Novel associations between sex hormones and diabetic vascular complications in men and postmenopausal women: a cross-sectional study.
Wang Chiyu,Zhang Wen,Wang Yuying,Wan Heng,Chen Yi,Xia Fangzhen,Zhang Kun,Wang Ningjian,Lu Yingli
Cardiovascular diabetology
BACKGROUND:Associations between sex hormones and vascular remodeling have been extensively studied, but the results vary widely among different races and sex. We aimed to investigate whether total testosterone (TT), estrogen (E2), and dehydroepiandrosterone (DHEA) associate with macrovascular complications and diabetic kidney disease (DKD) among community-dwelling patients with diabetes. METHODS:A total of 4720 participants with type 2 diabetes were recruited from Shanghai, China. Common carotid artery (CCA) plaques and diameter were assessed by ultrasound. Cardiovascular disease (CVD) was defined by prior diagnosis of coronary heart disease, myocardial infarction or stroke. DKD was defined according to the ADA Guidelines. RESULTS:(1) In men, TT was negatively associated with CCA diameter (regression coefficient (β) - 0.044, 95% CI - 0.087, 0). E2 levels were positively associated with CVD and CCA plaque prevalence (OR 1.151, 95% CI 1.038, 1.277 and OR 1.13, 95% CI 1.017, 1.255, respectively). DHEA was negatively associated with CVD (OR 0.809, 95% CI 0.734, 0.893). In postmenopausal women, TT levels were negatively associated with CCA diameter (β - 0.046, 95% CI - 0.083, - 0.010) and positively associated with CVD (OR 1.154, 95% CI 1.038, 1.284). (2) In both men and postmenopausal women, TT levels were negatively associated with the albumin/creatinine ratio and DKD (β - 0.098, 95% CI - 0.154, - 0.043 and OR 0.887, 95% CI 0.790, 0.997 vs. β - 0.084, 95% CI - 0.137, - 0.031 and OR 0.822, 95% CI 0.731, 0.924, respectively) and DHEA levels were positively associated with DKD (OR 1.167, 95% CI 1.038, 1.313 vs. OR 1.251, 95% CI 1.104, 1.418, respectively). CONCLUSIONS:Our study indicates that macrovascular complications were associated with low TT, DHEA and high E2 in men and with high TT in postmenopausal women. DKD was associated with low TT and high DHEA levels in both genders. Sex hormone replacement therapy requires careful and comprehensive consideration. Trial registration ChiCTR1800017573, http://www.chictr.org.cn . Registered 04 August 2018.
10.1186/s12933-019-0901-6
The Associations Between Gonadal Hormones and Serum Uric Acid Levels in Men and Postmenopausal Women With Diabetes.
Wan Heng,Zhang Kun,Wang Yuying,Chen Yi,Zhang Wen,Xia Fangzhen,Zhang Yunping,Wang Ningjian,Lu Yingli
Frontiers in endocrinology
In assessing the development of hyperuricemia in diabetic adults, the role of the sex steroid axis is underappreciated. Furthermore, dehydroepiandrosterone (DHEA) has been recommended as a nutritional supplement. However, is DHEA suitable for diabetic adults with hyperuricemia? This issue has received little attention. The objective of this study was to investigate the associations between gonadal hormones and uric acid (UA) levels in diabetic adults, paying particular attention to the association between DHEA and UA levels. We analyzed 4,426 participants out of 4,813 diabetic adults enrolled from seven communities in a cross-sectional survey conducted in 2018. Participants underwent several examinations, including assessments of anthropometric parameters, blood pressure, glucose, lipid profiles, UA, total testosterone (TT), estradiol (E2), the follicle-stimulating hormone (FSH), the luteinizing hormone (LH), and dehydroepiandrosterone (DHEA). Among men and compared with individuals in the first quartile, participants in the fourth quartile of TT and FSH had odds of hyperuricemia that were significantly decreased by so much as 48 and 34%, respectively (both < 0.05). However, participants in the fourth quartile of DHEA had 79% increased odds of hyperuricemia ( < 0.05). Among postmenopausal women, participants in the fourth quartile of DHEA, TT, and LH had odds of hyperuricemia that were significantly increased by 155, 99, and 76%, respectively (all < 0.05). These associations were adjusted for potential confounding factors. Sex differences were found in the associations between gonadal hormones and UA levels in diabetic men and postmenopausal women, which should be monitored to prevent hyperuricemia when sex hormone treatment, especially DHEA, is administered. Further studies are needed.
