Testosterone Abstracts 38

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Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone.
            (Budoff et al., 2017) Download
Importance:  Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. Objective:  To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Design, Setting, and Participants:  Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. Intervention:  Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcomes and Measures:  The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). Results:  Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. Conclusions and Relevance:  Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. Trial Registration:  clinicaltrials.gov Identifier: NCT00799617.

Testosterone supplementation and sexual function: a meta-analysis study.
            (Corona et al., 2014) Download
INTRODUCTION:  The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable. AIM:  The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i). METHODS:  An extensive Medline, Embase, and Cochrane search was performed. MAIN OUTCOME MEASURES:  All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi). RESULTS:  Out of 1,702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs. placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5is. TS is able to significantly ameliorate erectile function and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of possible publication bias was detected. After applying "trim and fill" method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completely supported by pharmaceutical companies (confidence interval [0.04-0.53] and [0.12; 0.52], respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed in placebo-controlled studies. The majority of studies, however, included mixed eugonadal/hypogonadal subjects, thus imparting uncertainty to the statistical analyses. CONCLUSIONS:  TS plays positive effects on male sexual function in hypogonadal subjects. The role of TS is uncertain in men who are not clearly hypogonadal. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure that persistently retain low testosterone levels are advisable.

Testosterone therapy in the new era of Food and Drug Administration oversight.
            (Desroches et al., 2016) Download
The Food and Drug Administration (FDA) introduced changes in labeling and indications for use to testosterone products in 2015 due to a possible increased risk of cardiovascular (CV) events. This decision was made based on six clinical studies-some that supported an increased CV risk, and some that did not. Since this decision, additional studies have been published examining the interplay between hypogonadism, CV risk, and testosterone, demonstrating that the risk may be lower than originally estimated. Clinicians are placed in a difficult position, as studies support an increased mortality risk in hypogonadal men, but also an increased risk of CV events in men on testosterone therapy. As a result, many clinicians will be more selective in their prescribing of testosterone. In this review, we examine how these new guidelines arose and how they may affect prescribing habits.

Effect modification of obesity on associations between endogenous steroid sex hormones and arterial calcification in women at midlife.
            (El Khoudary et al., 2011) Download
OBJECTIVE:  The aim of this study was to examine whether obesity modifies the effects of endogenous steroid sex hormones on arterial calcification in women at midlife. METHODS:  Associations between estradiol, testosterone, sex hormone-binding globulin, and free androgen index and the presence and extent of coronary and aortic calcification were evaluated in 187 obese (body mass index, ≥30 kg/m) and 281 nonobese (body mass index, <30 kg/m) women from the Study of Women's Health Across the Nation. Logistic and linear regressions were used as appropriate. RESULTS:  Prevalence rates of coronary and aortic calcification were significantly higher among obese compared with nonobese women (P < 0.001, for both). In multivariable analyses, steroid sex hormones were not associated with the presence of coronary calcification. However, for the extent of coronary calcification, significant interactions were found between obesity and both sex hormone-binding globulin (P < 0.0001) and free androgen index (P = 0.008). In nonobese women, higher sex hormone-binding globulin (P = 0.0006) and lower free androgen index (P = 0.01) were associated with a greater extent of coronary calcification, whereas lower sex hormone-binding globulin was associated with greater extent of coronary calcification in obese women (P = 0.05). For aortic calcification outcomes, higher sex hormone-binding globulin was associated with the presence of aortic calcification among nonobese women (odds ratio, 1.64; 95% CI, 1.16-2.32, for each 1-SD greater sex hormone-binding globulin). CONCLUSIONS:  Associations between endogenous steroid sex hormones and arterial calcification vary by obesity status among perimenopausal women. Further research is needed to better understand the possible mechanisms of these associations.

Controversies in testosterone replacement therapy: testosterone and cardiovascular disease.
            (Hwang and Miner, 2015) Download
The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term prospective studies to determine safety. Literature spanning over the past 30 years has suggested that not only is there a possible increased CV risk in men with low levels of testosterone, but the benefits from testosterone therapy may even lower this risk. We review here the recent studies that have garnered such intense scrutiny. This article is intended as a thorough review of testosterone levels and CV risk, providing the clinician with the facts needed to make informed clinical decisions in managing patients with clinical hypogonadism.

