Fallout from JAMA's HRT study continuing to land in MDs' offices

Barbara Sibbald

Physicians' offices were deluged with calls in July after results from a study involving the use of estrogen plus progestin hormone replacement therapy (HRT) were released early (JAMA 2002;288(3):321-33). Weeks later, doctors were still trying to figure out what findings from the Women's Health Initiative (WHI) trial actually mean.

Figure. Healthy aging post-HRT? Photo by: Health Canada

Dr. Morrie Gelfand, president of the North American Menopause Society (NAMS), says media coverage alarmed many women. “There was lots of sensationalism,” says Gelfand, who practises at Montreal's Jewish General Hospital. “Numbers can be used to make anything sound good or bad. We're talking 10 000 women-years here. What about the decrease in fractures and colorectal cancer rates? What does it really mean?”

NAMS (www.menopause.org/) has selected 10 experts to assess the study; findings will be released in October.

The trial, which involved 16 608 women aged 50 to 79, was stopped because preliminary results showed statistically significant increases in coronary disease, invasive breast cancer, stroke and pulmonary embolism in women being treated with estrogen plus progestin. The WHI trial, which was supposed to end in 2005, was designed to examine HRT's effect on the prevention of heart disease and hip fractures, and any associated change in risk for breast and colon cancer. The researchers concluded that “overall health risks exceeded benefits.”

The 8506 women treated with estrogen plus progestin had about 40 more coronary events, 40 more strokes, 80 more episodes of venous thromboembolism and 40 more instances of invasive breast cancer than the 8102 women assigned to the trial's placebo arm. However, Dr. Jennifer Blake, spokesperson for the Society of Obstetricians and Gynaecologists of Canada (SOGC), says data provided in the JAMA study are “small numbers among 16 000 women. The relative risk [of breast cancer because of this treatment] is the same as when a woman has her first baby after 35.”

The SOGC initially cautioned women not to overreact and said that the study assessed only one product (Prempro, which isn't available in Canada) and didn't necessarily apply to other products. Blake says the society is now “seriously” assessing the study's implications and may modify its guidelines.

Blake agrees that the study is “going to affect how we use HRT. It's thrown a spotlight on the use of progestin.”

Dr. Wulf Utian, executive director at NAMS, used more dramatic language: “This is the biggest bombshell to hit in my 30-some years in the menopause area.” — Barbara Sibbald, CMAJ

CMAJ

Yusuf S, Anand S. Hormone replacement therapy: a time for pause. p. 357.
Day A. Lessons from the Women's Health Initiative: primary prevention and gender health. p. 361.
Sackett DL. The arrogance of preventive medicine. p. 363.
Farquhar D. Postmenopausal hormone replacement therapy for chronic disease prevention: results from the Women's Health Initiative trial. p. 377.