Postmenopausal women who received combined hormone replacement therapy with estrogen and progesterone were at an increased risk of dying from non–small cell lung cancer, according to the results of a study published in The Lancet.[1]

Hormone replacement therapy (HRT) is often prescribed for women during menopause, which is a natural phase of the female lifecycle during which the ovaries produce significantly less estrogen, ovulation ceases, and menstruation ends. For many women, menopause has uncomfortable side effects such as hot flashes, sleep disturbances, depression, mood swings, and anxiety. Additionally, menopause may also be accompanied by increased urinary tract infections, incontinence, vaginal discomfort due to a lack of estrogen-based lubrication, and decreased bone density.

HRT has been effectively used to treat the side effects of menopause. HRT can contain estrogen alone, progesterone alone, or a combination of the two hormones. Although it has been widely prescribed for menopausal women, HRT has come under scrutiny because it may be linked to increased incidence of certain types of cancer and other health problems. Combined HRT is linked with an increased risk of breast cancer, heart disease, stroke, and blood clots, but a decreased risk of colorectal cancer and fractures. Researchers continue to evaluate single-agent HRT and combined HRT to determine the risks and benefits of its use.  Risks are thought to outweigh the benefits for most women.

The Women’s Health Initiative trial was a randomized, double-blind, placebo-controlled trial that involved 16,608 postmenopausal women aged 50-79 years. The women were randomly assigned to receive placebo or combined HRT and were then followed to determine incidence and mortality rates for lung cancer.

After a treatment period of nearly six years and an additional follow up of 2.4 years, 109 women in the combined HRT group had been diagnosed with lung cancer compared with 85 in the placebo group. While the incidence rate of lung cancer was not considered statistically different between the two groups, the mortality rate was: 73 women in the HRT group died from lung cancer compared with 40 from the placebo group.

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The incidence of small cell lung cancer was similar between the two groups; however, the incidence of non–small cell lung cancer was higher in the HRT group: 96 women versus 72 in the placebo group. The researchers noted that 62 of the 73 deaths in the HRT group and 31 of the 40 deaths in the placebo group occurred in women with NSCLC.

The researchers concluded that combined HRT did not increase the incidence of lung cancer in postmenopausal women; however, it did increase the number of deaths from lung cancer and in particular, from NSCLC. Women considering treatment with HRT will want to weigh the risks against the benefits.


[1] Chlebowski RT, Schwartz AG, Wakelee H, et al. Estrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): A post-hoc analysis of a randomized controlled trial. The Lancet [early online publication]. September 20, 2009. DOI: 10.1016/S0140-6737(09)61526-9.

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