Association Of Androgens Research Articles

Safety of gender affirming treatment in assigned female at birth transgender people and association of androgen and estrogen β receptor polymorphisms with clinical outcomes.

Gender affirming hormone treatment (GAHT) with androgens in assigned female at birth (AFAB) people with Gender Incongruence (GI) can induce and maintain variable phenotypical changes, but individual response may be genetically determined. To clarify the role of AR and ERβ polymorphisms we prospectively evaluated AFAB subjects undergoing virilizing GAHT. Fifty-two AFAB people with confirmed GI were evaluated before (T0) and after 6 (T6) and 12 months (T12) of testosterone enanthate 250 mg i.m. every 28 days. Hormone profile (testosterone, estradiol), biochemical (blood count, glyco-metabolic profile) and clinical parameters (Ferriman-Gallwey score, pelvic organs) were evaluated at each time-point, as well as number of CAG and CA repeats for AR and ERβ, respectively. All subjects have successfully achieved testosterone levels within normal male ranges and improved their degree of virilization, in absence of significant side effects. Hemoglobin, hematocrit and red blood cells were significantly increased after treatment, but within normal ranges. Ultrasound monitoring of pelvic organs showed their significant reduction already after 6 months of GATH, in absence of remarkable abnormalities. Furthermore, a lower number of CAG repeats was associated with a higher Ferriman-Gallwey score post treatment and a higher number of CA repeats was associated with uterine volume reduction. We confirmed safety and efficacy of testosterone treatment on all measured parameters. This preliminary data hints a future role of genetic polymorphisms to tailor GAHT in GI people, but evaluation on a larger cohort is necessary as the reduced sample size could limit data generalization at this stage.

Association of Androgens and Gonadotropins with Amnestic Mild Cognitive Impairment and Probable Alzheimer's Disease in Chinese Elderly Men.

Age-related hormone changes play important roles in cognitive decline in older men, and apolipoprotein E ɛ4 (APOEɛ4) is a risk factor for Alzheimer's disease (AD). This study aimed to investigate the interactive role of androgen decline and APOEɛ4 genotype in the pathogenesis of amnestic mild cognitive impairment (aMCI) and AD. In total, 576 elderly men over 65 years old from communities in Shijiazhuang were enrolled in this study, including 243 with normal cognition (NC), 271 with aMCI, and 62 with probable AD. Cognitive function was evaluated with a battery of neuropsychological tests. The serum levels of androgen and gonadotropin were detected by ELISA and chemiluminescence immunoassay. The levels of free testosterone (FT) and dihydrotestosterone (DHT) were lower in the aMCI group (p < 0.05), and even lower in the AD group (p < 0.001), but the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH)were higher in AD group (p < 0.01), comparing with that in NC or aMCI group. The interaction of lower FT or DHT levels with APOEɛ4 had a risk role in global cognitive impairment (p < 0.05). The area under the curve (AUC) of the ROC curve for predicting aMCI by serum FT levels was 0.745. These results indicated that the interaction of androgen decline and APOEɛ4 genotype play a role in aMCI and AD. Serum FT levels have a predictive value for aMCI and might be a potential biomarker for prodromal AD.

Sexual Dysfunction and Abnormal Androgen Level after Hematopoietic Stem Cell Transplantation

