Deslorelin takes the lead in quest for non-surgical birth control

From ANIMAL PEOPLE, September 2010:
(published October 5, 2010)
NAIROBI–Veterinary contraceptive
researcher Henk J. Bertschinger wowed the Africa
Animal Welfare Action conference in Nairobi on
September 8, 2010 with two presentations hinting
that the anti-GnRH agonist approach to animal
birth control may be applicable in cats and dogs.
Bertschinger, of the University of
Pretoria in South Africa, recapped and updated a
2007 paper he and colleagues published in the
journal Wildlife Research, describing “the
treatment and contraception of 23 captive and 40
free-ranging lionesses and four captive tigers in
South Africa,” using a range of different sized
deslorelin implants. Deslorelin is a hormone
analog, modeled on the natural hormone LHRH
(lutenizing-hormone releasing hormone) that turns
reproductive processes on and off in the brains
of both male and female animals.

“All combinations of deslorelin showed
the length of contraception to be around 30
months with one treatment lasting 40 months in
one captive lioness,” Bertschinger and four
co-authors wrote.
“No side effects occurred,” they
reported, “although several of the lionesses
were treated repeatedly for up to eight years.
Deslor-elin (Suprelorin formulation) is a safe
and effective means of controlling reproduction
in captive or free-ranging populations of lions,”
the team concluded. “Where contraception is to
be maintained,” Bertschinger et al wrote, “the
implementation of implants at 24-month intervals
is recommended.”
Bertschinger also described the results
of contraceptive studies he has done with African
elephants since 2000 at the Makalali Game Reserve
in South Africa, funded by the Humane Society of
the U.S. and Humane Society International.
HSUS/HSI also sponsored Bertschinger’s
participation in the Africa Animal Welfare Action
conference
The most noteworthy aspect of
Bertschinger’s work with deslorelin was longterm
contraceptive success in free-ranging female
felines. This had been believed to be possible,
based on laboratory studies and earlier studies
with captive animals. However, the deslorelin
formulation that Bertschinger used, Suprelorin,
made by the Australian firm Peptech Animal
Health, is in contraceptive use best known as a
product for male animals. Peptech literature
mentions use of Suprelorin for fertility control
of female animals only as a possible future
application.
But Peptech markets deslorelin under the
brand name Ovuplant for a very different use in
females: to induce ovulation in mares prior to
artificial insemination, and to stabilize
high-risk pregnancies in livestock. Deslorelin
is approved in the U.S. for use for these
purposes, and is being tested in the U.S. as a
possible treatment for human breast cancer.
Suprelorin used in males
“Suprelorin is implanted under the skin
between the shoulders to reduce a male dog’s
testosterone levels to zero and cease
reproductive function for six months,” explains
the Peptech web site. “Inserted with an
implanter similar to those used for
microchipping, Suprelorin slowly releases
deslorelin, a hormone similar to those used to
treat human prostate cancer,” says Peptech.
“The low, continuous dose of deslorelin prevents
the production of sex hormones. The
biocompatible implant disappears over time.
Trials show Suprelorin is [also] effective in
controlling populations of elephants, lions,
cheetahs, monkeys, dolphins, seals, koalas
and kangaroos.”
Suprelorin has been “approved and
available for use in male dogs in Australia, in
six-month and 12-month doses, since December
2004, and in New Zealand, in 6-month doses
only, since September 2005,” advises the
Alliance for Contraception in Cats & Dogs.
Suprelorin “received European Union regulatory
approval in March 2007, and is now available in
several E.U. countries, with plans to expand to
more,” says the ACC&D product summary.
The British National Office of Animal
Health in Britain allows the use of Suprelorin
“for the induction of temporary infertility in
healthy, entire, sexually mature male dogs.
Infertility is achieved from six weeks up to at
least six months after initial treatment,” the
NOAH data sheet on Suprelorin advises. “Treated
dogs should therefore still be kept away from
bitches in heat within the first six weeks after
initial treatment.”
“Because Suprelorin is not permanent (and
does not take immediate effect), it is not an
ideal product for population control,” says the
ACC&D web site. “However, we believe Suprelorin
may have potential to fill a niche, such as when
dogs must be held after rescue from natural
disasters, or as evidence in court cases.
Suprelorin may be able to be used in cats with
longer efficacy than in dogs. ACC&D is working
with Peptech to pursue this possibility, as we
believe even a long-term contraceptive (three or
more years) may be able to play a meaningful role
in feral cat population management.”
ANIMAL PEOPLE president Kim Bartlett
disagrees with the ACC&D criteria that a product
must prevent contraception for at least three
years to play a meaningful role: “Since true
street dogs–not ‘community dogs’–in the
developing world and feral cats have an average
life-span of around three years, with possibly
five breeding cycles for each female dog who
survives that long and a greater number of cycles
per cat, a birth control formula lasting even
six months would have the potential to cut
breeding by about 20% in dogs and a higher
percentage in cats. This would be a huge
reduction in the birth rate by itself, and if
the product were administered twice a year to all
the animals in an area, which is admittedly more
feasible with dogs than cats, the birth rate in
the treatment area would plummet. If the formula
lasted one year, the effect would be greater,
and a product lasting two years would likely
extend past the likely reproductive life of many
homeless animals.
“Of course,” Bartlett adds,
“contracepted animals are likely to experience
reduced mortality, because of diminished
reproductive stress. This includes complications
of pregnancy and delivery in females, combined
with risks associated with defending a litter and
providing nourishment, and for males
contracepted with products that diminish
testosterone production, there would be reduced
roaming in search of females in estrus and less
fighting with other males. There are a lot of
variables and plenty of opportunities for
improper or inadequate dosing,” acknowledges
Bartlett, “and we won’t know how quickly a
population decline might occur until there are
field studies, but I think that a contraceptive
lasting less than three years could still be very
helpful in attempting to non-lethally control a
homeless dog or cat population.”

