Combination HRT Linked to Lower Colon Cancer Rates Diagnosed at a Later Stage

Laurie Barclay, MD

March 03, 2004

March 3, 2004 — Women who received combination hormonal therapy had lower rates of colon cancer, but those who did develop the disease presented at a more advanced stage, according to additional data from the Women's Health Initiative (WHI) published in the March 4 issue of the New England Journal of Medicine.

"'Although the WHI trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group, the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer,"' write Rowan T. Chlebowski, MD, PhD, from Harbor–UCLA Research and Education Institute in Torrance, California, and colleagues from the WHI Investigators.

In the WHI trial, 16,608 postmenopausal women, aged 50 to 79 years with an intact uterus, were randomized to a combination of conjugated equine estrogens (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) or placebo. Invasive colorectal cancers developed in 43 women in the hormone therapy group and in 72 women in the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.38 - 0.81; P = .003).

Compared with invasive colorectal cancers in the placebo group, those in the hormone therapy group had similar histologic features and grade, but more positive lymph nodes (mean, 3.2 ± 4.1 vs. 0.8 ± 1.7; P = .002) and more advanced regional or metastatic disease (76.2% vs. 48.5%; P = .004). Women in the hormone therapy group with vaginal bleeding before development of colorectal cancer had a greater number of positive nodes than those who did not have vaginal bleeding (3.8 ± 4.3 vs. 0.7 ± 1.5 nodes; P = .006).

"'Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer,"' the authors write. "'However, colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo."'

The authors cannot explain these differences on the basis of a single hormonal effect. Screening frequency was similar in both groups. Most of the difference between the two groups arose from a difference in the risk of localized disease. This difference first became apparent early in the initial follow-up year, suggesting an effect on established cancers.

Based on their findings, the authors recommend wider implementation of bowel screening among postmenopausal women using hormone therapy, and they conclude that current data are insufficient to support the use of estrogen plus progestin to reduce the risk of colorectal cancer in any population.

"'The effects of estrogen plus progestin on breast and colorectal cancer suggest that the use of these hormones can delay the diagnosis of two of the three most common cancers in postmenopausal women,"' the authors write. "'Such findings should be part of the discussion of risks and benefits when combined postmenopausal hormone therapy is being considered."'

The National Heart, Lung, and Blood Institute and the Department of Health and Human Services supported this study. Wyeth-Ayerst supplied the active study drug and placebo.

N Engl J Med. 2004;350:991-1004

Reviewed by Gary D. Vogin, MD

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