By Frances Morin

BOSTON  April 6, 2016

Women treated with high-dose radioiodine (RAI) therapy for differentiated thyroid cancer (DTC) show reductions in ovarian reserves, measured by anti-Müllerian hormone (AMH) blood levels, and potentially have reduced fertility, according to a study presented here at the 98th Annual Meeting of the Endocrine Society (ENDO).

“This is the first study to prospectively address the impact of RAI treatment on ovarian reserve,” said Karen Tordjman, MD, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, on April 2.

To assess the effect of RAI on ovarian reserve, Dr. Tordjman and colleagues enrolled 30 premenopausal women (mean age, 33 years) who were scheduled to undergo RAI treatment for the first time after DTC surgery.

The women all had regular menses before treatment, and 19 had borne children.

Of 23 women with AJCC (American Joint Committee on Cancer) stage 1 cancer that was treated with a mean dose of 110.7 ± 9.9 mCi (range, 30 to 150 mCi), the researchers analysed 18 who were reevaluated after treatment.

The women had baseline AMH levels of 3.43 ± 0.65 ng/ml. At 3 months after the initial RAI treatment, the women exhibited a 45% decrease in AMH levels (1.9 ± 0.4 ng/mL; P = .001). Although the levels improved soon afterward, they remained significantly lower than those at baseline at 6 months (2.4 ± 0.5 ng/mL), 9 months (2.6 ± 0.6 ng/mL), and 12 months (2.8 ± 0.6 ng/mL).

Although a dose effect could not be determined because all subjects received high doses of RAI of 100 and 150 mCi, the researchers further compared 4 patients who received ablative doses of 30 mCi for DTC with 5 women who were treated with RAI for Grave’s disease with lower doses, ranging from 10 to 22 mCi.

Among the 9 patients, baseline AMH levels were 2.5 ± 0.7 ng/mL and showed no significant changes after treatment, with levels of 2.4 ± 0.8 ng/mL at 3 months, 2.5 ± 0.8 ng/mL at 6 months, 3.0 ± 1.0 ng/mL at 9 months, and 2.6 ± 0.8 ng/mL at 12 months.

The findings underscore that “large doses of RAI given as adjunct therapy to women with DTC appear to impair ovarian reserve as assessed by AMH levels, (and) a nadir for this effect is seen 3 months after treatment, but there is no complete recovery even after a year,” stated the researchers. “In contrast, lower doses of up to 30 mCi, such as those given for ablation of thyroid remnant of for hyperthyroidism, appear to be innocuous.”

Whether this effect translates in decreased fertility was outside the scope of the study, according to the researchers, but these data add weight to the precautions currently advocated in regard to RAI therapy in low-risk patients with DTC.

Dr. Tordjman cautioned that the findings have important implications in terms of cancer treatment choices.

“In our day and age, when growing numbers of women of reproductive age are diagnosed with thyroid cancer and when fertility problems are rampant, these findings should serve as an additional consideration for physicians contemplating RAI for their patients,” she concluded.