Integrative health providers commonly recommend diindolylmethane (DIM) — a beneficial phytonutrient from cruciferous vegetables — as part of a broader strategy to support hormone health in female patients, including during the postmenopausal years. In a 2024 study, Precision Analytical researchers showed that DIM produces significant alterations across the urinary estrogen profile in a way that lowers total estrogen levels and supports healthier estrogen metabolism in premenopausal women. But in postmenopausal women, it’s not entirely clear what happens to a woman’s estrogen profile when she takes DIM concurrently with estradiol (E2) in the context of menopause hormone therapy (MHT). While some supplements are considered generally safe to take alongside MHT, there is little research on the combined use of DIM and MHT. Recently, researchers at Precision Analytical investigated this issue in a peer-reviewed study published in Menopause. This is the first published study to address how DIM affects estrogen metabolism in postmenopausal women using MHT, which was made possible by the dried urinary sampling method used in DUTCH Testing.

Main Findings of the Study

Within a large sample of postmenopausal women (1458 total), Precision Analytical researchers compared dried urine samples between two groups —  one group that was using both DIM and MHT in the form of a transdermal E2 patch and another group that was using only an E2 patch. The results showed that women using both DIM and an E2 patch had significant differences in their urinary estrogen profile compared to those using an E2 patch alone. These differences included: 

• Lower levels of two forms of estrogen (estrone and estriol)
• Lower levels of total estrogens (estrone, E2, and estriol)
• Lower levels of 16-OHE1, an estrogen metabolite that promotes cell proliferation in estrogen-sensitive tissues (such as breast, uterus, and ovaries) and may contribute to overall estrogenic burden in the body
• Higher levels of 2-OHE1 and 2-OHE2, which are protective estrogen metabolites associated with less reproductive tissue proliferation and lower breast cancer risk
• Increase in the ratio of 2-OHE1 to 16-OHE1, suggesting a shift in estrogen metabolism away from the more estrogenic 16-OHE1 pathway. An increase in this ratio is linked with a lower risk of breast and other hormone-sensitive cancers.

Since each woman in this study also reported the dose of her E2 patch (ranging from 0.025 mg to 0.1 mg), the researchers were able to go one step further and analyze DIM’s effects based on dosage. Interestingly, the higher the E2 patch dose, the more pronounced the difference appeared to be in estrone, estriol, and total urinary estrogen concentrations between the women using an E2 patch alone and those using both DIM and an E2 patch. This suggests the possibility that DIM’s influence on estrogen metabolism might be enhanced when higher levels of exogenous E2 are present in the body. 

Overall, the results of this study in postmenopausal women largely echo those of Precision Analytical’s 2024 study in premenopausal women showing a general shift toward a potentially more favorable estrogen metabolism pattern with DIM use. However, our results suggest that DIM might reduce the overall estrogenic effects of E2 patch therapy by lowering E2 levels through increased metabolism. More research is needed to determine whether these DIM-induced changes might impact the E2 patch dose required to achieve desired E2 levels and clinical benefits.

Summary & Implications for Clinical Practice

Patients and providers are rightfully concerned about the safety of MHT. To address these concerns, DIM is often used concurrently with MHT to ensure optimal estrogen metabolism. While DIM was shown overall to have beneficial effects on estrogen metabolism in this study, the results suggest that women using an E2 patch have lower E2 levels if they concurrently take DIM, possibly reducing the benefits of E2 therapy. Whether and how DIM could affect the way that the body processes hormones used in MHT, especially estrogen, still require further research. But the findings of this study do underscore the importance of healthcare providers asking their female patients if they are taking DIM and consider its potential effects when managing MHT. The study’s findings also support the practice of monitoring the effects of DIM supplementation on urinary estrogen in postmenopausal patients on MHT. This would ultimately help providers to offer individualized recommendations about dietary supplements and to ensure that any potential interactions between MHT and supplements do not affect the desired clinical outcomes of MHT.  

Read the full study here.