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You are here: Home / Publications / Bibliographies and Resource Guides / Information Resources on Spaying and Neutering Cats, Dogs and Related Wildlife / Hormonal Methods of Contraception  Printer Friendly Page
Information Resources on Spaying and Neutering Cats, Dogs and Related Wildlife
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Hormonal Methods of Contraception

Baldwin, C.J., A.T. Peter, and W.T. Bosu (1996). Adrenocortical function in the domestic cat during treatment with levonorgestrel. Research in Veterinary Science 60(3): 205-208. ISSN: 0034-5288.
NAL Call Number: 41.8 R312
Abstract: Levonorgestrel was administered via a subcutaneous, slow-release silastic implant to 10 queens. Five other queens served as controls. Their adrenocortical function was assessed by the adrenocorticotrophic hormone (ACTH) stimulation test before and after one, two, six and 12 months of treatment. In addition, the gross anatomy and histology of the adrenal gland were examined post mortem in six of the treated cats. In both the control and treated queens the plasma cortisol concentrations (pre and post ACTH) were significantly different (P < 0.05) at different times. However, there were no significant differences between the plasma cortisol concentrations (pre and post ACTH) of the treated and control queens. No gross or microscopical abnormalities were visible in the adrenal glands of the treated queens.
Descriptors: adrenal cortex, cats, oral contraceptives, corticotropin, drug implants, female, hydrocortisone, levonorgestrel, reference values, silicone elastomers.

Baldwin, C.J., A.T. Peter, W.T. Bosu, and R.R. Dubielzig (1994). The contraceptive effects of levonorgestrel in the domestic cat. Laboratory Animal Science 44(3): 261-269. ISSN: 0023-6764.
NAL Call Number: 410.9 P94
Abstract: The effects of subdermal implantation of levonorgestrel (LNG) on reproduction were studied in domestic cats (Felis domestica). Levonorgestrel was administered via a slow-release subdermal silastic implant to 10 queens. The implants contained 16 mg of LNG and were designed to release 60 micrograms of the drug daily. Each treated queen received one implant. Five queens (control, group 1) received subdermal silastic implants containing no drug. Changes in body weight, mammary gland structure (determined by palpation), serum blood glucose concentrations, and reproductive factors (occurrence of estrous cycles, serum progesterone concentrations, and pregnancy) were monitored for 1 year. Four treated queens (treatment/recovery, group 2) were used to investigate reproductive function following 12 months of LNG treatment. To assess effects of treatment on macroscopic and microscopic anatomic features of reproductive and nonreproductive tissues, the remaining six cats (treatment/histology, group 3) were studied. Hemiovariohysterectomy was performed in two queens each at 0, 2, and 6 months of the study. Later, the remainder of the reproductive tract was harvested at necropsy (two after 2 months of treatment, two after 6 months, two after 12 months) to assess change in individual queens. Nonreproductive tissues were also examined at necropsy to determine effects of LNG in these six queens. All queens retained the implants during the period of study without detectable discomfort. Estrus was suppressed and no pregnancies were recorded in the four LNG-treated cats that were housed with a male. Treatment with LNG had no effect on body weight, physical mammary gland structure, or serum blood glucose concentrations.
Descriptors: animals, blood glucose, cats, contraceptive agents, drug implants, estrus, female, levonorgestrel, anatomy and histology of the ovary, pregnancy, progesterone.

Beier, S., F. Haase, B. Kosub, B. Dusterberg, and W. Elger (1979). The progestational activity of different gestagens used for human contraception in the beagle bitch. Contraception 20(6): 533-548. ISSN: 0010-7824.
NAL Call Number: RG136.A1C6
Descriptors: animals, chlormadinone acetate, contraception, cyproterone, dogs, dose-response relationship, endometrium, female, human, nandrolone, norethindrone, norgestrel, progestins.

Bell, E.T. and D.W. Christie (1971). The use of progestagens in the control of the canine oestrous cycle. The Journal of Small Animal Practice 12(7): 375-382. ISSN: 0022-4510.
NAL Call Number: 41.8 J8292
Descriptors: oral contraceptives, dog diseases, chemically induced endometritis, estrus, female, medroxyprogesterone, megestrol, norethindrone, adverse effects of progestins, uterine diseases.