Racial Differences in Age-Related Variations of Testosterone Levels Among US Males: Potential Implications for Prostate Cancer and Personalized Medication.
            (Hu et al., 2015) Download
AIM:  The magnitude of the age-related declines in testosterone rather than levels measured at single point in time may be related to the genesis of prostate cancer (PCa). We examined age-related variations of testosterone levels among black and white males, which may provide important insights into racial disparities in PCa incidence and mortality. METHOD:  We analyzed data from the 1999-2004 National Health and Nutritional Examination Survey to compare age-related variations in the testosterone levels of 355 black and 631 white males. RESULT:  Overall, between the ages of 12 and 15, black males had lower testosterone levels than white males. Testosterone levels increased rapidly with age and reached higher and earlier peak levels in black males compared to white males at 20-30 years of age. After reaching a peak level, testosterone levels declined earlier in blacks than in whites. Further analyses showed that black males had considerably higher levels of testosterone compared to white males aged 20-39 years after adjusting for covariates, including age, body mass index, cigarette smoking, physical activity, and waist circumference; however, no statistically significant differences were observed between the groups at any other age. CONCLUSION:  Our study revealed that testosterone levels in black males decrease substantially with increasing age compared to those in white males. This rapid drop in testosterone levels may contribute to racial disparities in PCa. Our findings also suggest that personalized medication for hormone replacement therapy may be necessary to avoid sudden drops in testosterone levels, particularly for black males.

Mammalian sex hormones in plants.
            (Janeczko and Skoczowski, 2005) Download
The occurrence of mammalian sex hormones and their physiological role in plants is reviewed. These hormones, such as 17beta-estradiol, androsterone, testosterone or progesterone, were present in 60-80% of the plant species investigated. Enzymes responsible for their biosynthesis and conversion were also found in plants. Treatment of the plants with sex hormones or their precursors influenced plant development: cell divisions, root and shoot growth, embryo growth, flowering, pollen tube growth and callus proliferation. The regulatory abilities of mammalian sex hormones in plants makes possible their use in practice, especially in plant in vitro culture.

Controversies in testosterone supplementation therapy.
            (Khera, 2015) Download
Testosterone has now become one of the most widely used medications throughout the world. The rapid growth of the testosterone market in the past 10 years is due to many factors. We currently have a worldwide aging population. In the US, the number of men 65 years old or older is increasing 2-3 times faster than the number of men younger than 65 years. In addition, poor general health and certain medical conditions such as diabetes/metabolic syndrome (MetS), cardiovascular disease (CVD), and osteoporosis have been associated with low serum testosterone levels. [1],[2],[3] There are now fewer concerns regarding the development of prostate cancer (PCa) after testosterone therapy, making it a more attractive treatment option. Finally, the introduction of different forms of testosterone supplementation therapy (TST) with increased promotion, marketing, and direct-to-consumer advertising is also driving market growth. As the demand for TST continues to grow, it is becoming more important for clinicians to understand how to diagnose and treat patients with low testosterone.

The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy.
            (Klap et al., 2015) Download
PURPOSE:  For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer. MATERIALS AND METHODS:  We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance. RESULTS:  We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines on total testosterone measurements. One of 18 series of low total testosterone and prostate cancer adhered to published guidelines while none of 17 showing a relationship of high total testosterone to prostate cancer and only 1 of 10 that identified no relationship between total testosterone and prostate cancer adhered to measurements recommended in the guidelines. In 11 studies the risk of exogenous testosterone was examined in patients with a prostate cancer history. Many studies were limited by small cohort size and brief followup. However, overall this literature suggests that the risk of exogenous testosterone replacement in patients with prostate cancer appears to be small. CONCLUSIONS:  The relationship between total testosterone and prostate cancer has been an area of interest among physicians for decades. Conflicting results have been reported on the relationship between total testosterone and subsequent prostate cancer. Much of this controversy appears to be based on conflicting study designs, definitions and methodologies. To date no prospective study with sufficient power has been published to unequivocally resolve the issue. The preponderance of studies of the safety of exogenous testosterone in men with a prostate cancer history suggests that there is little if any risk. However, because the risk has not proved to be zero, the most prudent course is to follow such men with regular prostate specific antigen measurements and digital rectal examinations.

