Mean Sex Hormone-binding Globulin Research Articles

Increased prevalence of type 2 diabetes mellitus and impaired glucose tolerance in first-degree relatives of girls with a history of precocious pubarche.

To assess whether abnormal responses to an oral glucose load, dyslipidaemia and hyperandrogenaemia, which are commonly found in girls with a history of precocious pubarche, can also be detected in first-degree relatives of these patients. Sixty first-degree relatives (age, 41.4 +/- 4.4 years; BMI, 26.9 +/- 3.3 kg/m2) of girls diagnosed with precocious pubarche were studied. The prevalence of gestational diabetes mellitus and the hirsutism score were assessed in the females. The study was performed during the early follicular phase of the menstrual cycle in females and at random in males. All subjects underwent a standard 75 g 2-h oral glucose tolerance test (OGTT). Serum lipids and lipoproteins were measured in baseline blood samples in all subjects, while serum testosterone, sex hormone-binding globulin (SHBG) levels and the free androgen indices were determined only in females. Impaired glucose tolerance (IGT) and type 2 diabetes mellitus were diagnosed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Seven subjects (11.6%) had type 2 diabetes while a further 14 (23.3%) had IGT; prevalences significantly higher than those reported for the present population of the same age (type 2 diabetes, 2.5% and IGT, 7. 5%; P < 0.001 and P < 0.001, respectively). BMIs were similar in patients with either normal or abnormal glucose tolerance. Abnormal levels of at least two lipid parameters were found in 40% of subjects. Four out of 10 hirsute women and six non-hirsute women reported gestational diabetes. Mean serum SHBG levels were lower in female relatives compared with population controls (P < 0.0005). First-degree relatives of girls with precocious pubarche are at a higher risk of impaired glucose tolerance and type 2 diabetes which, in most cases, is accompanied by an unfavourable lipid profile. Hyperandrogenism and an increased prevalence of gestational diabetes mellitus are frequent among females. These data may prove useful in identifying a specific subset of the population at increased risk of developing metabolic disturbances known to predispose to cardiovascular disease.

Dominant expression of sex-hormone-binding-globulin exon-7 splicing variant over wild-type mRNA in human ovarian cancers.

The intracellular expression of sex-hormone-binding-globulin(SHBG) exon-7-splicing-variant mRNA in human ovarian cancers was demonstrated by reverse-transcription/polymerase-chain-reaction, Southern-blot and DNA-sequencing analyses. Analysis of the missing base pairs proved that they corresponded to the entire exon 7, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-binding affinity of this variant might be different from that of the SHBG wild type. SHBG wild-type and variant mRNA was detected in all normal ovaries and in benign and malignant ovarian tumors analyzed. There were no significant differences in mean SHBG wild-type and variant mRNA levels among the 3 types of tissue, but the ratio of SHBG exon-7-splicing-variant to wild-type mRNA level in ovarian cancers was significantly higher (p < 0.05) than that in normal ovaries, with over-expression in some benign tumors. SHBG mRNA levels and the ratio of SHBG variant to wild-type mRNA was not associated with histological classification or clinical stages of ovarian cancers. These results suggest that over-expression of SHBG-exon 7-splicing-variant mRNA to the wild type might indicate the potential for neoplastic transformation.

Measurement of total serum testosterone levels using commercially available kits: high degree of between-kit variability