Briggs, M. (1977). The beagle dog and contraceptive steroids. Life Sciences 21(3): 275-284. ISSN: 0024-3205.
NAL Call Number: 442.8 L62
Descriptors: oral contraceptives, dogs, drug evaluation, mammary glands, progesterone, neoplasms.

Bryan, H.S. (1973). Parenteral use of medroxyprogesterone acetate as an antifertility agent in the bitch. American Journal of Veterinary Research 34(5): 659-663. ISSN: 0002-9645.
NAL Call Number: 41.8 Am3A
Descriptors: breeding, dogs, drug effects on estrus, analysis of feces, female, fertility, injections, medroxyprogesterone, pregnancy.

Burns, R., G. Mcrae, and L. Sanders (1990). A one year controlled release implant or the LHRH superagonist rs-49947 ii. Clinical performance results. Journal of Controlled Release 14(3): 233-242. ISSN: 0168-3659.
Descriptors: dog, reversible chemical castration, drug release profile and duration, plasma leve,l estrus, drug delivery.

Colon, J., M. Kimball, B. Hansen, and P.W. Concannon (1993). Effects of contraceptive doses of the progestagen megestrol acetate on luteinizing hormone and follicle-stimulating hormone secretion in female dogs. Journal of Reproduction and Fertility Supplement 47: 519-521. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Descriptors: anestrus, comparative study, dogs, female, follicle stimulating hormone, luteinizing hormone, megestrol acetate, ovariectomy.

Concannon, P.W., M. Temple, A. Montanez, and D. Frank (1993). Synchronous delayed oestrus in beagle bitches given infusions of gonadotrophin-releasing hormone superagonist following withdrawal of progesterone implants. Journal of Reproduction and Fertility Supplement 47: 522-523. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Descriptors: delayed estrus, contraceptive agents, drug implants, estrus synchronization, dogs, gonadorelin, progesterone.

Corrada, Y., D. Arias, R. Rodriguez, E. Spaini, F. Fava, and C. Gobello (2004). Effect of tamoxifen citrate on reproductive parameters of male dogs. Theriogenology 61(7-8): 1327-1341. ISSN: 0093-691X.
NAL Call Number: QP251.A1T5
Descriptors: tamoxifen, dog, sperm, prostate, testis, therapy.

Cukierski, M.J., P.A. Johnson, and J.C. Beck (2001). Chronic (60-week) toxicity study of DUROS leuprolide implants in dogs. International Journal of Toxicology 20(6): 369-381. ISSN: 1091-5818.
NAL Call Number: RA1190.J61
Descriptors: implants, leuprolide, dogs, chronic toxicity.

Drieu, K. and I. Osterburg (1989). Influence of decapeptyl on reproductive functions. Contraception Fertilite Sexualite 17(12): 1105-1108. ISSN: 1165-1083.
Descriptors: LHRH, fertility, castration, rat, dogs, preimplantation, embryogenesis.

Drill, V.A., K.S. Rao, R.G. McConnell, and E.N. Souri (1975). Ocular effects of oral contraceptives. I. Studies in the dog. Fertility and Sterility 26(9): 908-13. ISSN: 0015-0282.
Abstract: The administration of two oral contraceptives to female dogs for 5 years did not produce ocular lesions. Corneal and lenticular opacities occurred with equal frequency in control and treated groups, and fundic lesions, including papilledema, venous dilatation, and venous or arterial retinal thrombosis, were not produced by doses of Enovid-E or Ovulen 1, 10, and 25 times the human dose.
Descriptors: adverse effects of oral contraceptives, eye diseases, body weight, ocular lesions, lens, mestranol, norethynodrel.

Dube, D., A. Assaf, G. Pelletier, and F. Labrie (1987). Morphological study of the effects of an GnRH agonist on the canine testis after 4 months of treatment and recovery. Acta Endocrinologica 116(3): 413-417. ISSN: 0001-5598.
Abstract: After 4 months of treatment of adult male dogs with the GnRH agonist (GnRH-A) [D-Trp6]GnRH ethylamide, the seminiferous tubules contained only type A and B spermatogonia, Sertoli cells, and rare primary spermatocytes, thus causing a 64% decrease in testis weight. At the electron microscope level, Sertoli cells showed an increase in phagosomes and lipid droplets. Leydig cells were markedly atrophied with the accumulation of lipid droplets and showed a predominance of mitochondria with lamellar instead of vesicular cristae. Four months after cessation of treatment with GnRH-A, a complete return to normal spermatogenesis and Leydig cell morphology was observed. The full reversibility of spermatogenesis in the dog after chronic GnRH-A treatment suggests that this well-tolerated peptide could be used as a reversible method of male contraception.
Descriptors: GnRH agonist, testis weight decrease, spermatogenesis, reversible male contraception, dogs.

