At its meeting of 11 September 2002, the New Zealand Medicines Adverse Reactions Committee (MARC) reviewed studies examining the safety of hormone replacement therapy (HRT). On completion of its review, the MARC concluded that HRT provides a number of benefits with respect to control of symptoms associated with estrogen deficiency, such as flushing and night sweats, and in preventing loss of bone density. However, for most women, the risks associated with long-term use of HRT outweigh the benefits. These risks include:

• An immediate increase in the risk of venous thromboembolism (VTE) for all HRT products containing estrogen. The increase in relative risk seen for all forms of HRT is of a similar size to that seen for oral contraceptive pills. Given that the baseline risk of VTE increases with age, the absolute risk is larger than for oral contraceptives.

• An increase in the risk of stroke that becomes statistically significant beyond 2-3 years use of combined HRT.

• An increase in the risk of developing breast cancer that becomes evident following prolonged use (more than 4-5 years). While the increase in risk is small, it has been confirmed by several studies and applies to all forms of HRT. There is insufficient information available to determine how long the increased risk of breast cancer persists after cessation of HRT.

• A possible increase in the risk of coronary heart disease. The data clearly indicate that despite evidence of HRT lowering cholesterol levels in treated patients, use of combined HRT neither prevents nor inhibits the further progression of coronary heart disease. The MARC considered that the totality of research indicates that combined HRT may possibly increase the risk of developing coronary heart disease.

In the opinion of the MARC, the increased risk of breast cancer and stroke means that the benefit/risk ratio for combined HRT products becomes unacceptable for most women after about 3 to 4 years duration of use.

To improve the safe use of HRT, the MARC recommends that:

• HRT should normally be used only where menopausal symptoms are disruptive to the quality of life of the woman;

• HRT should not be used for the primary or secondary prevention of coronary heart disease or stroke;

• In most circumstances, the risks of long term treatment outweigh the benefits; and combined HRT generally should not be used for longer than 3-4 years;

• Estrogen-only HRT increases the risk of breast cancer and venous thromboembolism to a similar extent as combined HRT;

• All prospective and current users of HRT should be advised of the risks and benefits of estrogen and progestogens;

• The need for continued treatment with HRT should be reviewed at the woman's next visit to her general practitioner and thereafter on a yearly basis.

Reference: Prescriber Update, 23(3):30-34 (2002;) http://www.medsafe.gov.nz