13–16 Oestrogen therapy reduces coronary stenosis, HDAC inhibitor as documented by a repeat coronary angiogram.14,15 Oestrogen treatment also improves survival after coronary bypass surgery.17 Women with risk factors for CVD, such as smoking, hypertension or history of myocardial infarction, seem to be those who have the most to gain from HRT.10 Oestrogen therapy reduces serum total and LDL cholesterol.18,19 However, the Heart

and Estrogen/progestin Replacement Study (HERS) randomised control trial ultimately showed no benefit of oestrogen and progesterone in the secondary prevention of CHD.20 Moreover, the Women’s Health Initiative (WHI) study was terminated early based on increased risk of: Breast cancer (from 30 to 38 cases per 10 000 women). CHD (from 30 to 37 cases per 10 000). Stroke (from 21 to 29 cases per 10 000 women).21 The Million Women Study (MWS) also revealed an increased risk of breast cancer, with current HRT users more likely to develop it than past users and, moreover, an increased

risk of both incident and fatal ovarian cancer.22,23 Both of these studies were arguably flawed, with a large number of women randomised who were either obese, smokers or over 60 years of age (or all three), such that they would have been unlikely to have been offered HRT in normal clinical practice. Nevertheless, these studies serve to demonstrate the power of large Protein Tyrosine Kinase inhibitor RCTs over even the best case-controlled association studies. The Committee on Safety of Medicines subsequently recommended that: ‘HRT should not be used to prevent coronary artery disease. For menopausal symptoms or osteoporosis it is important Mannose-binding protein-associated serine protease for women to discuss risks and benefits of HRT with their GP. Thus, although the data on testosterone deficiency and the potential benefits of replacement therapy in men with obesity and/or type 2 diabetes are fascinating (and, incidentally, comparable in quality and scope to that for vitamin D – e.g. higher vitamin D status is associated with decreased

risk of type 2 diabetes),24 it would be inadvisable to recapitulate the over-enthusiastic appraisals of postmenopausal female HRT that were promoted prior to the MWS and WHI era.25 Until we have large studies available to change our practice, the primary focus for reducing mortality and morbidity in type 2 diabetic men must necessarily lie with reducing their HbA1c, blood pressure, lipids and weight. Fred Wu and colleagues26 studied 3369 men from the general population between the ages of 40 and 79 years in eight European centres, analysing cross-sectional data from questionnaires and a single serum testosterone measurement. The aim of the study was to examine the potential clinical symptoms associated with a low testosterone level, to identify the thresholds of testosterone below which such symptoms become increasingly prevalent, and to define essential criteria for the syndrome of late-onset hypogonadism on the basis of the presence of symptoms associated with a low testosterone level.