10.3389/fendo.2020.00055
Diabetes mellitus induced impairment of male reproductive functions: a review.
Jangir Ram Niwas,Jain Gyan Chand
Current diabetes reviews
Diabetes mellitus (DM) represents one of the greatest threats to human health all over the world. The incidence of DM is rising rapidly also including children and young persons of reproductive age. Diabetes has been associated with reproductive impairment in both men and women. Diabetes may affect male reproductive functions at multiple levels as a result of its effects on the endocrine control of spermatogenesis, steroidogenesis, sperm maturation, impairment of penile erection and ejaculation. A large number of studies both on diabetic men and experimental diabetic animals have been published on the impact of DM on male reproductive functions during the past few years but many of them have conflicting results. The present review summarizes the research finding of a large number of research papers on the reproductive functions especially on hypothalmo-pituitary-gonadal axis, spermatogenesis, histopathology of testis, synthesis and secretion of testosterone, sperm quality, ejaculatory function and fertility both in diabetic men and experimental diabetic animals.
10.2174/1573399810666140606111745
Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome.
Christian Rose C,Dumesic Daniel A,Behrenbeck Thomas,Oberg Ann L,Sheedy Patrick F,Fitzpatrick Lorraine A
The Journal of clinical endocrinology and metabolism
Polycystic ovary syndrome (PCOS), a common endocrine disorder of reproductive-aged women, is associated with multiple risk factors for coronary heart disease (CHD), such as diabetes mellitus, dyslipidemia, visceral obesity, and hypertension. However, premature coronary atherosclerosis has not been demonstrated in PCOS women. Electron beam computed tomography (EBCT) noninvasively measures coronary artery calcium (CAC), a marker for coronary atherosclerosis. We measured CAC by EBCT in 30- to 45-yr-old premenopausal PCOS women and compared the results to CAC in 1) recruited normal ovulatory volunteers matched for age and weight to the PCOS cohort, and 2) community-dwelling women of similar age in an extant coronary calcium database. Healthy, community-dwelling, ovulatory controls (n = 71) were matched by age and body mass index (BMI) to PCOS women (n = 36). Women with diabetes or known CHD were excluded. Subjects underwent EBCT scanning, oral glucose tolerance testing, and CHD risk factor assessment. PCOS women had significantly higher levels of serum total and low density lipoprotein cholesterol and testosterone levels than matched controls. PCOS and control women were obese and had a greater mean BMI than community-dwelling women (33 kg/m(2) for PCOS vs. 31 kg/m(2) for control; P < 0.001). CAC was more prevalent in PCOS women (39%) than in matched controls (21%; odds ratio, 2.4; P = 0.05) or community-dwelling women (9.9%; odds ratio, 5.9; P < 0.001). BMI, waist circumference, and total and low density lipoprotein cholesterol levels predicted CAC prevalence after adjustment for BMI. CAC is more prevalent in PCOS women than in obese or nonobese women of similar age. PCOS women are at increased risk for atherosclerosis and should be targeted for primary prevention of CHD.
10.1210/jc.2003-030334
Serum sex hormones in premenopausal women with coronary heart disease.
