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Blood pressure (mmHg) in hypogonadal men with a history of cardiovascular disease receiving long-term testosterone therapy.
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Background/objectives
Long-term testosterone therapy (TTh) in men with hypogonadism has been shown to improve all components of the metabolic syndrome. In this study, we investigated the effects of long-term TTh up to 8 years in hypogonadal men with a history of cardiovascular disease (CVD).
Patients and methods
In two urological clinics observati...
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Background:
Hypogonadism is a common comorbidity in human immunodeficiency virus (HIV)-infected men, although the real prevalence is difficult to be estimated. Moreover, in HIV settings, the efficacy of exogenous testosterone (Te) administration at improving body composition remains unclear.
Aim of the study:
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Citations
... The large majority of the other trials included in the present meta-analysis also enrolled men with characteristics compatible with functional hypogonadism. The present meta-analysis supports an even more protective role for TRT against MACE in trials enrolling obese men, as previously reported [28] or suggested by other authors in observational studies [142,143]. Considering that TRT can improve body composition in hypogonadal men by reducing fat mass and improving lean mass [14,[144][145][146], this can explain its protective effect on CV risk in obese individuals. However, the introduction of TRAVERSE data into the meta-analysis did not substantiate the negative association between obesity and CV risk, most probably because the enrolled subjects in the TRAVERSE study were already at high CV risk. ...
Introduction:
The cardiovascular (CV) safety of testosterone (T) replacement therapy (TRT) is still conflicting. Recent data suggested a TRT-related increased risk of atrial fibrillation (AF). To systematic review and meta-analyze CV risk related to TRT as derived from placebo controlled randomized trials (RCTs).
Areas covered:
An extensive Medline, Embase and Cochrane search was performed. All placebo-controlled RCTs reporting data on TRT-related CV safety were considered. To better analyze the role of T on AF, population-based studies investigating the relationship between endogenous circulating T levels and AF incidence were also included and analyzed.
Expert opinion:
Out of 3.615, 106 studies were considered, including 8.126 subjects treated with TRT and 7.310 patients allocated to placebo. No difference between TRT and placebo were observed when major adverse CV events were considered. Whereas the incidence of non-fatal arrhythmias and AF was increased in the only trial considering CV safety as the primary endpoint, this was not confirmed when all other studies were considered (MH-OR 1.61[0.84;3.08] and 1.44[0.46;4.46]). Similarly no relationship between endogenous T levels and AF incidence was observed after the adjustment for confounders Available data confirm that TRT is safe and it is not related to an increased CV risk.
... An observational study investigating long-term TRT effects among 77 hypogonadal men with a history of CVD who received IM testosterone undecanoate every 12 weeks for eight years found that TR significantly decreased weight, BMI, and WC whilst improving their cardio metabolic profiles [35]. Interestingly, there were no MACEs suffered by any participants throughout the study period. ...
... • Absence of placebo-treated or control group limits interpretation and generalization of results [29, 35,38]. ...
... • Supply interruption of testosterone and inability to source other medications affected some studies [28, 30,35]. ...
Introduction: Despite the limited pieces of evidence on the cardiovascular safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH) and functional hypogonadism (FH), its global use for hypogonadism management is surging. This review aims to determine TRT's long-term safety.
... An important clinical study documented that acute administration of TES in humans with cardiac failure decreases peripheral vascular resistance and improves cardiac output [77]. An observational study in men showed that long-term TES therapy, for up to 8 years, produced marked and sustained gradual decreases in systolic and diastolic BP [78]. One recent study showed that hypertensive men had lower levels of free TES, and bioavailable TES, compared to normotensive men [79]. ...
Arterial hypertension is a global public health concern. In the last few years, the interest in androgen deficiency has been growing, and the association between androgens and high blood pressure (BP) is still controversial. One purpose of this review was to summarize the available findings in order to clarify whether male sex steroid hormones have beneficial or harmful effect on BP. The second purpose was to enhance the recognition of the acute non-genomic sex–independent vasorelaxing effect of androgens. Remarkably, BP variation is expected to be a consequence of the androgen-induced vasorelaxation which reduces systemic BP; hence the in vivo vasodepressor, hypotensive, and antihypertensive responses of androgens were also analyzed. This article reviews the current understanding of the physiological regulation of vascular smooth muscle contractility by androgens. Additionally, it summarizes older and more recent data on androgens, and some of the possible underlying mechanisms of relaxation, structural-functional differences in the androgen molecules, and their designing ability to induce vasorelaxation. The clinical relevance of these findings in terms of designing future therapeutics mainly the 5-reduced metabolite of testosterone, 5β-dihydrotestosterone, is also highlighted. Literature collected through a PubMed database search, as well as our experimental work, was used for the present review.
