HRT is prescribed either in the form of oestrogen alone (unopposed oestrogen) or as oestrogen combined with synthetic progesterone or progestogen (combined HRT). While oestrogen on its own is effective in controlling menopausal symptoms and preventing osteoporosis, it is rarely used in women who have not had a hysterectomy. This is because it has been associated with an eight to ten- fold increase in the development of endometrial cancer (3). The addition of a progestogen opposes the effects of oestrogen on the endometrium. This reduces the risk and currrently this makes combined oestrogen/progestogen preparations appropriate for the majority of women. For women who have had a hysterectomy, oestrogen-alone HRT can be prescribed.
Randomised data on the risks and benefits of oestrogen-only HRT preparations compared with placebo have come from the oestrogen-only arm of the WHI study, the results of which have been recently published (35).
Combined HRT preparations vary according to the type and relative doses of oestrogen and progestogen. It can be delivered by oral, transdermal, nasal or vaginal routes or by subcutaneous implants. Also, combined preparations can be designed to deliver the two hormones in an intermittent, sequential, or continuous manner. The term ‘sequential HRT’ refers to oestrogen given in a continuous manner with progestogen added in for 12–14 days of each cycle. Continuous combined oestrogen and progestogen therapy delivers both drugs throughout each day of the cycle.
The available randomised data on the effects of combined HRT have come from studies investigating use of oral preparations containing 0.625mg of conjugated equine oestrogens with 2.5mg of medroxyprogesterone acetate (1, 5). There is debate over whether these results can be applied to other combined HRT preparations. In particular it has been suggested that the transdermal route may have quite different effects on the cardiovascular system compared with the oral route (6).
Five recently published randomised clinical trials have informed us about the potential risks and benefits of HRT. The results of these studies are discussed in detail below. They have confirmed that HRT is associated with increases in risk of heart attack, stroke and blood clots and do not confirm the previously perceived reduction in heart disease to women (1,5,7,8, 35).
There is clear evidence that combined HRT increases breast cancer risk. However, the randomised trial studying oestrogen only HRT showed no evidence of increased breast cancer risk for at least seven years.