Mohamad Mohamad Jaffer,Karayyem Mohamad,Mohammad Mukhallad A,Al-Alami Jamil,Al-Hader Adulfatah
Neuro endocrinology letters
OBJECTIVES:The objectives of this study were to investigate the relationship between the incidence of coronary heart diseases in premenopausal women and plasma level of total and free testosterone, estrogen, androstenedione and sex hormone binding globulin with coronary risk factors: fasting plasma concentration of glucose, triglyceride, total cholesterol, high and low density lipoproteins. METHODS:The study was conducted in Faculty of Medicine, Jordanian University of Science/Irbid Jordan and Technology and department of cardiology in Queen Alia Heart Institute/Amman Jordan during the period from April 2003 to March 2004. Serum sex hormones levels were measured in fifty-three premenopausal women; 25 women with coronary heart disease who had hypertension and/or diabetes mellitus and 28 women without coronary heart disease. Ages ranged from 34 to 48 years. Blood samples were collected just before performing coronary angiography and serum was obtained and frozen at -70 degrees C until use. RESULTS:We found that the mean triglyceride, fasting blood sugar total cholesterol, and low density lipoprotein concentration were significantly higher in coronary heart disease patients than in patients with normal coronaries. We also found that the low levels of sex hormone binding globulin and high levels of free testosterone are associated with development of coronary heart disease. No significant correlation could be established between other plasma sex hormones level and coronary heart disease. CONCLUSION:In young women, in the presence of coronary risk factors and normal level of serum estrogen, the high levels of serum free testosterone and low levels of serum sex hormone binding globulin are associated with development of atherosclerosis and increased incidence of coronary heart disease.
Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis.
van Koeverden Ian D,de Bakker Marie,Haitjema Saskia,van der Laan Sander W,de Vries Jean-Paul P M,Hoefer Imo E,de Borst Gert J,Pasterkamp Gerard,den Ruijter Hester M
Cardiovascular research
Aims:The effects of testosterone on cardiovascular disease (CVD) as reported in literature have been ambiguous. Recently, the interplay between testosterone and oestradiol as assessed by testosterone/oestradiol (T/E2) ratio was suggested to be better informative on the normal physiological balance. Considering the role in CVD, we hypothesized that a low T/E2 ratio in men with CVD is associated with increased inflammation, a more unstable plaque and a worse cardiovascular outcome. Methods and results:Testosterone and oestradiol concentrations were determined in blood samples of 611 male carotid endarterectomy patients included in the Athero-Express Biobank Study. T/E2 ratio was associated with baseline characteristics, atherosclerotic plaque specimens, inflammatory biomarkers, and 3 year follow-up information. Patients with low T/E2 ratio had more unfavourable inflammatory profiles compared with patients with high T/E2 as observed by higher levels of C-reactive protein [2.81 μg/mL vs. 1.22 μg/mL (P < 0.001)] and higher leucocyte counts [8.98*109/L vs. 7.75*109/L (P = 0.001)] in blood. In atherosclerotic plaques, a negative association between T/E2 ratio and number of neutrophils [B = -0.366 (P = 0.012)], plaque calcifications [OR: 0.816 (P = 0.044)], interleukin-6 (IL-6) [B = -0.15 (P = 0.009)], and IL-6 receptor [B = -0.13 (P = 0.024)] was found. Furthermore, in multivariate Cox regression analysis, low T/E2 ratio was independently associated with an increased risk for major cardiovascular events (MACE) during 3 year follow-up [hazard ratio 1.67 (95% confidence interval 1.02-2.76), P = 0.043]. In men with elevated body mass index (BMI), these effects were strongest. Conclusion:In male patients with manifest atherosclerotic disease, low T/E2 ratio was associated with increased systemic inflammation, increased inflammatory plaque proteins, and an increased risk of future MACE as compared to men with normal T/E2 ratio. These effects are strongest in men with elevated BMI and are expected to be affected by aromatase activity in white fat tissues. Normalization of T/E2 ratio may be considered as target for the secondary prevention of CVD in men.
10.1093/cvr/cvy188
Role of endogenous androgens on carotid atherosclerosis in non-obese postmenopausal women.
