Mean Sex Hormone-binding Globulin Levels Research Articles

Concentrations of endogenous sex steroid hormones and SHBG in healthy postmenopausal women

Studies reporting age-specific reference ranges of endogenous sex steroid hormones in postmenopausal women are relatively scarce. If levels differ by age, dosing and treatment regimens should vary among postmenopausal women accordingly. Our objective was to establish reference ranges for sex steroid hormones and sex hormone binding globulin (SHBG) by age group and overall, and to investigate their association with demographic characteristics.Serum samples were obtained from 1207 healthy postmenopausal women aged 41–92, not using hormone therapy, at the baseline visit of 3 clinical trials. Estrone (E1), estradiol (E2), and total testosterone (T) were measured by radioimmunoassay with preceding purification steps; SHBG was measured by direct chemiluminescent immunoassay. Free T (FT) was calculated.Women were categorized by 5-year age groups. There was little change in the mean estrogen levels among the different age groups (E2: 9−12 pg/mL; E1: 33−35 pg/mL). Mean total T levels increased gradually with age from 19.9–26.2 ng/dL, but FT mean levels were relatively constant (3.7–4.6 pg/mL). Mean SHBG levels increased with age from 43–68 nmol/L. A generalized linear model tested the association of each demographic characteristic with the hormones and SHBG. A significant association was derived.Our study provides valuable insight into the profiles of serum sex steroid hormones and SHBG in different healthy postmenopausal women aged 41–92 years.

Aging, Cardiovascular Risk, and SHBG Levels in Men and Women From the General Population.

AimsPrior studies have reported inconsistent results for the association between sex hormone-binding globulin (SHBG) and cardiovascular disease among men and women. Although it is suggested that SHBG levels change with aging, the exact trend of SHBG across age and cardiovascular risk and the underlying mechanisms of these changes remain to be elucidated.MethodsUsing data of 3264 men and women from a large population-based cohort study, we first visualized the distribution of serum SHBG levels across age. Second, we computed a cardiovascular risk factor sum score and investigated the mean SHBG levels across categories of the risk factor sum score and stratified per age-category. Next, linear regression models were used to investigate the associations between serum SHBG levels and age and potential regulators of SHBG, including body mass index (BMI), fasting insulin, sex steroids, thyroxine, and triglycerides.ResultsAmong men, a linear increase in SHBG levels with age and among women a U-shaped pattern was observed. Participants with larger number of cardiovascular risk factors had lower SHBG levels. When stratified by age, older participants had higher SHBG levels. A multivariate model including total testosterone and triglyceride levels in men and total testosterone, triglycerides, BMI, and fasting insulin in women explained, respectively, 46.2% and 31.8% of the variance in SHBG levels.ConclusionWe observed a clear sex-specific pattern for SHBG levels with age. Our findings highlight the importance of taking into account the age-related changes in SHBG levels to avoid controversial results in the assessment of the cardiovascular risk associated with SHBG.

SAT-219 A Novel 1-Year Contraceptive Vaginal System Delivering Segesterone Acetate and Ethinyl Estradiol: Effects on Lipids and other Hepatic Proteins