Introduction: Hematopoietic stem cell transplantation (HSCT) is a potentially curative or consolidative therapy for a large number of hematological diseases. Sexual dysfunction (SD) and abnormal level of the sexual hormone are common in patients after HSCT, which are usually caused by intensive myeloablative conditioning. The change of sexual hormone level and SD resulted in the poor quality of life in this population after transplantation. The current aims of this study were to determine: (i) the incidence rate of SD and the association with androgen post both autologous (auto) and allogeneic (allo) HSCT; (ii) multi-factors analysis between SD and clinical characteristics, primary diease, donor type, cGVHD, etc; (iii) the association of androgen with cGVHD and glucocorticoid (GC) therapy. Methods: From April 2010 to February 2019, a total of 126 (74 males and 52 females) patients with hematological diseases undergoing HSCT were enrolled in our study. The reason for the small sample of patients was that only 126 patients completed our Sexual Function Questionnaire. Controls were 108 healthy, age and gender matched persons came from Medical Examiniation Center of our hospital. Assessment indexes included clinical characteristics, donor type, GVHD incidence, sex hormone levels, and Sexual Functioning Questionnaire (SFQ). The SFQ was implemented by the team members of our research group through a telephone interview, email, paper letter, and WeChat. All of the information and privacy of each patient was strictly conserved. Results: 1. Clinical characteristics of the 126 patients who underwent HSCT were shown in Table 1. The median age of the patients was 38 years old (range 16-66) and the follow up after HSCT was from 6 months to 7 years. The predominant disease spectra were multiple myeloma (MM) and acute leukemia in auto- and allo-HSCT group, respectively. Our results showed a significant difference in gender (P&lt;0.004), donor type (P&lt;0.004), and GVHD development (P&lt;0.0001), indicating a higher incidence of SD when we included these indicators into our analysis. There was no singficant difference of SD development in age, education background, annual family income, primary disease, time post HSCT, and phycological state. 2. Figure 1 showed a higher incidence of SD in both female and male patients after HSCT compared to the healthy controls (P&lt;0.001). Most of them complained that they had trouble in normal sex life and sexual function had not yet recovered to the pre-transplantation level. Moreover, female patients exhibited much significantly decline in overall sexual function (OSD) than the male group (P&lt;0.004). As depicted in the figure 2a and 2b, 54% female and 44% of male developed at least one physical sexual problem. Almost all of the female patients of childbearing age were infertility, and only a small number of young (&lt; 30 years) male patients post transplantation could store fertility (data not shown). 3. From the foregoing data analysis, we confirmed that patients after allo-HSCT with or without GVHD usually acompanied with a higher incidence of SD compared to auto-HSCT group (Table 2). Female patients undergoing allo-HSCT who developed SD had a significantly lower level of androgen (P = 0.02, Table 3a), and that of the male patients was lower compared to healthy control with no significance (Table 3b). Female patients diagnosed with cGVHD had much lower adrongen level, especially in those received GC therapy (Table 4). 4. Although some young female patients had been given regular leuprolide injection every 28 days during their chemotherapy period or pre-transplantation, no significant difference was observed both in SD incidence and androgen level (P &gt; 0.05, due to a small sample, data not shown here). Conclusions: Our results here indicated SD remained a major obstacle for patients to have a better quality of life after HSCT. We should pay more attention to the female patients because they might be at a higher risk to develop SD, especially in those underwent cGVHD and received GC therapy. To improve the sexual function for this population, more intervention methods including optimization of conditioning, better controlling of cGVHD, and reproductive function reservation might be helpful to reduce the incidence of SD. Finally, our study suggested that low androgen levels may contribute to SD and androgen replacement therapy might be a promising choice to improve OSD for patients undergoing HSCT. Disclosures No relevant conflicts of interest to declare.

Sex Difference in the Association of Androgens with Aortic Calcification

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Cortisol reactivity correlates with subjective stress in women in their luteal phase but not in women using oral contraceptives or men

Findings on associations of androgens and sex hormone-binding globulin (SHBG) with anxiety and depressive disorders in the general population remain inconclusive.We used data of n = 993 men and n = 980 women from the Study of Health in Pomerania (SHIP, a prospective-longitudinal general population study from northeastern Germany). Immunoassay-measured serum concentrations of total testosterone, androstenedione and SHBG were assessed when participants were aged 20–80. 12-month, lifetime and incident DSM-IV anxiety and depressive disorders were assessed with the DIA-X/M-CIDI at 10-year follow-up, when participants were aged 29–89. Logistic regressions were adjusted for age, smoking, alcohol consumption, physical activity, waist circumference, hypertension and oral contraceptive use (women only) at baseline and follow-up interval.In men and women, androgens and SHBG were not associated significantly with incident anxiety and depressive disorders. In men, higher total testosterone predicted any 12-month (OR = 1.46) and lifetime (OR = 1.34) anxiety disorder, lifetime social phobia (OR = 2.15), and 12-month (OR = 1.48) and lifetime (OR = 1.39) specific phobia, but neither 12-month nor lifetime depression. Moreover, androstenedione in men interacted with age in predicting lifetime anxiety disorders (OR = 0.98): Higher androstenedione more strongly predicted lifetime anxiety in younger vs. older men. These findings, however, did not survive correction for multiple testing. In women, androgens and SHBG were not associated significantly with 12-month and lifetime anxiety and depressive disorders.The follow-up period was relatively long and other factors might have affected the examined associations.Higher serum total testosterone in men and androstenedione in younger men may relate to an increased risk of anxiety disorders.

