Research & Education

DIM to Promote Estrogen Homeostasis

Cruciferous vegetables (i.e., broccoli, cabbage, cauliflower, kale) contain bioactive precursor compounds called glucosinolates. Upon ingesting cruciferous vegetables, glucosinolates can be broken down into a phytochemical called indole-3-carbinol (I3C), a relatively unstable compound. Once I3C reaches the acidic environment in the stomach, I3C is converted into 3,3’-diindolylmethane (DIM). DIM has been shown to promote healthy estrogen homeostasis by modulating estrogen pathways and activating estrogen receptors.

Healthy estrogen homeostasis plays a vital role in overall health, where disturbances of this hormone can be associated with conditions relating to bone health, cardiovascular health, and the female reproductive tract. Estrogen is involved in normal glucose and lipid metabolism, bone strength, menstruation, and fertility.

Studies suggest that DIM promotes the production of the preferred pathway of estrogen/estrogen metabolites. There are three primary metabolic pathways that the main circulating estrogen hormone, estradiol (E2), can undergo within the body. Using cytochrome P450 (CYP) enzymes, E2 can be converted into 2-hydroxyestrone (2-OH), 4-hydroxyestrone (4-OH), or 16-hydroxyestrone (16-OH). Research indicates that the 2-OH pathway is the preferred pathway, as it may promote cellular health. Alternatively, an excess production of 4-OH and 16-OH pathway metabolites may contribute to cellular DNA damage and oxidative stress.

In vitro studies suggest that DIM promotes a healthy 2:16 metabolite ratio without elevating the 4-OH metabolites. This is likely due to its impact on CYP enzymes, supporting the expression of CYP1A1 over the other enzymes. This potential influence on estrogen homeostasis may support conditions associated with a higher status of the more harmful estrogen metabolites. DIM has also been shown to promote the activation of estrogen receptor-beta genes rather than estrogen receptor-alpha genes. Estrogen receptor-beta activation is associated with bone health and cellular health of the uterine and breast tissues.

In addition to promoting healthy estrogen homeostasis, DIM has been found in vitro and in rodent models to support a normal inflammatory response. Studies demonstrate that DIM may inhibit nuclear factor kappa B, tumor necrosis factor‐alpha, and transforming growth factor-beta-associated pathways.

DIM may be clinically relevant to women with endometriosis. One study observed the effect of DIM with dienogest, a commonly used progestin for pain management, on endometriosis outcomes in vitro and ex vivo and in a small cohort of women. Ten women were divided into two groups: a dienogest-only group and a dienogest plus DIM (100 mg three times daily) group. The combined dienogest-DIM group had decreased pelvic pain and significantly improved bleeding patterns compared to the group taking dienogest alone. Furthermore, tolerability was more favorable for the dienogest-DIM combined group. Due to the small nature of this study, future clinical studies are needed for further evaluation.

In the ex vivo model, DIM significantly reduced endometriotic tissue viability by 25%, whereas dienogest alone decreased viability by only 9%. The dienogest-DIM group resulted in a 40% cell viability decrease and a significant reduction of 17β-estradiol secretion (approximately 27%). Based on the results, the authors suggest that the dienogest-DIM combination may reduce E2 levels in endometriotic lesions.

Promising research suggests that DIM may promote estrogen homeostasis. Further research is needed to investigate how DIM may be clinically relevant to women seeking hormonal balance.

By Danielle Moyer, MS, CNS, LDN