7 reasons to consider bio-identical hormone replacement therapy

I recently wrote about the superiority of natural progesterone over the synthetic progestogens.

Let’s look now at the health benefits of naturally-derived estrogens in menopause…

You may have heard of synthetic estrogen brand names such as Premarin, Cenestin, and Enjuvia. These conjugated estrogens have been manipulated in a laboratory and don’t carry the same health benefits as hormones manufactured naturally in your body.

(As I understand it, just more than a year ago the manufacturers of Enjuvia and Cenestin have discontinued their production of these tablets.)

Take Cenestin for example; it is an unnatural hormone used to treat moderate to severe vasomotor symptoms (such as hot flashes/flushes) and vulvar/vaginal atrophy due to menopause. It is recommended that you take this at the “lowest effective dose and for the shortest duration” for safety’s sake. It is widely known that conjugated estrogens do not prevent heart disease or dementia, but rather, they increase your risk of these illnesses.

Conjugated estrogens are mixtures of unnatural estrogen molecules such as sodium equilin sulfate, 17 alpha & 17 beta-dihydroequilin, 17alpha-estradiol, ethinyl estradiol, mestranol, quinestrol and (formerly) diethylstilbestrol. You may remember that in 1971, researchers discovered the link between prenatal DES exposure and clear cell adenocarcinoma of the cervix and vagina (and soon after was banned from the market).

We know from the Women’s Health Initiative 2009 and 2010 reports in the New England Journal of Medicine that women who take synthetic, chemically modified prescription hormones for extended periods of time have an increased incidence of breast cancer, heart attack and stroke, and pulmonary embolism.

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Enter estradiol (E2) and estriol (E3) 

Natural estrogens that are made in a woman’s body and are called estrone (E1), estradiol (E2), and estriol (E3).  These are also made in nature (plants) and can be mixed into creams for therapeutic dosing.

However, be aware that even taking natural estrogen by mouth carries some health risks because when they pass through your liver, you can have unnatural metabolites created which can be a contributor for long term disease. Not so with creams, which absorb directly into your blood stream, then to target organs where they need to be.

There is no question that Estriol (E3) and estradiol (E2) are better for you than conjugated estrogens as I will explain below.

Health benefits of bio-identical transdermal estrogen

Let’s look at the reasons why a menopausal woman would want to consider taking bio-identical hormone replacement therapy (BHRT).

1. Reduces menopausal symptoms

You should first know that the natural estrogens E3 and E2 work well for reducing menopausal symptoms. Estriol (E3) naturally converts to estradiol (E2) in your body.

A study using estriol therapy that was reported in the November 1987 Hormone and Metabolic Research 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.

2. Improves sexual desire and functions

Apparently, vaginal administration of 50 mg ethinyl estradiol results in circulating ethinyl estradiol levels equivalent to those achieved after oral ingestion of 10 mg ethinyl estradiol.

3. Prevents memory loss

Animal and human studies show that transdermal estrogen replacement therapy, when started before menopause, decreases memory loss in older age.[  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.  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.

4. Improves heart health

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.  Estrogen lowers anti-thrombin III levels, thereby lowering recurrent venous thrombosis (vein clotting).

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5. Reduces breast cancer risk

Estriol protects against breast cancer according to a number of studies. When given with estradiol or with progestin, estriol showed clear breast cancer-protecting effects.  In a large study of 30,000 women reported in 2004, those who used estriol only had no increased rate of breast cancer, while those who used “estrogen” only did.  In a large case-control study of 3345 women, the risk for breast cancer among estriol users was the same as nonusers.  Estrogen plus progesterone clearly decreases breast cancer risk. This was shown to be true in a double-blind placebo-controlled trial 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 reported in 1998; and also in a primate animal study reported in 2007.

6. Strengthens bones

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.

7. Improves skin

Did you know that topical estrogen combined with nutrients (such as Hyaluronic Acid, Vitamin C, and other nutraceuticals) can be used topically on your face to improve your skin quality? A 2007 study found that topical estrogen helps increase skin collagen which may improve postmenopausal facial skin.

