What are the effects of taking Diindolylmethane (DIM) in postmenopausal women on hormone replacement therapy (HRT) including testosterone?

DIM Supplementation with HRT in Postmenopausal Women

Direct Answer

DIM (3'-diindolylmethane) significantly alters estrogen metabolism in postmenopausal women on transdermal estradiol, potentially reducing the therapeutic effectiveness of HRT by shifting estrogen metabolite profiles in ways that may diminish symptom relief and bone protection. 1

Evidence of DIM's Effects on Estrogen Metabolism

The most recent and highest-quality evidence comes from a 2025 study examining 1,458 postmenopausal women using transdermal estradiol patches, of whom 108 were concurrently taking DIM supplements. 1

Key metabolic changes with DIM supplementation include:

• Statistically significant alterations in urinary estrogen profiles across all measured metabolites (P < 0.001) 1
• Significant effects on 6 of 10 estrogen metabolites measured: estrone, estriol, 2-OHE1, 2-OHE2, 4-OHE2, and 16-OHE1 1
• Altered 2-OHE1/16-OHE1 ratio, which reflects the balance between different estrogen metabolic pathways 1

Clinical Implications for HRT Effectiveness

The magnitude and pattern of these metabolic changes suggest DIM may reduce the overall estrogenic impact of HRT on critical clinical endpoints. 1

• DIM's mechanism involves altering estrogen metabolism, creating a drug-supplement interaction that may interfere with HRT's intended therapeutic effects 1
• Potential reduction in symptom improvement from vasomotor symptoms (hot flashes, night sweats) that HRT is designed to treat 1
• Possible decreased bone mineral density protection, undermining one of HRT's key benefits in preventing the 2% annual bone loss during early menopause 1, 2

Specific Concerns with Testosterone-Containing HRT

While the available evidence specifically examined estradiol patches, the metabolic interference would theoretically extend to any estrogen component of HRT regimens. 1

• Testosterone is sometimes added to HRT in postmenopausal women, though less data supports this practice compared to estrogen-based therapy 3
• DIM's alteration of estrogen metabolism could affect the overall hormonal balance when testosterone is included in the regimen 1

Clinical Recommendations

Providers treating postmenopausal women with HRT should actively screen for DIM supplementation and consider discontinuing it. 1

• Explicitly ask patients about DIM use, as many may not volunteer supplement information 1
• Consider the potential implications for HRT dose management and effectiveness when DIM use is identified 1
• The presence and magnitude of metabolic changes warrant caution about concurrent use 1

Critical Knowledge Gaps

Further research is urgently needed to determine whether DIM's metabolic changes translate into clinically significant reductions in HRT benefits. 1

• Current evidence demonstrates biochemical changes but does not yet prove reduced clinical efficacy 1
• No studies have examined whether DIM affects bone mineral density outcomes in women on HRT 1
• No data exists on whether symptom control (hot flashes, vaginal atrophy) is compromised with concurrent DIM use 1

Common Pitfall to Avoid

Do not assume supplements are benign additions to HRT—DIM creates measurable drug-supplement interactions that may undermine the therapeutic goals of hormone replacement therapy. 1 The functional and integrative medicine communities sometimes recommend DIM to postmenopausal women without considering these interactions. 1