Low serum testosterone level was associated with extensive coronary artery calcification in elderly male patients with stable coronary artery disease.
            (Lai et al., 2015) Download
BACKGROUND:  Coronary artery calcification (CAC) is a pandemic condition in elderly patients with coronary artery disease (CAD) and associated with a worse prognosis. Although available data have shown an association between testosterone levels in men and CAD, the association between testosterone and CAC in elderly male patients with CAD remains unknown. METHODS:  A total of 211 consecutive male patients (age ≥ 65 years) who underwent first multidetector computed tomography and following angiography were enrolled from our institution between March 2009 and September 2014. CAD was angiographically documented as significant stenoses (reduction ≥ 50% of the lumen diameter) on any major coronary vessel. The standard Agatston calcium score was calculated. The relationship of serum testosterone level with the CAC score measured by multidetector computed tomography in elderly male patients with stable CAD was evaluated. For data analyses, the CAC score was divided into four categories: ≤ 10, 11-99, 100-399, and ≥ 400, corresponding to minimal, moderate, increased, and extensive calcification. RESULTS:  Patients with higher CAC scores had significantly lower testosterone levels than patients with lower CAC scores (P = 0.048). In logistic regression analysis, testosterone level remained an independent predictor of extensive CAC (odds ratio 0.997, 95% confidence interval 0.994-0.999, P = 0.043). CONCLUSION:  Our findings indicate an inverse association between testosterone level and the susceptibility to extensive CAC in elderly men with stable CAD.

Testosterone replacement therapy and the heart: friend, foe or bystander
            (Lopez et al., 2016) Download
The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, "beneficial (friendly use)", "detrimental (foe)" and "no effects at all (bystander)", based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT's). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT's does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not.

Testosterone increases coronary artery plaque in older men but helps anaemia and bone density.
            (Mayor, 2017) Download
Testosterone treatment increased the amount of coronary artery non-calcified plaque rather than reducing this early sign of increased cardiovascular risk in older men with low testosterone levels, a randomised study has shown. But a separate observational study published at the same time found a lower risk of cardiovascular events in men receiving testosterone treatment, while further randomised trials showed improvements in anaemia and bone density, although no increase was seen in cognitive function.


Testosterone therapy in men with prostate cancer: literature review, clinical experience, and recommendations.
            (Morgentaler and Conners, 2015) Download
For several decades any diagnosis of prostate cancer (PCa) has been considered an absolute contraindication to the use of testosterone (T) therapy in men. Yet this prohibition against T therapy has undergone recent re-examination with refinement of our understanding of the biology of androgens and PCa, and increased appreciation of the benefits of T therapy. A reassuringly low rate of negative outcomes has been reported with T therapy after radical prostatectomy (RP), radiation treatments, and in men on active surveillance. Although the number of these published reports are few and the total number of treated men is low, these experiences do provide a basis for consideration of T therapy in selected men with PCa. For clinicians considering offering this treatment, we recommend first selecting patients with low grade cancers and undetectable prostate-specific antigen following RP. Further research is required to define the safety of T therapy in men with PCa. However, many patients symptomatic from T deficiency are willing to accept the potential risk of PCa progression or recurrence in return for the opportunity to live a fuller and happier life with T therapy.

Controversies and Advances With Testosterone Therapy: A 40-Year Perspective.
            (Morgentaler, 2016) Download
Testosterone therapy (TTh) has become highly controversial. There are important health consequences of testosterone deficiency, and meaningful benefits with treatment. There is level 1 evidence that TTh improves sexual function and desire, body composition, and bone density. Concerns regarding cardiovascular risk were based on two deeply flawed retrospective studies and are contradicted by dozens of studies showing cardiovascular benefits of TTh or higher endogenous testosterone, including placebo-controlled studies in men with known heart disease (angina, heart failure). Prostate cancer should no longer be considered a risk of TTh. Testosterone is neither scourge nor panacea--it is just good medicine.

The perimenopausal atherosclerosis transition: relationships between calcified and noncalcified coronary, aortic, and carotid atherosclerosis and risk factors and hormone levels.
            (Munir et al., 2012) Download
OBJECTIVE:  Women of perimenopause age experience an upward transition of cardiovascular risk possibly in association with changing hormonal status. We examined the cross-sectional relationships between the atherosclerotic plaque within the coronary and carotid arteries and aorta and the menopausal hormone levels among asymptomatic perimenopausal women. METHODS:  The Assessment of the Transition of Hormonal Evaluation with Noninvasive Imaging of Atherosclerosis was a prospective substudy of the Prospective Army Coronary Calcium project. We screened 126 asymptomatic perimenopausal women (mean age, 50 y) using contrast-enhanced CT angiography (multidetector CT) and carotid ultrasound. Women had coronary calcium data from 5 to 10 years earlier. The measures included cardiovascular risk factors, serum hormone levels, 64-slice multidetector CT, and carotid ultrasound. RESULTS:  The prevalence of any coronary plaque was 35.5%. The prevalence of noncalcified plaque was 30.2%, and noncalcified plaque was the only manifestation of coronary artery disease in 10.7%. Markers of androgenicity (increased free testosterone and reduced sex hormone-binding globulin) were associated with an increased extent of calcified and noncalcified coronary artery plaque and aortic plaque. However, these relationships were not independent of cardiovascular risk factors. Follicle-stimulating hormone was directly associated with the number of aortic plaques. The levels of estrogen hormones were unrelated to plaque presence or extent. CONCLUSIONS:  Coronary, aortic, and carotid arterial plaque is prevalent in perimenopausal women without cardiac symptoms. The assessment of perimenopausal hormone status was not independently associated with subclinical atherosclerosis beyond standard cardiovascular risk factors.

