Progesterone Resource
Center
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)