Annovera™ is an FDA-approved contraceptive vaginal system (CVS) releasing 150 mcg segesterone acetate (SA), a new chemical entity, and 13 mcg ethinyl estradiol (EE) per day.1 We postulate that as a non-androgenic progestin, SA is unlikely to adversely affect lipids versus androgenic progestins. Here we review the effects of this CVS on lipids, glucose, coagulation factors and sex hormone-binding globulin (SHBG). Two pivotal, open-label, phase 3 trials and one PK trial evaluated women (18-40 years) who received the CVS for 13 cycles of 28 days over 12 months; one phase 3 study examined hepatic proteins in a substudy. The CVS was self-inserted, left in place for 21 days and removed for 7 days in each 28-day cycle. Lipids and glucose were measured at baseline and study end in the 3 trials. As previously reported, factor VIII, protein S (PS), fibrinogen, and SHBG were measured in the hepatic factors substudy.2 A total of 2308 women used the SA/EE CVS. Participants had a mean age of 26.7 years and mean BMI of 24.1 kg/m2. Most women were white (71%) and 14% were black. Women in the substudy (n=129) had similar mean ages and BMIs; 69% were white and 28% were black. In an integrated analysis of the phase 3 and PK studies, levels of total cholesterol increased by a mean +0.236 mmol/L from baseline to study end, as did HDL cholesterol (+0.162 mmol/L) and triglycerides (+0.193 mmol/L). At study end, LDL cholesterol decreased from baseline by a mean of -0.003 mmol/L. Glucose levels increased from baseline to study end by a mean +0.074 mmol/L. A prior study using the CVS showed lipid changes similar in direction and magnitude to other combined oral contraceptives (COC).3 Hepatic protein substudy results showed significant mean changes from baseline to study end for fibrinogen (+0.2±0.66 mg/mL [SD]; P=0.0052), factor VIII activity (+21%±55; P=0.0005), and PS activity (-8%±19; P=0.0043). Mean SHBG levels also significantly increased from baseline to study end by +81.7±94.3 nmol/L (P<0.0001).2 Another study comparing the CVS to an oral COC showed that the CVS had a hemostatic profile corresponding closely with that of the oral COC.4 Integrated safety data from two clinical studies, a hepatic substudy from one of the trials, and prior reports showed no clinically significant impact of the SA/EE CVS on lipids or glucose. The impact of the CVS on coagulation factors mirrored that of oral COCs. The significant increase in SHBG levels with the CVS was consistent with changes seen with other COCs containing EE and a non-androgenic progestin. The SA/EE CVS with a low dose of EE and the novel progestin, SA, has an acceptable metabolic profile with up to one year of use. 1. AnnoveraTM Prescribing Information. 2. Archer DF, et al. Contraception 2016;93(1):58-64. 3. Sitruk-Ware RL, et al. Contraception 2007;75(6):430-437. 4. Rad M, et al. Am J Obstet Gynecol 2006;195(1):72-77.

Association of serum bisphenol-A concentration and male reproductive function among exposed workers.

Bisphenol-A (BPA) can alter endocrine function in animals, yet the relationship between human exposure to BPA and male reproductive function is not well understood. We collected serum samples from 281 male workers exposed to BPA and 278 controls. Serum BPA concentrations were analyzed by gas chromatography-mass spectrometry after derivatization. The serum levels of sex hormone-binding globulin (SHBG) and total testosterone (TT) were detected by radioimmunoassay and levels of inhibin B (INB) and androstenedione (AD) by enzyme-linked immunosorbent assay. We examined the association of BPA exposure and male sex hormone levels by multivariable linear regression. Both serum BPA concentrations and detection rates were greater in males exposed than those not exposed to BPA, but the two groups did not differ in levels of SHBG, TT, INB, or AD. Compared with exposure for ≤5 years, exposure for >5 years was associated with increased serum BPA and SHBG 1evels and decreased AD levels. Compared with undetectable BPA and BPA ≤ 18.75 ng/mL, BPA level >18.75 ng/mL was associated with low AD and high SHBG levels (P < 0.05). On adjusted multivariable regression, increased serum BPA level was associated with decreased mean serum AD level (0.18 ng/mL; 95% confidence interval CI -0.22 to -0.13) and increased mean serum SHBG level (2.79 nmol/L; 95% CI 2.11-3.46). Serum BPA levels were increased after occupational exposure. BPA exposure was negatively associated with serum AD level but positively associated with serum SHBG level.

