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Hormone replacement therapy and the risk of thrombosis
What are the effects of hormone replacement therapy (HRT) on the risk of developing a harmful blood clot?

Introduction
What effect does HRT have on the development of blood clots?
Do other factors affect the risk of blood clots associated with HRT?
Should certain women therefore avoid HRT?
Summary

Introduction

The menopause marks the end of a woman's reproductive years, as her ovaries produce less and less of the hormones estrogen and progestogen, and her periods eventually stop. In most women it occurs naturally, usually in their 40s or 50s, but it can also be caused by certain surgical or medical treatments that affect the ovaries. In many women, these reduced hormone levels cause menopausal symptoms such as hot flashes, night sweats, vaginal dryness, depression, and tiredness. Hormone replacement therapy (HRT), as its name suggests, provides hormones to replace those no longer produced by the body, in order to relieve menopausal symptoms. HRT comes in 2 main types: estrogen-only therapy, and combined therapy containing both estrogen and progestogen.

This article describes how taking HRT may increase the risk of developing blood clots (thrombosis). Please note that whether or not HRT is suitable for you will depend on many factors, and not solely on the risks of thrombosis. Your physician is best placed to consider, and discuss with you, all of the risks and benefits of HRT for you as an individual. In October 2004, the American College of Obstetricians and Gynecologists (ACOG) published an updated review of the overall risks and benefits, which may prove useful as background information.

What effect does HRT have on the development of blood clots?
Evidence from clinical trials consistently shows that the risk of thrombosis is at least doubled in women taking HRT, and may be increased by up to about 3.5 times. In some of these trials, but not all, the increased risk was confined to the 1st year of use.

Remember that any increases in risk associated with HRT should be considered in the context of the background risk of developing thrombosis, which is relatively low for most women: for example, the landmark Women's Health Initiative (WHI) study of more than 16,000 women found that the incidence of thrombosis in those who were not taking HRT was about 16 cases for every 10,000 person-years. A doubling of this risk would therefore lead to 32 cases per 10,000 person-years, which remains a relatively low number and may be acceptable when all the risks and benefits for an individual are considered.

How HRT raises the risk of thrombosis is not absolutely clear. There is evidence that oral HRT (taken as tablets) leads to increased production of the thrombin, a protein that is involved in the formation of blood clots. Transdermal HRT (via a patch) appears to have less of an effect on the body's blood clotting system. One small study reported that the risk of thrombosis in women taken oral HRT was 4 times the risk of thrombosis in women taking transdermal HRT, although more extensive research is needed on the comparative benefits/risks.

The available forms of HRT vary by more than the method of delivery, of course. Different brands will contain different estrogens and/or progestogens, often at different doses. Most studies, however, tend to focus on one particular preparation: the WHI study, for example, investigated the effects of conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg daily. This raises the question of whether results can be extrapolated to other specific forms of HRT. The ACOG has considered this and singled out the large WHI study as providing "the most compelling evidence outlining the [overall] risks and benefits of hormone therapy", at least until larger and longer clinical trials of HRT preparations are conducted.

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