DECREASED SEX HORMONE BINDING GLOBULIN (SHBG) AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP-1) IN EXTREME OBESITY

Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in-vitro and in-vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin-like growth factor small binding protein (IGFBP-1). IGFBP-1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF-1, IGFBP-1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 +/- 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean +/- SEM; 21 +/- 2 mumol/l), a normal IGF-1, but reduced IGFBP-1 (14.6 +/- 2 micrograms/l); in 15 women IGFBP-1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24 +/- 2 nmol/l) but total testosterone values (1.9 +/- 0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio (P less than 0.01, r2 = 0.306) and inversely correlated with SHBG (P less than 0.01, r2 = 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P less than 0.001, r2 = 0.383). No correlation was found between IGFBP-1 and W/H ratio but a strong positive correlation was seen between IGFBP-1 and SHBG (P less than 0.001, r2 = 0.466). Furthermore, an equally significant inverse correlation was found between IGFBP-1 and insulin levels (P less than 0.001, r2 = 0.474).(ABSTRACT TRUNCATED AT 250 WORDS)     

Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease.

In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations, elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded.     

SEX HORMONE BINDING GLOBULIN IN WOMEN WITH ANOREXIA NERVOSA

In 29 women with anorexia nervosa, on a blood sample withdrawn at 0900 h before and during weight gain, the binding parameters of serum sex hormone binding globulin (SHBG) were measured by a solid phase method and the levels of testosterone, oestradiol and thyroid hormones were measured by radioimmunoassay. The binding capacity of SHBG was higher than the upper limit for normally menstruating women in 23 patients whilst its affinity for binding testosterone at 37 degrees C was normal (0.32-0.53 X 10(-9) mol/l). The mean levels of testosterone, oestradiol and free thyroxine were normal and the mean level of triiodothyronine was significantly (P less than 0.005) decreased. The binding capacity of SHBG did not correlate significantly with body mass index, percent weight lost, thyroid hormone or sex hormone levels. In 9 patients, an i.v. infusion providing 1200-1400 calories daily was given for 1 week. In these patients a significant decrease (P less than 0.005) in the binding capacity of SHBG (from 74.7 +/- 26.7 to 52.9 +/- 21.8 nmol/l) and a significant increase (P less than 0.001) in T3 levels (from 0.69 +/- 0.21 to 0.95 +/- 0.13 nmol/l) was observed. In 14 patients, when a weight gain of at least 5% was obtained, the binding capacity of SHBG fell into the normal range (25.6-62.9 nmol/l) while T3 levels rose to normal (0.85-2.30 nmol/l). These findings suggested that variations of calorie intake and/or body weight may influence the binding capacity of SHBG in the human.     

PLASMA ANDROGENIC ACTIVITY IN WOMEN WITH ACNE VULGARIS AND IN HEALTHY GIRLS BEFORE, DURING AND AFTER PUBERTY

The possible relationship between plasma androgenic activity and acne vulgaris was investigated. Plasma testosterone and sex hormone binding globulin (SHBG) levels were determined in healthy girls during different stages of puberty, in healthy adult women and in women with acne vulgaris. Testosterone increase during puberty, whereas SHBG decreased during the early stages before it increased and stabilized plasma concentrations of testosterone and SHBG. Women with severe acne vulgaris had testosterone levels in the same range but the SHBG levels were significantly lower than those of healthy women and women with mild acne. These results show a high androgenic activity in the intermediate stages of puberty, when acne vulgaris is a common complaint and an increased androgenic activity in adult women with severe acne vulgaris.     

THE PITUITARY-LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)     

EFFECTS OF HYPERTHYROIDISM ON BINDING PROTEINS FOR STEROID HORMONES

Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) binding capacities were examined weekly in eight normally cycling women and three women taking birth control pills during a 5-week baseline period and after daily ingestion of 75 micrograms of L-triiodothyronine (T3) for 30 days. The SHBG binding capacity increased whereas the CBG binding capacity decreased after T3 therapy. The binding capacities of proteins for steroid hormones were measured in 18 hyperthyroid subjects (Graves' disease) prior to and after 3 months of antithyroid drug therapy. SHBG binding capacity in hyperthyroid men or women was higher, and CBG binding capacity lower than those in euthyroid subjects. Thus, during hyperthyroidism, binding capacities of sex hormone binding globulin and corticosteroid binding globulin vary in opposite directions. A statistically significant correlation between the ratio of the sex hormone binding globulin to the corticosteroid binding globulin and triiodothyronine levels was found (P less than 0.01). Therefore the ratio of the sex hormone binding globulin to the corticosteroid binding globulin might be potentially useful as a biochemical index of thyroid hormone action in peripheral tissues.     