Objective: The measurement of total serum testosterone has an established clinical role in the management of male hypogonadism and female androgen excess disorders. We studied the between-kit variability and precision of six different commercially available testosterone assays and compared them with an established in-house method. Design: Laboratory observational prospective study. Setting: Tertiary university medical center clinical laboratory. Patient(s): Three groups of samples each of men (n = 36) and women (n = 15) who had high, normal, or low levels of sex hormone-binding globulin (SHBG), respectively, were studied. Intervention(s): Individual and pooled (male and female) serum samples were analyzed for total testosterone concentration using six different commercially available assays and one in-house method. Main Outcome Measure(s): The between-kit variability and the effect of the mean (± SD) SHBG level were determined, the results obtained with the use of the kits and the in-house method were compared, and the intraassay variability (i.e., precision) was evaluated. Result(s): Male samples demonstrated a 26.3%-40.8% variance in the results obtained with different kits, which was greatest for samples with the lowest SHBG levels. For female samples, between-kit variability ranged from 57%–115% (average, 77%). The percent deviation of the results obtained with the use of commercial methods from those obtained with the use of our in-house assay was greater for men (mean variance, 194%) than for women (mean variance, 67%). The female pool intraassay coefficient of variation was 3.8% with the use of the in-house method and ranged from 8.9%-21.2% with the use of the commercial kits. The male pool intraassay coefficient of variation was 3.1% with the use of the in-house method and ranged from 3.3%-5.5% with the use of the commercial kits. Conclusion(s): Most commercially available kits for measuring the total serum testosterone level demonstrated significant between-kit variability, which was greatest for female samples. Further, samples with the lowest SHBG levels had the highest between-kit variances. These data strongly suggest that the measurement of total serum testosterone using commercial kits may have limited utility, particularly for the detection of hyperandrogenemia.

Quantitative genetics of serum sex hormone—binding globulin levels in participants in the San Antonio Family Heart Study

Sex hormone—binding globulin (SHBG) is a steroid-binding plasma protein with a high affinity for testosterone that has been inversely associated with cardiovascular disease risk in many populations. SHBG may also act as a receptor in some tissues. Although the function of SHBG is relatively well understood, comparatively little is known about genetic factors contributing to the normal variation of serum SHBG levels. We estimated the heritability (h 2) of serum SHBG levels in 717 related Mexican-Americans participating in the San Antonio Family Heart Study (SAFHS). We found a significant heritability (h 2 = 0.31, P < .0001) for serum SHBG levels; age, exogenous hormones, smoking status, diabetic status, and adiposity showed significant associations ( P < .05) with mean levels of SHBG. Sex was associated with mean SHBG levels but not with genetic or environmental variance in SHBG levels; heritability estimates were the same for males and females. These results indicate a significant genetic influence on SHBG in Mexican-Americans. Thus, SHBG may prove to be an important indicator of genetic risk for cardiovascular disease in this population, as well as others.

Carriers of 21-hydroxylase deficiency are not at increased risk for hyperandrogenism.

