Impact of low testosterone on cardiac structure/function in aging

Heart disease increases with age in men and women as sex hormone levels fall. Since a women's risk of heart disease goes up after menopause, there has been a lot of interest in the idea that estrogen influences heart disease. However, it is now clear that testosterone decreases with age not only during "manopause" in men, but in women too. Marketing campaigns focused on the benefits of testosterone have led to an increase in the use of testosterone supplements in older people. This is important, because low testosterone increases the risk of diseases like heart failure, where the heart cannot pump blood very well, but high testosterone can be harmful too. We discovered that age decreases the ability of male hearts to contract by changing the ability of heart cells to regulate internal calcium. To mimic low testosterone in aging, we removed the testes from male mice. We found that low testosterone upsets the ability of heart cells to contract and regulate calcium, just like the effects of age. Some calcium is needed for the heart to contract, but the balance needs to be right. When calcium is disrupted it can lead to diseases like heart failure. There is still a great deal more to know about how testosterone affects the heart. We plan to look at how long term exposure to low testosterone changes contraction in whole hearts and affects contractions and calcium levels in individual heart cells in males and females. We will start to look at effects in middle age (1 year old mice) and follow them until they reach 2 years of age, which is about 85 human years. We will also treat male and female mice with testosterone to find out if testosterone therapy is beneficial or harmful and if this depends on the dose used. This research project will help us understand the links between testosterone, aging and heart disease. It will help us recognize whether testosterone supplementation is good or bad in vulnerable older people with heart diseases.