Yesterday it was a gift from the opposition. After stopping her bioidentical hormone therapy a few years ago and now on the verge of menopausal crisis, a former patient returned to my care. Why did you stop her HRT hormone replacement therapy? Because of the Women’s Health Initiative (WHI) study that reported an increased risk of cancer in those who used “progesterone” with “estrogen.”
First, let’s make it very clear that comparing the hormones used in the WHI study to bioidentical hormones from botanical sources is like comparing apples to oranges.
The WHI used Premarin derived from pregnant mare urine as the “estrogen” and Provera, a synthetic medroxyprogesterone, as the “progesterone.”
Years ago, when WHI began studying the effectiveness of HRT in preventing heart disease, the American Heart Association asked me to serve on a panel of local experts to answer women’s questions about hormones. As a nurse practitioner who had been treating menopausal women for years with natural hormones, I was honored to be part of the medical panel that included cardiologists and endocrinologists, but the WHI researcher wasn’t too thrilled when I started questioning her terminology. I argued that WHI was not using “progesterone” but a synthetic derivative and that the study would show an increase in cardiovascular disease for two reasons:
1. the hormones were oral, which would create havoc with the production of clotting factors in the liver (much like oral contraceptives increase the incidence of blood clots), and
2. Not using real progesterone would put subjects at risk for breast cancer.
Now, what I had to say was not well received, but the cardiologist surreptitiously asked me what I knew. Although I explained, the doctors, too afraid to break the protocol, continued to follow the pharmaceutical sponsored protocols until…the study was stopped. Why? Because the subjects had significant increases in…
1. blood clots leading to stroke and heart attack
2. and breast cancer, especially in subjects who received Provera.
Guess what? The endocrinologist on that panel is now using natural hormones.
How many women must suffer before health care providers switch to alternative therapies?
Needless to say, my former patient gladly returned to taking bioidentical hormones. I also recommended Genesis Gold® to help metabolize hormones in the safest way possible and to balance adrenal, thyroid, and hypothalamic function, as well as glucose metabolism. Finally, I counseled her on nutritional and lifestyle changes to encourage a healthier body composition and promote safer estrogen metabolism.
The WHI study investigated the effects of Premarin and Provera on cardiovascular disease in menopausal women and was closed because they erroneously determined that the use of hormone replacement therapy for five years increased the risk of cardiovascular disease and breast cancer. Why is this a wrong assumption? Because bundling all HRT, including bioidentical estrogen and progesterone, with the use of Premarin and Provera is like saying that eating fruit causes cavities because it has “sugar” in it!
Most of what we know about hormones is based on the older drug, Premarin, which is actually equine oestrone, the biological waste from estrogen metabolism in pregnant mares. Humans convert Premarin primarily to 4OH estrone, one of the most toxic forms of estrogen.
I will illustrate the types of estrogen and their metabolism in detail, but first let’s examine the “progesterone” used in the WHI study. They used Provera, a synthetically derived progestin. Yes, its chemical name is medroxyprogesterone named after its inventor, not natural, but artificial. What is the problem with Provera? Well, progesterone is a 21 carbon molecule, one of the largest steroid hormones. Don’t let the word steroid alarm you. All hormones that are made up of sterols (cholesterol) are called steroids. That includes naturally occurring 21-carbon pregnenelone, 19-carbon DHEA and testosterone, and 17-carbon estrogen and cortisol.
Medroxyprogesterone or Provera, a 19-carbon molecule, is more closely related to testosterone than the 21-carbon progesterone. In fact, the side effects of Provera are related to androgens (male hormone)…elevated cholesterol and midline weight gain. Yes, Provera reverses estrogenic effects on the lining of the uterus to prevent uterine hyperplasia or cancer, but guess what? Also natural progesterone!
What man-made Provera can’t do, what nature created progesterone to do, is protect against estrogen-fueled cancers. Think of estrogen as a fertilizer that feeds both roses and weeds. If estrogen fertilizes or promotes cell growth, then progesterone is like the gardener who picks up the weeds and leaves the flowers. Progesterone activates a very useful gene called P53, which is the cell death gene. It tells cells when they have outlived their welcome, like breast cells or uterine cells growing in preparation for a possible pregnancy. At the end of a menstrual cycle if the woman is not pregnant these cells, under the influence of progesterone, deteriorate (in the breast) or are shed (menstruation).
You see, mother nature has it all figured out.
Now back to Premarin. Why would our bodies convert equine estrones to the more dangerous type of estrogen? Because Premarin is the waste product of horse estrogen metabolism and our human livers can’t do anything else with it. Garbage in garbage out.
Now, estrogens are not all created equally. The human ovary produces estradiol (known as E2 because it was discovered after estrone or E1). Estradiol is a powerful growth-promoting hormone. Nourishes blood vessels, nerves, skin, hair, nails, the lining of the intestine, and promotes female secondary sexual characteristics, such as the development of breasts and hips that are wider than men, and enriches the lining of the uterus for a possible pregnancy. Studies have shown that estradiol stimulates the thymus to promote proper immune programming for reproductive females to produce enough antibodies to pass on to their offspring.
Since estradiol is short-acting, the body has a backup system of enzymes in fat cells that can convert estradiol to long-acting estrone. Now there are three main types of estrone whereby the carbon molecule carries a hydroxyl molecule.
o Estrone 2OH is the safest form that is produced in large quantities in young women with a healthy body weight. The enzyme that promotes the conversion of 2OH to estrone uses the micronutrients found in flaxseed, soybeans, fatty fish, and cruciferous vegetables (broccoli, cauliflower, cabbage, Brussels sprouts).
o Estrone 16OH is inflammatory and has been associated with breast and gynecological cancers. Overweight women, sedentary women, women who drink too much alcohol or who have been exposed to xenoestrogens (man-made estrogenic toxins like DDT) and certain drugs like cimetidine produce too much of this dangerous estrogen. Estrone 16OH can be converted to estriol.
o Estrone 4OH, the most volatile of the three, is associated with the most aggressive forms of breast and ovarian cancer. All factors that influence the conversion of 16OH affect 4OH, especially age.
Estriol: The pregnancy hormone is the third estrogen and appears to be the least inflammatory and the most nourishing for vaginal and urethral tissues. Estriol is my favorite bioidentical used topically to make a dry, atrophic vagina lush.
Unfortunately, getting older increases poor estrogen metabolism, which is why I don’t agree with high-dose hormone replacement. The levels of hormones produced by young women are safe for them because they have the means to safely metabolize hormones. Most older women do not have the means to safely metabolize hormones. Although they can take in plenty of IC3 indoles (the active ingredient in cruciferous vegetables) and plenty of EPA (fish oils), maintain a low weight, and drink alcohol in moderation, I believe that reversing age-related metabolic enzyme activity requires an approach multiple.
A holistic approach to hormone replacement therapy includes a complete metabolic and neuroimmune-endocrine evaluation. Functional medicine tests are available to assess an individual’s genetic and metabolic capabilities. There is no single recipe for all anti-aging or hormone replacement therapies.