The cost of Suprelorin

Peptech currently recommends that the
retail cost of Suprelorin in Australia and New
Zealand should be about $60 per male implant in
dogs, about $20 less than the price when it was
first introduced.
The price per implant in Britain runs around £50.
Suprelorin is also used off-label in
Australia to control reproductive behavior in
male parrots and show-grade exotic poultry.
“Cost can range from $80-$120 and upward per
implant, depending on your vet and which implant
your bird needs,” advises a posting on the
BackyardPoultry web site. “The bird can also
never be eaten after having the implant. Males
can also lose their secondary sexual
characteristics and become somewhat feminized in
appearance.”
Expense is one drawback to the widespread
use of deslorelin implants in street dogs and
feral cats. Another is that the implants–like
rabies vaccines–must be kept cold until use,
which can be difficult in the hot climates of the
developing world. Yet the refrigeration issue
is a challenge rather than an insurmountable
obstacle, as illustrated by the success of
street dog vaccination campaigns in Argentina,
Brazil, Uruguay, and parts of India, Thailand,
and Indonesia.
There are also some human health and
safety concerns associated with deslorelin-based
drugs. The British National Office of Animal
Health in Britain warns that, “Pregnant women
should not administer the product. Another GnRH
analogue has been shown to be foetotoxic in
laboratory animals. Specific studies to evaluate
the effect of deslorelin when administered during
pregnancy have not been conducted. Although skin
contact with the product is unlikely,” the NOAH
warning continues, “should this occur, wash the
exposed area immediately, as GnRH analogues may
be absorbed through the skin. When administering
the product, take care to avoid accidental
self-injection.”

Gonazon & GonaCon

A product similar to Suprelorin,
Gonazon, introduced by Intervet/Schering-Plough,
“received regulatory approval in November 2006 in
the European Union,” ACC&D notes. “Early
studies of Gonazon use in cats show three years
of contraception. Unfortunately, the product is
not currently being manufactured, so further
study on the potential use in cats is on hold.”
Another similar product, GonaCon, was
developed by the National Wildlife Research
Center, under the umbrella of USDA Wildlife
Services, along with a contraceptive for geese,
ducks, and pigeons called OvoControl. (See page
8.)
Field-tested in 2004-2005, GonaCon was
first used to control ground squirrel populations
in Berkeley, California. It cut their birth
rate by two thirds.
Next GonaCon was used to control the
feral fallow deer population at Point Reyes
National Seashore in Marin County, north of San
Francisco, and in elk at Rocky Mountain National
Park, near Denver. Based on findings from those
tests, GonaCon was approved by the Environmental
Protection Agency in September 2008 for
controlled use by state and federal agencies to
contracept deer and elk.
The introduction of GonaCon has
encountered political resistance from hunters.
Seven states now prohibit any use of wildlife
contraceptives, including Georgia, Illinois,
Iowa, Missouri, New Hampshire, New Jersey, and
South Carolina. Pennsylvania requires that
communities applying for GonaCon deployment must
demonstrate that hunting has not resolved, or
cannot resolve, their deer population problems.
GonaCon has not yet been used to
contracept feral cats. However, “GonaCon has
been shown, in preliminary research, to be
effective in approximately 75% of female cats for
two years,” says ACC&D, adding “We look forward
to receiving and reviewing additional data as
work on this approach progresses.”

Veterinary resistance

Though just now emerging as a leading
animal contraceptive method, contraceptive
applications of the pharmaceutical family
including deslorelin, Suprelorin, Gonazon, and
GonaCon are not a new approach. Researchers have
experimented with anti-GnRH compounds as a
contraceptive for both animals and humans for
more than 30 years.
Several anti-GnRH researchers reported
positive findings from experiments involving
female cats at the 2004 ACC&D conference in
Aspen, Colorado, including Henry Baker,
director of the Scott-Ritchey Research Center at
the Auburn University College of Veterinary
Medicine in Georgia, and Metamorphix Canada Inc.
bioevaluation unit head Sarah Robbins. But
anti-GnRH studies in the U.S. and Europe have so
far not been followed up with either private or
nonprofit investment in product development and
approval for marketing. This is why USDA
Wildlife Services funded the development and
approval process for GonaCon.
Valerie A. Ferro of the University of
Strathcyde in Glasgow, Scotland, told the 2004
ACC&D conference that she had done anti-GnRH
studies for 14 years with virtually no funding.
For four years Ferro received some support from
Novartis Pharmaceuticals, she acknowledged, but
Novartis withdrew, she indicated, because their
veterinary clients were worried that a successful
anti-GnRH injection might cut into their surgical
income.
“The initial [veterinary] response [to
Suprelorin] has been good,” Peptech general
manager Paul Schober told Joyce Briggs of ACC&D
in 2006, “although some vets were wary of the
product as they mistakenly believed that we were
trying to replace surgical castration,” which is
exactly what a street dog or feral cat
application meant to last at least three years
would be attempting to do, in trying to prevent
fecundity for the life expectancy of the animal.
“These vets were more receptive,” Schober said,
“when we explained that this product is mainly
for those who will not castrate their animals,
and once they realized that its use would likely
involve multiple visits by clients over time to
maintain the effect.”