Endogenous Sex Hormone Levels Research Articles

Sex Hormone Levels and Risks of Estrogen Receptor-Negative and Estrogen Receptor-Positive Breast Cancers

Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear. In a case-cohort study within the Women's Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided. The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors. Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.

Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians

BackgroundDifferences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo.MethodsA cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians.ResultsJapanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors.ConclusionsWe found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians.

Abstract P3-12-02: Polymorphisms, Endogenous Hormone Levels and Breast Cancer Risk in Premenopausal Women

Abstract Background: Endogenous sex hormone levels are widely believed to be implicated in the etiology of breast cancer through indirect evidence such as early menarche and late menopause, and from direct evidence of an association between circulating levels and breast cancer risk in postmenopausal women. Epidemiological studies suggest that levels may be partly genetically determined, particularly in premenopausal women. Few studies have attempted to identify polymorphisms associated with endogenous hormone levels in premenopausal women, and their findings have been limited. Quantification of hormone levels in premenopausal women is difficult because of their cyclical nature. In particular, estrogen has a marked peak in the follicular phase and a further wider peak in the luteal phase. Methods: 789 healthy premenopausal women from the Mammography Oestrogens and Growth Factors (MOG) study and the British Breast Cancer (BBC-NCRN) study each provided a single blood sample and up to 7 urine samples. We developed a protocol designed to capture peak follicular phase urinary estrone glucuronide (E1G), and luteal phase E1G. Repeated measurements of creatinine-adjusted E1G levels were used to describe features of the E1G curve such as mean and peak follicular E1G, and luteal E1G. Endogenous sex hormone binding globulin (SHBG) and the androgens testosterone, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were measured on single plasma samples. 691 tagging SNPs capturing common variation in genes within the estrogen synthesis and metabolism pathways were successfully genotyped. Linear regression was used to evaluate the effect of each polymorphism on (log-transformed) measures of urinary E1G levels, SHBG levels and plasma androgen levels. Results: We identified a SNP with minor allele frequency of 7%, in which the minor allele was associated with a 20% reduction in circulating levels of E1G (P<10-8) in healthy premenopausal women. We are currently genotyping this SNP in 12,000 breast cancer cases and 12,000 controls to test whether the reduction in circulating estrogen levels affects breast cancer risk. Conclusions: Circulating hormone levels in premenopausal women may provide a useful intermediate phenotype in the search for low-penetrance breast cancer risk alleles. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-02.

Inadequately Regulated Adrenal Steroids through HPA Axis In Chronic Idiopathic Thrombocytopenic Purpura

AbstractAbstract 5130Idiopathic thrombocytopenic purpura (ITP) is an immune disorder along with the condition of having a low platelet count of multiple etiologies. Endogenous steroids such as corticosteroids have been known to have potent immunomodulatory effect, and also altered expression of steroid metabolism have been reported on the immune related diseases. The level of endogenous steroids are closely related with the level of cytokines (IL-6, IL-1, TNF-α) through HPA axis. Therefore, the eluciadaton of the relationship between steroid hormones and immune cytokines through hypothalamic-pituitary-adrenal (HPA) axis may help to identify biochemical roles of steroid hormones in ITP. The metabolites of steroid hormones were assayed in the plasma obtained from 54 ITP patients and 44 controls using the validated GC-MS based signatures of 70 endogenous steroids including 22 androgens, 18 estrogens, 15 corticoids, 13 progestin, 2 sterols. We also measured the plasma concentration of three HPA axis-stimulating cytokines (IL-6, IL-1, TNF-α) and adrenocorticotropic hormone (ACTH) in chronic ITP patients and healthy subjects using Luminex xMAP technology. Patients were classified to active and remission state depending on the platelet count (active, less than 50,000/mm3; remission, over 100,000/mm3). The active ITP patients showed significant lower plasma levels of adrenal steroids such as pregnenolone (1.49 ± 0.71 ng/mL vs 3.07 ± 1.30 ng/mL, p = 2.3E–08), dehydroepiandrosterone (2.98 ± 1.57 ng/mL vs 4.82 ± 1.67 ng/mL, p = 7.1E-05) and cortisol (73.8 ± 11.3 ng/mL vs 112.7 ± 30.1 ng/mL, p = 2.6E–10) compared with healthy subjects, while the levels of adrenal steroids in remission ITP patients (pregnenolone, 1.87 ± 0.76 ng/mL; dehydroepiandrosterone, 3.70 ± 1.95 ng/mL, cortisol, 83.2 ± 16.2 ng/mL) were not recovered to normal levels. The cortisol/ACTH (ng/mL vs pg/mL) ratio representing pituitary-adrenal axis was not significantly different between patients (4.63 ± 0.72) and healthy subjects (5.17 ± 0.67). However, there was a positive correlation between ACTH and IL-6 in healthy subjects (R = 0.672, p = 0.0024), while no correlation in ITP patients. In conclusion, the low levels of endogenous adrenal steroids resulted from dysregulated HPA axis may have a role in the pathogenesis of ITP. Disclosures:No relevant conflicts of interest to declare.

