Use of menopausal hormone therapy and risk of fractures

During menopause, all women experience a drop in their hormone levels. One of these, oestrogen, is key to the physiology of the whole body. For many women the drop in oestrogen level causes a range of unpleasant mental and physical side effects, which may require the use of menopausal hormone therapy (MHT) [commonly also referred to as hormone replacement therapy (HRT)]

Oestrogen deficiency also aggravates the change in bone structure, osteoporosis, which is related to age and particularly found in older women. Statistics show that, after the age of 50, every second woman will experience a bone fracture – a burden both for the women affected and for society. Many past studies have confirmed the protective role with respect to fractures of the oestrogen component found in all MHT treatments, and current use of MHT is known to decrease the rate of fractures. Details about any differences in effect between the full range of the most common treatments is, however, still lacking.

MHT is also associated with some serious side-effects, including increased risk of developing breast cancer and blood clots. In particular, long-term exposure to HRT among older women is not recommended, so, for women using HRT either partly or wholly to counteract increasing bone fragility, it is important to know how long the protective effects of their treatment may last after stopping treatment. Information from previous studies on this aspect is both partial (not covering many HRT treatments) and, in some cases, conflicting.

This study, therefore, proposes to produce detailed information on how levels of risk of fractures are reduced for specific hormonal combinations – facilitating in combination with known risks of deleterious side effects for specific treatments, the optimal choice of an MHT treatment. It also proposes to do a detailed study of how long the beneficial effects on fracture risk last for different treatments and the patterns of decline of effectiveness. This will further help women and their doctors to improve the safety of MHT treatment for countering osteoporosis and reducing the risk of fractures.

The proposed study is a nested case-control study using both components of the UK primary care database, CPRD, to examine the associations between HRT treatments and the risk of bone fracture, during and after treatment. The study will compare use of HRT between fracture cases and matched controls. We will adjust findings using all available data for potential confounding variables, assess the associations relating to cumulative dosages and durations of treatment, and stratify the analysis to examine whether risks differ according to the age at which treatment was started.

Amount Awarded: £24,513