Now that we are ten years out from the now infamous “Women’s Health Initiative” trial that shocked the world into believing that hormones were actually bad for us, there are still many patients and clinicians alike holding onto that old paradigm. It is very unfortunate because it is preventing a good number of people from being able to use therapies that have been proven repeatedly in many clinical trials in this country and abroad to decrease morbidity and mortality. To quickly summarize a few of the downfalls of the WHI trial, the average age of women in that trial was age 64, the trial was a prevention trial rather than a treatment trial, and it combined a synthetic estradiol that is derived from horses with a synthetic progesterone that has no true equivalent in the human body. The outcome of that trial, after a decade of dissecting the data, was that estradiol, even that derived from horses, did in fact reduce the rate of cardiovascular disease in patients and the effects were best seen if the hormone was started within ten years of menopause or before age 60, and continued for at least five years. There was also a significantly lower rate of breast cancer in the premarin group, despite a higher rate in the patients receiving both premarin and synthetic progesterone (Provera). The increased thrombosis risk was seen in patients receiving synthetic progesterone, but not estrogen alone. Overall, the quality of life of patients receiving HRT was subjectively significantly better. Both prior to and since the WHI trial, there have been hundreds of trials conducted in the US and abroad which have shown a significant clinical benefit when comparing synthetic and non-synthetic hormone replacement and have also shown a benefit over women using no HRT at all. In the realm of cancer prevention, Fournier et al published a large trial in 2008 involving 80,000 post-menopausal women that were followed for eight years comparing HRT users to non-users. They found that use of estradiol had no significant increase in breast cancer occurence. Synthetic progesterone and estrogen was associated with a 1.69 times relative risk, and use of bio-identical estrogen plus progesterone had a significant decreased risk of breast cancer. (Br. Ca Research Treat 2008; 107(1)103-111). In another large prospective trial of 5963 pre-menopausal women, progesterone levels were measured and tracked and those with the highest levels had an 88% reduction in risk for breast cancer. (Int. Journal of Cancer 2004, Nov1; 112(2)312-8). Another large prospective epidemiologic trial of 1083 women treated for infertility found that those with the lowest progesterone levels had a 5.4 times increased risk of breast cancer. They also had ten times as many all-cancer deaths and had a worse breast cancer survival rate. (Am. Jour. Epidemiolog 1981 Aug 114 (2) 209-17) The benefit with estradiol seems to also hold with estriol, a less potent form of natural estrogen, also referred to as E3. In a trial of 3345 women age 50-74 of breast cancer was not increased by those using estriol compared to non-users. (Int. J Of Cancer 1999 Mat 5; 81(3)339-44). In addition, the use of transdermal or intravaginal estriol was NOT associated with an increase in endometrial cancer . (Lancet 1999, May 29, 353(9167); 1824-8) (Eur. Jour. ObstetGynecol/Reprod. Biol 1995 Sep 62 (1); 101-6 From a cardiovascular standpoint, we know that the natural estrogens etradiol and estriol and natural progesterone all have extensive benefits. These include but are not limited to improving lipid parameters by decreasing LDL and LDL oxidation, increasing HDL, decreasing Lp(a), decreasing hs-CRP, decreasing blood pressure, relaxing vasospasm/constriction of blood vessels, decreasing platelet aggregation, and decreasing atherosclerosis. In animal trials, estriol decreased cardiovascular disease by 75%. Trials showed that the vasospasm felt responsible for strokes and heart attacks was seen with synthetic medroxyprogesterone and estradiol, not natural progesterone. (Journal Endocrinol Met 1998; 83(2)649-659)(Nat Med 1997; 3(3) 324-327) (Metab 2005; 90 (6) 3706-3714) In women with known coronary artery disease (atherosclerosis), the time to exercise-induced ischemia was increased when they were given progesterone. ( J. Am. Coll, Cardiol 2000; 36 (7); 2154-2159) When bio-identical progesterone was added to oral estradiol therapy it actually decreased the risk of venous thrombosis. ( Circulation 2007 Feb 20; 115(7) 840-5). Estrogen plays a role in the control of several HUNDRED functions in the human body. What we know about the cardio-protective benefit is the tip of the ice berg. We also know it helps protect the brain in many ways including protecting from oxidative damage and beta-amyloid plaque deposition. It also helps protect bones and muscle, preventing osteopenia and sarcopenia. It preserves the vaginal mucosa and pelvic floor muscles preventing against vaginal atrophy, pelvic pain, incontinence and recurrent urinary infections. ( Climacteric 2012 Apr; 15 Supp 1:11-7) So I ask, why are more doctors not aware of the data and working to educate their patients on these life-preserving treatments rather than suggesting that bio-identical hormones are no different than synthetics and will cause clots and cancers and heart disease? I personally believe that within the next 5-10 years we will be using more specific bio-identical estrogens and progesterones combined with hormone enhancing natural treatments as mainstream treatment of breast cancer and other gynecologic cancers, even if they are estrogen and progesterone receptor positive. There is mounting evidence that this may be effective, much like tamoxifen binds on estrogen receptors and prevents the deleterious estrogen from acting. One must look at all the latest information with an open mind and embrace it when it is based on hard data. More patients need to educate their doctors on some of these issues since that may be the only way that their doctors will ever learn that there is a brave new world out there.