The WHI study researched the effects of Premarin and Provera on cardiovascular disease in menopausal women and closed down because they erroneously determined that using hormone replacement therapy over five years increased the risk of cardiovascular disease and breast cancer. Why is this an erroneous assumption? Because lumping all HRT including bio-identical estrogen and progesterone with Premarin and Provera use is like saying that to eating fruit causes cavities because it has “sugar” in it!

Most of what we know about hormones is based on the oldest pharmaceutical—Premarin.
Which is in fact equine estrones—the bio-waste of pregnant mare estrogen metabolism and humans convert Premarin primarily into 4OH estrone, one of the most toxic forms of estrogen.

I will illustrate estrogen types 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 by its inventor—not natural, but man-made. What’s 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 by sterols (cholesterol) are called steroids. That includes naturally occurring 21 carbon pregnenelone, 19 carbon DHEA and testosterone, and 17 carbon estrogen and cortisol.

19 carbon medroxyprogesterone is more closely related to testosterone than 21 carbon progesterone. In fact the side effects of medroxyprogesterone (Provera) are androgen related (male hormone)….elevated cholesterol and mid-line weight gain. Yes, Provera reverses estrogenic effects on the uterine lining proven to prevent hyperplasia or uterine cancer, but guess what? So does natural progesterone!

What man-made Provera cannot do, that progesterone was created by nature to do, is protect against estrogen fed cancers. Think of estrogen as fertilizer feeding both the roses and the weeds. If estrogen fertilizes or promotes cell growth, than progesterone is like the gardener which picks the weeds and leaves the flowers. Progesterone turns on a very handy gene called P53 which is the cell death gene. It tells the cells when they have out lived their welcome, like breast cells or uterine cells that grow in preparation for a potential pregnancy. At the end of a menstrual cycle if the woman is not pregnant those cells under the influence of progesterone deteriorate (in the breast) or slough off (menstruation).

You see mother nature has it all figured out.

Now let’s go back to Premarin. Why would our bodies convert equine estrones into the most dangerous kind of estrogen? Because Premarin is the waste product of horse estrogen metabolism and our human livers can do nothing 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. It nourishes blood vessels, nerves, skin, hair, nails, lining of the gut as well as promotes female secondary sexual characteristics like breast development and wider hips than men, and enriches the uterine lining for potential pregnancy. Studies have shown that estradiol stimulates the thymus to promote proper immune programming so that reproductive women produce sufficient antibodies to pass on to their offspring.

Since estradiol is short-lived, the body has a back up system of enzymes in the fat cells that can convert estradiol to long acting estrone. Now there are three main types of estrone named by which carbon molecule carries a hydroxyl molecule.
• 2OH estrone is the safest form made in great quantities in young women of healthy body weight. The enzyme that promotes 2OH estrone conversion uses the micronutrients found in flax, soy, fatty fish, and cruciferous vegetables (broccoli, cauliflower, cabbage, brussel sprouts).
• 16OH estrone 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 make too much of this dangerous estrogen. 16Oh estrone can be converted to estriol.
• 4OH estrone is the most volatile of the three associated with the most aggressive forms of breast and ovarian cancer. All the factors that influence 16OH conversion affect 4OH as well as age.

Estriol—the pregnancy hormone is the third estrogen and seems to be the least inflammatory and the most nourishing to vaginal and urethral tissues. Estriol is my favorite bio-identical used topically to make an atrophic dry vagina lush.

Unfortunately, getting older increases poor estrogen metabolism, which is why I do not 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 the hormones. Most older women do not have the means to metabolism the hormones safely. Although they can take lots of Dim or IC3 indoles (the active ingredient in cruciferous vegetables) and lots of EPA (fish oils), keep their weight down and drink alcohol in moderation, but I believe reversing age related metabolic enzyme activity takes a multi-pronged approach.

A holistic approach to hormone replacement therapy includes complete neuro-immune-endocrine and metabolic evaluation. Functional medicine testing is available to assess genetic and metabolic capabilities of an individual. There is no one size fit all prescription for hormone replacement or anti-aging therapies.