... Частота гипогонадизма у мужчин с СД2 по результатам нашего наблюдения составила 50,81%, что соответствует и международным данным. Полученная достоверная корреляция между низким уровнем Т и СС событиями у пациентов с СД2 позволяет предположить, что гипогонадизм может быть использован в качестве дополнительного критерия СС риска, а назначение ТЗТ мужчинам с гипогонадизмом и СС заболеваниями может рассматриваться как дополнительная мера профилактики развития острых СС событий наряду с контролем других факторов риска (артериальное давление, глюкоза крови, липидный профиль) [31]. ...
Introduction. Androgenic deficiency is an important pathogenetic element in the development of metabolic syndrome and cardiovascular diseases in men. It has been proven that in male patients with type 2 diabetes, hypogonadism develops much more often. Objective – to study the metabolic and cardiovascular features of the course of type 2 diabetes mellitus (T2DM) in men with androgen deficiency.
Mat erials and methods. The study included 124 men with type 2 diabetes. To diagnose hypogonadism, the levels of total testosterone (T), sex hormone binding globulin (SHBG), albumin and luteinizing hormone (LH) were measured. Free testosterone (free T) levels were calculated using a calculator from Ghent University Hospital, Belgium. A retrospective analysis of case histories was carried out (spectrum of late complications, the presence of heart attacks and strokes, laboratory data – total cholesterol (CS), triglycerides (TG), fasting blood plasma glucose, basal insulin level, glycated hemoglobin (HbA1c)). The HOMA-IR index was used to determine the degree of insulin resistance.
Results. The average age of men was 57.39 ± 9.41 years. The incidence of laboratory-confirmed hypogonadism is 50.81%. An average positive correlation was found between androgen deficiency and the incidence of non-fatal cardiovascular events (r = 0.45, p < 0.05). There was no statistically significant relationship between the presence of hypogonadism and the incidence and degree of late complications of T2DM. Patients with low T levels tended to have higher HOMA-IR values compared to patients with normal T levels (p < 0.05). At the same time, the indicators of carbohydrate and lipid metabolism did not differ significantly in these groups (p > 0.05).
Conclusions. The revealed incidence of hypogonadism in men with T2DM corresponds to the data of international studies. The presence of a significant correlation between low testosterone levels and cardiovascular events in patients with T2DM suggests that hypogonadism can be used as an additional criterion for cardiovascular risk. Testosterone deficiency exacerbates insulin resistance, which can lead to weight gain and impair carbohydrate metabolism.
... Hypogonadism is also involved in cardiovascular health and homeostasis, being associated with both increased cardiovascular and all-cause mortality. 5,6 Men with hypogonadism are subject to a higher risk of developing insulin resistance and diabetes, which has led the American Diabetes Association to recommend routine testosterone level assessment in patients with type 2 diabetes. 7 Although less specific, fatigue is also a concern in these patients, impairing quality of life and well-being. ...
Background: Testosterone replacement therapy (TRT) is one of the main lines of treatment for men with hypogonadism. This study sought to evaluate the influence of TRT in men with late-onset hypogonadism (LOH), regarding fatigue, coronary artery disease (CAD), carotid intima-media thickness (CIMT) and cardiovascular risk.
Methods: This study compared men with LOH already on TRT for >1 year to newly diagnosed men with LOH who recently started TRT (controls). We included men aged >18 years with clinical manifestations of testosterone deficiency and testosterone levels of 1 year and 45 (±12.2) years in the control group (p=0.18). CAD was present in 14 (46.7%) patients in the control group and in 3 (9.1%) in the study group (p1 year was not associated with lower rates of CAD in multivariable analysis. Fatigue Severity Score was significantly higher in the control group (39.2±15.0), compared to TRT >1 year (23.5±8.1; p1 year was associated with a 14.8-point decrease in Fatigue Severity Score (p1 year was associated with significantly lower fatigue scores. No differences were observed regarding CIMT, CAD and cardiovascular risk according to the WHO-ISH scale.
