Over the last several days, I have seen a couple of posts concerning the use
of Lupron, a common anti-estrogen hormone (actually a analog of human
gonadotropin releasing hormone) used in human medicine for the treatment of
adrenal disease in ferrets.
 
Unfortunately, I have some major concerns about the use of this compound as
a treatment for the adrenal disease which requires me to speak up.  Let me
first state that I don't not think that Lupron will necessarily harm the
ferrets on which it is used, however, from my knowledge of its
pharmacokinetics, a review of the literature, and my conversation today with
a M.D. reproductive endocrinologist (who uses it in humans on a daily
basis) there is no indications that it would treat adrenal-associated
endocrinopathy in the ferret.  This is very new ground, it may not work, and
it certainly should not be thought as a cure for AAE.
 
Lupron is a drug that is used to elevate levels of luteinizing hormone (LH)
and follicle stimulating hormone (FSH) in humans.  The end result is an
initial increase in estrogen, however, if the rise in LH and FSH is
prolonged, levels of estrogen secretion by the ovary in females, and
testosterone by the testis in males will drop to castrate levels.  One
indication for Lupron in humans is the syndrome of precocious puberty, where
female children secrete estrogen too early in life, develp secondary sexual
characteristcs, and other unwanted side effects such as growth retardation,
etc.  It is also used to regulate menstrual cycles during infertility
treatment, and in men, it is used as a palliative treatment for prostate
cancer, which is testosterone-responsive; (however, prostate cancer is not a
problem in ferrets.) It is NOT used in the treatment of any estrogen- or
testosterone-secreting tumors in humans.
 
In ferrets with AAE there is a neoplasm in the adrenal which is autonomous -
it does not listen to the levels of FSH or LH in the body when it produce
estrogens - it just produces it, as much as it wants.  Even if you drop the
FSH and LH levels to nothing with Lupron, those cells will likely continue
to secrete estrogen.  And we also have know idea, in any species, whether
Lupron has any effect on normal organs other than the ovary or testis.
 
As far as using it in ferrets with cystic prostatic disease - Lupron does
not lessen the effects of estrogen, so the cysts will continue to get bigger
as long as teh estrogen levels stay high.  Cystic prostatic disease is not
prostate cancer at all, but an enlargement of the normal glands of the
prostate into large cysts due to changes in the lining.  What is worse -
when treatment with Lupron is started in humans, estrogne levels for the
first 1-2 weeks actually get HIGHER- perhaps worsening prostatic disease in
affected ferrets. In my opinion - if a ferret is dysuric, this is a
potentially life threatening condition, and immediate surgery is indicated.
Estrogen has a half-life of several weeks - the sooner you get the source of
secretion out of there, the better.
 
As far as alleviating hair loss -- once again, because Lupron is not an
estrogen blocker, it will not alleviate the damage that the ongoing high
levels of estrogen are doing to the hair follicle cells which produce and
give nutrition to the hair.  So the hair continues to fall out.
 
Perhaps the most imporant point of all - Lupron does not do anything to
shrink or kill tumor cells.  Even if some of the clinical signs abate, this
is a symptomatic treatment.  Although Lysodren is not very effective in
ferrets, we know that in high doses, it will kill adrenal cells (sometimes
too effectively, wiping out most the entire adrenal cortex).  Lupron does
not have this effect, and we don't even know if it affects adrenal cells at
all - the only effects we know of in humans are on cells in the ovary and
testis.
 
Honestly, we don't know how all drugs work.  Perhaps we will one day find
some hidden mechanism that enables Lupron to work in ferrets - certainly AAE
is a unique syndrome in the animal kingdom.  And I have also not seen the
hard data from Dr. Johnson-Delaney - I would like to see the levels of
estradiol and other hormones in the test group after Lupron administration.
However, by looking at the normal actions of Lupron in the body, there is no
logical reason why it should work, and in male ferrets with dysuria, you may
actually worsen the problem.
 
As of yet, there is no good medical treatment for AAE, not even Lysodren.
What we need (and what is a huge area of research in human medicine) is an
estrogen BLOCKER - something that occupies the estrogen receptors on target
cells and prevents its effects.  However, even if this is developed, we will
still need to remove that source of elevated estrogen for a cure, and in
ferrets, we can only effectively and reliably, do that with surgery.
 
Bruce Williams, DVM
Diplomate, ACVP
[Posted in FML issue 2208]