Low-dose supplemental testosterone treatment in men with chronic stable angina reduces exercise-induced myocardial ischemia.

It is well recognised that oestrogens possess vasodilatory properties, and similar responses to testosterone have been demonstrated. However, vasomotor effects of other steroid hormones have not been well described. Direct comparisons of the relative vasoactivity of different steroid hormones in different vascular beds in male and female genders have not been made. Coronary and pulmonary arteries from adult Wistar rats were mounted in a wire myograph, loaded to 100 and 17 mmHg respectively, maximally pre-contracted with 1 x 10(-4) M prostaglandin-F-2-alpha, and dose response curves to 1 x 10(-6) to 1 x 10(-3) or 3 x 10(-3) M of 17 beta-oestradiol, testosterone, progesterone, and cortisol dissolved in water were constructed. Addition of each steroid hormone caused acute, dose dependent dilatation in coronary and pulmonary vessels. In coronary arteries the order of activity was testosterone > progesterone > 17 beta-oestradiol > cortisol, p < 0.001. In pulmonary arteries, the order of activity was progesterone > testosterone > cortisol > 17 beta-oestradiol, p < 0.001. Pulmonary arteries from male animals were more sensitive to the effects of testosterone than those from female animals, p = 0.003, whereas coronary arteries from female animals were more sensitive to the effects of 17 beta-oestradiol than those from male animals, p < 0.001. We have demonstrated significant differences in the in vitro vasomotor effects of different steroid hormones in two distinct vascular beds. Gender differences in vasomotor responses to steroid hormones may play a role in the aetiology of vasospastic diseases.

The effect of smoking on androgen levels is important given the recent interest in the link between low levels of androgens and the development of cardiovascular disease. Numerous studies examining the effects of cigarette smoking on the levels of total and free testosterone have reported conflicting findings, but there has been no accurate assessment of the effects of cigarette smoking on the levels of bioavailable testosterone [not bound to sex hormone-binding globulin (SHBG)]. We attempted to determine whether smoking affects the level of bioavailable testosterone. We undertook a case-control study of 25 healthy male smokers and 25 healthy never-smokers, matched by age and body mass index. Early morning levels of total, free and bioavailable testosterone, 17beta-oestradiol, SHBG and cotinine were determined and compared between the two groups. Levels of total (18.5+/-4.6 nM versus 15.1+/-4.9 nM, P=0.01) and free testosterone (462+/-91 pM versus 402+/-93 pM, P=0.03) were found to be higher in smokers compared with non-smokers respectively, as was SHBG (34.1+/-12.8 versus 28.1+/-9.0 nM, P=0.06). There were no significant differences in the levels of bioavailable testosterone (3.78+/-1.59 versus 3.51+/-1.26 nM, P=0.49) or 17beta-oestradiol (44.5+/-11.4 versus 42.3+/-11.5 pM, P=0.50) between smokers and non-smokers respectively. These data suggest that cigarette smoking has no significant effect on the biologically active fraction of testosterone, but may influence the levels of total and free testosterone through changes in the levels of SHBG.

No abstract

Objective: In women, sex hormones cause increased morbidity and mortality in patients with coronary heart disease (CHD) and adversely affect the coagulation profile. We have studied the effect of physiological testosterone replacement therapy in men on coagulation factor expression, to determine if there is an increased risk of thrombosis. Methods: Double-blind, randomized, placebo-controlled trial of testosterone in 46 men with chronic stable angina. Measurements of free, total and bioavailable testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH), estradiol, plasminogen activator inhibitor-1 (PAI-1), fibrinogen, tissue plasminogen activator (tPA) and full blood count were made at 0, 6 and 14 weeks.

No abstract

Women with a Fontan circulation have a high rate of miscarriage and, even if pregnancy progresses to a viable gestational age, a high rate of obstetric and neonatal complications.

Background: Long-term outcomes for women with Fontan repairs have improved, meaning more women will embark upon pregnancy. Counseling women remains challenging, as pregnancies are relatively uncommon. Recent reports suggest favourable maternal outcomes but poorer fetal and neonatal outcomes. Purpose: To evaluate fetal, neonatal and maternal outcome in women with Fontan physiology Methods: A retrospective multicentre study of pregnancy in women with a Fontan circulation between 2000-2016.All identified pregnancies were reviewed, including those resulting in miscarriage or termination, as well as live births. Results: 45 women had 112 pregnancies resulting in one termination, 63 miscarriages (54-1st trimester, 9 2nd trimester),49 livebirths and one intra-uterine death at 30 weeks gestation. Age at first pregnancy was 28 [range 21-34] years and gestation of delivery was 33 [range [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] weeks. 68% of babies were born before 37 weeks; two thirds of these as a result of medical intervention due to concerns regarding fetal wellbeing. Median birth weight centile (corrected for sex and birth order) was nine. Women with ventricular impairment had babies with lower birth weight (p=0.045, two sided t test). Maternal saturations and booking haemoglobin were not associated with birthweight, however all 8 women (100%) with baseline oxygen saturations <85% miscarried, compared with 49 of 105 (47%) with baseline saturations at or above 85% (p=0.006 Fisher's exact test). There were three neonatal deaths (all preterm). There were no cases of fetal congenital heart disease. Blood loss was lowest with spontaneous vaginal birth (median 400ml, 30% Post Partum Hemorrhage (PPH)) and elective caesarean section (CS) (median 600ml, PPH 20%) followed by emergency CS (median 775ml, PPH 28%) and assisted delivery (median 900ml, PPH 82%) (PPH defined as ≥500ml vaginal delivery and ≥1000ml caesarean section (p=0.01, Pearson Chi square). On linear regression including maternal age, height, weight, smoking, NYHA class, mode of delivery and use of aspirin and low molecular weight heparin, the only significant additional correlation with estimated blood loss was prior use of warfarin (p=0.035). Maternal morbidity was low; 7 women required diuretics during pregnancy for symptoms of heart failure, 6 had episodes of arrhythmia (4 atrial arrhythmia, 2 episodes SVT (one patient both pregnancies) and one woman suffered a post natal venous thromboembolism (poor compliance LMWH). There was no maternal mortality. Median follow up was 4.5 years (range 6 months-11 years) years; no women had increased NHYA class at follow up review. Conclusions: Rates of fetal and neonatal complications are high in Fontan pregnancies and this is substantiated by our findings. Maternal health is well maintained during and early after pregnancy when women are managed in specialist obstetric cardiac services. It is unknown whether pregnancy accelerates failure of Fontan physiology over longer term. Background/Introduction...