The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine disorder associated with metabolic dysfunction and changes in cardiovascular risk markers, and using oral contraceptives (OCs) may exert a further negative effect on these alterations in patients with PCOS. Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS. Study DesignThis was a randomized, controlled clinical trial. Fifty women with PCOS between 18 and 35 years of age were randomized by a computer program to use OC or OC+SPL. Brachial artery flow-mediated vasodilation, carotid intima-media thickness and the carotid artery stiffness index were evaluated at baseline and after 6 and 12 months. Serum markers for cardiovascular disease were also analyzed. The intragroup data were analyzed using analysis of variance with Tukey's post hoc test. A multivariate linear regression model was used to analyze the intergroup data. ResultsAt 12 months, the increase in mean total cholesterol levels was greater in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The increase in mean sex hormone-binding globulin levels was greater in the OC group than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically significant differences between the groups were found for any of the other variables. ConclusionThe addition of spironolactone to an OC containing chlormadinone acetate and ethinylestradiol conferred no cardiovascular risk-marker advantages in young women with PCOS.

Hyperthyroidism: A Risk Factor for Female Sexual Dysfunction

Hyperthyroidism is a common hormonal disorder in women that may cause female sexual dysfunction (FSD). To assess sexual function in women with hyperthyroidism. A total of 40 women with clinical hyperthyroidism and 40 age-matched voluntary healthy women controls were included in the study. All the subjects were evaluated with a detailed medical and sexual history, including a Female Sexual Function Index (FSFI) questionnaire for sexual status and the Beck Depression Inventory (BDI) for psychiatric assessment. The levels of serum thyroid-stimulating hormone (TSH), thyroid hormones, sex hormone binding globulin (SHBG), total testosterone (tT), free testosterone (fT), prolactin, estradiol, follicle-stimulating hormone, and luteinizing hormone were measured. The mean total FSFI scores were 24.2 ± 9.96 in the hyperthyroidic group and 29 ± 10.4 in the control group (P < 0.0001). Desire (P < 0.040), arousal (P < 0.0001), lubrication (P < 0.0001), orgasm (P < 0.0001), satisfaction (P < 0.0001), and pain (P < 0.007) domain scores were also significantly lower in women with hyperthyroidism. The mean BDI score for hyperthyroidic patients was significantly greater than the score for the control group (P < 0.0001). The mean SHBG level in the hyperthyroidic group was found to be significantly higher than the level in the controls (P < 0.0001), whereas the mean fT level in the hyperthyroidic group was lower than in the control group (P < 0.0001). The FSFI score showed a significant negative correlation with the serum SHBG (r = -0.309, P = 0.005), free triiodothyronine (r = -0.353, P = 0.006) and free tetraiodothyronine (r = -0.305, P = 0.018) levels, BDI scores (r = -0.802, P = 0.0001) and positive correlation with tT (r = 0.284, P = 0.011), fT (r = 0.407, P = 0.001), and TSH (r = 0.615, P = 0.0001) levels. A significant percentage of women with clinical hyperthyroidism had sexual dysfunction. Increased depressive symptoms, increased SHBG level, and decreased fT levels were all found to be associated with FSD in clinical hyperthyroidism.

Testosterone, sex hormone-binding globulin and free androgen index among adult women: chronological and ovarian aging

In this study, levels and rates of change in total testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were related to chronological age and to the final menstrual period (FMP) as an indicator of ovarian aging. Data were annually acquired over a 15-year period in 629 women of the Michigan Bone Health and Metabolism Study cohort. Data were censored for hormone therapy use. Endogenous androgen patterns over time were described with stochastic processes and bootstrapping. With ovarian aging, T levels rose from a mean of 18 ng/dl commencing 10 years prior to the FMP to 27 ng/dl at the FMP. Over the 20-year period encompassing the FMP, modeled mean SHBG levels changed from 58 to 34 nM and the FAI ratio increased from 1.6 to 2.9 in a non-linear manner. With chronological aging, total T levels increased (P < 0.0001) from 43 to 50 years, but not thereafter. SHBG declined steadily with age with a modestly greater rate of change between 49 and 54 years. The FAI increased from 1.3 to 2.5 from 34 to 58 years. T increased from approximately age 40 until the FMP whereas SHBG had rate of change patterns reflecting both chronological and ovarian aging components. These data provide new insight into the endogenous androgen patterns at mid-life.

