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The regular use of statins, particularly among women, was associated with an increased risk of thyroid cancer, Taiwanese researchers reported.

Compared with controls, patients who routinely used statins had an adjusted odds ratio for having thyroid cancer of 1.40 (95% CI 1.05-1.86, P<0.05), according to Shiu-Dong Chung, MD, of Far Eastern Memorial Hospital in New Taipei City, and colleagues.

And among women, the adjusted OR was 1.43 (95% CI 1.07-1.90, P<0.05), the researchers reported online in

Interest has increased recently about the possibility that the benefits of statin therapy may go beyond cholesterol lowering.

"Several observational studies raised the possibility that the use of statins may decrease the overall risk of cancer and of specific cancers," including colorectal, breast, and prostate cancers, the researchers observed.

However, no data are available for the possible effects on thyroid cancer. Hung's group identified 500 patients, ages 40 and older, in the Taiwan National Health Insurance program who had been diagnosed with a malignant neoplasm of the thyroid gland between 2008 and 2011, matching them with 2,500 controls.

Patients' mean age was 56, and more than two-thirds were women.

The researchers first considered a possible effect of prior hyperlipidemia on thyroid cancer risk, and found that among cases, the OR was 1.30 (95% CI 1.03-1.65, P<0.05).

After adjusting for hyperlipidemia, they then looked at regular versus nonroutine use, and whether gender was an influential factor.

Unlike with regular statin use, patients who had taken the drugs only intermittently or had not been given continuous prescriptions for 2 months or more in the 6 months before enrollment had no increased risk for thyroid cancer (OR 1.35, 95% CI 0.88-2.07).

In addition, unlike for women, men had no increased risk (OR 1.28, 95% CI 0.75-2.17).

When a possible link between statin treatment and risk of cancer first emerged 10 years ago, considerable controversy erupted. identified a 28% decreased risk for any cancer over a median of 2.7 years among individuals taking statins compared with those treated with bile acid binding resins, but other studies suggested an increased risk or

"The molecular mechanisms for statins affecting the carcinogenesis process originate from HMG-CoA reductase inhibition-related growth-suppressing properties," Hung and colleagues explained.

Among these mechanisms are suppression of cancer cell growth, increased apoptosis, and proteasome inhibition.

In vitro studies also have shown that these inhibitory effects are less pronounced when estradiol is present, and thyroid function and cancer development have been reported to be associated with estrogen. In addition, disturbances of the hormone's metabolism have been seen in patients with thyroid cancer.

"It is possible that in female subjects, the cancer-protective effects of statins are neutralized due to relatively higher estrogen levels than in males," the researchers suggested.

However, the national database contained no information about menopause or hormone replacement therapy, so "this hypothesis remained unproven," they conceded.

They also pointed out several limitations to the study, including a lack of information about thyroid cancer subtypes and body mass index, possible surveillance bias, and the difficulties associated with establishing the duration and regularity of statin use.

Nonetheless, "our present data suggest that regular statin use is associated with thyroid cancer in female patients," Hung and colleagues concluded.

"We recommend that physicians be more alert in managing patients under regular statin use, as this popular therapy might potentially contribute to more problems than previously thought," they advised.

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