A deficiency of 21-hydroxylase activity is one of the most commonly inherited genetic disorders in man, with heterozygosity for CYP21 mutations affecting approximately 1 in 60 of the non-Jewish Caucasian population. We have hypothesized that heterozygosity for CYP21 mutations in women increases their risk of developing clinically evident hyperandrogenism, and that this risk is related to the severity of the mutation of CYP21 and/or the 17-hydroxyprogesterone (17-OHP) response to ACTH stimulation. To test these hypotheses, we studied 38 obligate carriers for 21-hydroxylase deficiency (i.e. mothers of children with congenital adrenal hyperplasia or nonclassic congenital adreanl hyperplasia), comparing them to 27 weight-, parity-, and age-matched controls. Premenopausal carriers, not receiving hormonal treatment (n = 27), had higher mean total and free testosterone [T; 2.02 +/- 0.55 vs. 1.56 +/- 0.65 nmol/L (P < 0.007) and 0.018 +/- 0.007 vs. 0.012 +/- 0.006 nmol/L (P < 0.007), respectively] and lower mean sex hormone-binding globulin (214 +/- 62 vs. 277 +/- 129 nmol/L; P < 0.03) levels compared to controls. There was no difference in the mean basal levels of dehydroepiandrosterone sulfate, androstenedione (A4), or 17-OHP between carriers and controls. As expected, carriers exhibited higher stimulated and net increment 17-OHP levels than controls [21.1 +/- 27.1 vs. 6.2 +/- 3.1 nmol/L (P < 0.01) and 19.0 +/- 26.5 vs. 4.4 +/- 2.8 nmol/L (P < 0.009), respectively]. However, no difference was observed in the response of A4 to ACTH-(1-24) stimulation. Of the 27 carriers studied biochemically, 2 (7.4%) had a stimulated 17-OHP value between 30.3-60.6 nmol/L, and 1 (3.7%) had a 17-OHP level above 60.6 nmol/L, suggestive of nonclassic adrenal hyperplasia. Of all carriers studied genetically (n = 36), 50.0% (18 of 36) had 1, 33% (12 of 36) had 2, and 16.7% (6 of 36) had 3 or more mutations. In 27.8% (10 of 36) of carriers, the mutations were contiguous, consistent with a large gene conversion. All 38 carriers were examined for historical and physical features of hyperandrogenism. Hirsutism was defined as a Ferriman-Gallwey score of 6 or more, menstrual/ovulatory dysfunction as a history of menstrual cycles of more than 35-day, and hyperandrogenemia as total or free T, A4, and/or dehydroepiandrosterone sulfate levels above the upper 95th percentile of control values. Further, defining functional androgen excess (FAE) as the presence of at least 2 of the 3 hyperandrogenic features, 4 of 38 (10.5%) of carriers appeared to be affected (95% confidence interval, 2.9-24.8%). Assuming an expected prevalence rate of FAE in the general population of 5-20%, the frequency of FAE among our carriers was not significantly higher than expected. In conclusion, heterozygosity for CYP21 mutations does not appear to increase the risk of clinically evident hyperandrogenism, although carrying the defect was associated with higher mean and free T levels. Finally, due to the low frequency of androgen excess in our heterozygote population, we were unable to correlate the severity of the CYP21 mutation and/or the 17-OHP response to ACTH stimulation with the presence of the phenotype.

Changes in androgens during treatment with four low-dose contractptives

The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest ®, Femodeen ®, Marvelon ®, or Mercilon ®. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5α-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17α-hydroxy-progesterone (17OHP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon ® group when compared to Cilest ® and Marvelon ® (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon ® (−75%) as compared to the others (−100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.

Expression of sex hormone-binding globulin mRNA in human ovarian cancers

To know the role of sex hormone-binding globulin (SHBG) in the intracellular steroidal actions in human ovarian cancers, the expression of SHBG mRNA as a substitute for intracellular SHBG expression was investigated in normal ovarian tissues and ovarian tumors. In the present study, we used competitive reverse transcription-polymerase chain reaction-Southern blot analysis to evaluate SHBG mRNA levels. The expression of SHBG mRNA was detected in all normal ovaries and benign and malignant ovarian tumors analyzed. There were no significant differences in the mean SHBG mRNA levels among the three types of tissue. The expression in normal ovaries was significantly higher (p < 0.01) in premenopause, suggesting the predominance of a sex steroid hormone effect on ovarian SHBG synthesis. Relative overexpression of SHBG mRNA was observed in six out of 22 cases (27%) of ovarian cancer (three cases of endometrioid adenocarcinoma, two cases of serous cystadenocarcinoma and one case of mucinous cystadenocarcinoma) in comparison with normal ovaries and benign ovarian tumors. There was no difference in expression among the clinical stages of ovarian cancers. These data suggest that normal human ovaries and ovarian tumors might synthesize SHBG intracellularly, ovarian cancers might conserve an estrogen-associated property via SHBG and the regulation of intracellular SHBG expression might be changed in some cancers.

