Women who use hormone replacement therapy combining estrogen and progestin may have a higher risk of lung cancer than non-users, a new study finds.

Whether hormone replacement therapy (HRT) itself is to blame is not certain, researchers say. But the findings add to the complicated mix of potential health effects of HRT.

The study, published in the Journal of Clinical Oncology, looked at new lung cancer diagnoses among more than 36,000 women ages 50 to 75 who were followed over six years. During that time, 344 women developed the cancer.

Overall, researchers found, the risk was greater among women who had used HRT containing estrogen and progestin (a synthetic version of the hormone progesterone) compared with women who had never used HRT.

The link was strongest among women who had used combination HRT for 10 years or more; compared with non-users, they were almost 50 percent more likely to be diagnosed with lung cancer, even with factors like age and smoking history considered.

Among women who had used the hormones for one to 9 years, the increased risk of lung cancer was not significant in statistical terms.

The vast majority of HRT users did not develop lung cancer during the study period. Of the more than 4,300 women who had used combination HRT for a decade or longer, 54 were diagnosed with the cancer.

“This study doesn’t prove that HRT causes lung cancer,” lead researcher Dr. Christopher G. Slatore, of the Oregon Health and Sciences University in Portland, told Reuters Health in an email.

“But it does say that after adjusting for other factors associated with lung cancer and HRT use, users of (estrogen-plus-progestin) HRT for longer than 10 years had a higher risk of lung cancer.”

The study found no link between estrogen-only HRT and lung cancer risk.

Millions of women stopped using HRT after a large U.S. government study in 2002 found that postmenopausal women given estrogen-plus-progestin had higher risks of heart attack, stroke, breast cancer and blood clots than women given a placebo.

HRT has positive effects as well. It remains the most effective therapy for menopausal symptoms like severe hot flashes and night sweats; some alternatives, such as soy supplements, the herb black cohosh and acupuncture, have been studied, but with mixed results. HRT has also been shown to preserve women’s bone mass, and some studies have linked it to a decreased risk of colon cancer.

Given the list of risks, however, experts now advise that when women use HRT for menopausal symptoms, they should take it at the lowest dose and for the shortest time possible.

When it comes to lung cancer and HRT, past studies have come to conflicting conclusions. This latest study sheds more light on the question, according to Slatore, because it looked at HRT use over a long period, showing a stronger association between lung cancer and long-term use.

The bottom line, the researcher said, is that women considering HRT should be aware of the lung cancer-HRT link - particularly if they have a history of smoking.

“And since we don’t know a ‘safe’ length of time to use HRT,” Slatore said, “I’d recommend using it for as short of time as necessary to control (menopausal) symptoms.”

It is not entirely clear why HRT would contribute to lung cancer. Lung cancer tumors do have receptors for estrogen and progesterone, Slatore and his colleagues point out, and lab research has shown that estrogen can promote growth in lung cancer cells, while anti-estrogen compounds block that growth.

More studies are needed to understand the potential biological mechanisms, the researchers say. One question is why combination HRT, but not estrogen alone, would be linked to a higher lung cancer risk.

SOURCE: Journal of Clinical Oncology, online February 16, 2010.