Natural Versus Synthetic Hormone Replacement Therapy

Are hormones such as Prempro, given to post-menopausal women, natural or synthetic?

I have received a number of questions about natural versus synthetic medications and have not answered before because of a number of problems that I have with this distinction.

First of all, I don’t really know what makes a hormone — or any other medication — natural. Prempro is a combination of conjugated estrogens — commonly referred to by the brand name Premarin — and medroxyprogesterone — commonly referred to by the brand name Provera. Hence Prempro.

Prempro brings together the most commonly used dosages of these two drugs, which are the most commonly prescribed hormones for hormone replacement therapy (HRT) after menopause. The combination would be used in a woman who has a uterus — that is, she has not had a hysterectomy. The progesterone prevents the lining of the uterus from being over-stimulated and possibly becoming cancerous.

A woman who has had a hysterectomy should not take the combination. Plain conjugated estrogen is all that is needed in that situation. It is the estrogen alone that appears to account for all the benefits of HRT, including the slowing or reversal of osteoporosis, the improvement of cardiac risk, and the maintenance of skin and mucus membranes, especially in the vagina. Studies are also now appearing that seem to show that HRT reduces the risk of Alzheimer’s disease by about 40 to 50 percent.

The “pro” of Prempro, which is a progesterone, is synthetic, according to the Physician’s Desk Reference (PDR). But it is almost certainly synthesized from a naturally occurring steroid molecule, which is chemically manipulated to make the desired hormone. Many medicines are the result of chemical manipulation of naturally occurring molecules. When one adds chemical groups to the basic penicillin molecule, which is purified from a mold, to make a more effective antibiotic, is the result natural or synthetic? When one implants a special gene in yeast, which forces the yeast to produce a new drug, is that drug natural or synthetic? Certainly the yeast that produces it is natural. The PDR states that Premarin, the Prem in Prempro, is made from natural sources.

Medroxyprogesterone is synthesized from chemical precursors. I doubt that the natural or synthetic sources of these hormones — or indeed of most drugs — makes any difference in effectiveness or side effects.

My next problem stems from the implication of many of the questions that natural is better. How does one define better in terms of drugs? It seems to me that there are basically two parts to that definition: Is the natural product more effective? And, is the natural product safer? That is, does it produce fewer side effects while maintaining the same efficacy?

The problem I have with many natural products is that we often don’t know what the ingredients of the product are, to say nothing about its effectiveness and safety. By and large, such products have never been tested in large well-constructed studies. Their effectiveness stems from hearsay evidence, like testimonials. One person, or an expert, tells someone else that the product made Uncle Jack feel ten years younger. One rarely hears about the people who took the product and didn’t feel ten years younger, because they were disappointed and didn’t have much to say. One also rarely hears about bad reactions that are produced by natural products, unless they lead to death.

I would love to be able to recommend more natural products, and in fact many of our modern drugs are derived from plant, yeast, or bacterial sources. Taxol, an exciting new anti-cancer drug, is purified from the bark of the Pacific yew tree. But we know what the active ingredient is, and it has been tested in many studies for effectiveness and safety. Other natural products need to be similarly tested before I can recommend them. I certainly can recommend Prempro and other similar combinations because the ingredients — both natural and synthetic — have been extensively tested for effectiveness and safety.

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