SIMULTANEOUS DETERMINATION OF CORTISOL, CORTISONE, AND CORTICOSTERONE IN HUMAN PLASMA OF PARACHUTISTS IN VIEW OF PHARMACOKINETIC STUDIES

A rapid high-performance liquid chromatographic method with UV detection (HPLC-UV) for the simultaneous quantification of cortisol, cortisone, and corticosterone was developed and validated. The method involved solid-phase extraction (SPE) followed by chromatographic separation using a Nucleosil 100 C-18, 5 µm, 250 × 4 mm i.d. chromatographic column. The mobile phase was binary mixture of acetonitrile and water (30:70 v/v) at a flow rate of 1 mL/min. The proposed method was validated for specificity, linearity, limits of detection and quantitation, precision, and accuracy. Calibrations curves prepared in human plasma extracts were linear with r > 0.9997 for all analytes. The concentration of each steroid was determined in the range from 2 to 300 ng/mL and accuracy ranged from 95.10 to 103.88% for cortisol, from 101.40 to 102.47%, and from 94.00 to 102.21% for cortisol, cortisone, and corticosterone, respectively. Good repeatabilities (RSD <9.74%) were found for all compounds in the biological matrix. The limit of quantitation (LOQ) was 2 ng/mL for cortisol, cortisone, and corticosterone, respectively. The described method was successfully applied for monitoring three endogenous steroid levels in human plasma. Studies were performed on 20 healthy volunteers of both sexes, comprising two sociably diversified groups of people, namely, 10 parachutists before and after effort and 10 patients with depression. The method proposed is simple, inexpensive, and reproducible with the capabilities of accurate quantification of steroids. The method is suitable for a wide applications in human and physiological studies, thus appearing as a fast and reliable alternative to be used for routine steroids analysis.

E0272 Low testosterone levels are inversely associated with carotid artery plaque formation

ObjectiveTo study the relationship between endogenous sex hormone levels and atherosclerosis of the carotid artery measured by ultrasonography.MethodsAnalysis of the healthy elders from a population-based cohort study in 9 communities...

Effects of physical activity on endogenous sex hormones in postmenopausal women

Background: It is hypothesized that physical activity lowers postmenopausal breast cancer risk at least in part via hormonal pathways. Thus, we investigated whether recent physical activity was associated with lower circulating levels of endogenous sex hormones after menopause. Methods: We conducted a cross-sectional study in 1260 postmenopausal women recruited as controls in the population-based breast cancer case-control study MARIE. Serum concentrations of estrone, estradiol, androstenedione, testosterone, and sex-hormone-binding-globulin (SHBG) were measured, and their associations with different physical activity variables were investigated (recent leisure-time physical activity, sports, bicycling, and walking). Regression models were adjusted for potential confounders. As postmenopausal production of sex hormones takes place primarily in adipose tissue, we especially focused on confounding and effect modification by anthropometric factors (BMI, body weight, waist and hip circumference, and waist-to-hip ratio). Results: Sports was inversely associated with levels of estrone and total and free testosterone in adjusted models. After further adjustment for BMI (or any other anthropometric factor), the associations were attenuated but still significant (p-trend for estrone: 0.034, testosterone: 0.015, free testosterone: 0.035). None of the physical activity variables were significantly related to total and free estradiol, androstenedione, or SHBG. Additionally, we did not observe effect modifications by any anthropometric factor. Conclusion: Our data suggest that sports may lead to lower circulating levels of estrone and total and free testosterone in postmenopausal women. This effect might be partly due to favourable effects on body weight and body composition; however, it appears to be independent of anthropometric factors to some amount. This independent effect could be one explanation for the frequently observed reductions in postmenopausal breast cancer risk through physical activity, even after accounting for BMI. However, further studies (especially randomised controlled trials) are needed to confirm our results.

