Study summary

This observational study, published online in the European Heart Journal on 1 October 2008, looks at the effects of HRT post the Women's Health Initiative trial. The research followed 698,098 healthy Danish women, aged 51-69, between 1995-2001.

The study found that overall there was no increased risk of heart attacks in current users of HRT compared to women who had never taken it.

Explaining the findings

Heart attack findings for all women in the study

Increase in heart attack rate 

Untreated - the study also found that for the entire group of women in the study aged 50 to 69, the untreated heart attack rate was 17.3 per 10,000 women per year and the continuous combined oestrogen and progesterone rate was 20.7 per 10,000 per year - an absolute increase in risk of 3.4 per 10,000 women per year (approximately 1 in 3,000 absolute increase).  

Decrease in heart attack rate

Tibolone - the Tibolone-treated rate is 12 women per 10,000 per year - an absolute decrease in risk of 5 per 10,000 women per year, or a 29% decrease.

Dermal - the dermal-treated rate is 7.7 women per 10,000 per year -  an absolute decrease in risk of 9.6 per 10,000 women per year, or a 55.5% decrease.

Vaginal - the vaginal-treated rate is 10 women per 10,000 per year - an absolute decrease in risk of 7.3 per 10,000 women per year, or a 42% decrease.

Heart attack findings for younger women aged 51-54

The study did find that in younger women (aged 51-54) who were taking HRT during the period of the study, their risk of heart attacks increased from 6 per 10,000 women on no treatment to 8 per 10,000 women on HRT - an absolute increase of risk of 1 in 5,000 per year.

Comment from Professor Henry Burger AO

Director of the Jean Hailes Foundation for Women's Health

The largest previous observational study of the effects of HRT on CVD risk was the American Nurses Health Study, which demonstrated a 30-50 per cent decrease in CVD risk for nurses initiating HRT around the time of menopause, and mostly taking oestrogen alone.

The current large observational study has also reported protective effects of some forms of HRT. Of interest was the reduction in heart disease risk in women taking Tibolone or non-oral forms of oestrogen.

It reports the somewhat unusual finding of a very small increase in heart attack in current users of combined continuous HRT aged 51-54 in Denmark. The absolute risk is 1 in 5,000 per year, meaning that the risk remains very low. It should be noted that the investigators had no information on the menopausal status of the women not on HRT, many of whom may still have been premenopausal. This may have led to a falsely high estimate of risk in the treated women.

Content Updated October 2, 2008

Is tibolone (Livial) associated with an increased risk of breast cancer?

Comments from: Professor Henry Burger AO, MD, FRACP, FCP, FRCP (London), FRCOG, FRANZCOG, FAA
Director and Consultant Endocrinologist, The Jean Hailes Foundation for Women's Health, and Emeritus Director, Prince Henry's Institute of Medical Research.

Tibolone (Livial) is not associated with an increased risk of breast cancer. The most recent data is from the LIFT trial¹, showing a decreased risk (HR 0.32) in a RCT (randomised controlled trial) where the dose was half of that conventionally used, 1.25 mg daily. There is a large case-control study from the UK general practice research database² where there was no increase in risk (HR 0.86). The data suggesting an increased risk in the Million Women Study³ is almost certainly due to selection bias.

The other recent data, presented in Madrid at the International Menopause Society (IMS) meeting in May 2008, is from the LIBERATE trial, a RCT of tibolone versus placebo in women who were symptomatic after breast cancer treatment. After three years, there was a significant increase in risk of recurrence in those treated with tibolone. In the placebo arm the risk was 10.7 per cent and in the tibolone arm, 15.2 per cent. It was concluded that a history of breast cancer should remain as a contraindication for the use of tibolone. It could be hypothesised that the tibolone may have impaired the risk reducing effects of the adjuvant therapy which many of the women were receiving.

References

1. Cummings SR, Ettinger B, Delmas PD, et al. for the LIFT Trial investigators. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359:697–708 (http://content.nejm.org/cgi/content/abstract/359/7/697) 

2.  Opatrny L, Dell'Aniello S, Assouline S, Suissa S. Hormone replacement therapy use and variations in the risk of breast cancer. BJOG. 2008 Jan;115(2):169-75 (http://www3.interscience.wiley.com/journal/119421258/abstract)

3. Breast Cancer and hormone-replacement therapy in the Million Women Study, Lancet 2003; 362419-427

Content Updated August 22, 2008

Comments from researchers at the Jean Hailes Foundation for Women's Health

Introduction

The Foundation strongly advocates that women and health professionals take a balanced, evidence-based and informed approach to health. All risks and benefits should be taken into perspective when considering the use of HRT for menopausal symptom relief.

For example, having more than two standard drinks per day, being overweight or obese, having your first child over the age of 35 or going into menopause at a later age are higher risk factors for breast cancer than taking HRT.

January 9, 2008

The U.S. Food and Drug Administration (FDA) announced that it has begun enforcement action against compounding pharmacies making false and misleading claims about the safety and efficacy of 'bioidentical hormones'.