Early in 2002 the National Heart, Lung, and Blood Institute of the National Institutes of Health stopped a major clinical trial of the risks and benefits of combined estrogen and progestin in healthy menopausal women due to their finding of an increased risk of invasive breast cancer. The large multi-center trial, a part of the Women’s Health Initiative study, also found an increase in coronary heart disease, stroke, and pulmonary embolism in participants of the study who were on estrogen and progestin compared to women taking the placebo. There were some benefits of estrogen plus progestin, including fewer cases of hip fractures and colon cancer, but over all, the harm was greater than the benefit. The study, which was scheduled to run until 2005, was stopped after an average follow-up of only 5.2 years.
When the study came out in 2003, most people, including well-meaning conventional medical doctors, were shocked. They could not believe this long-held “safe” therapy was dangerous. The consensus was estrogen should not be used because it had the potential to cause breast cancer and some other negative health problems, but progestin was supposed to counteract the negative effects of estrogen.
Unfortunately, the research on estrogen failed to take into account the important issue of estrogen metabolism and how it relates to specific biochemical individuality that exists in different people. The inability to properly metabolize estrogen could be the real culprit for many women with increased risk of developing breast cancer with estrogen replacement therapy.
Estrogen is produced in the ovaries, the corpus luteum and the placenta. However, it is where estrogen is broken down—the liver—that we begin to see real health problems. Estrogen is metabolized into several distinct forms of chemicals, which we call metabolites in the liver. The two main pathways in the body produce either 2-hydroxy and 4 –hydroxy or 16-alpha-hydroxy forms of estrone and estradiol. For simplicity sake, I will call them 2-OHE, 4-OHE and 16-OHE.
2-OHE tends to have anti-cancer activity. 4-OHE and 16-OHE are carcinogenic, causing cancer. How the body metabolizes estrogens into these metabolites impacts the possibility of cancer development in different women. The more 16-OHE and 4-OHE a woman produces, the higher the risk she has for developing breast cancer. Research has shown that diet factors can alter the amount of production of these compounds by either increasing or decreasing them. Measuring the amounts and ratio of these metabolites provide an important indication of risk for future development of estrogen-sensitive cancers in women.
The following may contribute to the risk of developing estrogen-sensitive cancer, including breast, cervical, and head and neck cancers:
- Prolonged use of oral contraceptives
- Synthetic hormone replacement therapy
- Family history of breast cancer
- Obesity or sedentary lifestyle
- Consumption of 2 or more alcoholic drinks per day
- Aging
- Never having children or having the first after 35
- Having high breast density on a mammogram
- High bone density
- Being exposed to large amounts of radiation
A simple urine test has been developed to assess the balance between the estrogen metabolites. If a woman found out she has increased 16-OHE, she can change that by consuming food factors that encourage the production of 2-OHE and decreases 16-OHE. The serum 2:16 OHE ratio is indicative of risk if it is too low. If you have family history of breast cancer, assessing this ratio may help you decide your course of action for proactive prevention. The higher the ratio, the less association there is with estrogen-sensitive cancers. A ratio greater than 0.4 is thought to be protective.
Foods that will cause the shift to a beneficial estrogen metabolites pattern are cabbage family vegetables such as broccoli, brussel sprout, kale, cabbage and cauliflower; as well as Omega-3 fatty acid and indole-3-carbinol as supplements. Exercise also causes a beneficial shift. Indole-3-carbinol is found in cabbage family vegetables.
Chemicals that could cause the increase in 16-OHE are insecticides, herbicides, plastics compounds, household cleaning products, industrial chemicals such as PCB and dioxin, and toxic heavy metals. Once you know what type of estrogen metabolites your liver is making, you can modify them by increasing the nutritional factors and reducing the chemicals that cause the bad estrogen metabolites to be produced. 4- and 16-OHEs are the bad guys!
How well is your body metabolizing estrogen? Talk to your doctor and ask for this simple test.
Reference:
http://www.metametrix.com/content/DirectoryOfServices/Estronex216OHRatio