Cigarette smoking and endogenous sex hormone levels in postmenopausal women

Cigarette smoking and endogenous sex hormone levels in postmenopausal women

Does exposure to testosterone significantly alter endogenous metabolism in the marine mussel Mytilus galloprovincialis?

Mussels ( Mytilus galloprovincialis) were exposed to different concentrations of testosterone (T: 20, 200 and 2000 ng/L) in a semi-static water regime (1-day dosing intervals) for up to 5 days in an attempt to see whether endogenous steroid levels and steroid metabolism were altered by exogenous exposure to testosterone. Whole tissue levels of total testosterone (free + esterified) sharply increased in a concentration-dependent manner, from 2 ng/g in controls to 290 ng/g in organisms exposed to the highest concentration. In contrast, levels of free testosterone were only significantly elevated at the high-exposure group (5-fold increase with respect to controls). Increased activity of palmitoyl-CoA:testosterone acyltransferase (ATAT) was detected in organisms exposed to the highest concentration of testosterone, while those exposed to low and medium concentrations showed significant alterations in their polyunsaturated fatty acid profiles. The obtained results suggest that esterification of the excess of T with fatty acids might act as a homeostatic mechanism to maintain endogenous levels of free T stable. Interestingly, a decrease in CYP3A-like activity was detected in T-exposed mussels together with a significant decrease in the metabolism of the androgen precursor androstenedione to dihydrotestosterone (5α-DHT). Overall, the work contributes to the better knowledge of androgen metabolism in mussels.

Depression and low bone mineral density: The correlation among Chinese

Background Depression is usually associated with changes in the endogenous hormonal system. The most important hormonal modifications are elevation of the serum cortisol level as well as the reduction of endogenous sex hormone levels. These changes have advanced side effects on a bone metabolism and bone remodelling process, which consequently, lead to the declining in bone mineral density and increase the risk of bone fractures, which is reported by current studies. Objective To evaluate the association of low bone density with depression among Malaysian Chinese. Methods 91 Chinese participants with depression were chosen from psychiatric clinics in Penang General Hospital and Penang Adventist Hospital, and 98 Chinese volunteers were employed from the community as controls of both genders, with their ages ranging from 25 to 65 years. Bone mineral density was detected by measuring the T-score and Z-score of the calcaneus bone at the heel; this was measured using the CM200 Furuno ultrasound bone densitometry. Results The bone mineral density of the depressed group was observed to be significantly lower in terms of the T-score ( P = 0.020) and insignificantly lower in terms of Z-score as compared with the control group. Participants with depression had 1.5-fold relative risk (RR) of having T-score less than −1.0 (low bone density). Logistic regression was then used to adjust all confounding variables which showed a significant association between depression and low bone mineral density with an odds ratio of 2.28. Conclusion Depression may be associated with low bone mineral density among the Malaysian Chinese.

Influence of Sex Hormones on Cancer Progression

To review the influence of sex hormones on the progression of breast, prostate, gynecologic, and colorectal cancer. The literature was reviewed in an informal manner utilizing the authors' prior knowledge to collate the current evidence for the involvement of sex hormones, particularly estrogens and androgens in the progression of a range of hormonally responsive cancers. In particular, the effect of treatment involving hormone withdrawal treatment was considered strong evidence for involvement. The impact of basal levels of endogenous steroids was considered. Data from clinical trials indicate the efficacy of therapeutic interventions that result in ablation or antagonism of host steroids for a range of cancers. Demonstration of the correlation of the completeness of withdrawal with clinical outcome together with direct evidence of progression from studies looking at the influence of tissue and circulating levels of sex hormones more recently in conjunction with gene expression profiles all provide compelling evidence for the involvement of steroids in the progression of disease. The involvement of steroids in the progression of cancer in hormone-sensitive tissues is well established and an important target for therapy.

