The impact of 3,3'-diindolylmethane on estradiol and estrogen metabolism in postmenopausal women using a transdermal estradiol patch.

OBJECTIVES

3,3'-diindolylmethane (DIM) is a supplement, investigational drug, and the primary in vivo product of indole-3-carbinol. DIM is sometimes recommended to postmenopausal women by functional or integrative medicine providers. Some of these women may be concurrently receiving menopausal hormone therapy (MHT), and since DIM's mechanism of action involves the alteration of estrogen metabolism, it is possible that a drug-supplement interaction exists. The objective of this study was to examine the effect of DIM on the estrogen profiles of postmenopausal women receiving MHT in the form of a transdermal estradiol (E2) patch.

METHODS

This was a retrospective, observational cohort study for which data were collected from a database containing laboratory results for patients processed between January 1, 2016 and December 9, 2019. Laboratory measurements included urinary E2 and 9 other estrogen metabolites. From this database, we identified 1,458 results that were from postmenopausal women using a transdermal E2 patch. Of these 1,458 women, 108 indicated they were concurrently taking a DIM supplement. Wilcoxon rank sum tests were used to assess differences between groups. Multivariable linear regression models were created to confirm the effect of DIM on individual estrogen metabolites.

RESULTS

When compared with postmenopausal women using a transdermal E2 patch alone, postmenopausal women using a patch and concurrently taking DIM had statistically significant alterations in their urinary estrogen profiles ( P < 0.001 for all metabolites with differences). Multivariable linear regression models indicated that DIM had a significant effect on 6 of the 10 estrogen metabolites measured, including estrone, estriol, 2-OHE1, 2-OHE2, 4-OHE2, and 16-OHE1, as well as the 2-OHE1/16-OHE1 ratio.

CONCLUSIONS

Postmenopausal women who are prescribed transdermal E2 patch therapy who choose to concurrently use a DIM supplement may have unexpected changes in their urinary estrogen profiles. Further research is needed to assess whether these changes are clinically significant, as there is a possibility that they may decrease the overall estrogenic impact of MHT on key clinical endpoints such as symptom improvement and bone mineral density. The presence and magnitude of these changes suggest that providers treating postmenopausal women with MHT should ask their patients if they are taking a DIM supplement and, if so, consider the potential implications of drug-supplement interactions for MHT dose management and effectiveness.