WHI and beyond: controversies in HRT

Many women have abandoned hormone therapy (HT) following concern over the findings of increased risk of cancers and heart disease in the Women's Health Initiative and Million Women studies.

The AMS provides here links to the original publications plus some later studies which pose important caveats to the WHI findings.

Issues which doctors and women considering HT should consider include:

• Randomised controlled trials provide the highest level evidence, and evidence of association between HT and disease from observational trials does not prove causation.
• Absolute risk, as well as relative risk, should be considered when weighing risks and benefits for individual women.
• Tailoring HT to the individual can maximise its benefits and minimise its risks.
• Re-analysis of the WHI findings on HT and breast cancer show no increase in breast cancer for oestrogen-only therapy and no significant increase with combined therapy in the first seven years of use in women who had previously not taken HT.
• The International Menopause Society states that for women aged 50 to 59 years, HT remains first line treatment for menopausal symptoms.

The Women's Health Initiative study:

Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women.

JAMA 2002; 288:321-333

The HERS II study:

Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD.

JAMA 2002; 288:49-57

The Million Women study:

Current use of HRT is associated with an increased risk of incident and fatal breast cancer; the effect is substantially greater for oestrogen-progestagen combinations than for other types of HRT.

Lancet  2003; 362:419-427

The following commentaries and reviews may be useful:

• IMS: HRT in the Early Menopause. 
• The benefits of oestrogen following menopause: why hormone replacement therapy should be offered to postmenopausal women. MJA 2009; 190 (6): 321-325
• Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society.
• Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer. J Clin Oncol 2008;26(8):1260-68
• Progestins in hormone replacement therapies reactivate cancer stem cells in women with pre-existing breast cancers: a hypothesis. The Journal of Clinical Endocrinology and Metabolism 2008;93:3295-98
• Combined postmenopausal hormone therapy and cardiovascular disease: toward resolving the discrepancy between observational studies and the Women's Health Initiative Clinical Trial. American Journal of Epidemiology 2005; 162(5):404-414

Content updated 15 June 2009