Serum sex hormone levels and renin-sodium profile in men with hypertension

Both a high renin-sodium profile and abnormal levels of sex hormones have been linked to myocardial infarction (MI) in men. The present study was carried out in men with hypertension to determine whether renin-sodium profile and sex hormone levels are related to each other. Renin-sodium profile, estradiol, testosterone, sex-hormone binding globulin (SHBG), and risk factors for MI, ie, cholesterol, insulin, glucose, and blood pressure, were determined in 45 men with hypertension. The mean serum estradiol level of the 13 men with high renin profile (30.1 +/- 6.5 pg/mL) was significantly higher (P = .01) than that of the nine men with low renin profile (22.6 +/- 3.9), while the mean level of the 23 men with normal renin profile was intermediate (26.2 +/- 5.3). The levels of estradiol and plasma renin activity correlated in the 45 patients before (r = 0.48, P = .001) and after (r = 0.46, P = .002) controlling for age. The mean estradiol-to-testosterone ratio was also higher (P = .04) and the mean SHBG level lower (P < .02) in the high renin group, but the mean testosterone level was not significantly different between the high and low renin groups. Although none of the risk factors was significantly different between the high and low renin groups, all of the mean values in the high renin group were in the direction of increased MI risk. These findings suggest that in men with hypertension, renin profile may be related to estradiol level and possibly to risk factors for MI.

Gemfibrozil treatment is associated with elevated adrenal androgen, androstanediol glucuronide and cortisol levels in dyslipidemic men

We have investigated the role of steroid hormones as coronary risk factors in Helsinki Heart Study population of dyslipidemic middle-aged men. We compare here the effects of gemfibrozil and placebo on the serum levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), their metabolite androstanediol glucuronide (3α-AdiolG), androstenedione, cortisol, testosterone, and sex-hormone binding globulin (SHBG) in non-smokers. We also examined the associations between steroid and lipoprotein levels in both treatment groups. Compared with placebo gemfibrozil treatment was associated with significant elevations of the mean levels of DHEA 10.2 vs 8.0 nmol/1; P<0.005, of DHEAS 8.0 vs 5.8 μmol/1; P<0.001, of 3αAdiolG 18.3 vs 8.4 nmol/1; P<0.001, ofandrostenedione 5.7 vs 5.1 nmol/1; P<0.02, and of cortisol 426 vs 358 nmol/1; P<0.001. The mean SHBG levels decreased from 46.4 to 41.7 nmol/1; P=0.03 with gemfibrozil treatment. No difference was found in testosterone levels 17.7 vs 18.8 nmol/1; P=0.11, or the ratio of testosterone/SHBG 0.45 vs 0.43; P=0.23. Positive correlations were found between high density lipoprotein-cholesterol and DHEAS (r=0.267; P<0.01) and DHEA (r=0.282; P<0.01) levels and negative correlations between low density lipoprotein-cholesterol and 3α-AdiolG (r=−0.400; P<0.001) and cortisol (r=−0.281; P<0.01) levels in the gemfibozil group. Our results indicate that gemfibrozil treatment increases the production and turnover of adrenal androgens and cortisol, and suggest that activation of the adrenocorticol function and increased metabolism of androgens are related to the improved lipoprotein pattern during gemfibrozil treatment.

Effects of different doses of norethisterone on ovarian function, serum sex hormone binding globulin and high density lipoprotein-cholesterol

The ovarian effects of different doses of norethisterone (NET) were compared in 45 normally menstruating women in order to find the lowest effective dose of the Chinese NET “visiting pill”. Subjects were randomly divided into 3 groups. Each subject in each group was taking 0.5, 1.5 or 3.0 mg per day from days 5 to day 18 of the cycle. Blood samples were taken on days 5, 8, 11, 14, 17, 20, 23, 26 and 29 of the cycle. Serum oestradiol (E 2), progesterone (P), sex hormone binding globulin (SHBG), high density-lipoprotein cholesterol (HDL-C), and NET concentrations were measured. Ovulation, delayed ovulation, ovulation inhibition and follicular activity were classified by the analysis of the peripheral serum levels of sex hormones. Ovulation occurred in 7 women in the 0.5 mg group, in 2 women in the 1.5 mg group and in none of the 3.0 mg group. Mean serum SHBG levels were reduced progressively by 6.6% (Group 0.5), 15.5% (Group 1.5) and 23.4% (Group 3.0). There were no significant changes in HDL-C levels in any group. There was a significant correlation of mean serum NET concentrations with dose. The lack of complete inhibition of ovulation in most women in the 1.5 mg and 0.5 mg groups might suggest that the dose of NET required when used as a visiting pill could not be reduced below 3.0 mg.

