Women who are very obese and go through early menopause may have a substantially elevated risk of endometrial cancer, a new study suggests.

Endometrial cancer arises in the endometrium, the lining of the uterus, and various factors related to women’s hormone production - such as timing of menopause, number of pregnancies and body weight - have been linked to the risk of developing the disease.

These latest findings, from a study of 3,600 U.S. women ages 20 to 54, confirm the relationship between obesity and higher endometrial cancer risk.

But they also suggest that the timing of menopause is key in that relationship, according to the researchers, led by Cheryll C. Thomas of the U.S. Centers for Disease Control and Prevention.

They found that among women who had had their last menstrual period before age 45 and a body mass index (BMI) of at least 35 (obese=30) were nearly 22 times more likely to develop endometrial cancer than normal-weight women.

Of women who reached menopause later, very obese women had a roughly four-fold greater risk of the cancer.

Women who were less severely overweight also had a higher endometrial cancer risk than normal-weight women, regardless of when they entered menopause, Thomas and her colleagues report in the journal Obstetrics & Gynecology

The reasons for the interplay between high BMI and earlier menopause are not clear. While obesity has often been tied to a higher risk of endometrial cancer, earlier menopause has typically been linked to a lower risk.

Both factors are thought to affect endometrial cancer risk via estrogen; earlier menopause limits a woman’s lifetime exposure to estrogen, possibly lowering her risk of the cancer. Obesity, in contrast, may increase a woman’s risk because excess fat tissue can raise estrogen levels.

It’s possible, according to Thomas and her colleagues, that obese women with an earlier menopause were more likely to have irregularities in their menstrual cycles throughout life. And that, they note, could indicate hormonal irregularities that may affect endometrial cancer risk.

Whatever the reasons for the findings, the high cancer risk linked to obesity “underscores the need for clinicians to counsel young women on the benefits of maintaining or achieving a normal weight throughout childbearing years and before entering menopause,” the researchers conclude.

SOURCE: Obstetrics & Gynecology, July 2009.