Abstract
We read with interest the study by Evranos et al. (1), which described the effect of radioactive iodine (RAI), given as part of the treatment for differentiated thyroid cancer, on ovarian reserve of premenopausal women as reflected by the serum levels of anti-Müllerian hormone (AMH). We were very pleased to see our own results so precisely validated (2). Although both study protocols were almost identical, there were slight differences between the two studies. Our cohort of cancer patients was slightly smaller (n = 24 vs. 33), the women in the study by Evranos et al. were somewhat younger than those in ours (31.15 ± 4.8 years vs. 34.3 ± 7.8 years; p = 0.052), and, most importantly, all of the subjects in the study by Evranos et al. received RAI activities ranging from 75 to 150 mCi, whereas 25% of our subjects received activities between 30 and 50 mCi. This notwithstanding, the basal AMH concentrations were identical, with 3.25 ng/mL in both studies. The degree of decline observed at three months in the study by Evranos et al. was even more pronounced (∼70%) than the one we had witnessed (42%). Although we had seen a trend for recovery at subsequent time points, the data from the study by Evranos et al. do not indicate a recovery of AMH from the radiation injury to the ovaries. While it is possible that we missed a dose effect in our study due to the rather limited sample size and wide spectrum of activities, the more pronounced AMH reduction and lack of recovery in the study by Evranos et al. could be due to the higher RAI activity used in their subjects. We were therefore surprised to see that this effect was not accompanied by a concomitant rise in gonadotropins. We had not included these data in our study, as we could not be completely confident that all the samples had been taken in the early follicular stage of the menstrual cycle, and some data were missing. However, we did observe a rise in both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) at three and six months following RAI therapy, with a return to baseline levels by one year, thus paralleling the partial AMH recovery. Indeed FSH, was 8.9 ± 2.2 mIU/mL at baseline and went up to 23.9 ± 12.8 mIU/mL and 27.6 ± 20 mIU/mL at three and six months, respectively, while LH went from 11.9 ± 3.4 mIU/mL to 20.9 ± 8.9 mIU/mL and 21.7 ± 16.4 mIU/L. After one year, the gonadotropin levels were back close to their baseline values.
Temporary amenorrhea after RAI has long been recognized (3). We were therefore intrigued that Evranos et al. did not report on such an observation. Of note, in their 2005 study of 50 women, Souza Rosario et al. showed a significant, albeit reversible, increase of FSH six months after RAI, while 20% of their patients experienced amenorrhea for up to six months after 100–150 mCi RAI (4). Although we recognize that seemingly normal ovarian function and fertility are the rule after RAI, we still believe this treatment is potentially damaging to the ovary. We therefore wish to reiterate that caution needs to be employed whenever RAI treatment is contemplated in a woman in her reproductive years.