Associations of androgens with depressive symptoms and cognitive status in the general population.

ObjectivesAssociations between androgens and depressive symptoms were mostly reported from cross-sectional and patient-based studies.Study design/main outcome measuresLongitudinal data from 4,110 participants of the Study of Health in Pomerania were used to assess sex-specific associations of baseline total and free testosterone, androstenedione and sex hormone-binding globulin with incident depressive symptoms and cognitive status at 5- and 10-year follow-up.ResultsDespite sex-specific differences in depressive symptoms prevalence at baseline (women: 17.4%, men: 8.1%), cross-sectional analyses showed no associations between sex hormones and depressive symptoms. In age-adjusted longitudinal analyses, total testosterone was associated with incident depressive symptoms (relative risk at 5-year follow-up: 0.73, 95% confidence interval: 0.58–0.92). Similarly, age-adjusted analyses showed a positive association between sex hormone-binding globulin and cognitive status in men (β-coefficient per standard deviation: 0.44, 95% confidence interval: 0.13–0.74). In women, age-adjusted associations of androstenedione with baseline depressive symptoms (relative risk: 0.88, 95% confidence interval: 0.77–0.99) were found. None of the observed associations remained after multivariable adjustment.ConclusionsThe present population-based, longitudinal study revealed inverse associations between sex hormones and depressive symptoms. However, the null finding after multivariable adjustment suggests, that the observed associations were not independent of relevant confounders including body mass index, smoking and physical inactivity. Furthermore, the low number of incident endpoints in our non-clinical population-based sample limited the statistical power and reduced the chance to detect a statistically significant effect.

Abstract 813: The association of androgen metabolizing enzymes and prostate cancer in a multiethnic study

Abstract Introduction: Uridine 5’-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal tissue. The expression of the UGT2B15, UGT2B17, and UGT2B28 enzymes has not been evaluated in prostate tissue samples from hormone therapy-naïve patients. Methods: We determined the expression of the three enzymes in 190 prostate tissue samples from surgical specimens of a multiethnic cohort of patients undergoing radical prostatectomy at the Durham Veterans Affairs Medical Center. The association between each biomarker's percent positive and H-score and the risk of biochemical recurrence (BCR) was tested using separate Cox proportional hazards models. In an exploratory analysis, UGT2B17 total positive and H-score were split at the median and we tested the association between UGT2B17 group and risk of BCR. Results: The median follow-up was 118 months (IQR: 85-144). We found no association between UGT2B15 or UGT2B28 and risk of BCR. However, there was a trend between UGT2B17 and BCR (HR = 1.01, 95% CI 1.00-1.02, p = 0.11), though not statistically significant. Upon further investigation, we found patients with UGT2B17 total positive above the median had a significant increased risk of BCR on univariable analysis (HR = 1.57, 95% CI 1.02-2.43, p = 0.041) but this association was attenuated in the adjusted model (HR = 1.50, 95% CI 0.94-2.40, p = 0.088). Conclusions: Our findings suggest that UGT2B17 overexpression was associated with a significant increased risk of BCR. These results are consistent with previous reports that show UGT2B17 significantly expressed in prostate cancer metastases. Citation Format: Delores J. Grant, Lauren Howard, Emily Wiggins, Amanda De Hoedt, Adriana Vidal, Skyla T. Carney, Jill Squires, Clara E. Magyar, Jiaoti Huang, Stephen J. Freedland. The association of androgen metabolizing enzymes and prostate cancer in a multiethnic study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 813.

