Bone imaging with 99m Tc methylene diphosphonate is not a specific method of making the diagnosis of costochondritis.

PURPOSE : To determine whether consultation by an individual endocrinologist or by a multidisciplinary diabetes team (endocrinologist, diabetes nurse educator, and registered dietitian) can impact length of hospital stay of patients with diabetes. PATIENTS AND METHODS : Hospital stays of consecutive patients with a principal diagnosis of diabetes were compared. Forty-three patients were seen by an individual endocrine consultant and 27 were managed by the internist alone. Thirty-four patients were seen in consultation by the diabetes team. All consultations were performed at the request of the primary physician. There were no statistically significant differences among groups with respect to age, duration of diabetes, admitting diagnosis, glucose levels, or concomitant acute or chronic illness. RESULTS : Average length of stay of diabetes-team patients was 3.6 ± 1.7 days, 56% shorter than the value, 8.2 ± 6.2 days, of patients in the noconsultation group (P

The 24-h mean plasma concentration of total testosterone (T) was measured in 33 healthy, regularly cycling, nonobese women between 21 and 51 yr of age. Percent free T was measured in 17 of them. Plasma dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were measured in 24 of them, and the DHEA-to-T and DHEAS-to-T ratios were calculated. It was found that the concentration of total T showed a steep decline with age; the regression equation was: T (nanomoles per L) = 37.8 x age-1.12 (r = -0.54; P < 0.003). According to this equation, the expected T concentration of a woman of 40 would be 0.61 nmol/L, about half that of a woman of 21 (1.3 nmol/L). The percent free T did not vary significantly with age, so free T concentration likewise showed a steep decline with age. The DHEA-to-T and DHEAS-to-T ratios were both age invariant, clearly because the levels of DHEA and DHEAS also decline steeply with age, as previously reported.

The question of whether estrogen therapy increases the risk of breast cancer is reviewed. Despite more than 60 epidemiological studies and several meta-analyses over a five-decade period, there is no consensus about the answer. At present, the majority of ivestigators agree that short-term or medium-term therapy (less than 10 years) poses no measurable risk; some, but not all, investigators feel that there is a modest risk with long-term therapy (more than 15 years). Even this semi-consensus is clouded by the startling and clear-cut-finding of the largest ever epidemiological study, the Nurses Surveillance Study, that a small increase in risk with estrogen therapy occurred only in women who also ingested alcohol, itself a known risk factor for breast cancer; wpmen who did not ingest alchol were at no increased risk. Because virtuallu none of the other epidemiological studies has contolled for alcohol ingestion, the conclusions of all of them are placed in doubt. To try to shed light on this problem, the 60-year-old studies of Lacassagne et al. on the induction of breast cancer in mice by estrogens were reviewed. They found that the magnitude and timing of the inducing effect of estrogen depended on the spontaneous breast cancer incidence in the mouse strain studied: in no-incidence strains, no cancer was induced; in high-incidence strains, induction was rapid and universal; in low-incidence strains, only a low percentage of animals had cancer induced, and it required prolonged estrogen administraion. Because (in animal terms) humans are a low-incidence goup, it is to be expected that any increase in breast cancer incidence with estrogen therpay would be modest and would require prolonged administration. This is approximately what is actually ovserved, but several factors may confound the picture: (1) the role of alcohol ingestion may ge important; (2) genetic variability in the capacity to 16α-hydroxylate may be important, because increased 16α-hydroxylation has been found to be a risk factor for breast cancer; (3) the specific estrogen administered may be important, because different estrogens vary in their ability to be 16α-hydroxylated; (4) the presence of atypical duct-cell hyperplasia may increase the risk; (5) a personal history of breat cancer or of premenopausal breast cancer in a mother or sister may increase the risk. In view of the overwhelming benefits of menopausal estrogen replacement therapy (diminished coronary disease, diminished osteoporosis, and prolongation of life-span, as well as relief of menopausal symptoms), it is concluded that all postmenopausal women should receive it unless they themselves have had breast cancer or a mother or sister has had premenopausal breast cancer.