Polymorphisms, endogenous hormone levels and familial breast cancer risk in premenopausal women

Epidemiological studies provide strong evidence of a role for endogenous sex hormone levels in the aetiology of breast cancer [1] and suggest that levels may be partly genetically determined. Quantification of hormone levels in premenopausal women, however, is difficult because of their cyclical nature. In particular, oestrogen has a marked peak in the follicular phase and a further wider peak in the luteal phase.

Evaluation of 4-nonylphenol in vivo exposure in Dreissena polymorpha: Bioaccumulation, steroid levels and oxidative stress

Nonylphenol (NP) represents the most critical metabolite of alkylphenols (APs) and alkylphenol ethoxylates (APEs), non-ionic surfactants widely used in the formulation of domestic and industrial products. On the basis of in vitro and in vivo animal studies 4-nonylphenol (4-NP) is considered an endocrine disrupting chemical (EDC). The evidence to date indicates that mollusks are able to synthesize sex steroids from the precursor cholesterol and their endocrine pathways are theoretically susceptible to disruption. The aim of this study was to investigate the endocrine modulating potency of 4-NP in the freshwater mussel Dreissena polymorpha by looking at endogenous steroid levels in control and exposed individuals. 4-NP bioaccumulation in mussels tissues and alterations in the activity of enzymes related both to oxidative stress (catalase — CAT- and glutathione peroxidase — GPX-) and phase II metabolism (glutathione-S-transferase — GST-) were also assessed. The results highlighted a build-up of 4-NP in exposed mussels and an overall decrease of 17-β-estradiol and testosterone levels. On the other hand this chemical at the tested concentrations does not interfere with the antioxidant defense mechanisms in D. polymorpha. The mechanisms by which 4-NP alter steroids levels are unknown and require more in-depth investigations.

Endogenous plasma estradiol in healthy men is positively correlated with cerebral cortical serotonin 2A receptor binding

Sex-hormones influence brain function and are likely to play a role in the gender predisposition to mood and anxiety disorders. Acute fluctuations of sex-hormone levels including hormonal replacement therapy appear to affect serotonergic neurotransmission, but it is unknown if baseline levels affect serotonergic neurotransmission. This study was undertaken to examine if baseline levels of endogenous sex hormones are associated with cerebral serotonin 2A (5-HT(2A)) receptor binding in men. In a group of 72 healthy men (mean age 37.5 years ±17.4 SD, range 19.6-81.7) we studied the effect of plasma sex hormone levels on neocortical 5-HT(2A) receptor binding as imaged with [(18)F]altanserin PET. The effect of endogenous sex-hormone levels was evaluated by multiple linear regression analysis. Mean neocortical 5-HT(2A) receptor binding was positively correlated with estradiol (p=0.0001), whereas no independent effects of testosterone could be demonstrated. Correction for other factors of importance for 5-HT(2A) receptor binding did not change the result. A voxel-based analysis suggested that there were no regional differences in the estradiol effect on cortical 5-HT(2A) receptor binding. Our data show a positive correlation between endogenous plasma estradiol levels and cortical 5-HT(2A) receptor binding in healthy men, whereas, no independent effect of testosterone was demonstrated. We speculate that this association could be mediated through effects on gene transcription.

Endogenous Steroids Measured by High-Specificity Liquid Chromatography-Tandem Mass Spectrometry and Prevalent Cardiovascular Disease in 70-Year-Old Men and Women