Association of androgen with gender difference in serum adipocyte fatty acid binding protein levels

Clinical investigations have indicated women have higher levels of adipocyte fatty acid binding protein (A-FABP) than men. The present study aimed to identify factors related to gender difference in serum A-FABP levels. A total of 507 participants (194 men, 132 premenopausal women, and 181 postmenopausal women) were enrolled in the present study. Serum A-FABP levels increased in the order from men to premenopausal women to postmenopausal women in both body mass index categories (<25.0 and ≥25.0 kg/m2; all P < 0.05). Multiple stepwise regression analyses showed that after adjustment for factors related to serum A-FABP levels, the trunk fat mass was an independent and positive factor of serum A-FABP levels. For men, total testosterone was associated independently and inversely with serum A-FABP levels. For pre- and postmenopausal women, bioavailable testosterone and total testosterone were independent and positive factors associated with serum A-FABP levels, respectively. The present study demonstrated that the androgen was correlated with the serum A-FABP levels negatively in men, but positively in women. With these effects on the fat content, especially trunk fat, androgen might contribute to the gender difference in serum A-FABP levels.

Circulating androgens are associated with mood disturbances in young postmenopausal women

Objectives We aimed to evaluate the association between circulating androgens and the presence of psychological symptoms in a sample of healthy middle-aged women.Methods Psychological and depressive symptoms were evaluated in a total of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the Zung Depression Scale, respectively. We investigated the associations between the SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well as serum levels of androgens.Results The free androgen index was positively associated with scores of depression (b-coefficient ± standard error (SE) = 0.2 ± 0.2, p = 0.040), anxiety (b-coefficient ± SE = 0.2 ± 0.2, p = 0.028), anger/aggressiveness (b-coefficient ± SE = 0.3 ± 0.2, p = 0.026), psychotism (b-coefficient ± SE = 0.3 ± 0.1, p = 0.013) as well as with the global index of the SCL-90R scale (b-coefficient ± SE = 0.2 ± 0.1, p = 0.036), while sex hormone binding globulin was negatively associated with depression (b-coefficient ± SE = −0.2 ± 0.0, p = 0.046) and psychotism (b-coefficient ± SE = −0.2 ± 0.0, p = 0.047). These associations were independent of vasomotor symptomatology, smoking and hormone therapy intake and were more pronounced in younger (≤ 5.5 years) compared to older postmenopausal women. Levels of dehydroepiandrosterone sulfate were positively associated with interpersonal sensitivity (b-coefficient ± SE = 0.3 ± 0.3, p = 0.042), psychotism (b-coefficient ± SE = 0.4 ± 0.2, p = 0.007) and the global index (b-coefficient ± SE = 0.3 ± 0.2, p = 0.040) in women < 5.5 years postmenopausal. No significant associations were observed between the Zung or Greene Scale scores and levels of androgens.Conclusion Higher androgenicity was positively associated with symptoms of anxiety and depression in postmenopausal women. These associations were stronger in women closer to the menopausal transition, a finding which may suggest that menopause rather than aging may mediate the association of androgens with mood disorders.

P329: Association of androgen with skeletal muscle mass and muscle function among men and women aged 50 years and older in Taiwan

P329: Association of androgen with skeletal muscle mass and muscle function among men and women aged 50 years and older in Taiwan

The association of androgens with QT interval and heart rate in US men

The association of androgens with QT interval and heart rate in US men

Association of Androgen with Skeletal Muscle Mass and Muscle Function Among Men and Women Aged 50 Years and Older in Taiwan: Results from the I-Lan Longitudinal Aging Study

