Purswell Targets & Historical approaches

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Presented by Dr. Beverly Purswell at the Alliance for Contraception in Cats & Dogs’ 4th International Symposium on Non-Surgical Contraceptive Methods of Pet Population Control, April 8-10, 2010, in Dallas, Texas, U.S.

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History of Contraception in Dogs and Cats : 

History of Contraception in Dogs and Cats Beverly J. Purswell and Wolfgang Jöchle

Surgical Castration : 

Surgical Castration Many millennia Documentation in 7-6000 BC Reliable Permanent Not documented in early literature for husbandry of dogs – Breeding, Management, Health Care *1575 book on hunting mentions castration giving no technical details Sharp contrast to amount of literature of castration of male and female horses and mules

Early History : 

Early History Over 3 millennia No apparent attempts for contraception Neither temporary or permanent Exception – Induction of abortion 13th Century – oral mixture with vaginal deposition of ash paste France – 19th and early 20th Century – mismating cases referred to a Veterinarian (details not available) Low status of animals – may not be worthy of human methods for contraception or abortifacients

Second Half of 20th Century : 

Second Half of 20th Century Efforts began to control reproduction non-surgically 1960 – “The Pill” for women became available Spawned efforts to control animal reproduction Concern grew about over-population and unplanned offspring – horror of destruction of increasing numbers of animals In Europe – first pill marketed (1963)

Slide 5: 

1Medroxyprogesterone acetate, tablets 2Megestrol acetate, tablets 3Mibolerone, solution 4Norethisterone, tablets Oral Progestins

Slide 6: 

Injectable Progestins 1Medroxyprogesterone acetate 2Chlormadinone 3Delmadinone 4Proligestone

Problems Encountered : 

Problems Encountered In the United States, injectable depot progestin Promone® - medroxyprogesterone acetate Duration – 6 months Results were predictable Side effects – catastrophic cystic endometrial hyperplasia pyometra Withdrawn after 2 years

Realizations : 

Realizations Knowledge on canine cycle was grossly insufficient No longer could we assume dogs were “little cows” Small animal practitioners (USA) had lost confidence in hormone-based contraception Mibolerone acceptance suffered (1978 introduced) Withdrawn in 1990

Mibolerone : 

Mibolerone Marketed in the United States Oral daily use required Put in canned dog food - unsuccessful Undesirable side effects - androgenic Clitoral enlargement Vaginal discharge Behavioral changes Did raise awareness of the need for contraception Still used through compounding pharmacies

Cultural Differences : 

Cultural Differences In the USA, surgical methods became preferred Better anesthetic drugs became available Benefit of permanent resolution In Europe, surgical methods were not preferred Resistance for unnecessary surgeries Promoted development of new compounds and strategies for contraception Decreased dose, Defined timing

Racing Greyhounds : 

Racing Greyhounds Small segment of the US dog population Testosterone used for estrus control Oral tablets Injectable esters Effective Side effects – virilization Desirable in the athlete Undesirable in pet populations

Contraception - Mismating : 

Contraception - Mismating Disruption of pregnancy Early – prevention of nidation Late – elective abortion of litter Estrogen – given during estrus to prevent pregnancy Available since 1930-40’s Effective if used at proper time and dose Safety issues – pyometra, bone marrow suppression

Prostaglandin and Prolactin Inhibitors : 

Prostaglandin and Prolactin Inhibitors Prostaglandin – available in 1980 Luteolysis Uterine contraction Multiple doses required to eliminate pregnancy Dose related side effects – limit use Prolactin inhibitors Bromocriptine, cabergoline Ergot derivatives Prolactin luteotropic in dog and cat Used to lysis the CL – disruption of pregnancy Used together – more effective than either alone

GnRH analogs – New approach : 

GnRH analogs – New approach Decapeptide and nonapeptide Occupy GnRH receptors at pituitary level Short stimulation period followed by suppression Renders receptor insensitive to endogenous GnRH Receptor Down Regulation Reversible Lupron® (leuprolide) – human use – expensive Suprelorin®(deslorelin) – promising Gonazon® (azagyl-nafarelin) - promising

Male Contraception : 

Male Contraception General resistance to male sterilization Surgical castration meets greatest resistance Zinc gluc0nate – Neutersol® Safe and effective Intratesticular injection Irreversible

ImmunoContraceptive Vaccines : 

ImmunoContraceptive Vaccines Anti-zona pellucida vaccines Effective in a variety of species – safe, reversible Ruminants, horses, seals, elephants Derived from porcine oocytes Ineffective in the queen Caused ovarian pathology in bitch GnRH vaccines Promising alternative Needs appropriate adjuvant Male or female uses

GnRH Vaccines : 

GnRH Vaccines Commercially available Improvac® - Swine, boar taint Bopriva® - Cattle – bull behavior Canine GnRF® - benign prostatic enlargement Multiple uses Male Female Booster injection needed

Future of Non-surgical contraception : 

Future of Non-surgical contraception Many possibilities Desire from the pet owning population Safety Efficacy Reversibility Feral populations Desperate need Single dose 100% efficacy Inexpensive

Thank you : 

Thank you

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