NON-SURGICAL CASTRATION IN MALE DOGS POSSIBILITY, AVAILABILITY AND HUMANITY Suppawiwat Ponglowhapan DVM (Hons), MS, MSc, PhD Department of Obstetrics Gynaecology and Reproduction, Faculty of Veterinary Sciences Chulalongkorn University Introduction Dr. Patricia N Olson Introduction 1970’s First awakening to pet over population at animal care & control facilities “ … hundreds of dogs seems to have been euthanized due to some horrific diseases that was not one we have been taught about in veterinary school !” and “most of them are young and look healthy”. Introduction “ How would the veterinary community respond to a disease that resulted in the death of between 10-25% of all dogs and cats each year? ” a vet student asked. Introduction In USA, over half of all households own a dog or cat (1:3 in UK,1:4 in BKK) The human society of the United Stated estimated 8-10 millions dogs and cats enter shelters each year 4.5 millions of them are euthanized Introduction How many stray dogs in Mexico city? 1962: 460,000 dogs 1974: 900,000 dogs 2006: 3,000,000 dogs Introduction How many stray dogs in Bangkok? 2540 2542 2548 Family dogs 580,000 523,000 - Stray dogs - 110,000 823,000 Introduction Introduction In some countries, such as Sweden and Norway, pet overpopulation is not a problem and neutering pets is UNCOMMON. Pet owners: responsibilities > rights Pet overpopulation Year Cat Year Dog 1 12 1 16 2 67 2 128 3 376 3 512 4 2,107 4 2,048 5 11,801 5 12,288 6 66,088 6 67,000 7 370,092 8 2,072,514 www.spayusa.com Pet overpopulation 1. Social problem 2. Hygiene problem 3. Health problem: zoonosis Texas (1977): stray dogs can produce 94,950 gallons of urine and 38.6 tons of feces per day. Control of pet overpopulation The complexity of pet overpopulation Human-animal bond Pet owner responsibility Animal sterilization/neutering Non purpose-bred dogs must be neutered! Neuter Neuter (Latin) = Neither (neither masculine or feminine) adjective = The German word for 'book', 'das Buch', is neuter. verb = Has your dog been neutered? Neutering is the removal of an animal's reproductive organ, either all of it or a considerably large part. It is the most drastic surgical procedure with sterilizing purposes. (Wikipedia) Sterilizing (sterilize = to perform a medical operation on someone in order to make them unable to have children) Female; spaying (removal of the ovaries) ovariectomy / ovariohysterectomy OVH Male; neutering, castration (removal of the testicles) Castration Surgical VS Non-surgical (Permanent VS temporary) Surgical Castration Traditional neutering of male dogs Surgical removal of the testicles of a male animal or human Removing or inhibiting the function or development of the testes Spermatozoa Testosterone Dog testicles Surgical Castration Spermatozoa Testosterone Sterility Loss of testosteronedependent characteristics libido, roaming, urine spraying, aggression, etc. Vasectomy Cooper (1930) : first experimental vasectomy on a dog Vasectomy & Castration Vasectomy Vasectomy Surgical Castration Not all owners prefers to have their pets surgically sterilized. In Brazil (Soto et al., 2005) 56.5% of owners (adopted shelter dogs) against surgical sterilization - Compassion (58.1%) - Unnecessary procedure (11.4%) - Cost (9.5%) - Behavioral change (4.8%) Surgical Castration In Thailand (Swangchan-uthai et al., 2005) 38.3% against contraception in dogs and/or cats (170/446) - Breeding purpose - Able to confine male dogs - Not necessary to have males neutered - Behavioral and physical change, i.e. obesity Unsafe procedure กลัวว่าตัวเองหรือแฟนจะเป็ นหมัน ... บาป !!! 