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Menopause facts: Synthetic versus bio-identical hormones

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Beginning in the 1970s pharmaceutical companies told us that these synthetic hormones were proven to be safe based on small studies.  And doctors prescribed them almost universally to woman nearing menopause.

But when larger studies were completed in 2002, called the Women’s Health Initiative (WHI), 1 it was revealed that synthetic oral estrogen plus progestin therapy is actually not as safe as we thought.

These studies showed women taking synthetic, chemically modified prescription hormones for extended periods had an increased incidence of breast cancer, 2 a higher risk of heart attack and stroke, 3 and more pulmonary embolism.

As a result of the headline news about these studies, approximately 50 million women were then faced with going “cold turkey” off their hormones and living with symptoms. The good news is that recent studies show us the safety of transdermal natural estrogen and real progesterone.

Real versus synthetic estrogen and progesterone

You may have heard of estrogen manufactured from horses urine (Pre-mare-urine, or Premarin®) and the synthetics Cenestin, Enjuvia, Congest, or the esterified estrogens Menest, Femogen, and Estratab. There are many brands being manufactured and marketed as “estrogen” yet contain unnatural molecules such as sodium equilin sulfate, 17 alpha 17 beta-dihydroequilin, and 17alpha-estradiol.

It’s easy to get confused with all the different names, but what’s important to realize is this: These estrogens are synthetic, meaning they have been manipulated in a laboratory and are not the same 17 beta-estradiol that your body makes.

Synthetic progestins are also unnatural hormones. Your doctor may have mentioned some of these to you… medroxyprogesterone (Provera®), Norethindrone, Levonorgestrel, and Norethindrone acetate. Biochemically, our bodies do not know how to manufacture synthetic progestins, nor do we naturally make any enzymes (that science has identified) to properly metabolize them.

In light of the studies that have clearly shown the danger associated with synthetic hormones, it’s interesting that the American College of Gynecology still promotes the use of synthetic progestins while calling bio-identical progesterone a “so-called” hormone.

However, the scientific literature shows us that synthetic progestins promote breast cancer, while real progesterone does not. The 1995 Nurse’s Health Study reported that in 58,000 postmenopausal women were followed for 16 years, estrogen (oral) alone increased risk for breast cancer by 23 percent, but addition of synthetic progestin resulted in tripling the risk. 4 But natural progesterone supplementation affects breast cancer quite differently. There are 8 well designed studies showing with clear clinical significance that the use of natural progesterone lowers the risk of breast cancer.

Why take natural estrogen and progesterone even after menopause?

Natural estrogen replacement (as a cream or troche under the tongue, not pills you swallow) simply works better than synthetic estrogen pills for reducing menopausal symptoms. A study using estriol therapy that was reported in the November 1987 Hormone and Metabolic Research 5 showed that it reduced menopausal symptoms in 92% of subjects, and completely elimination hot flashes and sweating in 71% of the subjects.  It completely eliminated depressed moods in 24% and this was reduced in severity for another 33%. It also reduced headaches by two-thirds and skin improved in some of the subjects. And there were no significant side effects reported.

Furthermore, large clinical trials have now verified that natural (bio-identical) estrogens and progesterone are effective for curbing menopausal symptoms. Even more importantly, they reduce diseases such as breast cancer, cardiovascular disease, osteoporosis, and Alzheimer’s dementia.  Let me tell you even more…


Estrogen for better memory

In the Italian Longitudinal Study on Aging reported in 1998, researchers found that among the 2,816 women aged 65 to 84 years who were followed, the rate of Alzheimer’s disease was only a fourth as much among estrogen users compared with the general female population of the same age and multiple other risk factors. 6  A study reported in 1996 found that that among 156 women who reported taking estrogen after onset of menopause, those who later developed Alzheimer’s disease did so much later (delayed onset) and significantly less (60 percent fewer) compared with women who did not take estrogen. Also, those who had used estrogen longer than a year had even a greater risk reduction for Alzheimer’s disease. 7

Estrogen decreases cardiovascular disease risk

We know that transdermal estrogen lowers bad cholesterol (LDL) and raises good cholesterol (HDL). Coronary artery spasm, which precipitates a heart attack by squeezing down areas of the vessel where there is already atherosclerotic plaque, is decreased with the use of estrogen and also estrogen plus progesterone. 8  Estrogen lowers anti-thrombin III levels, thereby lowering recurrent venous thrombosis (vein clotting).