Estrogen dosing

Estrogen is usually taken along with progesterone in order to lower the otherwise increased risk of uterine cancer.

The usual dose of estrogen cream for menopausal symptoms is 0.5 mg to 2.0 mg or more per day of “biest” (estradiol and estriol in a 1:4 ratio or 1:1 ratio). If the woman is still having periods, she can use it days 5-25 of her cycle. If she is menopausal she can use it continuously or with a 3-5 day break every 3 months along with progesterone.

To healthy hormones and longevity,

Michael Cutler, M.D.


  1. PREMARIN® (conjugated estrogens tablets, USP) — premarin.com
  2. CENESTIN — RxList
  3. Discontinuation of Enjuvia® Tablets — National Pharmaceutical Services
  4. Conjugated estrogens (oral) (Cenestin, Enjuvia, Premarin) — emedicinehealth.com
  5. Diethylstilbestrol (DES) and Cancer — National Cancer Institute
  6. Chlebowski RT, et al. Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women. N Engl J Med 2009; 360:573-587.
  7. Colditz GA, Hankinson SE, Hunter DJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995 Jun 15;332(24):1589-93.
  8. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women JAMA. 2002;288(3):321-333.
  9. Lauritzen C. Results of a 5 years prospective study of estriol succinate treatment in patients with climacteric complaints. Horm Metab Res. 1987 Nov;19(11):579-84
  10. Synthetic estrogens — Science Direct
  11. Craig MC, Murphy DG. Estrogen therapy and Alzheimer’s dementia. Ann N Y Acad Sci. 2010 Sep;1205:245-53
  12. Baldereshi M, Di Carlo A, et al. Estrogen-replacement therapy and Alzheimer’s disease in the Italian Longitudinal Study on Aging. Neurology 1998 Apr;50(4):996-1002.
  13. Tang MX. Jacobs D, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 1996 Aug17;348(9025):429-32.
  14. Minshall RD, et al. Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys. J Clin Endocrinol Metab 1998;83(2):649-659.
  15. Melamed M, et al. Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol. Mol Endocrinol 1997;11(12):1868-1878
  16. Bakken K, et al. Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study. Int J Cancer 2004;112(1):130-134.
  17. Magnusson C, et al. Breast cancer risk following long term oestrogen and oestrogen-progestin replacement therapy. Int J Cancer 1999;81(3):339-344.
  18. Chang KJ, et al. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril 1995;63(4):785-791.
  19. Foidart JM, et al. Estradiol and progesterone regulate the proliferation of human breast epithelial cells. Fertil Steril 1998;69(5):963-969.
  20. Wood CE, et al. Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys. Breast Cancer Res Treat 2007;101(2):125-134.
  21. Lufkin EG, Wahner HW, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 1992;117(1):1-9.
  22. Cicinelli E, Galantino P, et al. Bone metabolism changes after transdermal estradiol dose reduction during estrogen replacement therapy: A 1-year prospective study. Maturitas 1994;19(3):133-139.
  23. Effects of topical estradiol on the facial skin collagen of postmenopausal women under oral hormone therapy: a pilot study. Patriarca MT, Goldman KZ, Dos Santos JM, Petri V, Simões RS, Soares JM Jr, Simões MJ, Baracat EC. Eur J Obstet Gynecol Reprod Biol. 2007 Feb;130(2):202-5. Epub 2006 Jun 23.
Dr. Michael Cutler

By Dr. Michael Cutler

Dr. Michael Cutler is a graduate of Tulane University School of Medicine and is a board-certified family physician with more than 20 years of experience. He serves as a medical liaison to alternative and traditional practicing physicians. His practice focuses on an integrative solution to health problems. Dr. Cutler is a sought-after speaker and lecturer on experiencing optimum health through natural medicines and founder of the original Easy Health Options™ newsletter — an advisory on natural healing therapies and nutrients. His current practice is San Diego Integrative Medicine, near San Diego, California.