Testosterone Therapy Among Prostate Cancer Survivors.
            (Nguyen and Pastuszak, 2016) Download
INTRODUCTION:  The use of testosterone in men with a history of prostate cancer remains controversial in light of established findings linking androgens to prostate cancer growth. However, hypogonadism significantly affects quality of life and has negative sequelae, and the risks and benefits of testosterone therapy might be worthwhile to consider in all men, even those with a history of high-risk prostate cancer. AIM:  To discuss the effects of testosterone on the prostate and the use of testosterone therapy in hypogonadal men with a history of prostate cancer. METHODS:  Review of the literature examining the effects of testosterone on the prostate and the efficacy and safety of exogenous testosterone in men with a history of prostate cancer. MAIN OUTCOME MEASURES:  Summary of effects of exogenous and endogenous testosterone on prostate tissue in vitro and in vivo, with a focus on effects in men with a history of prostate cancer. RESULTS:  Testosterone therapy ameliorates the symptoms of hypogonadism, decreases the risk for its negative sequelae, and can significantly improve quality of life. Recent studies do not support an increased risk for de novo prostate cancer, progression of the disease, or biochemical recurrence in hypogonadal men with a history of non-high-risk prostate cancer treated with testosterone therapy. Evidence supporting the use of testosterone in the setting of high-risk prostate cancer is less clear. CONCLUSION:  Despite the historical reluctance toward the use of testosterone therapy in men with a history of prostate cancer, modern evidence suggests that testosterone replacement is a safe and effective treatment option for hypogonadal men with non-high-risk prostate cancer. Additional work to definitively demonstrate the efficacy and safety of testosterone therapy in men with prostate cancer is needed, and persistent vigilance and surveillance of treated men remains necessary.

Inverse relationship between bioavailable testosterone and subclinical coronary artery calcification in non-obese Korean men.
            (Park et al., 2012) Download
Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with apparently low cardiometabolic risk. This study was performed to investigate the association between male sex hormones and subclinical coronary artery calcification measured as coronary calcium score in non-obese Korean men. We examined the relationship of total testosterone, sex hormone-binding globulin, bioavailable testosterone and free testosterone with coronary calcium score in 291 non-obese Korean men (mean age: 52.8±9.3 years) not having a history of cardiovascular disease. Using multiple linear regression, we evaluated associations between log (sex hormone) levels and log (coronary calcium score) after adjusting for confounding variables in 105 men with some degree of coronary calcification defined as coronary calcium score ≥ 1. In multiple linear regression analysis, bioavailable testosterone was inversely associated with coronary calcium score (P=0.046) after adjusting for age, body mass index, smoking status, alcohol consumption, regular exercise, mean blood pressure, resting heart rate, C-reactive protein, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, hypertension medication and hyperlipidemia medication, whereas total testosterone, sex hormone-binding globulin and free testosterone were not (P=0.674, P=0.121 and P=0.102, respectively). Our findings indicate that bioavailable testosterone is inversely associated with the degree of subclinical coronary artery calcification in non-obese men.

Testosterone, epitestosterone and androstenedione in the pollen of Scotch pine P. silvestris L.
            (Saden-Krehula et al., 1971) Download
A study measured testosterone, epitestosterone and androstenedione in the pollen of Scotch pine P. silvestris L.

Vitamin D and its metabolites in the pollen of pine. Part 5: Steroid hormones in the pollen of pine species.
            (Saden-Krehula and Tajíć, 1987) Download
Unconjugated vitamin D and its metabolites were investigated in the pollen of Pinus nigra Ar. and Pinus sylvestris L. by TLC, HPLC and competitive radiochemical determination of 25-hydroxycholecalciferol (25-OHD3). It was found that vitamin D (D2, D3) was present in the pollen in amounts about 2 micrograms/10 g and 25-OHD3, 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] between 0.1 and 3 micrograms/10 g of pollen, dependent on pollen species and methods.