Sex Hormone-binding Globulin: A Novel Marker for Nodal Metastases Prediction in Prostate Cancer Patients Undergoing Extended Pelvic Lymph Node Dissection

To examine the association between sex hormone-binding globulin (SHBG) and lymph node invasion (LNI) in patients treated with radical retropubic prostatectomy and extended pelvic lymph node dissection (ePLND). The preoperative serum SHBG level was measured in a cohort of 168 consecutive patients (mean age 63.9 years, range 48-77) who underwent radical retropubic prostatectomy with ePLND for clinically localized prostate cancer. Logistic regression models tested the association between the predictors (including prostate-specific antigen, clinical stage, primary and secondary biopsy Gleason grades, and SHBG) and LNI. Logistic regression coefficients were used to calculate the predictive accuracy, which was subjected to 200 bootstrap resamples to reduce overfit bias. Thirteen patients (7.7%) had LNI. The mean serum SHBG level was significantly greater in the patients with LNI than in those without LNI (50.0 vs 35.1 nmol/L, respectively; P < .001). Univariate analysis indicated that preoperative SHBG was the single most informative predictor of LNI (77.8% vs 71.7% for prostate-specific antigen, 63.9% for clinical stage, and 63.1% and 54.2% for primary and secondary Gleason grade, respectively). On multivariate analysis, preoperative SHBG was still significantly associated with LNI (P < .001), after accounting for the other variables. The addition of preoperative SHBG increased the predictive accuracy of the base model using clinically established predictors from 72.7% to 82.8% (10.1% gain; P < .001). The results of this study provide novel evidence that SHBG might serve as a significant multivariate predictor of LNI in patients with prostate cancer undergoing ePLND. The use of preoperative serum SHBG could help to identify patients at risk of LNI who should undergo ePLND.

Effect of insulin sensitivity on SHBG levels in premenopausal versus postmenopausal obese women

This study was performed to evaluate the impact of insulin sensitivity on sex hormone-binding globulin (SHBG) and sex steroids in premenopausal and postmenopausal euthyroid obese women. A total of 227 women were eligible for this study. All were euthyroid, obese, and overweight; ages ranged from 25 to 69 years. Women were divided into premenopausal (n=151) and postmenopausal (n=76) groups. SHBG, sex steroids, thyrotropin, fasting and postprandial glucose, lipid profile, uric acid, serum insulin, and blood pressure were measured. No significant difference was found in mean SHBG levels between premenopausal and postmenopausal women. The investigators observed that during transition from premenopause to postmenopause, SHBG levels increased in insulin-sensitive women in the postmenopausal group; however, SHBG levels decreased in insulinresistant women. It was concluded that SHBG blood concentration factors are likely to change during transition from premenopause to postmenopause. The positive effect of estradiol on SHBG levels is probably stronger in premenopausal women than in postmenopausal women. It has been noted that after menopause, the impact of insulin resistance on SHBG level seems more important than the effect of estradiol.