Montalcini T,Gorgone G,Gazzaruso C,Sesti G,Perticone F,Pujia A
Nutrition, metabolism, and cardiovascular diseases : NMCD
BACKGROUND:Recent randomized trials on hormone replacement therapy in postmenopausal women raised many doubts about their role in cardiovascular disease prevention. Therefore the role of other sex hormones needed to be investigated. In particular androgens seem to have a protective role on atherosclerosis. The present study was performed to assess the role of endogenous sex hormones on carotid atherosclerosis in postmenopausal women. METHODS AND RESULTS:We consecutively enrolled 101 postmenopausal women aged 45-75 (mean age 57.4) years referred to our University hospital menopausal health-screening clinic. The subjects underwent a medical history, a physical examination and biochemical analysis. Extracranial carotid arteries were assessed by ultrasound. Fifty percent of our sample had carotid plaques. On the multivariate logistic regression analysis age, glycaemia (positively) and testosterone (negatively) (P=0.02) were significantly correlated to carotid atherosclerosis. In non-obese subjects we found that participants in the third tertile had a significantly lower prevalence of carotid atherosclerosis (P=0.02) compared to those in the first tertile of testosterone. CONCLUSIONS:These results suggest a possible protective role of endogenous androgens at least on carotid atherosclerosis. Of course these preliminary results should be supported by prospective studies. Also the different role of these hormones on obese and non-obese subjects needs to be clarified.
10.1016/j.numecd.2006.09.007
Low plasma testosterone and elevated carotid intima-media thickness: importance of low-grade inflammation in elderly men.
Soisson Véronique,Brailly-Tabard Sylvie,Empana Jean-Philippe,Féart Catherine,Ryan Joanne,Bertrand Marion,Guiochon-Mantel Anne,Scarabin Pierre-Yves
Atherosclerosis
CONTEXT AND OBJECTIVE:An inverse correlation between plasma testosterone levels and carotid intima-media thickness (IMT) has been reported in men. We investigated whether this association could be mediated or modified by traditional cardiovascular risk factors as well as inflammatory status. METHODS:In the Three-City population-based cohort study, 354 men aged 65 and over had available baseline data on hormones levels and carotid ultrasonography. Plasma concentrations of testosterone (total and bioavailable), estradiol and sex hormone-binding globulin (SHBG), together with cardiovascular risk factors were measured. IMT in plaque-free site and atherosclerotic plaques in the extracranial carotid arteries were determined using a standardized protocol. Multiple linear regression models were used to analyze this association and interaction study. RESULTS:Analyses with and without adjustment for cardiovascular risk factors showed that carotid IMT was inversely and significantly correlated with total and bioavailable testosterone levels but not with SHBG and estradiol levels. This association depended on C-reactive protein (CRP) levels (p for interaction <0.05). Among men with low-grade inflammation (CRP ≥2 mg/L), mean IMT was higher in subjects with bioavailable testosterone ≤ 3.2 ng/mL than in those with bioavailable testosterone > 3.2 ng/mL (0.76 mm and 0.70 mm respectively, p < 0.01). By contrast, among men with CRP ≤ 2 mg/L, mean IMT was similar in both groups (0.72 mm and 0.71 mm respectively, p = 0.77). Similar results were found for total testosterone although not significant. No association was found between plasma hormones levels and atherosclerotic plaques. CONCLUSION:In elderly men, low plasma testosterone is associated with elevated carotid intima-media thickness only in those with low-grade inflammation. Traditional risk factors have no mediator role.
10.1016/j.atherosclerosis.2012.05.009
Association of Low Serum Free Testosterone with Carotid Atherosclerosis in Male.
Nahid K A,Akter K,Saqueeb S N,Zaman M S,Khalilullah M I,Jesmin S,Iqbal M G,Islam M A,Wadud M A,Aziz A S,Hoque M M
Mymensingh medical journal : MMJ
The cross sectional descriptive type of observational study was aimed to evaluate the association of serum free testosterone in 59 patients of carotid atherosclerotic male {<50% stenosis (n=26); >50% stenosis (n=33) } from March 2015 to February 2016 in the Department of Radiology & Imaging of Bangabandhu Sheikh Mujib Medical University (BSMMU) & National Institute of Neurosciences (NINS), Dhaka, Bangladesh. Twenty seven patients who had normal carotid doppler findings were taken as control. Serum total testosterone and sex hormone binding globulin was measured by chemiluminescence micro particle immunoassay and free testosterone was done by using Vermeulen formula. Concentration of free testosterone differed significantly among groups (p=0.004) and it was significantly lower in <50% stenosed group. Logistic regression analysis revealed that low free testosterone (free testosterone ≤0.24 nmol/L) was independently associated with development of carotid atherosclerosis (p=0.04, OR 3.07, 95% CI 1.14-9.30). In conclusion low serum free testosterone was associated with carotid atherosclerosis in male.
Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease.
Chan Yi X,Knuiman Matthew W,Hung Joseph,Divitini Mark L,Handelsman David J,Beilby John P,McQuillan Brendan,Yeap Bu B
Endocrine journal
Clarifying the relationship of sex hormones to preclinical atherosclerosis could illuminate pathways by which androgens are associated with cardiovascular events and mortality. Our aim was to determine hormone profiles associated with carotid intima-media thickness (CIMT) and carotid atheroma, in men with and without known coronary artery disease (CAD). We included 492 community-based men aged 20-70 years (Group A) and 426 men with angiographically proven CAD aged <60 years (Group B). Fasting early morning sera were assayed for testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) using mass spectrometry. CIMT and carotid plaque were assessed ultrasonographically. Mean (±SD) age was Group A: 53.8±12.6 and Group B: 49.6±5.1 years. Higher T was associated with reduced CIMT (-0.011 mm per 1-SD increase, p=0.042) and lower prevalence of carotid plaque (odds ratio [OR] per 1-SD increase, 0.68, p=0.012) in Group A, but not B. E2 was associated with increased CIMT in Group A (0.013 mm, p=0.011) but not B. Higher DHT and E2 were associated with reduced carotid plaque in Group B (DHT: OR=0.77, p=0.024; E2: OR=0.75, p=0.008), but not A. In community-dwelling men, higher T is associated with favourable CIMT and lower prevalence of carotid plaque, while higher E2 is associated with worse CIMT. In men with CAD, higher DHT or E2 are associated with less carotid plaque. T, DHT and E2 are differentially associated with preclinical carotid atherosclerosis in a cardiovascular phenotype-specific manner. Interventional studies are needed to examine effects of exogenous T and its metabolites DHT and E2, on atherogenesis.
10.1507/endocrj.EJ15-0196
Associations of Endogenous Estradiol and Testosterone Levels With Plaque Composition and Risk of Stroke in Subjects With Carotid Atherosclerosis.
Glisic Marija,Mujaj Blerim,Rueda-Ochoa Oscar L,Asllanaj Eralda,Laven Joop S E,Kavousi Maryam,Ikram M Kamran,Vernooij Meike W,Ikram M Arfan,Franco Oscar H,Bos Daniel,Muka Taulant
Circulation research
RATIONALE:Sex steroids may play a role in plaque composition and in stroke incidence. OBJECTIVES:To study the associations of endogenous estradiol and testosterone with carotid plaque composition in elderly men and postmenopausal women with carotid atherosclerosis, as well as with risk of stroke in this population. METHODS AND RESULTS:Data of 1023 postmenopausal women and 1124 men (≥45 years) with carotid atherosclerosis, from prospective population-based RS (Rotterdam Study), were available. At baseline, total estradiol (TE) and total testosterone (TT) were measured. Carotid atherosclerosis was assessed by ultrasound, whereas plaque composition (presence of calcification, lipid core, and intraplaque hemorrhage) was assessed by magnetic resonance imaging. TE and TT were not associated with calcified carotid plaques in either sex. TE was associated with presence of lipid core in both sexes (in women odds ratio, 1.48 [95% confidence interval [CI], 1.02-2.15]; in men odds ratio, 1.23 [95% CI, 1.03-1.46]), whereas no association was found between TT and lipid core in either sex. Higher TE (odds ratio, 1.58 [95% CI, 1.03-2.40]) and lower TT (odds ratio, 0.82 [95% CI, 0.68-0.98]) were associated with intraplaque hemorrhage in women but not in men. In women, TE was associated with increased risk of stroke (hazard ratio, 1.98 [95% CI, 1.01-3.88]), whereas no association was found in men. TT was not associated with risk of stroke in either sex. CONCLUSIONS:TE was associated with presence of vulnerable carotid plaque as well as increased risk of stroke in women, whereas no consistent associations were found for TT in either sex.
10.1161/CIRCRESAHA.117.311681