FDA Cracks Down on Estriol

Julian Whitaker, MD

Well, it’s finally happened. In an unprecedented action, the FDA has started cracking down on physicians and compounding pharmacies that use estriol.

Estriol, a natural form of estrogen, is an excellent therapy for easing symptoms of menopause and treating multiple sclerosis. It’s also the safest form of estrogen because it protects against the adverse effects of other, stronger estrogens. For decades, estriol has been recognized by the United States Pharmacopoeia (USP), the official standards-setting authority for all drugs, supplements, and other healthcare products in the US.

Never has a USP-listed ingredient with no evidence of toxicity been summarily removed from the market at the behest of a drug company. Never!

For this, we can thank Wyeth Pharmaceuticals.

Sales Trump Women’s Health

In October 2005, Wyeth asked the FDA to “initiate enforcement action, in the form of seizures, injunctions, and/or warning letters” with regard to the compounding, distribution, and advertising of bioidentical hormones.

The reasons for this couldn’t be more transparent. Wyeth is in a world of trouble. They’ve had delays in the approval process of four new drugs, and two of the company’s best-selling drugs—the stomach acid–reducer Protonix and the antidepressant Effexor—are facing stiff competition from generic drugs that may cut into 40 percent of their profits.

Wyeth is also dealing with diminished sales and thousands of lawsuits—with payouts of hundreds of millions of dollars so far—stemming from damages caused by their hormone replacement drugs Premarin (conjugated estrogen derived from horse urine) and Prempro (a combo of Premarin and Provera, a progestin or synthetic progesterone). In a 2007 case, Nevada jurors agreed that these drugs caused breast cancer and awarded three women $134 million in compensatory and punitive damages.

It’s no wonder this company is trying to cut its losses, but using the government to edge out competition is a sleazy way to go about it. If compounded bioidentical hormones were unavailable, women who are going through menopause, have had a hysterectomy, or require hormone replacement therapy for other reasons would have no choice but to use Premarin, Prempro, and the other commercially available, patented, side effect–riddled hormones.

Conventional Hormones Are Harmful

The fallout on hormone replacement therapy started in 2002, when the Women’s Health Initiative, a government-funded study of Prempro, was prematurely halted because of safety concerns. Women taking Prempro were found to have a 100 percent increase in blood clots, 41 percent increase in strokes, 29 percent increase in heart attack, and 26 percent increase in breast cancer.

Considering that more than 6 million women were taking Prempro and other related drugs, it has been estimated that conventional hormone replacement therapy drugs are responsible for more than 100,000 breast cancer diagnoses over the last 12 years. And who knows how many heart attacks, strokes, and other serious problems they might have caused.

As you can imagine, this scared away many of the women taking these drugs, and sales dropped from more than $2 billion in 2001 to $880 million in 2004. You’d think it would have also scared Wyeth into taking the drugs off the market, or at least making them safer, but it didn’t. All they did was to come out with a lower dose of Prempro and strengthen their warnings of side effects. Obviously, this company is most concerned about their bottom line.

Now that you understand where this FDA action came from, let’s look at bioidentical hormones in general and estriol in particular.

Natural, Safe, and Beneficial

You don’t have to be a rocket scientist to understand that natural substances familiar to the body are safer and more effective than compounds derived from synthetic sources or animal byproducts. Drug developers aren’t stupid, but they also know that natural compounds can’t be patented. Therefore, there will never be much emphasis on the research and development of such compounds. There’s just no profit motive.

However, it’s ridiculous for the FDA to insist that bioidentical hormones “have not been demonstrated to be safe and effective” and that synthetic progestins and horse estrogen are as safe as natural estrogen and progesterone. Given all the problems with Prempro, even conventional physicians are beginning to see the light.