61.7% prefer to have their pets neutered (276/446) - 13.7% males, 39.8% females, 46.5% both 72.5% orchiectomy, 19.8% vasectomy, 7.7% reversible hormone implant Non-Surgical Castration No scalpel castration Chemical castration Expectations for non-surgical castration As effective as gold standard (bilateral orchiectomy) No adverse effects (short-term and long-term) Safe Inexpensive Quick (can be applied to large-scale population) Reversible (?) Non-Surgical Castration Hormonal treatment Progestogens, Androgens, GnRH analogues (agonist/antagonist) Intratesticular/intraepididymal injection Immunocontraception Ultrasound testicular ablation Hormonal treatment Hormonal treatment Hormonal treatment Steroid hormone (Progestogens, Androgens) Non-steroid hormone (GnRH analogues) Progestogen Androgens GnRH Hormonal treatment Exogenous hormone Down regulation Temporary suppression of fertility Hormonal treatment Steroid Hormone In early 1930, isolated and determined structure of steriods In 1937, reported progesterone inhibits ovulation in rabbits No new products for control of reproduction in the dog and cat have been introduced during the last two decades, other than revised formulations and new brands of progestogens. Non-steroid Hormone GnRH agonist Suprelorin (Deslorelin, Virbac) Gonazon implant (Nafarelin, Intervet) Progestogen Progestogen Clinical use in the bitch • Control of oestrus (suppression/prevention) • Pseudopregnancy • Hypoluteoidism Clinical use in the dog • Antisocial behaviour • Epilepsy • Benign Prostatic Hyperplasia • Contraception (+/-) • Circum-anal adenoma Progestogen: female Prevention of anoestrus Medroxyprogesterone Perlutex 2.5-3 mg/kg at 5 mth interval Promone-E 50 mg/bitch at 6 mth interval Proligestone Covinan 10-33 mg/kg - early proestrus - a series at 3, 4 and 5 mth intervals Side effects : type of hormone, dose, duration of repeated treatment, treatment regimen, stage of oestrus cycle and age of the animal Progestogen: female Side effect Selman et al., 1994 glucose intolerance diabetes mellitus mammary tumors (50%) in treated OVH-bitches Use with Cautions • Type of hormone • Route of administration • Dosage • Duration of repeated treatment • Stage of the cycle at initiation of the treatment • Age of the animal Progestogen: male LH/FSH Spermatogenesis progestogen Progestogen: male England , 1997 Progestogens Dosage Route Duration Results Megestrol acetate 2 mg/kg PO 7d No change in semen quality Megestrol acetate 4 mg/kg PO 7d Minor sperm abnormalities MPA 10 mg/kg SC - No change in semen quality MPA 20 mg/kg SC - Rapid decline in sperm motility, morphology and output No change in plasma LH concentration was detected as seen in females !!! The male dog appears to differ in the sensitivity of hypothalamo-pituitary response to progestogen feedback Megestrol acetate MPA; medroxyprogesterone acetate Progestogen: male Not recommended for contraception in the male dog 1. ineffective 2. adverse effects Selman et al., 1994 glucose intolerance diabetes mellitus Androgen Androgens Dosage Results References Mixed testosterone ester 5 mg/kg Decline in sperm motility (wk 3-15 post injection) England, 1997 Methyltestosterone 50 mg (90 d) Decreased daily sperm output Freshman et al., 1990 GnRH analogues Agonists Suprelorin (Deslorelin, Virbac) Gonazon implant (Nafarelin, Intervet) Antagonists Acyline (Merrion Pharmaceuticals) Deslorelin implant Hypothalamus GnRH Anterior pituitary LH, FSH Ovary, Testis Oestrogen Testosterone Deslorelin implant Deslorelin implant Deslorelin implant 15 d pre-implant 15 d post-implant recovery Deslorelin implant Deslorelin Suprelorin 4.7 mg implant for dogs has been licensed in EU. Indication: For the induction of infertility in healthy, non-castrated, sexually mature male dogs Deslorelin implant Castration 50% in 3rd week 70% in 9th week (Barsanti and Finco, 1995) Finasteride 40% in 16th week (Sirinarumitr et al., 2001) Deslorelin 40% in 4th week (Ponglowhapan et al., 2010) Deslorelin implant SAMSON Golden retriever 7 years old Urination difficulty BPH Before and 14-day post treatment of Deslorelin implant Deslorelin implant Prostatic volume [(L x W xD)/2.6] + 1.8 (Kamolpatana et al., 2000) Before = 42.0 cm3 14-d after = 38.5 cm3 Intratesticular injection Intratesticular injection In 1953, Freund et al. Aspermatogenesis in the guinea pig induced by