Endogenous sex steroid levels in women with generalised osteoarthritis

Summary Epidemiologic and clinical observations have suggested a relationship between generalised osteoarthritis (GOA) and hormonal and menopausal factors in women. We explored the hypothesis that postmenopausal women with GOA have altered sex hormone status compared with control women. We studied 112 women (mean age 64) with GOA. Controls were 151 women (mean age 54) from the general population without clinical evidence of hand or knee OA. All women were postmenopausal. Serum was assayed by RIA for testosterone, oestradiol, sex hormone binding globulin (SHBG), and dyhydroepiandrosterone sulphate (DHEAS). Because of the differences in mean ages, the results were compared according to equal age groups divided on the basis of tertiles. SHBG was lower in the GOA group, reaching significance in the middle group 53–61 years (58.0 vs 67.9nmol/l p<0.05). Testosterone was slightly higher in GOA women aged under 53. No consistent differences were seen in the older age group or for the other sex steroids. These preliminary data suggest that middle-aged women with GOA have lower circulating SHBG levels. This implies that higher circulating free oestrogens and androgens are present suggesting a role in the aetiopathogenesis of GOA.     

Increased upper body and overall adiposity is associated with decreased sex hormone binding globulin in postmenopausal women

An unfavorable body fat distribution is associated with many metabolic abnormalities including a high prevalence and incidence of noninsulin dependent diabetes mellitus and decreased high density lipoprotein cholesterol and increased triglyceride levels. One mechanism for the effect of body fat distribution on metabolic variables may be through sex hormones. We examined the relationship of body mass index (BMI), ratio of subscapular-to-triceps skinfold ratio (centrality index) and ratio of waist-to-hip ratio (WHR) to sex hormone binding globulin (SHBG) (an in vivo measure of androgenicity) in 101 postmenopausal Mexican-American and non-Hispanic white women from the San Antonio Heart Study, a population based study of diabetes and cardiovascular disease. SHBG was significantly correlated with BMI (r = -0.440, P less than 0.001), WHR (r = -0.255, P less than 0.01) and centrality index (r = -0.210, P less than 0.05). In a multiple linear regression analysis, SHBG remained significantly associated with BMI (P less than 0.001) and WHR (P less than 0.05) but not with age, ethnicity or centrality index. This work suggests that in postmenopausal women overall adiposity and an unfavorable body fat distribution are associated with increased androgenicity as measured by a lower SHBG concentration. Our finding may help to explain the association of body fat distribution with diabetes and cardiovascular risk factors in older women.     

A COMPARISON OF THE EFFECTS OF DANAZOL AND GESTRINONE ON TESTOSTERONE BINDING TO SEX HORMONE BINDING GLOBULIN IN VITRO AND IN VIVO

Danazol and gestrinone are both effective agents in the treatment of endometriosis. Their mechanism of action is unknown but may be related to their androgenic activity, which is at least partly dependent on increases in the proportion of testosterone which circulates unbound to plasma protein. We have quantified these increases in patients on treatment, and by experimentation in vitro have demonstrated the relative importance of the reduction of sex hormone binding globulin (SHBG) binding capacity and competition with testosterone for SHBG binding sites by the drugs and some of their metabolites. The mean SHBG binding capacity in patients treated with danazol (400 mg/d, n = 7) and gestrinone (5 mg/week, n = 7) fell from 66.9 and 56.4 nmol/l to 36.1 and 28.1 nmol/l, after 1 week's treatment and to 11.1 and 7.1 nmol/l after 4 weeks respectively. Despite the similarity between the falls in SHBG binding capacity there was a significantly greater increase in % free testosterone in plasma samples from patients treated with danazol than in those from patients treated with gestrinone at 1 week. Experiments in vitro suggest that this was largely due to ethisterone (a major metabolite of danazol) competing with testosterone for SHBG binding sites. After 4 weeks on treatment there was a similar, near maximal reduction in SHBG binding of testosterone in both treatment groups. At the low levels of SHBG binding capacity reached by this time the extra effect of any competition for binding sites was much reduced.     