One form of natural estrogen, estradiol, is growing in popularity, and natural progesterone is gaining ground. In a 2007 review article, Harvard researchers stated, “Synthetic progestins marketed as Provera, Prempro, and Cycrin are widely used but may produce a number of significant side effects [fatigue, fluid retention, lipid level alterations, anxiety and restlessness, increased risk of blood clots, and acne]…. Micronized natural progesterone is available for oral administration, has better bioavailability and fewer side effects…. Therefore, micronized natural progesterone appears to be a safe and effective alternative….”

The Truth About Estriol

The hormone under the gravest threat is estriol. Along with estradiol and estrone, estriol is one of the three major types of natural estrogen. Physicians typically prescribe these hormones in proportions akin to what the body produces naturally. Of the three, estriol is the weakest and safest. Yet the FDA has singled it out primarily because it isn’t sold as a conventional prescription drug. You can fill a script for natural micronized progesterone (Prometrium) and estradiol (Climara and Estraderm) at your corner drugstore, but you can only get estriol from compounding pharmacies.

This would be laughable if the consequences weren’t so serious. Estriol is unbelievably safe. During pregnancy, estriol levels go up 1,000-fold. If high doses are safe for fetuses, low doses are certainly safe for women.

Additionally, we’ve known for decades that estriol actually protects against breast cancer. In 1966, H.M. Lemon, MD, published a study in JAMA demonstrating that women with breast cancer had lower levels of estriol. Twelve years later in the same journal, Alvin Follingstad, MD, implored, “Do we as clinicians have to wait the years necessary for the completion of these [costly FDA clinical] trials before estriol becomes available to us? I think not. Enough presumptive and scientific evidence has been accumulated that we may say that orally administered estriol is safer than estrone or estradiol.”

Thirty years later, despite the fact that the FDA admits there have been no reports of adverse events related to estriol, they’ve jerked it off the market.

Save Our Hormones

Natural estriol, estradiol, and progesterone, alone or in personalized combinations, can be a real blessing for patients. They relieve menopausal hot flashes and mood swings, increase bone density, ease symptoms of PMS, enhance sexual function by lubricating the vagina, and improve symptoms of multiple sclerosis. (In fact, estriol’s effects on MS are the focus of FDA-endorsed clinical trials currently underway at UCLA. What’s going to happen with that?)

Compounded hormones are available in whatever dosage your doctor orders in oral, sublingual, or transdermal forms. This allows physicians to individualize drugs to meet the needs and preferences of their patients—an impossibility with conventional drugs, which usually come only in pills and in no more than two or three strengths.

Taking away estriol and squeezing out other bioidentical hormones will harm the hundreds of thousands of women who have benefited from them. However, I’m also concerned about the untold millions who are suffering with the above-mentioned conditions but are afraid to use conventional hormones. Rather than placing more restrictions on safe, natural alternatives, the FDA should be encouraging their use.

What You Can Do

When we first became aware of Wyeth’s petition in 2006, I urged you to participate in a letter-writing campaign to the FDA. In the ensuing months, the FDA received more than 70,000 comments, virtually all of them expressing their displeasure with the petition and telling the FDA to keep their hands off compounding pharmacies.

Now, all we can do is keep the pressure on by contacting our congressional representatives and let them know how we feel about issue. There is growing encroachment on all aspects of our lives, including our medical care. If we allow this kind of irrational activity to continue unabated, in a few years we’ll be left with an economically unsustainable system that offers little choice. Bioidentical hormones, nutritional supplements, and other alternative therapies will be a distant memory, and our health will deteriorate as a result.

References

• Follingstad, AH. Estriol, the forgotten estrogen? JAMA. 1978 January 2;239(1):29–30.
• Goletiani NV, et al. Progesterone: review of safety for clinical studies. Exp Clin Psychopharmacol. 2007 Oct;15(5):427–444.
• Lemon HM, et al. Reduced estriol excretion in patients with breast cancer prior to endocrine therapy. JAMA. 1966;196(13):1128–1136.

Modified from Health & Healing with permission from Healthy Directions, LLC. Copyright 2008. Photocopying, reproduction, or quotation strictly prohibited without written permission from the publisher. To subscribe to Health & Healing, click here.