Estrogen has gotten a bad rep a while back and some of the issues is just really a misunderstanding. It’s complicated, but I want to try to explain some of it. Because it really is a good thing when it is understood. Let me explain…
So why has Estrogen become Evil?
Prior to the Women’s Health Initiative Study published in 2002 prescriptions for menopausal hormone therapy (HT) were soaring. The Women’s Health Initiative Study was designed to look at using HT in women 60 years old or older for the prevention of osteoporosis and coronary heart disease (CHD). The WHI study tested standard dose oral conjugated equine estrogens with and without standard dose continuous medroxyprogesterone acetate. In 2002, the trial of estrogen plus progestin in women with an intact uterus was stopped early because of increased risk of breast cancer, CHD, stroke, and pulmonary embolism. Risks exceeded the benefits from reductions in hip fractures and colorectal cancer. The findings from the trial of only estrogen therapy were less adverse effects than those with both Estrogen and Progestin in showing no effect on CHD, a small reduction in risk of breast cancer, and a more favorable benefit-risk profile for younger than older women.
In order to explain the initial question we need to look at a couple things.
What is oral conjugated equine estrogens and medroxyprogesterone acetate?
Oral conjugated equine estrogens comes from urine collected from pregnant horses. The problem with this version of estrogen is that when it is metabolized a lot of it ends up as estrone. Estrone is 50-70% less active than estradiol, is produced in human fat cells, and is a little harder to metabolize.
What’s the problem with medroxyprogesterone?
Medroxyprogesterone is a synthetic (non natural) way to produce progesterone. While medroxyprogesterone has been linked to an increased risk in breast cancer micronized progesterone hasn’t been. We can’t reasonably apply evidence good or bad from one molecule to the other as can so often be done with other chemicals. Progesterone and synthetic progestins have different effects on lipids, clotting factors, glucose, and insulin and therefore could impact cardiovascular risk differently.
In another study, 300mg of progesterone daily showed no adverse changes in blood pressure, weight, or markers of inflammation or coagulation.
So what is the real problem?
The real problem with synthetic hormones is that they are metabolized differently in the liver than natural hormones. Conjugated equine estrogens are not the same as naturally occurring estradiol, estriol, or estrone. Both men and women’s bodies produce estrone, estradiol, and testosterone naturally. Based on genetics we metabolize and eliminate them differently. For eliminating estrogens we have three different pathways:
- 4- hydroxyestrone
The biggest difference in these pathways is the efficiency in which estrogen is detoxified and eliminated. When methylation is taking place within the 2-estrogen pathway it can quickly take the estrogen molecule and prepare it for elimination. If it can not be methylated or goes down the 4 hydroxyestrone or 16-estrogen pathway it just takes longer to get to the same place. This is where trouble comes from. When it takes longer to be eliminated it has more opportunities to be changed into something that is toxic and can not be eliminated and this is how cancer can begin.
Knowledge is the basis of understanding.
The real question is how do we optimize estrogen metabolism naturally?
From my understanding, diindolylmethane (DIM) found in cruciferous vegetables when incorporated into our diet or supplement regimens. Cruciferous vegetables when crushed and chewed produce Indole-3-carbinol (I3C) and when combined in the stomach with stomach acid produce (DIM). Current data on I3C and DIM suggest that these phytonutrients support breast, cervical, uterine, and prostate health. When produced together they help guide the 2-estrogen metabolites to be produced rather than 4-hydroxy or 16-estrogen.
Another supplement that could help with estrogen metabolism is Calcium D-Glucarate. This form of calcium is produced naturally and can be consumed from certain fruits and vegetables. Calcium d-glucarate has been shown to inhibit beta-glucuronidase, and enzyme found in certain bacteria in the gut . By inhibiting this enzyme we can support the body’s ability to detoxify estrogens and fat soluble toxins.
Hormone replacement therapy is a tricky subject and can be really confusing. I know during pharmacy school we really didn’t learn the difference between synthetic hormones and natural hormones. However, I think it is important to continue to ask the right questions.
These questions include:
- How do we get more estrogens in our diet?
- What are the benefits of estrogens?
- What are the different types of estrogens and how do they differ?
I hope to expand on this topic in future blog post here to get people to ask better questions that elicit better answers.