Alternatives to sterilization surgery still delayed

From ANIMAL PEOPLE, June 2002:

ATLANTA– “A commercialized alternative to surgical
castration or ovario-hysterectomy for either dogs or cats” may still
be 10 years away, AlcheraBio senior partner Linda Rhodes, DVM,
told the 2002 International Symposium on Nonsurgical Methods for Pet
Population Control, held April 19-21 in Atlanta.
Rhodes’ prediction came as a letdown after the optimism of
many of the same speakers two years earlier.
At the Spay/USA symposium on immunocontraceptives and
chemosterilants, held in July 2000 at Bentley College in Waltham,
Massachusetts, at least two researchers hoped that their products
could clear the regulatory hurdles and be on the market by now. In
Atlanta, however, neither those researchers nor any others ventured
even a hypothetical timetable for bringing any contraceptive or
sterilant drug or antigen for animals into commercial production.

Despite 30 years of increasingly successful product
development, Rhodes explained, meeting the regulatory requirements
of the U.S., European Union, and other nations for product safety
and efficacy are just the beginning of the process of introducing a
new pharmaceutical.
“For a company to decide to move a product forward,” Rhodes
said, “a technically feasible, stable formulation must be developed
and large-scale manufacturing must be possible. Formulations used
for research rarely are suitable for full-scale development. The
final formulation needs to be reasonably stable– that is, the
active drug or antigen has to remain intact over a reasonable shelf
life,” and “must be cheap enough to enable profit.”
Beyond that, Rhodes continued, “The regulatory path must be
clear and relatively low-risk. The cost of development must be
reasonable. The market must be clearly defined. Money must be
available to take the project through to completion and to support
initial marketing. Finally, a company or a group of investors must
be willing to risk the long and costly development process.”
All of those obstacles combined to block the anticipated U.S.
release of a canine contraceptive drug called mibolerone, which from
1975 until 1985 the Upjohn Company and Carnation Company repeatedly
announced would soon be available.
Mibolerone has been used in the U.S. by prescription to
suppress estrus in racing greyhounds, sled dogs, some show dogs,
and zoo animals, and is widely used by prescription in northern
Europe, but has not been marketed to U.S. humane groups or the
general public because it is chemically similar to RU-486, the
active ingredient of the so-called “abortion pill.” The U.S. Food
and Drug Administration finally authorized the manufacture and
marketing of RU-486 in September 2000, after years of debate, but
Upjohn and Carnation have not yet moved to make mibolerone more
widely available.
As mibolerone is only a short-term contraceptive,
administrated by feeding, it would be most useful in temporarily
limiting street dog reproduction while humane organizations capture
the dogs a few at a time for surgical sterilization. That scenario
occurs chiefly in the underdeveloped world, where the profit
potential is least, the chance of misuse to induce human abortion is
greatest, and U.S. drug patents are often not respected by local
makers of generic copies. [More about mibolerone is posted at
<www.animalpeoplenews.org/ru4861100.html>.] “The perfect nonsurgical sterilization method for companion
animals would cause permanent loss of fertility, cause permanent
loss of sexual behavior, be effective in both dogs and cats, be
effective in both males and females, be given in a single delivery,
be inexpensive, and be safe both to targeted animals and to humans
inadvertantly exposed,” summarized Geraldine R. Dodge Foundation
consultant Ted Mashima, DVM–but no known method meets all of these
criteria, and pursuit of “perfection” may distract researchers from
pursuing methods which could immediately help to prevent surplus dog
and cat births.
Data presented by Min Wong, M.D., of the Center for
Reproductive Science and Technology at the Univ-ersity of
Missouri-Columbia indicated that testicular injections of the
chemosterilant drug Neutrosol are approximately 99% effective in
suppressing sperm production by male dogs. Neutrosol does not
influence dog behavior, nor does it prevent females from conceiving
litters, or offer the level of “perfection” that petkeepers might
demand, but it does offer a way to inhibit street dog reproduction
which has already showed promise in field tests in Mexico. Like
mibolerone, it could be used to buy time while surgical
sterilization is pursued as the preferred longterm method.

Cat problem

There is as yet no effective time-buying alternative to
surgery for limiting the reproduction of feral cats. Cats and
rodents have proved able to thwart the chemosterilant and
immunocontraceptive strategies than have worked in most other
mammals. The potential value of a way to delay the first pregnancy
of feral cats, however, was implied in statistics collected by
Julie Levy, DVM, and fellow participants in her Opteration Catnip
feral cat sterilization projects in Florida and South Carolina–which
confirmed data collected by ANIMAL PEOPLE and Arnold Brown, DVM,
during a 1991-1992 feral cat sterilization project in Connecticut.
The gist is that feral cat mothers produce an average of 5.4
kittens in their lives: 3.6 kittens per litter on average–and only
about half of the cats who produce one litter live long enough to
produce another. The mortality rate among feral cats is so high that
if their first pregnancy came at age two instead of age one, total
births would fall by two-thirds. Even if delaying the first
pregnancy tended to increase longevity so that half again as many
female cats reached age two, the total number of births would fall
by half. That would drop feral cat fecundity to the replacement
level–but because only about half of all feral kittens survive to
weaning, and only half of those reach maturity, reducing feral cat
births to the replacement level would bring a drastic decrease in the
reproducing population.
Animal shelter intake data indicates that the U.S. feral cat
population may be down by half since 1990, partly because of reduced
recruitment from the pet cat population.
John New Jr., DVM, of the College of Veterinary Medicine at
the University of Tennesse, presented findings by the American Pet
Product Manufacturers Association indicating that the percentage of
cat owners who keep their cats indoors by day is going up about half
a point per year, and is approaching two-thirds. The percentage
keeping their cats in by night is going up by a full percentage point
per year, and has probably reached 75%.
New also presented National Council on Pet Population
Study findings which indicate that the potential breeding populations
of owned pets in the U.S. include up to 21 million dogs and 14
million cats.
Other studies indicate that the U.S. dog population
has reproduced at approximately the replacement level since the
mid-1980s, holding relatively steady at 54 million to 60 million.
The rate of sterilization has held steady as well, according to
American Veterinary Medical Association data, at about 8% of all
veterinary visits.
During the same years, the U.S. owned cat population has
grown from about 56 million to as high as 70 million, paralleling
the growth in numbers of petkeeping households. The percentage of
dogkeeping households has actually decreased somewhat, while the
percentage of catkeeping households has steadily climbed for 20 years.
The rate of cat sterilization, according to the AVMA, has
increased from 14% of veterinary visits in 1987 to 21.4% in 1996.
The owned cat population has reproduced at about 75% of replacement,
with adoptions of feral or stray cats accounting for the remainder of
cat acquisition.

Wildlife applications

The development of immunocontraceptive vaccines for wildlife
has rapidly advanced in recent years, reported Kathleen A.
Fagerstone and Lowell A. Miller of the USDA/Fish and Wildlife Service
National Wildlife Research Center in Fort Collins, Colorado. Two
annual doses of an immunocontraceptive vaccine for deer brought an
89% reduction in fawning during those years, a 74% reduction over
five years, and a 72% reduction over seven years, even though no
further vaccinations were done after the first two years, Fagertone
and Miller said.
The political obstacles to controlling deer populations with
an immunocontraceptive will be immense, due to the strength of
hunting lobby demands for abundant targets, but the
technology–still being improved and field-tested–seems almost ready
for use.