Estrogen treats and prevents osteoporosis

It is clearly known that transdermal estrogen supplementation reduces bone fracture rates in postmenopausal women.  Subjects using only a low dose of only 0.1 mg per day stopped losing bone density and dramatically reduced their fracture rate as demonstrated in two clinical trials. 910

Estrogen plus progesterone lowers breast cancer risk

Estrogen plus progesterone clearly decreases breast cancer risk. This was shown to be true in a double blind placebo-controlled trial 11 of women given estrogen plus progesterone prior to breast surgery reported in 1995. This was shown to be true in a randomized double-blind study 12 reported in 1998; and also in a primate animal study 13 reported in 2007.

Note that estrogens are naturally made in a woman’s body and are called estrone (E1), estradiol (E2), and estriol (E3).  Be aware that taking estrogen by mouth carries some health risks from the unnatural metabolites created when it passes through your liver, but this does not occur when it taken as a troche or cream. And real progesterone from can safely be taken by mouth or as a cream.


Progesterone levels usually drop even before estrogen levels when nearing the menopausal years. Low progesterone levels cause the classic symptoms of PMS (premenstrual syndrome) which include irregular, heavy, or painful periods, breast tenderness, mood swings, irritability, insomnia, migraine headaches, and bloating (puffy face and extremities). Therefore, progesterone supplementation becomes very useful for many women even before menopause.

Progesterone is calming and provides for restful sleep. In addition to treating PMS symptoms, progesterone supplementation during near the menopause years acts much like estrogen in treating menopausal symptoms (hot flashes, breast tenderness, decreased sex drive, vaginal dryness, irregular periods, and even urinary leakage or urgency). A one-year trial of bio-identical transdermal progesterone cream in postmenopausal women produced a significant reduction in hot flashes according to a 1999 report in Obstetrics and Gynecology. 14 But it has important long term health effects too.

Progesterone lowers breast and uterine cancer risk

These studies taught us that natural progesterone helps reduce breast cancer:

  • In 1981 the Journal of Epidemiology 15 reported that 1083 women were treated for infertility and followed for 13-33 years for incidence of breast cancer. The premenopausal risk for breast cancer was 5.4 times higher in women with low progesterone levels compared to those with normal levels, and there were 10 times more deaths from cancer in the low progesterone group compared with those with normal progesterone levels.
  • A 2002 study reported in Cancer Epidemiology, Biomarkers Prevention 16 showed in a case-control study looking at third trimester progesterone levels and breast cancer risk that increasing levels of progesterone were associated with decreased risk of breast. This association was strongest before the age of 50. They also found that those in the highest quartile of progesterone levels had a 50 percent reduction in breast cancer compared with those in the lowest quartile of progesterone levels.
  • In 2003 researchers found that transdermal or vaginal progesterone cream for four weeks reduced uterine lining thickening caused by an estrogen drug in postmenopausal women. 17
  • In 2004 a prospective study of progesterone levels and associated breast cancer risk in 5963 women was reported in the International Journal of Cancer. 18
  • In 2008 researchers reported that they had followed 80,000 postmenopausal women for over 8 years. They showed that using natural progesterone along with estrogen significantly reduced breast cancer risk compared to the use of synthetic progestin. 19

Progesterone improves heart health

Progesterone also is beneficial to heart health. It has a vascular relaxation effect (to lower blood pressure and the strain on the heart). The Women’s Health Initiative studies showed that progesterone (unlike synthetic progestins) increases the cardio-protective effects of estrogen and reduces the risk of heart attack and stroke. Progesterone also improves lipid profiles and helps estrogen to improve lipid profiles (unlike synthetic progestins). There are several similar studies to show this beneficial heart health effect from natural progesterone.

Progesterone’s effect on bone strength

Scientists have observed that natural progesterone stimulates osteoblast activity (new bone formation) and helps prevent osteoporosis. 20  Estrogen does too, and when added together, progesterone and estrogen collaborate for maximal prevention of bone loss. 21

To feeling good in health,

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