Reduced sex hormone binding globulin and derived free testosterone levels in women with severe acne

Reduced circulating sex hormone binding globulin (SHBG) levels were found in 54% of a group of women with moderate to severe acne and in 60% of another group of twenty-three women who had acne complicated by hirsutism and/or irregular menstrual cycles. The concentrations of SHBG for the women with acne alone (mean 48 ± 24 nmol/l) and for those with acne and hirsutes (mean 39 ± 18 nmol/l) were compared with the SHBG concentrations of fifteen unaffected women with normal menstrual cycles (mean 70 ± 19 nmol/l). The differences in mean SHBG values for both groups of women with acne were significant ( P < 0·001) on comparison with the mean for the unaffected women.
Twenty-nine per cent of the women with acne had elevated testosterone values (mean testosterone concentration for the group 1·5 ± 0·3 nmol/l) and 41% had elevated'derived'free testosterone levels (mean 21 ± 6 pmol/l). Of the women with acne and hirsutes 65% had elevated plasma testosterone levels (mean 2·1 ± 0·6 nmol/l) and 89% had elevated free testosterone concentrations (mean 31 ± 10 pmol/l). The mean values for testosterone and free testosterone in the plasma of unaffected women (mean testosterone concentration 1·1 ± 0·3 nmol/l and free testosterone 13 ± 4 pmol/l) were significantly lower than in women with acne alone ( P < 0·01 and P < 0·001) and in women with acne and hirsutism ( P < 0·001).
This study indicates that a deficiency in SHBG and an elevation in'derived'free testosterone is a frequent finding in women with severe acne and may be a significant factor in the aetiology and/or perpetuation of this condition.     

PLASMA C19 STEROID SULPHATE LEVELS AND INDICES OF ANDROGEN BIOAVAILABILITY IN FEMALE PATTERN ANDROGENIC ALOPECIA

Female pattern androgenic alopecia (AA) is a relatively common endocrine abnormality in premenopausal women. However, unlike hirsutism, little is known about the androgen metabolism and plasma C19 steroid sulphate profiles in this disorder. We have therefore measured the plasma levels of dehydroepiandrosterone sulphate (DHEA-S), 5-androstene-3β, 17/β-diol sulphate (5-ADIOL-S), 5α-androstane-3α, 17β-diol sulphate (3α-DIOL-S), androstenedione (AD), total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), non-SHBG bound T, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and have calculated the free androgen index (FAI): 100 × T (nmol/1) ÷ SHBG (nmol/1), in premenopausal women with AA ( n = 25-45) and in normal premenopausal women ( n = 17–73). While mean plasma concentrations of DHEA-S and T were not significantly different from controls, mean SHBG concentrations were significantly lower (47 ± 3 vs 64±3 nmol/1) and the mean free androgen index (4.4±0.4 vs 2.4±0–2), and mean concentrations of free testosterone (45 ± 5 vs 26 ± 1.4 pmol/ 1), non-SHBG bound T (0.9 ±0.2 vs 0.6±0.1 nmol/1) and androstenedione (4.3±0.3 vs 3.4±0.2 nmol/1) were significantly elevated in women with AA. Furthermore, mean plasma concentrations of 5-ADIOL-S (512±42 nmol/1) and 3a-DIOL-S (76±7 nmol/1) were significantly higher than levels found in normal women (272±12 nmol/1 and 52±2 nmol/1 respectively). The nature of the hyperandrogenism associated with AA may thus only be revealed by a comprehensive plasma androgen and androgen sulphate profile, which may explain apparently aberrant data for a given patient. In addition, 5-ADIOL-S and 3α-DIOL-S may serve as excellent plasma markers of both the existence of the disorder and the efficacy of its treatment.     

