Bio-identical Estrogens: Not Your Mother’s Premarin
Since 1942, Premarin has been the most commonly prescribed estrogen supplement in the United States. In the 1960s, Dr. Robert Wilson put it firmly on the map with his book “Feminine Forever” as a panacea for what ails all women who have either undergone menopause or a hysterectomy. It quickly became the most popular cure-all for the aging woman.
However, in the 1970s, Premarin’s heyday came to a screeching halt when it was discovered that unopposed estrogen therapy dramatically increased the risk of uterine cancer in women with an intact uterus and sales plummeted.
Ingenuity, spurred by Wyeth’s lagging pharmaceutical sales, brought about progestin in the 1980s, a progesterone-type hormone that counteracted the impact of estrogen on uterine tissue. Suddenly, Wyeth was back in business with the Premarin-PremPro one-two, hormone replacement punch. From 1992 through 2001 Premarin and PremPro were the most widely prescribed drugs in the United States.
The problem is that although Premarin had merit and helped alleviate menopausal symptoms and boosted bone health, neither it nor Prempro are bio-identical. This means that unlike the female’s endogenous hormones (the kinds the human body makes), these two hormones did not entirely fit the body’s cell receptor sites, which can cause side-effects and lack the properties to fully protect the female body from disease states.
In this article, we’ll focus primarily on Premarin vs. Bio-Identical Estrogen and how the two differ.
What is Premarin? Premarin is isolated from PREgnant MARes’ urINe and is a mixture of conjugated equine estrogens (CEE) (some unique only to horses), steroids, and various other substances. These hormones are only approximately 30% identical to human hormones. Broken down, the two key estrogens in Premarin are estrone sulfate (50 to 60%) and equilin sulfate (22.5 to 32.5%).
Although Premarin has been shown to alleviate menopausal symptoms and increase bone density, bio-identical estrogen has been shown to do that and much more!
What Are Bio-identical Estrogens? Premenopausal women produce 3 biologically active estrogens, estrone (E1), estradiol (E2) and estriol (E3). Estradiol is the most abundant estrogen produced and both estrone and estradiol are considered potent estrogens. Estriol is considered the weakest estrogen. Estrogens are the family of hormones largely responsible for development and maintenance of the female reproductive system. They also help control and maintain a number of other body systems, including bone production, cardiovascular health, and cognitive development.
Bio-identical hormones are often plant-based (yam or soy) and synthesized to have the exact same chemical and molecular structure as hormones that are produced in the human body. Because of this, it is believed that they have more natural reactions in the body without the unwanted preservatives and additives.
Animal research has shown that the Premarin (CEE) metabolite 4-hydroxyequilenin is more mutagenic than its human equivalent, 4-hydroxyestrone. Similarly, cell research found that equine metabolite 4-hydroxyequilenin induced considerably more DNA damage and apoptosis in breast cancer cells than 4-hydroxyestrone, illustrating that structure and type of hormones matter in the human body.
How Does This Translate in the Body? What Other Studies Say?
Brain: When initiated soon after menopause, hormone therapy with estradiol prevented degeneration in key brain regions of women who were at heightened dementia risk, according to a new study led by Stanford University School of Medicine researchers. The investigators also found that Premarin was far less protective.
Heart: Estradiol may have cardioprotective effects and may have fewer adverse effects on blood pressure than conjugated equine estrogens. On the other hand, oral CEE significantly increases matrix metalloproteinase (MMP-9), which plays a significant role in the mechanics of atherosclerotic plaque rupture. Estradiol also has favorable effects on lipoprotein levels (increases HDL (good) cholesterol and lowers LDL (bad) cholesterol, vasomotor function, LDL oxidation, and coagulation.
Bones: Estrogen promotes osteoblasts, which are cells that produce bone. A study of older women showed that estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects.
Emotional Health: In a study of 172 perimenopausal and early postmenopausal women ranging in age from 45 to 65 who were experiencing low-level symptoms of depression found that bio-identical estradiol and progesterone was more effective than the placebo in preventing the development of clinically significant depressive symptoms.
Mortality: In 2015, a Finland study of almost 500,000 women showed that those who took hormone therapy had a lower mortality rate than women who did not. Broken down by cause, the study showed that in the patients on hormone therapy the risk of heart disease was reduced by 18-54%, the risk of stroke decreased by 18-39%, and risk of all-cause mortality was reduced in the hormone users by 12-38%. There was also strong correlation with the duration of hormone use, and benefits were magnified by starting hormones closer to the onset of menopause.
If we are to take away anything from the above studies, it’s that hormones, specifically hormones designed to mimic the body’s endogenous hormones, have huge benefits to a woman’s short-term well-being and long-term health. Not only do they promote normal homeostasis in most systems, they also protect women from all causes of mortality!
How Can I Find a Doctor Who Prescribes Bio-Identical Hormones?
The Academy of Preventive and Innovative Medicine trains physicians in hormone therapy. We have not only identified competent and forward-thinking physicians throughout the country who offer these therapies, most of them are also trained by our experts to offer you the best care. To find a doctor near you, simply go to www.worldlinkmedical.com and click on ‘find a provider’.
Chu MC, Cushman M, Solomon R, Lobo RA. Metabolic syndrome in postmenopausal women: the influence of oral or transdermal estradiol on inflammation and coagulation markers. Am J Obstet Gynecol. 2008;199(5):526.e1-7.
Samar R. El Khoudary et al. Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial, Journal of the American Heart Association (2019).
Pisha E, Lui X, Constantinou AI, Bolton JL. Evidence that a metabolite of equine estrogens, 4-hydroxyequilenin, induces cellular transformation in vitro. Chem Res Toxicol 2001;14:82-90.
Tikkanen MJ, Nikkila EA, Vartianen E. Natural oestrogen as an effective treatment for type-II hyperlipoproteinemia in postmenopausal women. Lancet.1978; 2:490-491.
Granfone A, Campos H, McNamara JR, Schaefer MM, Lamon-Fava S, Ordovas JM, Schaefer EJ. Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women. Metabolism.1992; 41:1193-1198.
Lobo RA. Effects of hormonal replacement on lipids and lipoproteins in postmenopausal women. J Clin Endocrinol Metab.1991; 73:925-930.
Guetta V, Cannon R. Cardiovascular Effects of Estrogen and Lipid-Lowering Therapies in Postmenopausal Women. Circulation. 1996;93:1928–1937
Chen Y, Liu X, Pisha E, et al. A metabolite of equine estrogens, 4-hydroxyequilenin, induces DNA damage and apoptosis in breast cancer cell lines. Chem Res Toxicol. 2000;13(5):342-350.
Conway E. Bioidentical Hormones: An Evidence-Based Review for Primary Care Providers. The Journal of the American Osteopathic Association, March 2011, Vol. 111, 153-164.
Mikkola, Tomi S.; Tuomikoski, Pauliina; Lyytinen, Heli; Korhonen, Pasi; Hoti, Fabian; Vattulainen, Pia; Gissler, Mika; Ylikorkala, Olavi. “Estradiol-based Postmenopausal Hormone Therapy and Risk of Cardiovascular and All-cause Mortality” Menopause. Sept. 2015: Vol.22- Iss. 9. Pp. 976-83.