The main aim of this study was to explore the association between skeletal muscle mass and muscle function by three different measures of bioactive testosterone, as well as dehydroepiandrosterone sulfate (DHEA-S) among men and women aged 50 years and older in Taiwan to facilitate further investigations of sarcopenia and androgen profile. The data of 532 participants (mean age 64.6±9.5 years; male, 53.0%) recruited from the I-Lan Longitudinal Aging Study was retrieved for analysis. Appendicular muscle mass, grip strength, and walking speed were stratified into quartiles in both genders to explore their associations with different hormones measures. Among three different bioactive testosterone measures, the free androgen index had significant positive association with muscle mass (p both <0.001) and muscle strength in both genders (p<0.001 in men and p=0.03 in women), whereas free testosterone and bioavailable testosterone displayed similar correlations only in the skeletal muscle mass of woman (p both <0.001) and muscle strength of men (p=0.007, p=0.002, respectively). Serum levels of DHEA-S were correlated positively with skeletal muscle mass in men (p=0.013) and women aged 65 years and older (p=0.004) and handgrip strength in both genders (p<0.001 in men and p=0.009 in women). None of the bioactive testosterone measurements was associated with walking speed, whereas DHEA-S was significantly positively correlated with gait speed in both genders (p both=0.001). In conclusion, the free androgen index increased remarkably along with muscle mass and muscle strength among men and women aged 50 years and older. Moreover, DHEA-S was positively associated with muscle mass in men and older women and muscle strength in both sexes, and was also associated with aging and gait speed in both genders.

Disorders of Sex Development and Hypogonadism: Genetics, Mechanism, and Therapies

Disorders of Sex Development and Hypogonadism: Genetics, Mechanism, and Therapies

Association of serum sex steroid receptor bioactivity and sex steroid hormones with breast cancer risk in postmenopausal women

Postmenopausal women with elevated serum sex steroids have an increased risk of breast cancer. Most of this risk is believed to be exerted through binding of the sex steroids to their receptors. For the first time, we investigate the association of estrogen receptor (ER) and androgen receptor (AR) serum bioactivity (SB) in addition to hormone levels in samples from women with breast cancer collected before diagnosis. Two hundred postmenopausal women participating in the UK Collaborative Trial of Ovarian Cancer Screening who developed ER-positive breast cancer 0.6–5 years after sample donation were identified and matched to 400 controls. ER and AR bioassays were used to measure ERα, ERβ, and AR SB. Androgen and estrogen levels were measured with immunoassays. Subjects were classified according to quintiles of the respective marker among controls and the associations between SB and hormones with breast cancer risk were determined by logistic regression analysis. ERα and ERβ SB were significantly higher before diagnosis compared with controls, while estrogens showed no difference. Women had a twofold increased breast cancer risk if ERα SB (odds ratio (OR), 2.114; 95% confidence interval (CI), 1.050–4.425; P=0.040) was in the top quintile >2 years before diagnosis or estrone (OR, 2.205; 95% CI, 1.104–4.586; P=0.029) was in the top quintile <2 years before diagnosis. AR showed no significant association with breast cancer while androstenedione (OR, 3.187; 95% CI, 1.738–6.044; P=0.0003) and testosterone (OR, 2.145; 95% CI, 1.256–3.712; P=0.006) were significantly higher compared with controls and showed a strong association with an almost threefold increased breast cancer risk independent of time to diagnosis. This study provides further evidence on the association of androgens and estrogens with breast cancer. In addition, it reports that high ER but not AR SB is associated with increased breast risk >2 years before diagnosis.

Selective cell cycle arrest and induction of apoptosis in human prostate cancer cells by a polyphenol-rich extract of Solanum nigrum.

Progression of prostate cancer is associated with escape of tumor cells from cell cycle arrest and apoptosis. Agents capable of selectively eliminating cancer cells by cell cycle arrest and/or induction of apoptosis offer a highly desirable approach. Here we demonstrate that a polyphenolic extract derived from ripe berries of Solanum nigrum (SN) differentially causes cell cycle arrest and apoptosis in various human prostate cancer cells without affecting normal prostate epithelial cells. Virally transformed normal human prostate epithelial PZ-HPV-7 cells and their cancer counterpart CA-HPV-10 cells, were used to evaluate the growth-inhibitory effects of the SN extract. SN treatment (5–20 μg/ml) of PZ-HPV-7 cells resulted in growth inhibitory responses of low magnitude. In sharp contrast, SN treatment of CA-HPV-10 cells increased cytotoxicity, decreased cell viability and induced apoptosis. Similar results were noted in the human prostate cancer LNCaP, 22Rv1, DU145 and PC-3 cell lines, where significant reductions in cell viability and induction of apoptosis was observed in all these cells, an effect independent of disease stage and androgen association. Cell cycle analysis revealed that SN treatment (5–20 μg/ml) resulted in a dose-dependent G2/M phase arrest and subG1 accumulation in the CA-HPV-10 but not in the PZ-HPV-7 cell line. Our results, for the first time, demonstrate that the SN extract is capable of selectively inhibiting cellular proliferation and accelerating apoptotic events in prostate cancer cells. SN may be developed as a promising therapeutic and/or preventive agent against prostate cancer.