Sex hormone binding globulin and non-protein-bound oestradiol in postmenopausal patients with primary biliary cirrhosis and normal controls

Several studies have suggested that patients with primary biliary cirrhosis (PBC) have an increased risk of a number of medical conditions related to their oestrogen levels. This study has measured sex hormone binding globulin (SHBG) binding capacity, total oestradiol levels and percentage non-protein-bound (NPB) oestradiol and calculated the concentration of NPB oestradiol, in postmenopausal subjects in the following groups; normal controls, early PBC, advanced PBC and advanced PBC who were receiving therapy. Mean SHBG levels were higher in all groups of patients with PBC than in controls. No significant difference was observed in total or biologically active oestradiol between the four groups.

Group comparison of serum ethinyl estradiol, SHBG and CBG levels in 83 women using two low-dose combination oral contraceptives for three months

Serum ethinyl estradiol (EE2), sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were studied in healthy young women randomly allocated to one of two low-dose combination oral contraceptives containing 30 micrograms EE2 and either 75 micrograms gestodene (F) or 150 micrograms desogestrel (M) per unit. There was either no (formerly non-pill users) or one (pill users) wash-out cycle before the study started with a pill-free pretreatment cycle in which the hormone status and basal SHBG and CBG levels were measured. Treatment was for three months. During treatment cycles 1 and 3, there were three test days each. Seven serum samples were obtained up to four hours and one sample 24 hours after intake of the first, tenth and the last (21st) pill. Additional samples were taken prior to morning ingestion of pills 5 and 15. For each individual and each test day, a representative serum pool has been constructed for SHBG and CBG analysis. EE2 concentrations were analyzed in all individual samples by means of a specific and sensitive RIA using anti-EE2-6 beta-CMO-BSA antiserum. Area under the curves (AUC) up to 4 and 24 hours, Cmax and tmax were evaluated and compared between the two treatment groups (n = 40 for F, n = 43 for M). SHBG and CBG concentrations were measured using commercially available immunoassay kits. Groups were large enough to detect a difference in group means of 75% of one standard deviation (alpha = 0.05, 1-beta = 0.9) of target variables, which is equivalent to 28 pg EE2/ml for Cmax, 69 pg.h.ml-1 for AUCEE2 0-4h, 257 pg.h.ml-1 for AUCEE2 0-24h, 39 nmol/l SHBG and 13.4 micrograms CBG/ml. Results clearly demonstrate that there were no differences between the two treatment groups in any of the target variables at any of the six test days distributed over a three-month period. Mean SHBG and CBG pretreatment levels of about 70 nmol/l and 37 micrograms/ml, respectively, increased to about 210 nmol/l and 88 micrograms/ml during the first treatment cycle and to about 230 nmol/l and 93 micrograms/ml during the third treatment cycle. Whereas the time of maximum EE2 serum levels did not differ significantly between test days, Cmax, AUCEE2 0-4h and AUCEE2 0-24h values increased by 30-35% or 40-50%, respectively, when test days 10 and 21 were compared to test day 1. Similar results were found for the third treatment cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum levels of 5-androstene-3β, 7β-DIOL sulphate, 5α-androstane-3α,17β-DIOL sulphate and glucuronide, in late onset 21-hydroxylase deficiency