The consequences of sleep deprivation and stress in residency training have not been quantified. In the course of assembling a control group for other studies, we unexpectedly observed a significant (P less than 0.005) and marked depression of serum testosterone levels in healthy male internal medicine residents (means = 11.8 +/- 1.1 nmol/L, n = 7) compared with other hospital personnel (means = 20.6 +/- 5.3 nmol/L, n = 18). Testosterone concentrations in the two groups were entirely nonoverlapping, while luteinizing hormone levels were not significantly different. We conclude that the stress of residency training leads to a quantifiable depression of gonadal function, and that gonadal steroid concentrations may be useful in evaluating measures intended to reduce that stress.

Because we had observed that smoking has a pronounced effect on serum progesterone levels, we reinvestigated in healthy nonsmokers the relative progesterone levels of men and follicular-phase women. Each of eight women had multiple measurements of serum progesterone during the follicular phase of a menstrual cycle (10 days through 3 days prior to the luteinizing hormone peak of that cycle), and the average of those values was taken to represent the basal progesterone level for that woman. Seven men had blood samples drawn at 20-minute intervals between 6:00 and 9:00 am, through an indwelling venous catheter, and the average of those values was taken. The mean follicular-phase serum progesterone level in the women was 21.4 ± 5.4 ng/dl and the mean level in the men was 18.1 ± 3.1 ng/dl. The difference was not statistically significant. In view of this finding, we conclude that there is essentially no ovarian secretion of progesterone during the follicular phase of the menstrual cycle. (Steroids 55: 557–559, 1990)

Since smoking has been shown to affect serum progesterone and estradiol levels in postmenopausal women, we evaluated the levels of these hormones and luteinizing hormone (LH) over an entire menstrual cycle (17 points) in eight healthy nonsmokers and eight healthy smokers. The total length of the cycle and the lengths of the follicular and luteal phases did not differ between the groups. There was no difference in estradiol, progesterone, or LH levels during the periovulatory and luteal phases. Follicular-phase serum progesterone, which had a level 37% higher in smokers, showed a plateau in both groups (28.3 +/- 5.7 ng/dl versus 20.7 +/- 5.7; P less than 0.0001). Follicular-phase serum estradiol showed a rising curve in both groups. The mean value in smokers was slightly higher than that in nonsmokers (107 pg/ml versus 95; P approximately 0.05); during the early part of the follicular phase, prior to the rapid preovulatory increase, the difference was greater (23%) and of higher statistical significance (80 pg/ml versus 65; P less than 0.001). The follicular-phase LH levels of smokers were skewed downward from the levels in nonsmokers, presumably by negative feedback from the elevated estradiol and progesterone levels; the difference was significant (P less than 0.001). The elevations of serum progesterone and estradiol in smokers probably represent activation of adrenocortical secretion by smoking. The greater and more clear-cut rise of progesterone than of estradiol is probably due to the fact that essentially all of the follicular-phase serum progesterone is secreted by the adrenal, while only part of the follicular-phase serum estradiol comes from the adrenal (via androstenedione and estrone).

It is known that plasma total testosterone (T) is decreased in obese men in proportion to the degree of obesity, but similar information is not available for plasma free T and non-sex-hormone-binding globulin (SHBG)-bound T. We measured the 24-h mean plasma total T in 48 healthy (non-weight-stable men, aged 18-55 yr, with body mass indexes (BMI) ranging from 21-95 kg/m2. Free T and non-SHBG-bound T were calculated using the measured total T, the concentrations of albumin and SHBG, and the association constants of T to albumin and SHBG. Total body fat content was measured by deuterium-water isotope dilution. Findings were as follows. 1) BMI was very highly correlated with total body fat content (r = 0.96; P less than 0.001); thus, the degree of obesity can be calculated just as appropriately from simple height and weight measurements as from measurements of total body fat content. 2) Total, non-SHBG-bound, and free T were all highly correlated inversely with BMI; for total T, r = -0.727, P less than 0.01; for non-SHBG-bound T, r = 0.677, P less than 0.01; and for free T, r = -0.653, P less than 0.01. Thus, free T and non-SHBG-bound T are decreased in obese men in proportion to the degree of obesity, just as is the case for total T; percentage-wise, the decrease was the same for all 3 parameters.