Sex hormones in amenorrheic women with alcoholic liver disease

Urinary excretion of estrogens and plasma concentrations of estrone, estradiol, LH, FSH, PRL, progesterone, testosterone, and sex hormone binding globulin were measured in nine chronic alcoholic women with cirrhosis or alcoholic fatty liver. They were aged 24-40 yr and all had secondary amenorrhea which had lasted for at least 3 months. The response of pituitary gonadotropin secretion to administration of LHRH and estradiol benzoate and of PRL secretion to TRH were also investigated. Urinary excretion of estrogens in the alcoholic women with liver disease was similar to that in normal postmenopausal women and less than half that in normal women of the same age in the midfollicular phase of the menstrual cycle. Plasma estradiol levels in the alcoholic women were lower than in the menstruating women but higher than in the postmenopausal women, whereas their plasma estrone levels were higher than in the menstruating women. Plasma concentrations of progesterone and testosterone in the alcoholic women did not differ from those in the postmenopausal women but were lower than in the menstruating women. In spite of the relative estrogen deficiency plasma LH and FSH levels were not elevated in the alcoholic women. The responses of LH and FSH to LHRH were similar in the patients and in the menstruating women. Intramuscular administration of estradiol benzoate did not increase plasma LH and FSH concentrations in the alcoholic women. Hyperprolactinemia was not found and there were no differences in the PRL responses to TRH between the patients and the control groups. In conclusion, disturbed regulation of gonadotropin secretion is an important factor in the genesis of estrogen deficiency and amenorrhea in alcoholic women with liver disease, although ovarian function may also be directly impaired.     

绝经后代谢综合征女性雌激素水平的变化

目的观察绝经后代谢综合征(metabolic synd rome,MS)女性雌激素及性激素结合球蛋白的变化。方法随机调查绝经期后女性168例,其中健康体检者78例(对照组),MS患者90例(MS组)。测静脉血雌二醇、性激素结合球蛋白、黄体生成素及卵泡刺激素水平。结果与绝经≤10年女性比较,绝经11～20年、≥21年的对照组和MS组女性雌二醇均明显降低,差异有统计学意义(P0.05)。与对照组比较,MS组女性绝经≤10年、11～20年、≥21年者体重指数明显升高,性激素结合球蛋白明显降低;绝经≤10年女性雌二醇、黄体生成素、卵泡刺激素明显降低,绝经11～20年女性卵泡刺激素、黄体生成素明显降低,差异有统计学意义(P0.05,P0.01)。结论低雌激素水平对代谢的影响在绝经10年内;低性激素结合球蛋白水平是预示绝经后女性MS的独立危险因素。     

Sex hormones in postmenopausal women with primary biliary cirrhosis.

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.     

Relationship of high density lipoprotein cholesterol with total and free testosterone and sex hormone binding globulin

A cross-sectional study was performed to see if the previously described association between high density lipoprotein (HDL) cholesterol and plasma total testosterone concentration reflected a relationship with free testosterone or with sex hormone binding globulin (SHBG). In 295 employed middle-aged men, measurements were made of total testosterone and SHBG in serum and of testosterone in saliva, and also of plasma total and HDL cholesterol, plasma triglycerides and other factors which might influence HDL cholesterol levels such as body mass index, alcohol and smoking habits and thyroid hormone levels. In a multiple regression analysis using the GLIM package programme total testosterone concentrations had a persistent positive association with HDL cholesterol (t = 3.5, P less than 0.001) - this association was independent of SHBG (which had a negative association with HDL: t = -1.8, P less than 0.07. The association of HDL cholesterol with testosterone was independent of and stronger than the association of HDL cholesterol with body mass index, alcohol intake and cigarette smoking. Salivary testosterone (a measure of the circulating free hormone) also had a positive independent association with HDL cholesterol. The relationship between HDL cholesterol and testosterone thus appears to reflect an association with circulating hormone levels rather than with the hormone binding globulin.     