There is a need for increased knowledge about endogenous sex hormone levels and clinical outcomes of risk/benefit. Immunoassays have poor specificity to reliably measure low steroid concentrations in elderly. The objective of the study was to evaluate plasma steroid concentrations with regard to prevalent cardiovascular disease (CVD) in elderly, using mass spectrometry. The study was conducted at a university hospital research unit. Plasma samples were analyzed from 202 70-yr-olds as part of a large population-based study, Prospective Investigation of the Vasculature in Uppsala Seniors. Twenty-eight of these had prevalent CVD. Eleven steroids were quantified, using liquid chromatography-tandem mass spectrometry. Women with current/previous menopausal hormone therapy (n = 35) were excluded. Men without prevalent CVD had higher plasma 17beta-estradiol (E2), compared with women. Men with prevalent CVD, compared with those without, had lower 17-hydroxypregnenolone (17OHPregn), 17-hydroxyprogesterone, and higher estrone/androstenedione and E2/testosterone (T) (aromatase activity). Women with prevalent CVD had lower pregnenolone, 17OHPregn, and dehydroepiandrosterone (DHEA) but higher DHEA/17OHPregn, androstenedione/DHEA, E2/T, E2/estrone, and E2/SHBG. The aromatase index, E2/T, was higher for prevalent CVD in both sexes. Adjustment for statin use, smoking, and body mass index yielded additional significant differences in men, whereas some were lost in women. Logistic regression indicated strong associations between prevalent CVD and low 17OHPregn, adjusted odds ratio of 0.18, 95% confidence interval (0.06-0.61); P = 0.006, in women and low 17-hydroxyprogesterone, 0.45 (0.25-0.80); P = 0.007 in men, most likely caused by increased throughput (consumption) toward estrogen synthesis. Prevalent CVD was associated with indications of lower androgen precursors, increased aromatase activity, and higher estrogen levels in both sexes. Results might represent an endogenous response to a condition of developing atherosclerosis, rather than a causative relationship. Furthermore studies are needed.

Circulating Steroid Hormone Levels and Risk of Breast Cancer for Postmenopausal Women

Epidemiologic studies have consistently reported that endogenous steroid hormone levels are associated with postmenopausal breast cancer risk, but little is known on the associations by tumor grade, hormone receptor status, or age at diagnosis. We performed a case-cohort study of naturally postmenopausal women within the Melbourne Collaborative Cohort Study that included a random sample of 857 women and 197 breast cancer cases diagnosed during a mean of 9.2 years of follow-up. Concentrations of total estradiol, estrone sulfate, testosterone, DHEA sulfate, androstenedione, and sex hormone binding globulin were measured in plasma collected at baseline before diagnosis; free estradiol plasma concentration was calculated. Cox regression was used to estimate associations adjusted for known and potential confounders. The HR for breast cancer comparing fourth and first quartiles was 1.44 [95% confidence interval (95% CI), 0.89-2.35] for total estradiol, 1.75 (95% CI, 1.06, 2.89) for free estradiol, 2.05 (95% CI, 1.24-3.37) for estrone sulfate, 1.25 (95% CI, 0.78-2.01) for testosterone, 1.41 (95% CI, 0.88-2.27) for DHEA sulfate, 1.49 (95% CI, 0.91-2.44) for androstenedione, and 0.33 (95% CI, 0.19-0.55) for sex hormone binding globulin. These associations did not differ by tumor grade and estrogen receptor/progesterone receptor status (all test for heterogeneity, P > 0.05). Risks associated with estrogen and androgen levels were stronger at older ages (test for interaction across age groups, P = 0.59 for total estradiol and P = 0.01 for testosterone). Our prospective study confirms earlier findings and suggests that the associations of endogenous hormones with postmenopausal breast cancer risk are independent of tumor grade, and hormone receptor status and might increase in strength with age.

Population differences in the testosterone levels of young men are associated with prostate cancer disparities in older men

Although there is evidence that greater exposure to testosterone is associated with an increased risk of prostate cancer, a recent analysis of 18 prospective studies found no relationship between levels of endogenous sex hormones and prostate cancer development. However, the reviewed studies were subject to methodological constraints that would obscure any potential relationship between prostate cancer and androgenic hormones. If prostate cancer risk is mediated by lifetime exposure to testosterone, then case-control studies that concentrate on endogenous sex hormones near the ages that prostate cancer is diagnosed would provide limited information on cumulative testosterone exposure across the lifespan. Alternately, early adulthood has been suggested as the most salient period to evaluate the influence of steroid physiology on prostate carcinogenesis. As such, an exhaustive literature search was completed to obtain testosterone values reported for study samples of younger men, along with prostate cancer incidences for the larger populations from which the study populations were sampled. A novel analytical method was developed to standardize, organize, and examine 12 studies reporting testosterone levels for 28 population samples. Study populations were generally apportioned according to ethnicity and geographic residence: Americans of African, Asian, Caucasian, and Hispanic ancestry from several different regions within the United States as well as men from China, Germany, Japan, Kuwait, New Zealand, South Korea, and Sweden. Population differences in the testosterone levels of young men were significantly associated with population disparities in the prostate cancer incidence of older men (Spearman's rho = 0.634, p = 0.002).