Androgens and social status in female rock hyraxes

Androgens have been linked to social behaviour in males across many vertebrate species. Despite the lack of gender specificity in steroid hormones, the association of androgens with behaviour in females remains obscure. We analysed steroid hormone levels in male and female rock hyraxes, Procavia capensis, and found strong ties between androgens and cortisol in females but not in males, despite the latter being the sex that usually shows this association. In the past we have shown that both female and male hyraxes have similar testosterone levels. In the present work, we found a significant interaction between testosterone levels and social status. Testosterone levels differed only between lower-ranking males and females, with females showing higher levels. Furthermore, dominant females had significantly lower testosterone levels than subordinate females. No association was detected between litter size and female rank, testosterone or cortisol levels. At this stage, we can only hypothesize that the assumed detrimental effects of high circulating androgen levels, reflected in the hair samples, influence the reproductive output or the offspring survival of subordinate females in some other ways, which require further investigation to be revealed.

Testosterone Making an Entry Into the Cardiometabolic World

Testosterone, the predominant sex hormone in men, is produced by the testes under stimulation by the gonadotrophs in the pituitary, which in turn are controlled by gonadotropin-releasing hormone neurons in the hypothalamus. A young adult man generally produces 3 to 10 mg of testosterone daily, which translates into serum values of 300 to 1000 ng/dL. The consequences of classical male hypogonadism (primary or secondary) have been long known to physicians and patients alike and include decreased libido, erectile dysfunction, osteoporosis, reduced sexual hair, and changes in body habitus. Recently, we have come to appreciate that reductions in serum testosterone resulting from aging or chronic disease have signs and symptoms similar to those seen in classical male hypogonadism, along with increased fat mass, decreased lean body mass, decreased muscle strength, and diminished quality of life.1 During the past decade, reports have been trickling in, mainly from laboratory and epidemiological studies (and a few clinical studies), linking differences in serum testosterone levels to various cardiovascular risk factors and also directly to cardiovascular disease and death. The article by Khaw et al2 in this issue of Circulation is another link to this growing chain. Article p 2694 Thirteen years ago, Phillips et al3 reported that low total and free testosterone levels were inversely linked to coronary artery disease, even after adjusting for age and adiposity. This observation still holds true, as was recently supported by a study showing that men with angiographically proven coronary artery disease had lower levels of testosterone than those of controls.4 Furthermore, testosterone levels were negatively correlated to the degree of coronary involvement. A few population-based studies have been published that relate low serum testosterone level with risk of death. A study of male veterans showed that low testosterone was associated with increased risk of …

Associations of androgens with physical activity and fitness in young black and white men: The CARDIA Male Hormone Study

Objective. The association between physical activity or cardiovascular fitness and chronic disease risk in men might be mediated, in part, through androgens. Limited data exists on the potential associations of activity or fitness with serum hormones. We examined the associations of serum testosterone and sex hormone binding globulin (SHBG) concentrations with physical activity and cardiorespiratory fitness in black and white young men. Method. Data were collected from 391 black and 604 white male participants of the Coronary Artery Risk Development in (Young) Adults (CARDIA) Male Hormone Study aged 24–32 in 1992–1993. Cross-sectional associations of serum total testosterone (TT), bioavailable testosterone (BT) and SHBG levels with self-reported total physical activity score, and in a subset of men ( n = 617) with cardiorespiratory fitness measured via duration on a treadmill test were assessed. Five-year longitudinal associations of change in hormones with changes in physical activity also were examined. Results. There were no cross-sectional or longitudinal associations of physical activity with SHBG, TT or BT in either black or white men. Fitness was positively associated with SHBG only in white men, but was not associated with TT or BT in either group. Conclusion. Overall the results do not support an association of self-reported physical activity with androgens, whereas they do suggest that fitness might be associated with SHBG in white men.