... In females, T2D is associated with higher free testosterone as well as lower SHBG [15]. Finally, there is accumulating evidence that testosterone treatment in males with a testosterone deficiency improves cardiometabolic health, reduces mortality related to cardiovascular risk, ameliorates insulin sensitivity and glycaemic control, and reduces the likelihood of developing T2D [16][17][18][19]. In our report, we extend these clinical findings in the context of sexrelated continuous traits, identifying the female pattern of effects in males, and the male pattern of effects in females. ...
The genetic architecture of testosterone is highly distinct between sexes. Moreover, obesity is associated with higher testosterone in females but lower testosterone in males. Here, we ask whether male-specific testosterone variants are associated with a male pattern of obesity and type 2 diabetes (T2D) in females, and vice versa. In the UK Biobank, we conducted sex-specific genome-wide association studies and computed polygenic scores for total (PGSTT) and bioavailable testosterone (PGSBT). We tested sex-congruent and sex-incongruent associations between sex-specific PGSTs and metabolic traits, as well as T2D diagnosis. Female-specific PGSBT was associated with an elevated cardiometabolic risk and probability of T2D, in both sexes. Male-specific PGSTT was associated with traits conferring a lower cardiometabolic risk and probability of T2D, in both sexes. We demonstrate the value in considering polygenic testosterone as sex-related continuous traits, in each sex.
... Hypogonadism is also involved in cardiovascular health and homeostasis, being associated with both increased cardiovascular and all-cause mortality. 5,6 Men with hypogonadism are subject to a higher risk of developing insulin resistance and diabetes, which has led the American Diabetes Association to recommend routine testosterone level assessment in patients with type 2 diabetes. 7 Although less specific, fatigue is also a concern in these patients, impairing quality of life and well-being. ...
Introduction:
Anxiety and fear are common among pregnant women undergoing cesarean delivery. In addition to psychologically unpleasant, they can elicit endocrine and metabolic changes. Administration of benzodiazepines in this patient group is uncommon and investigation focusing on the topic is rare. This study aimed to determine anxiolysis efficacy of low-dose midazolam administered preoperatively, right before cesarean delivery, and to evaluate whether its administration impacts neonatal vitality, maternal consciousness and recall of the moment the baby was born.
Methods:
Fifty pregnant women with indication for cesarean delivery were included in this randomized, double-blind, placebo-controlled clinical study and allocated into two groups of 25 participants each (Midazolam and Control group). Midazolam (0.0125 mg.kg-1) or a placebo solution was administered immediately before spinal anesthesia and the anxiolytic effect was assessed using a visual analogue scale before and after administration. We registered the Apgar score at 1 and 5-minutes, the Ramsay scale and recall of the moment of birth, that was assessed 90-minutes after birth.
Results:
Pregnant women from the Midazolam group presented a 1.3-point reduction in anxiety on the visual analogue scale, while the Control group showed virtually no change (p = 0.027). We observed no statistically significant changes in Apgar scores, level of maternal consciousness and recall of the moment of delivery.
Conclusions:
Low-dose midazolam can provide anxiety management in pregnant women undergoing cesarean delivery with no significant undesirable effects.
... Indeed, several observational trials have reported an increased risk of cardiovascular diseases in men with PCa on ADT (8)(9)(10). Likewise, an association between lower plasma levels of testosterone and hypertension has been reported (11)(12)(13)(14)(15). ...
Introduction: Androgens have been described as important players in the regulation of vascular function/structure through their action on the release and effect of vasoactive factors, such as prostanoids. Patients with prostate cancer (PCa) under androgen deprivation therapies (ADTs) present increased risk of cardiovascular mortality. Since thromboxane A 2 (TXA 2 ) is one of the most studied prostanoids and its involvement in different cardiovascular diseases has been described, the aim of this study was to investigate: (i) the effect of ADT on the serum levels of TXA 2 in PCa patients and its possible link to the redox status and (ii) the effect of the non-hydrolyzable TXA 2 analog U-46619 on the function of the aorta of male rats.
Methods: The levels of TXA 2 and total antioxidant status in 50 healthy subjects, 54 PCa patients, and 57 PCa under ADT were evaluated. These determinations were accompanied by levels of testosterone and C-reactive protein as an inflammation marker. In aortic segments from male rats, the U46619-induced effects on: (i) the vasomotor responses to acetylcholine (ACh), to the NO donor sodium nitroprusside (SNP), to the carbon monoxide-releasing molecule-3 (CORM-3), and to noradrenaline (NA) and (ii) the expression of cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), and phosphorylated ERK1/2 were analyzed.