Endogenous estrogen levels are associated with endothelial function in males independently of lipid levels

Estrogens and androgens may play an important role in vascular health in both sexes. The aim of this study was to examine the relation of endogenous sex hormone levels with early markers of atherosclerosis in a cohort of apparently healthy males. 124 males (age 46.25 ± 9.56) attending a preventive medicine program were examined for unrecognised features of the metabolic syndrome. Flow-mediated dilatation (FMD) and intima-media thickness (IMT) of the common carotid artery were evaluated. Obesity parameters were recorded; estradiol, testosterone, SHBG, free testosterone, insulin, as well as glucose and lipid levels were measured. FMD was positively correlated with estradiol (r = 0.201, P = 0.041) and negatively with total cholesterol (r = -0.205, P = 0.022), low density lipoproteins (r = -0.232, P = 0.009), and triglyceride levels (r = -0.179, P = 0.046). In multivariate analysis, the association of FMD with estrogen was independent of BMI and lipid levels. No significant association between FMD and testosterone levels was found. Subjects with an increased mean IMT (> 0.73 mm, i.e., > 3rd tertile) had lower levels of free (P = 0.021) and bioavailable (P = 0.016) testosterone. In multivariate logistic regression analysis, this association was no longer significant when age or cholesterol levels were considered. Endogenous estrogen levels are associated with FMD, independently of age and lipid levels, showing a protective effect in middle-age male subjects. Circulating androgens are associated, although not independently, with structural changes such as the IMT of carotid artery; this effect is possibly influenced by lipid levels and age.

Sex steroid hormones and cognitive functioning in healthy, older men

The precise impact of age-related changes in hormone levels on cognition in men is still unclear due to differing study designs and contradictory findings. This study was undertaken to examine the relationship between endogenous sex hormone levels and cognitive functioning in healthy older men using a comprehensive battery of neuropsychological tests and measurement of serum sex hormone levels. Verbal learning and memory, visual-motor processing, spatial abilities, working memory and attention, and levels of testosterone and estradiol were evaluated in 54 healthy older men. Regression analyses revealed significant curvilinear associations between working memory function and both free and bioavailable testosterone levels, suggesting that an optimal hormone level may exist for maximal performance on tasks of executive/frontal lobe functioning. However, no other relationships were evident between either estradiol or testosterone levels and any of the other cognitive functions evaluated. Hormone assays performed at the end of the study revealed that a considerable portion of the healthy elderly men in our sample met criteria for hypogonadism and suggests that their low hormone levels may have mitigated against discovering other significant hormone–cognition relationships.

Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men

To study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes. Population-based prospective cohort study. For the analyses, 1454 men who participated in the fourth Tromsø study (1994-1995) were used. Cases of diabetes were retrieved and validated until 31.12.05 following a detailed protocol. The prospective association between sex hormones and diabetes was examined using Cox proportional hazard regression analysis, allowing for multivariate adjustments. There was a significantly lowered multi-adjusted risk for later diabetes with higher normal total testosterone levels, both linearly per s.d. increase (hazard ratio (HR) 0.71, confidence interval (CI) 0.54-0.92) and in the higher quartiles of total testosterone than in the lowest quartiles (HR 0.53, CI 0.33-0.84). A reduced multi-adjusted risk for incident diabetes was also found for men with higher sex hormone-binding globulin (SHBG) levels, both linearly per s.d. increase (HR 0.55, CI 0.39-0.79) and when comparing the third (HR 0.38, CI 0.18-0.81) and the fourth quartile (HR 0.37, CI 0.17-0.82) to the lowest quartile. The associations with total testosterone and SHBG were no longer significant after inclusion of waist circumference to the multivariate models. Estradiol (E(2)) was positively associated with incident diabetes after multivariate adjustments including waist circumference when comparing the second (HR 0.49, CI 0.26-0.93) and the third (HR 0.51, CI 0.27-0.96) quartile to the highest quartile. Men with higher E(2) levels had an increased risk of later diabetes independent of obesity, while men with lower total testosterone and SHBG had an increased risk of diabetes that appeared to be dependent on obesity.