Association of Androgens with Physical Activity and Fitness in Young Men

It is hypothesized that the association between physical activity or cardiovascular fitness and chronic disease risk might be mediated, in part, through sex hormones in men. Limited observational data exists on the potential association of either physical activity or cardiovascular fitness with androgens. PURPOSE: To examine the cross-sectional association of serum androgen concentrations with self-reported physical activity and cardiorespiratory fitness in black and white young men. METHODS: Data were collected from 391 black and 604 white male participants of the Coronary Artery Risk Development in (Young) Adults (CARDIA) Male Hormone Study who were aged 28 to 42 years. Cross-sectional associations of serum total testosterone (TT), bioavailable testosterone (BT) and sex hormone binding globulin (SHBG) levels with self-reported total physical activity score (activity), and in a subset of men (n=617) with cardiorespiratory fitness measured via duration on a treadmill test (fitness) were assessed. Analyses were jointly stratified by body mass index (BMI) (30 kg/m2) and race. RESULTS: Age-adjusted activity scores were higher PMong black than white men at all levels of BMI. Conversely, age-adjusted fitness was higher PMong whites than blacks for all BMI groups. Age-adjusted TT, SHBG and BT tended to be higher in blacks than whites across levels of BMI. For both black and white men, BMI was inversely associated with TT and SHBG, but not with BT. TT was not associated with activity for any BMI-race group, except obese white men where a positive association (p=0.01) was observed. The age and BMI adjusted mean TT concentration was 4.5 ng/ml for obese white men in activity quartile 1 and 5.6 ng/ml for obese white men in quartile 4; BT also was positively associated (p=0.0004) with activity only PMong obese white men. SHBG was unassociated with activity across BMI-race groups. TT and BT were not associated with fitness for any BMI-race group. SHBG was positively associated with fitness in obese white men (p=0.0008) and marginally positively associated with fitness in normal weight white men (p=0.06). PMong obese white men, TT and SHBG levels increased, but BT levels were similar across quartiles of fitness. CONCLUSION: Physical activity is modestly positively associated with BT in obese white men. However, physical fitness was not significantly associated with BT or TT despite significant positive associations with SHBG. The different associations of fitness and activity with BT suggest different biological mechanisms. These results suggest physical activity might be a determinant of androgen levels independent of its association with BMI in obese white men only.

Sex steroids and plasma lipoprotein levels in healthy women: the importance of androgens in the estrogen-deficient state

The role of endogenous estrogens and androgens and their potential interaction in atherosclerosis is not well understood. Therefore, we investigated the effects of natural menopause and endogenous sex steroids on triglycerides (TG), a major risk factor for cardiovascular disease in women. Fasting lipid and lipoprotein concentrations, postheparin lipase activities, kinetic indicators of triglyceride lipolysis, and various hormone levels, including dehydroepiandrostenedione-sulfate (DHEA-S), (bioavailable) testosterone, and androstenedione, were determined in 18 premenopausal and 18 postmenopausal women, matched for age and body composition. Fasting plasma TG were 0.69 ± 0.29 mmol/L in postmenopausal women and 0.73 ± 0.33 mmol/L in premenopausal women (difference not significant [NS]). Approximately 30% of all plasma TG were present in the very-low-density lipoproteins (VLDLs) in both groups. No differences were found between groups in plasma lipolytic potential of TG-rich lipoproteins. Univariate analysis revealed that VLDL-TG concentrations were strongly related to insulin ( r = 0.84, P = .0001) and androstenedione ( r = 0.65, P = .004) in postmenopausal women. Multivariate analysis of potential determinants of VLDL-TG showed that insulin, androstenedione, and bioavailable testosterone were independent variables, explaining 87% of the variability ( r = 0.93, P = .0001) in postmenopausal women. In contrast, in premenopausal women, the only identified predictor of fasting VLDL-TG in univariate and multivariate analysis was insulin ( r = 0.72, P = .001). Our results show that the association of androgens with TG varied depending on androgen concentrations, the relative androgenic potential, and most importantly on hormonal milieu. Endogenous androgens were only related to plasma VLDL-TG in the estrogen-deficient state.