Estrogens are well known for their ability to create both health and disease. Estrogen hormones are integral to female development, and they also play a role in male health such as maintaining skeletal health.1

Among the general population, estrogen is usually talked about as a single entity. However, there are a few different forms of “estrogen” in the human body: estradiol, estrone, and their metabolic product estriol. And while the overall importance of estrogens is widely understood, this hormone group is most often vilified with good reason, for its ability to cause disease, namely cancers in women. Interestingly, newer research is exploring the role of estrogens and cancer in men as well.2

Estrogens, in a very general sense, incite the growth of tissues in the body. Developmentally this is a positive effect that predominately underlies female maturation. In its wisdom, the body creates these and other hormones to achieve a purpose, and then promptly metabolizes and removes them from the body (ideally). However, this is when we begin to see the problems associated with estrogens. If these hormones are not adequately metabolized and subsequently removed, they can stay in our bodies and begin to wreak havoc.

Removal of hormones is achieved in two main ways. First, they are chemically altered (metabolized) in a way that prepares them for removal. Second, they must be physically removed via the organs of elimination. While physical removal is a relatively straightforward process (urination and bowel movements), the chemical processing can go awry if the proper nutrients are not available to the liver where the majority of hormone metabolism takes place. Removal of hormones also is affected by thyroid health. This is particularly true for individuals who have undiagnosed low thyroid or under treated thyroid insufficiency and explains the link between hypothyroidism and breast and prostate cancer.

Good vs. Bad Estrogen Metabolism

There are two main metabolic pathways of estrogen processing. The first pathway (16 alpha-hydroxylation) appears to be more active in women with estrogen-related cancers3-4 and produces the carcinogenic estrogen metabolite 16 alpha hydroxy estrone. The second main pathway (2 hydroxylation) produces the “protective” estrogen metabolite known as 2 hydroxy estrone, which appears to provide a lower estrogen-related cancer profile.5 Research is showing that by positively modulating the ratio of 2 hydroxy estrone to 16 alpha hydroxy estrone, there is a decreased cancer risk. This increased 16 alpha-hydroxylation activity has been shown to precede clinical evidence of cancer, and it represents a significant risk factor for developing estrogen-dependent tumors. Healthy individuals not at risk for breast or endometrial cancer bypass the 16-alpha route and instead metabolize estrogen through this preferable pathway.

Some of the ways estrogens are metabolized in our bodies depends on our genetic expression, our diet and lifestyle, and elimination habits. The enzymes in our liver that are responsible for metabolizing hormones and other chemicals can also be affected by lifestyle choices, i.e. diet. One such dietary constituent that has a positive effect on the way estrogens are metabolized are cruciferous vegetables. This vegetable group, of which broccoli, cabbage, kale, cauliflower and Brussels sprouts are members, exerts potent effects on the way estrogens are metabolized in terms of reducing cancer risk.

These vegetables were discovered to have anti-cancer effects on the development of breast, prostate, cervical and other hormone dependent cancers.6 Epidemiologic studies initially suggested that people consuming very large amounts of these vegetables each day had less hormone-related cancers than their non-vegetable eating cohorts.7

One of the compounds responsible for cancer prevention in these vegetables is diindolylmethane, also known as DIM. DIM is the major metabolite of another compound derived from cruciferous vegetables known as indole-3-carbinol, or I3C. It is estimated that roughly 10-20 percent of ingested I3C is converted to DIM in the stomach.8 DIM itself has preventive effects against breast cancer,9-10 works as an estrogen receptor antagonist and agonist in human breast cancer cells,11 and stimulates programmed apoptosis in human breast cancer cells as well.12

Once the conversion of I3C to DIM occurs, DIM can then exert its anti-cancer effects throughout the body.

Supplements vs. Dietary Sources

Individuals would have to consume prohibitively large quantities of raw cruciferous vegetables in order to achieve the known effects. Studies suggested that 1-2 pounds of these vegetables must be consumed in order to achieve this clinical effect.13 While consuming large amounts of fruits and vegetables is sound health advice, cruciferous vegetables in particular are difficult to digest for many people, especially 1-2 pounds’ worth. Furthermore, eating large quantities of cruciferous vegetables is known to be goitrogenic (enlarging the thyroid gland) and can lead to thyroid problems. Interestingly, while cruciferous vegetables have been found to be goitrogenic, DIM has actually been found to inhibit the growth of primary goiter cells by 70 percent compared to untreated controls. The same study found that DIM inhibited a number of different thyroid cancer cell lines.14

For individuals who want to confer protection against hormone dependent health conditions, supplementation with DIM is therefore preferable to eating large quantities of cruciferous vegetables.

Estrogen in Males

Estrogen is not just a problem for women. Men also make estrogen in their bodies as they both age and gain weight. Male fat tissue will manufacture the enzyme aromatase that then converts testosterone to estrogen. Coupled with the natural decline in testosterone production, this leads to substantial decreases in testosterone availability, and may preclude the onset of several diseases including prostate cancer. Aromatization of androgens to estrogens is a physiologic consequence and can occur within various tissues including the adipose tissue.15 With increased weight gain, men may thus manufacture greater amounts of estrogens.

Alcohol consumption may also raise estrogen levels in the body, via impaired liver detoxification of estrogens.16 (Table 1) All of these factors may contribute to possible estrogen-related disease in men.

Evidence continues to accumulate that shows estrogens may in part be responsible for prostate cancers.2 This is fueled by newer findings that show that elevated androgen levels are associated with a lower risk of prostate cancer,17 and given the anti-estrogenic activity of androgens (testosterone), it furthers the hypothesis that estrogens may assist with prostate cancer initiation in the presence of low testosterone.18

Supplementation with DIM in men will affect estrogen metabolism the same way as women, leading to the creation of safer estrogen metabolism by products, thereby reducing the overall estrogen load in men. Weight loss and limiting alcohol consumption are additional key methods of reducing overall estrogen burden in men.

Cruciferous vegetables also have potent antioxidant effects and may thereby also protect against cancers in this regard. Cruciferous vegetable intake, in epidemiological studies, has inhibited prostate, breast, cervical and colon cancers and appears to alter metabolism of dietary carcinogens in humans.19-21

Conclusion

Estrogen-induced cancers are prevalent for a variety of reasons today, environmental and genetic causes being most indicated. Improper estrogen metabolism into the 16 hydroxy form is one way that estrogen-related diseases can occur. Supplementation with cruciferous vegetables and their extracts in the form of DIM can afford a means to steer estrogen metabolism away from carcinogenic estrogen metabolites such as 16-hydroxy and toward the safer metabolite 2 hydroxy.

References

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13. Bradlow HL. Personal Communication with Vitamin Research News editor Kimberly Pryor, 1999.
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17. Raynaud JP. Prostate cancer risk in testosterone-treated men. Steroid Biochem Mol Biol. 2006 Dec;102(1-5):261-6.
18. Carruba G. Estrogen and prostate cancer: an eclipsed truth in an androgen-dominated scenario. J Cell Biochem. 2007 Nov 1;102(4):899-911.
19. Voorrips LE, Goldbohm RA, Verhoeven DT, et al. Vegetable and fruit consumption and lung cancer risk in the Netherlands Cohort Study on diet and cancer. Cancer Causes Control. 2000;11(2):101-115.
20. Feskanich D, Ziegler RG, Michaud DS, et al. Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst. 2000;92(22):1812-1823.
21. Walters DG, Young PJ, Agus C, et al. Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. Carcinogenesis. 2004;25(9):1659-1669.

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