Results: The serum level of TXA 2 in patients with PCa was increased with respect to healthy subjects, which was further increased by ADT. There was no modification in the total antioxidant status among the three experimental groups. In aortic segments from male rats, the TXA 2 analog decreased the endothelium-dependent relaxation and the sensitivity of smooth muscle cells to NO, while it increased the vasoconstriction induced by NA; the expression of COX-2, HO-1, and pERK1/2 was also increased.
Conclusions: ADT increased, along with other inflammatory/oxidative markers, the serum levels of TXA 2 . The fact that TXA 2 negatively impacts the vascular function of the aorta of healthy male rats suggests that inhibition of TXA 2 -mediated events could be considered a potential strategy to protect the cardiovascular system.
... In addition, epidemiological studies have shown a correlation between low plasma testosterone (TES) levels and hypertension in men [9][10][11][12]. Likewise, clinical studies have reported beneficial effects of TES therapy in men with a history of cardiovascular disease [13][14][15], pointing to androgens as physiological modulators of blood pressure. In recent times, more attention is being paid to the 5-dihydroreduced metabolites of TES. ...
Androgens may exert cardiovascular protective actions by regulating the release and function of different vascular factors. In addition, testosterone (TES) and its 5-reduced metabolites, 5α- and 5β-dihydrotestosterone (5α- and 5β-DHT) induce vasorelaxant and hypotensive effects. Furthermore, hypertension has been reported to alter the release and function of the neurotransmitters nitric oxide (NO), calcitonin gene-related peptide (CGRP) and noradrenaline (NA). Since the mesenteric arteries possess a dense perivascular innervation and significantly regulate total peripheral vascular resistance, the objective of this study was to analyze the effect of TES, 5α- and 5β-DHT on the neurogenic release and vasomotor function of NO, CGRP and NA. For this purpose, the superior mesenteric artery from male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to analyze: (i) the effect of androgens (10 nM, incubated for 30 min) on the neurogenic release of NO, CGRP and NA and (ii) the vasoconstrictor-response to NA and the vasodilator responses to the NO donor, sodium nitroprusside (SNP) and exogenous CGRP. The results showed that TES, 5α- or 5β-DHT did not modify the release of NO, CGRP or NA induced by electrical field stimulation (EFS) in the arteries of SHR; however, in the arteries of WKY rats androgens only caused an increase in EFS-induced NO release. Moreover, TES, and especially 5β-DHT, increased the vasodilator response induced by SNP and CGRP in the arteries of SHR. These findings could be contributing to the hypotensive/antihypertensive efficacy of 5β-DHT previously described in conscious SHR and WKY rats, pointing to 5β- DHT as a potential drug for the treatment of hypertension.
... Moreover, a longitudinal study including 702 middle-aged men showed that low testosterone levels independently predicted the development of metabolic syndrome and DM after a follow-up period of 11 years, with odds ratios of 2.23 and 2.28, respectively [24]. On the other hand, in 77 hypogonadal men with a history of CVD who received TRT, Haider et al. observed that weight, waist circumference, lipid pattern, glycemic control, blood pressure, heart rate, and pulse pressure, which are cardio-metabolic parameters, all improved significantly and sustainably in up to 8 years [25]. Therefore, low testosterone levels may contribute to an increased risk of CVE by promoting new metabolic risk factors or worsening existing coronary risks factors. ...
Aim: We investigated whether low plasma free testosterone (FT) levels could predict cardiovascular events (CVE) in Japanese men with coronary risk factors.
Methods: Male patients with classical coronary risk factors who had undergone serum FT testing were enrolled. New incidences of CVE were retrospectively investigated among all eligible participants based on their medical records.
Results: Overall, 466 male outpatients with coronary risk factors without a previous history of CVE were identified. Throughout the follow-up period (median = 92 months), 126 CVE occurred. The Kaplan–Meier survival analysis according to the tertiles of plasma FT levels revealed that patients with the lowest FT tertile (<6.5 pg/mL) had a higher likelihood of developing CVE than those with the highest tertile (>9.3 pg/mL) (p<.01). Multivariate analysis showed that increased frequency of CVE was observed with lower FT tertiles, independent of other coronary risk factors, with hazard ratios of 0.617 (95% CI, 0.389–0.976; p=.030) and 0.524 (95% CI, 0.309–0.887; p=.016) for the second and highest tertile relative to the lowest FT tertile, respectively.
Conclusion: Among Japanese men with coronary risk factors, a lower FT level was a predictor for the development of cardiovascular diseases independent of other coronary risk factors and age.