Free testosterone index: comparison with plasma free testosterone

Blood-free testosterone indices were measured among 28 normal men (age; 24-48 yrs.), 20 normal women (20-36 yrs.), 18 pregnant women (22-31 yrs.), 17 males with hypogonadism (23-56 yrs.), 17 males with chronic hepatitis (20-42 yrs.), 24 males with liver cirrhosis (29-68 yrs.), 34 males with hyperthyroidism (20-42 yrs.) and 7 hirsute women (18-31 yrs.), and these were compared with the plasma concentrations of free testosterone. The testosterone index was obtained by multiplying the plasma concentration of testosterone by the percent of sex hormone-binding globulin (SHBG), non-bound testosterone precipitated by dextran-coated charcoal. A significant increase of plasma testosterone was observed in patients with chronic hepatitis (p less than 0.001) and hyperthyroidism (p less than 0.001) as compared with normal men and was also observed in pregnant (p less than 0.01) and hirsute women (p less than 0.01) as compared with normal women. The close negative correlation between plasma levels of testosterone and the percent of SHBG non-bound testosterone (r = -0.87, n = 79, p less than 0.001) was observed among normal men, male patients with chronic hepatitis and hyperthyroidism. The sex hormone binding capacity was increased from two to three fold in patients with chronic hepatitis and hyperthyroidism. The patients with compensated liver cirrhosis had increased plasma testosterone and a decreased percent of SHBG non-bound testosterone, and those with decompensated liver cirrhosis had decreased plasma testosterone and a normal percent of SHBG non-bound testosterone. The plasma concentration of free testosterone was normal in patients with chronic hepatitis and hyperthyroidism. It decreased in pregnancy (p less than 0.01) and increased in hirsute women (p less than 0.01). The blood free testosterone index was slightly high in one third of the patients with chronic hepatitis and hyperthyroidism as compared with that in normal men. However, a close correlation of the percent of SHBG non-bound testosterone and fractional free testosterone (%) measured by equilibrium dialysis (gamma = 0.82, p less than 0.001) was obtained in all subjects (n = 170). These data suggest that the blood free testosterone index parallels the plasma concentration of free testosterone and is useful to evaluate the status of androgenicity.     

Hepatic uptake of sex steroids in men with alcoholic cirrhosis

We attempted to determine to what extent the degree of liver function impairment might affect the hepatic uptake and, as a consequence, alter the systemic plasma levels of endogenous sex steroids in male patients with alcoholic cirrhosis. The plasma levels and hepatic uptake of the steroids dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, progesterone, and 17-hydroxyprogesterone were assessed. Systemic plasma levels of testosterone and dehydroepiandrosterone were significantly (p less than 0.05) reduced, whereas those of androstenedione, estrone, and estradiol were significantly (p less than 0.05) elevated in men with alcoholic cirrhosis when compared to controls. Sex hormone binding globulin levels were also significantly elevated (p less than 0.01). The hepatic uptake of sex steroids depended on the degree of liver function impairment as shown by the linear significant relationship between their hepatic extractions and that of indocyanine green (r = 0.74-0.92, p less than 0.05; except for dihydrotestosterone, r = 0.17, not significant). In addition, the hepatic uptake of sex steroids depended on the binding affinity to sex hormone binding globulin. The higher the affinity for sex hormone binding globulin, the lower the hepatic uptake influenced by liver function impairment. It was estimated that hepatic clearances accounted for only 20%-50% of the metabolic clearance of sex steroids. No significant relationship between plasma levels of sex steroids and their hepatic clearance was found. We show here that in alcoholic cirrhosis the extent of hepatic uptake of sex steroids depends partly on the degree of liver function impairment and partly on the degree to which they are bound to sex hormone binding globulin. Production rate or peripheral metabolism, or both, rather than hepatic uptake alone may account for the altered circulating levels of sex steroids.     

Effects of physical exercise on sex hormone binding globulin, high density lipoprotein cholesterol, total cholesterol and triglycerides in postmenopausal women.

