Oral HRT carries higher risk than low-dose patches

Hormone replacement therapy (HRT) skin patches containing low doses of estrogen carry less risk of stroke than oral therapy and may represent a safer alternative, according to a study conducted by researchers at the Lady Davis Research Institute of the Jewish General Hospital, published June 4 in the British Medical Journal.

The study assessed the risk of stroke associated with HRT in post-menopausal women in the United Kingdom using data from the General Practice Research Database (GPRD). Researchers found that low-dose patches have 26% less risk than oral forms of HRT, though the risk with patches is elevated with high doses.

For the oral form of HRT, low-dose estrogen was defined as: ≤0.625 mg of equine oestrogen or ≤2 mg of estradiol and high dose as >0.625 mg of equine oestrogen or >2 mg of estradiol.

For the patch, researchers defined low-dose estrogen as: ≤50 µg and high dose as >50 µg.

"We obtained the medical records of more than 870,000 women aged 50 to 79 years from 1987 to 2006 and found 15,710 cases with a first diagnosis of stroke occurring in these women," lead researcher Samy Suissa, PhD, James McGill Professor of Epidemiology, Biostatistics and Medicine, McGill University, and head of the Centre for Clinical Epidemiology at the Lady Davis Institute, Montreal, Quebec, Canada, told Formulary.

Dr Suissa pointed out that this is a sufficiently large study (almost 1 million women) to study the risk of stroke associated with various ways of delivering HRT. "It is also sufficiently large to evaluate the risk with lower and higher doses," he added.

Each case was matched to 59,958 controls. "The risk of stroke was not increased with use of low oestrogen dose patches compared with no use, whereas the risk was increased with high-dose patches," Dr Suissa said.

The use of oral HRT increased the rate of stroke by 25% to 30%. "Our study suggests that there are formulations of HRT that may be safer than others," he said. "This study is important because previous trials have focused on the risks associated with oral HRT formulations, never the patch."

A large, multicenter heart disease prevention study, part of the Women's Health Initiative (WHI) study, found that estrogen-alone hormone therapy had no effect on coronary heart disease risk but increased the risk of stroke for postmenopausal women.

According to Dr Suissa, the WHI was a trial of an oral HRT. "We closely replicated the findings of WHI and meta-analyses for oral agents, that reported a 30% increase in the risk of stroke, while our study found 25% to 30% increases with this formulation. Our study, however, was able to study the patch, at low and high doses, which the WHI did not and could not."

This study was funded by the Canadian Institutes of Health Research (CIHR) and the Canadian Foundation for Innovation (CFI) and in part by an unrestricted grant from Organon, a maker of HRT but not of the patch.