Endometriosis is a prevalent gynecological disease affecting 6% to 10% of women of reproductive age. Endometriosis consists of endometrium-like tissue present outside of the uterine cavity. Characteristics of the disease include dysmenorrhea, dyspareunia, dysesthesia, dysuria, and infertility, along with unspecific complaints like pelvic pain, fatigue, bloating, and back pain. The pathogenesis of endometriosis is not fully understood. However, the most widely accepted theory is menstruation retrograde. Despite the wide prevalence of the disease, there is little research on the effects of nutrition on endometriosis. 

Indole-3-carbinol (I3C) is present in cardamom and cruciferous vegetables like cabbage, brussels sprouts, and broccoli. I3C acts as a precursor to the phytochemical 3,3’-diindolylmethane (DIM) in an acidic environment like the stomach. DIM has been shown to ameliorate estrogen effects in estrogen-sensitive cells by inhibiting estrogen receptor-alpha signaling. DIM is being studied for its potential clinical relevance to endometriosis due to its potential suppression of estrogen receptor gene expressions and its antiproliferative and proapoptotic properties. 

One in vitro and ex vivo study observed the effect of DIM with dienogest, a commonly used progestin for the management of pain, on endometriosis outcomes. Ten women were divided into two groups: one group with dienogest alone and one with dienogest combined with 100 mg of DIM three times per day. The combined dienogest-DIM group had decreased pelvic pain and significantly improved bleeding patterns compared with the group taking dienogest alone. Furthermore, tolerability was more favorable for the dienogest-DIM combined group with no side effects reported. Due to the small nature of this study, future clinical studies are needed for further evaluation. 

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

One rodent study looked specifically at I3C, the DIM precursor, and found it to be effective in decreasing endometroid heterotopias and endometriosis-induced pain. The authors highlighted that I3C has been shown to regulate the metabolism of estrogen by restoring the physiological ratio of 16-alpha and 2-hydroxymetabolites, normalizing hormone-sensitive tissue cell division in the female reproductive system. They also explain that I3C is prone to being converted into DIM in the stomach, and DIM exhibits its own clinically relevant properties. 

More research is needed to investigate the science on DIM and endometriosis. However, DIM may help support hormonal balance in women with endometriosis. 

By Danielle Moyer, MS, CNS, LDN