Serum sulphates of 5-androstene-3β,17β-diol (5-ADIOL-S), 5α-androstane-3α,17β-diol (3α-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as 5α-androstane-3α,17β-diol glucuronide (3α-DIOL-G) and unconjugated androstenedione (AD) and testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI) and 17α-hydroxyprogester-ne (17OHP) were measured by specific radioimmunoassays (RIA) in 14 women with late-onset 21-hydroxylase deficiency (LOCAH), and in normal women ( n = 73). The diagnosis of LOCAH was made on the finding of a (17OHP) response level greater than 30 nmol/1 following ACTH stimulation, and/or an elevation of urinary metabolites of 17OHP. Mean values for serum concentrations of all steroids measured and the free androgen index (100 × T nmol/1 ÷ SHBG nmol/1) were significantly elevated, and SHBG levels depressed in patients with LOCAH. These studies show that in LOCAH, in addition to the unconjugated steroids AD and T, the sulphoconjugated steroids DHEA-S, 5-ADIOL-S and 3α-DIOL-S are increased, as is the glucuronide conjugate 3α-DIOL-G and the index of bioavailable testosterone (FAI), and that mean SHBG levels are depressed. These data suggest that as well as AD, 5-ADIOL-S and DHEA-S may act as pro-hormones for more potent steroids (T and 5α-dihydrotestosterone) in peripheral tissues, while 3α-DIOL-S and 3α-DIOL-G may both reflect peripheral androgen metabolism in patients with LOCAH.

The relationship of free fatty acids with the binding of oestradiol to SHBG and to albumin in women

Free fatty acid concentration, sex hormone binding globulin (SHBG) concentration, % free oestradiol and % SHBG-bound oestradiol were measured in fasting and non-fasting serum samples from 48 women. Free fatty acids were 128% higher (P < 0.001) and % SHBG-bound oestradiol was 11% lower (P = 0.001) in fasting than non-fasting samples, but these changes were not significantly correlated (r = −0.16, P = 0.287). Mean SHBG concentration and % free oestradiol did not differ significantly between fasting and non-fasting samples. Between subject correlations were calculated for measurements from 30 premenopausal women: % free oestradiol was inversely correlated with SHBG and free fatty acids and positively correlated with Quetelet's Index; % SHBG-bound oestradiol was positively correlated with SHBG but was not consistently or significantly related to free fatty acids or Quetelet's Index. It was concluded that physiological increases in free fatty acid concentrations do not increase % free oestradiol and that free fatty acids are less important than SHBG concentration and perhaps other variables in determining differences between individuals in oestradiol binding to SHBG.

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-3 beta,17 beta-diol sulphate (5-ADIOL-S), 5 alpha-androstane-3 alpha, 17 beta-diol sulphate (3 alpha-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 x T (nmol/l) divided by SHBG (nmol/l), 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/l) 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/l), non-SHBG bound T (0.9 +/- 0.2 vs 0.6 +/- 0.1 nmol/l) and androstenedione (4.3 +/- 0.3 vs 3.4 +/- 0.2 nmol/l) were significantly elevated in women with AA. Furthermore, mean plasma concentrations of 5-ADIOL-S (512 +/- 42 nmol/l) and 3 alpha-DIOL-S (76 +/- 7 nmol/l) were significantly higher than levels found in normal women (272 +/- 12 nmol/l and 52 +/- 2 nmol/l 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 3 alpha-DIOL-S may serve as excellent plasma markers of both the existence of the disorder and the efficacy of its treatment.

Decreasing serum levels of sex hormone-binding globulin around the menopause and temporary relation to changing levels of ovarian steroids, as demonstrated in a longitudinal study

AbstractBlood samples collected longitudinally in 17 women over a period of 3 years, starting 1½ years before the menopause, were assessed for sex hormone-binding globulin (SHBG), 17β-estradiol (E2), progesterone, and total testosterone. A slight (7.2%) decrease in mean SHBG from 4.25 ± 1.67 (standard deviation) mg/l to 3.95 ± 1.61 mg/1 was observed within the 6-month period encompassing the menopause. More specifically, the decrease appeared to commence at the menopause and to become clearly significant (P = 0.01) some 2 to 6 months later. During the subsequent year, a further decrease to 3.64 ± 1.42 mg/l was observed, amounting to a total decrease in mean SHBG by 14.4% (P < 0.001). Of the hormones, only E2 exhibited a marked decrease (P < 0.01) within this same 6-month period. The changes in SHBG during the 6-month transition period from premenopause to postmenopause correlated significantly (P = 0.013) only with those of E2. It is concluded that decreasing E2 levels appear to play a significant role in the downward modulation of SHBG levels commencing at the menopause.