Circulating Sex Steroids and Vascular Calcification in Community-Dwelling Men: The Framingham Heart Study.
            (Travison et al., 2016) Download
CONTEXT:  The relationship between sex steroids and atherosclerosis is poorly understood. OBJECTIVE:  To describe the association of serum total T (TT), calculated free T (cFT), estrone (E1), estradiol (E2), and SHBG to vascular calcification in adult men. DESIGN:  Observational study (Framingham Heart Study). Analyses are cross-sectional. TT, E1, and E2 were measured by liquid chromatography-tandem mass spectrometry, and SHBG by immunofluorometric assay. Estimates of association were obtained by Tobit regression, which acknowledges the influence of floor effects on outcomes. SETTING:  General community. PARTICIPANTS:  A total of 1654 community-dwelling men from the Offspring and Third Generation cohorts of the Framingham Heart Study. MAIN OUTCOME MEASURES:  Coronary artery calcification (CAC), abdominal aortic calcification, and thoracic aortic calcification were measured by computed tomography. RESULTS:  Mean (standard deviation [SD]) age was 49 (10) years. Mean (SD) TT, cFT, and SHBG were: 616 (224) ng/dL, 111 (45) pg/mL, and 46 (23) nmol/L, respectively. Mean (SD) E2 and E1 were 28 (10) and 39 (14) pg/mL. Vascular calcification at all sites was negatively associated with TT and cFT and positively associated with E2 and E1. A 100-ng/dL between-subjects increase in TT was associated with a mean (95% confidence interval) age-adjusted difference in CAC of -23% (-41%, -4%) (P = .02). After model adjustment for other cardiovascular risk factors, the estimated associations between T and vascular calcification scores were statistically nonsignificant. CONCLUSIONS:  Decreased circulating T and E2 levels are associated with an age-adjusted increase in CAC, but these associations appear to express relationships either attributable to or mediated by established cardiovascular risk factors.

 


References

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Desroches, B, et al. (2016), ‘Testosterone therapy in the new era of Food and Drug Administration oversight.’, Transl Androl Urol, 5 (2), 207-12. PubMed: 27141448
El Khoudary, SR, et al. (2011), ‘Effect modification of obesity on associations between endogenous steroid sex hormones and arterial calcification in women at midlife.’, Menopause, 18 (8), 906-14. PubMed: 21471825
Hu, H, et al. (2015), ‘Racial Differences in Age-Related Variations of Testosterone Levels Among US Males: Potential Implications for Prostate Cancer and Personalized Medication.’, J Racial Ethn Health Disparities, 2 (1), 69-76. PubMed: 26863244
Hwang, K and M Miner (2015), ‘Controversies in testosterone replacement therapy: testosterone and cardiovascular disease.’, Asian J Androl, 17 (2), 187-91. PubMed: 25652628
Janeczko, A and A Skoczowski (2005), ‘Mammalian sex hormones in plants.’, Folia Histochem Cytobiol, 43 (2), 71-79. PubMed: 16044944
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Lai, J, et al. (2015), ‘Low serum testosterone level was associated with extensive coronary artery calcification in elderly male patients with stable coronary artery disease.’, Coron Artery Dis, 26 (5), 437-41. PubMed: 25968306
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Nguyen, TM and AW Pastuszak (2016), ‘Testosterone Therapy Among Prostate Cancer Survivors.’, Sex Med Rev, 4 376-88. PubMed: 27474995
Park, BJ, et al. (2012), ‘Inverse relationship between bioavailable testosterone and subclinical coronary artery calcification in non-obese Korean men.’, Asian J Androl, 14 (4), 612-15. PubMed: 22522505
Saden-Krehula, M, M Tajić, and D Kolbah (1971), ‘Testosterone, epitestosterone and androstenedione in the pollen of Scotch pine P. silvestris L.’, Experientia, 27 (1), 108-9. PubMed: 5549221
Saden-Krehula, M and M Tajíć (1987), ‘Vitamin D and its metabolites in the pollen of pine. Part 5: Steroid hormones in the pollen of pine species.’, Pharmazie, 42 (7), 471-72. PubMed: 3671475
Travison, TG, et al. (2016), ‘Circulating Sex Steroids and Vascular Calcification in Community-Dwelling Men: The Framingham Heart Study.’, J Clin Endocrinol Metab, 101 (5), 2160-67. PubMed: 26930184