This study was performed on 18 postmenopausal female volunteers in order to examine changes in sex hormone binding globulin (SHBG), high density lipoprotein cholesterol (HDLC), total cholesterol (TC) and serum triglyceride (TG) levels in a period of four months of moderate physical exercise. While SHBG decreased significantly (from 55.3 +/- 20.9 to 48.3 +/- 21.0 nM, P < 0.05), TG increased significantly (from 87 +/- 41.7 to 120.5 +/- 57.5 mg/dl, P < 0.001). These changes were accompanied by a significant decrease (P < 0.001) in body fat content. Other parameters such as HDL-cholesterol, TC and BMI did not change significantly. Plasma levels of SHBG were negatively correlated to serum TG both at the beginning (r = 0.492, P < 0.05) and at the end (r = 0.538, P < 0.05) of the period of moderate exercise. Also, changes in SHBG were negatively correlated with changes in BMI (r = 0.585, P < 0.05) and this could indicate that SHBG levels are more related to nutritional status than androgen/estrogen imbalance.     

Correlation of plasma insulin and insulin-like growth factor-I with indices of androgen transport and metabolism in women with polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen transport and metabolism in women with PCOS. DESIGN: Within-group analysis of clinical and biochemical characteristics of a consecutive series of women with PCOS, focusing on correlations of plasma insulin with clinical presentation and androgens. Insulin levels were also compared with a control group of normal women. PATIENTS: Forty-seven women who presented with hirsutism, cycle abnormalities or both, with ultrasound proven PCOS, were recruited. Mean age was 26.6 +/- 0.7 years (mean +/- SEM), BMI 27.3 +/- 1.2 kg/m2. MEASUREMENTS: Plasma insulin levels were measured at 30-minute intervals for 3 hours following a 75 g glucose load. Blood was also taken for measurement of testosterone (T), androstenedione (A), free testosterone (fT), sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I). Androsterone glucoronide (AG), a marker of peripheral androgen metabolism, was also measured. RESULTS: Neither basal insulin nor the sum of insulin measurements during the glucose tolerance test (sumINS) in women with PCOS were significantly different from a control group with normal ovaries. Within the PCOS group, basal insulin was greater in women with irregular cycles or amenorrhoea than in those with regular ovulatory menses (8.0 +/- 1.1 vs 3.1 +/- 1.5 mU/l, P less than 0.01) despite similarly raised androgen levels. Both basal insulin and sumINS correlated with BMI in women with PCO (r = 0.37, P less than 0.05 and r = 0.64, P less than 0.01 respectively) but not in controls. There was no significant correlation between insulin or IGF-I levels and T, A or AG despite a positive correlation of AG (but no other androgen) with BMI. SHBG showed an inverse correlation and fT correlated positively with sumINS (r = -0.51, P less than 0.01; r = 0.39, P less than 0.05). Regression analysis of each of the androgens on the other variables demonstrated no significant relationship between insulin and androgens. CONCLUSIONS: These data suggest that, in vivo, the major effect of insulin on androgen secretion is mediated by changes in SHBG rather than by direct stimulation of ovarian androgen production. Higher insulin concentrations in anovulatory compared with ovulatory women with hyperandrogenaemia may indicate that insulin resistance in the ovary contributes to the mechanism of anovulation in PCOS.     

Regulation of human ovarian insulin receptors in vivo

Insulin participates in regulating ovarian function in normal and in pathological states. This effect of insulin may be mediated by ovarian insulin receptors. We have previously characterized human ovarian insulin receptors and began to examine their regulation in vitro. The present study examines regulation of human ovarian insulin receptors in vivo. Stromal ovarian tissue was obtained from 21 women during an indicated surgical procedure. Ten women were premenopausal and 11 were postmenopausal. Specific 125I-insulin binding to stromal ovarian fragments ranged from 2.5% to 7.3%/mg protein. 125I-insulin binding to stromal fragments correlated positively with 125I-insulin binding to circulating leucocytes (r = .57; P less than .01). When postmenopausal and premenopausal women were analyzed separately, this relationship persisted in postmenopausal women (r = .70; P less than .05), but not premenopausal women. 125I-insulin binding to stromal ovarian fragments correlated negatively with age (r = -.63; P = .005). 125I-insulin binding to stromal ovarian fragments tended to correlate negatively with plasma insulin levels in postmenopausal women (r = -.67; P = .06), but not in premenopausal women. Plasma insulin levels correlated negatively with serum SHBG (r = -.62; P = .003). The percent free testosterone levels correlated positively with plasma insulin levels in premenopausal women (r = .95; P = .0001), but not in postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)