The relationships of SHBG with current and previous use of oral contraceptives and oestrogen replacement therapy

Sex hormone binding globulin (SHBG) concentration was measured in serum samples from 2077 premenopausal and 901 naturally postmenopausal women who had no history of disease or of recent drug use likely to affect SHBG. Current users of oral contraceptives (OCs) and of oestrogen replacement therapy had higher mean SHBG values than non-current users. Both premenopausal and postmenopausal women who had previously used OCs had a lower mean SHBG concentration than never users of OCs. Previous use of oestrogen replacement therapy was not related to SHBG.

Hormonal and nonhormonal factors affecting sex hormone-binding globulin levels in blood.

Researchers in Utrecht, the Netherlands have studied the effects of different factors, such as oral contraceptives (OCs), on sex hormone binding globulin (SHBG) levels in blood. The SHBG levels in women who continuously used OCs consisting only of .05 mg of ethinyl estradiol (EE2) rose as high as 260% + or - 25% of those in women not using OCs. Further, mean SHBG levels of women using combination OCs of EE2 and levonorgestrel were 10-60% higher than women not using OCs. SHBG levels were significantly higher than the use of a sequential OC containing decreasing amounts of EE2 and increasing amounts of levonorgestrel than those cause by use of a continuous combined OC with .03 mg and .15 mg respectively. As the dosage of EE2 increased in combination OCs with 2.5 mg lynestrenol, the SHBG increased from 20% (.05 mg EE2) to 150% (.75 mg EE2). SHBG levels after taking EE2 and cyproterone acetate increased significantly more (240%) than levels after EE2 and desogestrel (170%), or after EE2 and gestoden (140%) [p.001]. SHBG levels of women who took OCs containing only .03 mg of levonorgestrel daily decreased 35% (p.01). These levels fell by 30% in women who received 150 mg of medroxyprogesterone acetate intramuscularly every 3 months (p.001). SHBG concentrations increased when estrogens were taken orally for noncontraceptive purposes, but they did not change when they were administered percutaneously. As body weight increased the SHBG levels decreased despite hormonal status or sex. Further, the lower the fat content of one's diet the higher the SHBG levels and vice versa. SHBG levels are higher in males with flaccid lungs than they are in males with healthy lungs.

Androgen and estrogen dynamics in the female baboon ( Papio anubis)