The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study

Changes in adiposity affecting total testosterone (TT) and free testosterone (FT) levels have not been examined in a population-based survey. We aimed to determine whether changes in adiposity predict follow-up levels and rates of change in TT, FT and sex hormone-binding globulin (SHBG) in men. The Massachusetts Male Aging Study is a randomly sampled, population-based cohort interviewed at baseline (T(1), 1987-1989; n = 1,709; aged 40-70 years) and followed-up approximately 9 years later (T(2), 1995-1997; n = 1,156). Men were categorized as overweight (body mass index (BMI) >or= 25 kg/m(2)) or having obesity (BMI >or= 30 kg/m(2)), waist obesity (waist circumference >or= 102 cm), or waist-to-hip ratio (WHR) obesity (WHR>0.95). For each adiposity group, we constructed four categories to represent changes between T(1) and T(2): overweight (or obese, etc.) at neither wave, T(1) only, T(2) only, or both waves. After adjustment for confounding variables, men who were overweight at T(2) only, or at both waves, had significantly lower mean T(2) TT and SHBG levels than men in the neither group (P<0.05). Mean FT did not differ between any overweight group and the neither group. Men who were obese at both times, had the highest mean BMI, the highest fraction of severely obese men, and significantly greater rate of decline in FT than the neither group. In men who become overweight, the greater rate of decline in TT, but not FT, is related mostly to a lesser age-related increase in SHBG. Since weight gain is highly prevalent in older men, over-reliance on TT levels in the diagnosis of androgen deficiency could result in substantial misclassification.

Racial difference in circulating sex hormone–binding globulin levels in prepubertal boys

Racial differences in disease risk (eg, osteoporosis, metabolic cardiovascular syndrome, and prostate cancer) may arise partly on a hormonal basis. While reports of racial differences in gonadal steroid hormone levels in middle-aged men have produced conflicting results, there is evidence that high sex hormone–binding globulin (SHBG) and estradiol levels are more common among young adult African American men than white men. To determine whether this difference relates to pituitary-testicular functioning or to other factors, we conducted a cross-sectional study of 47 healthy prepubertal African American and white boys aged 5 to 9 years at the time of their annual school physical examination. Height, weight, blood pressure, waist and hip circumference, and Tanner staging were determined, and a fasting blood sample was obtained. The African Americans studied were slightly older than the whites (mean ± SD, 82.4 ± 15.0 vs 70.5 ± 10.3 months, P = .003). African Americans were also slightly taller and heavier and had a lower waist-to-hip ratio, but these differences could be explained by the difference in age. Mean SHBG levels were 25% higher ( P = .15) in African Americans than in whites (197 ± 104 vs 157 ± 79 nmol/L), and when adjusted for age, values were 46 nmol/L higher among African Americans. The fifth quintile for SHBG (values > 245 nmol/L) included 1 (4.2%) of 24 whites and 8 (35%) of 23 African Americans studied ( P = .003). There was no significant correlation between age, body mass index, waist circumference, or fasting insulin and SHBG. Total testosterone, the free androgen index, and dehydroepiandrosterone increased with age in both groups, but after adjusting for age, no racial differences were found. Estradiol, estrone, and inhibin B levels, as well as systolic and diastolic blood pressures, were also comparable in both groups. We conclude that high levels of SHBG are more common among African American than in white boys and hypothesize that this difference and its effect on the ratio between bound and free steroid hormones may contribute to racial differences in disease risk in adult men.

Estrogens, Testosterone and Sex Hormone Binding Globulin in Relation to Liver Cancer in Men

Objective: Liver disease in men has been associated with an imbalance of serum estradiol and testosterone. We have evaluated whether serum estradiol and testosterone levels are altered in male liver cancer patients as a result of a specific effect of the disease or because of the associated liver damage. Methods: We have performed a hospital-based case-control study in Greece. The study subjects were all men; 73 patients with hepatocellular carcinoma (HCC), 25 with metastatic liver cancer (MLC) patients and 111 control subjects. Serum estradiol, testosterone and sex hormone binding globulin (SHBG) levels were measured for each subject. Data were analyzed by multiple linear regression. Results: Mean serum estradiol levels were significantly higher among HCC patients as well as among patients with MLC compared to controls. Mean serum testosterone levels were significantly lower among HCC patients as well as among patients with MLC compared to controls. The mean SHBG levels did not differ significantly between the groups. After controlling for the degree of liver damage, the elevated serum estradiol and reduced serum testosterone levels among HCC and MLC patients were no longer significant. Conclusions: Changes in sex steroid levels among patients with liver damage are due to the liver damage per se and not to specific disease processes.

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.

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.

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)