the testicular tissue and adjuvants. J Exp Med. 97:711-26. Injection of sclerozing/necrotizing agents into the testes to induce aspermatogenic orchitis and tissue sclerosis resulting in infertility Local inflammatory response Autoimmone response Different Sites of injection Vas deferen injection Intraepididymal injection Intratesticular injection Intratesticular injection Sclerosing agents o Zinc gluconate (Levy et al., 2008) o 20% hypertonic saline (Emir et al., 2008) o Glycerol (Immegart et al., 2000) o 1.5% chlorhexidine gluconate in 50% DMSO (Pineda et al., 1977) o Calcium chloride (Jana and Samanta, 2007) Intratesticular injection Zinc-based solution Active ingredient Dogs treated Dosage/Route Results References Zinc arginine 2-3.5 yr, n = 10 50mg (0.5mL)/Caudal epididymal injection azoospermia in 90 days postinjection Fahim et al., 1993 Balanced zinc solution Adults, n = 5 Intratesticular injection Tepsumethanon et al., 2005 Zinc gluconate with or without 0.5% DMSO Adults, n=25 13.1 or 26.2mg/ Intratesticular injection Zinc gluconate neutralized in physiological vehicle 8 mo to 4 yr, n = 10 2.6 – 13.1 mg depending on testicular width/ Intratesticular injection azoospermia in 4 out of 5 dogs beginning between Day 26-51 post-injection azoospermia, oligozoospermia, asthenospermia depending on dosage used and the presence of DMSO Histological changes including degeneration, vacuolation, fewer germ cells, lack of spermatid in atrophic seminiferous tubules Soto et al., 2007 Oliverira et al., 2007 Neutersol/Esterilsol FDA approved in 2003 Neutersol/Esterilsol Zinc gluconate neutralized by arginine Recommendations 1. Labeled for chemical castration via intratesticular injection in the male dog 2. Age 3-10 months (puppy) 3. 4. Predetermined amount of zinc solution based on scrotal width into each testis Sedation is recommended Range of testicular width (cm) mL per testis Mg Zinc 10-12 0.2 2.6 13-15 0.3 3.9 16-18 0.5 6.6 19-21 0.7 9.2 22-24 0.8 10.5 25-27 1.0 13.1 Neutersol/Esterilsol Neutersol injection Atrophy of the testis, epididymis, seminiferous tubles and prostate gland Scar tissue formation Prevention of sperm movement from seminiferous to epididymis 3-10 mth old puppies: 99.6% success (223/224) Neutersol/Esterilsol Spermatocyte necrosis Giant cell Surgical castration vs Intratesticular injection Surgical Method Intratesticular Injection เทคนิคและบุคคลากร ต้องการเทคนิคและอุปกรณ์การผ่าตัด และต้องการ สัตวแพทย์ผชู้ านาญการผ่าตัด ไม่ตอ้ งการเทคนิคมาก ใช้บุคลากรน้อย ไม่ จาเป็ นต้องมีทกั ษะการผ่าตัด การวางยาสลบ ต้องวางยาสลบ (General Anesthesia) ไม่จาเป็ นต้องวางยาสลบ แต่ FDA (USA) แนะนาให้ใช้ยาซึมก่อนการฉี ด ความเจ็บปวด สามารถวางแผนระงับความเจ็บปวดได้อย่างมี ประสิ ทธิภาพ เกิดความเจ็บปวดจากการบวมอักเสบ ภายหลังการฉี ด ร้ อยละในการคุมกาเนิด 100% 99.6% Surgical castration vs Intratesticular injection Surgical Method Intratesticular Injection ระยะเวลาที่เริ่มมีผลในการ คุมกาเนิด 7 วัน 60 วัน สาหรับการใช้ Neutersol ลักษณะและจานวนอสุ จิ Azoospermia Oligozoospermia Asthenospermia Azoosspermia ฮอร์ โมน ไม่สามารถผลิต Testosterone สามารถผลิต Testosterone เนื่องจากยังมี Leydig’s cell เหลืออยูบ่ างส่วน พฤติกรรม ไม่มีพฤติกรรมทางเพศ ยังมีพฤติกรรมทางเพศ Surgical castration vs Intratesticular injection Surgical Method Intratesticular Injection ร้ อยละของปัญหาแทรกซ้ อน (Levy et al., 2008) 3.4 3.9 ลักษณะของปัญหาแทรกซ้ อน และการแก้ไข แผลแตก : ทาแผล เย็บซ่อม แผลหายเร็ว เนื้อตาย แผลรู เปิ ด ติดเชื้อรุ นแรง : รักษาภาวะติดเชื้อ ผ่าตัดเอาอัณฑะออก เย็บตกแต่ง แผลหายช้า ลักษณะภายนอก ไม่เห็นอัณฑะที่อยูภ่ ายในถุงหุม้ อัณฑะในถุงหุม้ มีขนาดเล็กลง และอาจไม่เท่ากัน Identification required* ค่าใช้ จ่าย 800 – 2,000 บาทโดยประมาณราคาใน 1,651 บาท โดยคิดจาก Neutersol หนึ่ง ประเทศไทย โดสต่อตัว 49.95 เหรี ยญสหรัฐอเมริ กา Intratesticular injection Recommendations 1. Information 2. Family dog / stray dog 3. Large scale control population 4. Skill 5. Animal identification 6. National policy Non-surgical castration in male dogs Possibility, availability and humanity