Androgen and estrogen dynamics were studied in 5 female baboons ( Papio anubis) using constant infusions of [ 3H]androstenedione/[ 14C]estrone and [ 3H]testosterone/[ 14C]estradiol. Blood samples were obtained prior to the infusions and both blood and plasma was used for measurements of androstenedione (A), testosterone (T), dihydrotestosterone (DHT), estrone (E 1), estradiol (E 2). Plasma was used for measurements of sex-hormone binding globulin (SHBG), and the percents of T and E 2 free, bound to SHBG, and to albumin. Blood samples obtained during the infusions were analyzed for radioactivity as purified androgens and estrogens. Metabolic clearance rates (MCR), and transfer factors ([ρ] BB; fraction of steroid infused which is converted to and measured in blood as product) and blood production rates were calculated from whole blood data. All urine was collected for 96 h and an aliquot analyzed for radioactivity as the glucuronides of estrone and estradiol and the % peripheral aromatization calculated. The MCR's, calculated in whole blood, of A, E 1, E 2 and T were 53 ± 6 I/day/kg, 39.3 ± 31/day/kg, 29.9 ± 5.21/day/kg and 10.1 ± 2.31/day/kg, respectively. Each MCR was different ( P < 0.05) from the others. The P b of E 1 was 15± 2μg/day and was not different from that of E 2 (12 ± 3 μg/day). The P B of A, 231 ± 55μg/day, was greater than that of T, 13± 5μg/day. The interconversions of both the androgens (18.9 ± 3.4% vs 3.9 ± 1.0%) and the estrogens (48.8 ± 10.7% vs 4.0 ± 0.8%) favored the oxidative pathway, i.e. conversion of 17-OH to 17-oxo steroids. The conversion ratio of A to DHT was greater than that of T to DHT (16.4 ± 2.1% vs 5.3 ± 0.7%), and A is a more important source of DHT than is T. The percent of T bound to SHBG (80.7 ± 0.9%) was greater than percent of E 2 (36.9 ± 9.8%) and inversely the percents of T bound to albumin and free (17.5 ± 0.8% and 1.65 ± 0.16%) were less than the respective percents for estradiol (60.5 ± 9.5% and 2.40 ± 0.27%). The mean SHBG concentration was 54 ± 6 nM. The peripheral aromatization of androstenedione, 1.36 ± 0.05%, was greater than of testosterone, 0.18 ± 0.02%. This difference is, in part, due to the lack of SHBG-binding of androstenedione. The general pattern of androgen and estrogen dynamics is similar to that in women. This similarity is due, in part, to the presence of SHBG in both baboons and women.

Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the value of changes after short term triiodothyronine administration.

Thyroid hormone is one of several factors that modulate the level of sex hormone-binding globulin (SHBG) in serum. SHBG levels are usually elevated in thyrotoxicosis and have been reported to be normal in a few patients with generalized resistance to thyroid hormone (GRTH). This study was designed to determine whether basal serum SHBG levels or the SHBG response to short term T3 administration could be used as an index of thyroid hormone action and thus serve as a test for the evaluation of patients suspected of having peripheral tissue resistance to thyroid hormone. Serum SHBG, total T4, free T4 index (FT4I), total T3, and TSH levels were measured in 21 normal subjects, 28 hypothyroid patients, 20 thyrotoxic patients, and 10 patients with GRTH. Excluding patients with GRTH, serum basal SHBG values were correlated with FT4I values (r = 0.66; P less than 0.0001). Mean SHBG levels in the patients with GRTH [37.6 +/- 16.2 (+/- SD) nmol/L] were not significantly different from those in the normal subjects (35.1 +/- 19.3 nmol/L) or hypothyroid patients (26.3 +/- 17.1 nmol/L), but were significantly lower than those in the thyrotoxic group (64.7 +/- 19.2 nmol/L; P less than 0.001). All 10 patients with GRTH had basal SHBG values in the normal range, but 7 of 20 (35%) thyrotoxic patients also had normal basal SHBG values. T3 was given orally for three sequential 3-day periods at doses of 50, 100, and 200 micrograms daily to 7 normal subjects, 11 hypothyroid and 3 thyrotoxic patients, and all 10 patients with GRTH. The serum SHBG concentration was measured on the last day at each dosage level. During T3 administration, SHBG levels increased in all individuals with normal tissue responsiveness. The increase above the basal value (delta SHBG) at each T3 dose was similar in normal, hypothyroid, and thyrotoxic individuals (non-resistant subjects). After administration of 50 micrograms T3 daily, the mean delta SHBG level was decreased [-2.9 +/- 5.3 (+/- SD) nmol/L] in the resistant patients and increased (4.0 +/- 4.9 nmol/L; P less than 0.005) in the nonresistant subjects. After administration of 100 micrograms T3 daily, the mean delta SHBG was -4.5 +/- 6.8 nmol/L in the resistant patients and 8.6 +/- 5.1 nmol/L (P less than 0.0001) in the nonresistant subjects. Serum SHBG decreased by more than 2 nmol/L in 6 of 10 (60%) resistant patients, but in no nonresistant subject.(ABSTRACT TRUNCATED AT 400 WORDS)