Progesterone or Progestin - A Mistaken Identity

by George Gillson, M.D., Ph.D.

I'm writing to vent my spleen about the quality of some of the information about progesterone being dispensed in the throwaway CME "journals", so I hope you will indulge me, as it is difficult to get negative comments published in the magazines themselves. My first rant concerns an article entitled "Surviving menopause without HRT" which appeared in The Canadian Journal of Diagnosis, pg 62, May 2004. The author, Dr. Christiane Kuntz notes that many of the adverse outcomes seen in the Premarin/Provera arm of the WHIS were not seen in the Premarin only arm. She finds this "fascinating" and goes on to ask "Could progesterone be causing some of the perceived increase in risk? [risk demonstrated in the combined HRT arm]. Dr. Kuntz, this would indeed be a "fascinating" finding, since progesterone was not even studied in the WHIS !!!

People!! Please, please, please make the critical distinction between progesterone and progestins in your mind and in your vocabulary! There is only one progesterone, and the word progesterone is not a catch-all or substitute for the words "progestin" or "progestagen". Similarly with the molecules themselves. Outside of contraceptive and oncologic uses, progestins are no substitute for progesterone, and the sooner the medical profession gets this message, the better. Casual interchange of these terms has helped us into the hormone pickle in which we now find ourselves.

My second rant concerns an article authored by Dr. Wendy Wolfman entitled "Hormone Replacement Therapy: Best Advice in 2004" which appeared in Patient Care Canada, pg 61, June 2004. Overall this is not a bad article, but it needs to be taken with a grain of progesterone. On page 67 the author cites "an Italian study" which demonstrated that progesterone cream is beneficial for hot flashes. The article in question was authored by Helene Leonetti, who may very well be Italian, but the study was actually performed at St. Luke's Hospital in Bethlehem, Pennsylvania. A minor point, admittedly, but it makes me wonder if the author actually reads all the papers she cites. Unfortunately this impression is only strengthened by the next sentence, in which she cites a "review" article indicating that topical progesterone is not beneficial for hot flashes. First of all, that study (Wren B et al. Menopause 2003;10:13-18.) was not a review article, it was an actual study. If you read the study carefully, you discover that there was no elevation of the serum progesterone level above baseline (<1 ng/ml), when the topical progesterone was used. This does not mean that topical progesterone in general is poorly absorbed. It means that the cream used in that particular study had poor absorption characteristics. (Interestingly, negative findings pertaining to endometrial protection by topical progesterone were demonstrated in an earlier paper by the same author, using the same cream, and again, that cream failed to establish serum progesterone levels in the range 2-4 ng/ml, as demonstrated by numerous other studies. One wonders why the same cream was used in both studies, unless the intent was to discredit topical progesterone. But then again, Dr. Wren did go on to publish a paper extolling the virtues of a novel sublingual hormone delivery system he was developing, so one has to wonder about motive, ties to the pharmaceutical industry, secondary gain issues and so forth. But I digress.)

One minute on Medline will turn up numerous articles indicating that by and large, progesterone is well absorbed through the skin, and establishes stable serum levels in the aforementioned range: 2-4 ng/ml. This contradicts Dr. Wolfman's next assertion: "Transdermal progesterone is poorly absorbed." I say assertion because she does not cite any literature to support her contention. (Progesterone is about 5 times more permeable through human skin than estradiol and testosterone. So if we already have commercially available topical gels for both these other hormones, why are we questioning the skin absorption of progesterone? But I digress.) I have a great little paper entitled "Over-the-Counter Progesterone Cream Produces Significant Drug Exposure Compared to an FDA-approved, Oral Progesterone Product" which was presented earlier this year at a Clinical Pharmacology meeting in the US. This paper has not been published but I would be happy to email a copy to anyone who is interested. This study was a head to head comparison of Prometrium and Progest, an OTC progesterone cream. The authors concluded that "the use of over-the-counter progesterone cream Pro-gest results in equal systemic 24 hour exposure compared to the FDA-approved progesterone product Prometrium." (This crossover study demonstrated equal areas under the whole blood progesterone concentration vs time curves, when integrated over 24 hours.) Sadly, the authors go on to conclude that since the WHIS showed us that progesterone is dangerous, people should not be able to buy OTC progesterone cream in the US because it is too well absorbed. You can bet your boots that a topical progesterone product will be on the market in the next 2-3 years, once the OTC competition has been removed. But I digress.

Bottom line: there is alot of nonsense being printed about progesterone these days. Don't be mislead by poorly-researched articles. Do your own homework and your own thinking. You will benefit in the end.

Article written by:
George Gillson M.D., Ph.D.
Rocky Mountain Analytical
Unit A, 253147 Bearspaw Rd NW
Calgary, AB T3L2P5
Canada
403 241 4514 (4516 fax)