Dusterberg, B. and S. Beier (1984). Plasma levels and progestational activity of levonorgestrel after repeated intravenous and subcutaneous administration in the beagle bitch. Contraception 29(4): 345-357. ISSN: 0010-7824.
NAL Call Number: RG136.A1C6
Abstract: In pharmacological test models providing repeated daily administrations of steroid hormones, differing time courses of the drug level depending upon the pharmacokinetics can be observed often. The present study should make a contribution to the question whether the time course of the drug level can have an influence on the effectiveness of a given dose of a synthetic gestagen. On the basis of existing pharmacokinetic and pharmacodynamic data in the beagle dog, levonorgestrel (LN) was selected as progestogen. LN was administered daily in equal dosages (0.1 mg) over a period of 14 days subcutaneously (s.c.) and intravenously (i.v.). The gestagenic potency of LN was assessed in an established bioassay by the histological evaluation of the endometrial transformation. Whereas the s.c. administration resulted in a low, but almost constant, LN level, high peaks of short duration could be determined after i.v. administration. Following s.c. injection, LN was released only to a degree of 60% in the observation period compared with 100% after i.v. administration. Nevertheless, 0.1 mg LN given s.c. had stronger endometrial effects than 0.1 mg LN given as bolus i.v.
Descriptors: oral contraceptives, estrus, injections, dogs, levonorgestrel, endomedrial effects, progestogen.

England, G.C. (1997). Effect of progestogens and androgens upon spermatogenesis and steroidogenesis in dogs. Journal of Reproduction and Fertility Supplement 51: 123-138. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Abstract: Two different progestogens, mixed testosterone esters, and a combination of progestogen and androgens were evaluated for their effect on semen quality and peripheral plasma testosterone and LH concentration in dogs. Megestrol acetate (2 mg kg-1) given orally for 7 days, and medroxyprogesterone acetate (10 mg kg-1) given subcutaneously produced no change in semen quality compared with that of control dogs. Higher doses of megestrol acetate (4 mg kg-1) produced minor secondary sperm abnormalities, whereas 20 mg medroxyprogesterone acetate kg-1 produced a rapid and significant decrease in sperm motility, morphology and output. The effect of progestogen was probably mediated by action upon the epididymis, since semen quality declined rapidly, morphological changes were the result of more secondary sperm abnormalities, and there was no suppression of plasma LH concentration. Mixed testosterone esters (5 mg kg-1) produced a significant decline in semen quality, which occurred 3 weeks after treatment and persisted for 3 months. There was an increase in the number of primary sperm abnormalities, and it was thought that the effect was probably related to suppression of gonadotrophin resulting in an effect on spermatogenesis. The combination of mixed testosterone esters (5 mg kg-1) and medroxyprogesterone acetate (20 mg kg-1) produced a rapid and profound decrease in semen quality. It was postulated that the effect of this combination of treatment on semen quality was mediated directly by the progestogen upon the epididymal phase of development, and the androgen causing suppression of gonadotrophins. Indeed a reduction in the plasma LH concentration was noted, and both primary and secondary sperm abnormalities were present. The dog appears to differ from other species in the sensitivity of the pituitary-hypothalamus to progestogen feedback. Gonadotrophin suppression does not occur even when high doses of progestogens are used and there are no significant effects on libido. However, combinations of progestogens and androgens may provide a clinically useful method of reversible contraception in the dog.
Descriptors: reversible contraception, progestogens, androgens, semen quality, plasma testosterone, luteinizing hormone concentration, dogs.

Evans, J.M., O. Uvarov, and D.K. Valliance (1969). Hormonal control of the oestrus cycle in the bitch. The Veterinary Record 85(8): 233-234. ISSN: 0042-4900.
NAL Call Number: 41.8 V641
Descriptors: oral contraceptives, dogs, drug effects on estrus, female, megestrol, pregnancy, pregnanes, progestins.

Findlay, M.A. (1975). Letter: Oral progestagens in cats. The Veterinary Record 96(18): 413. ISSN: 0042-4900.
NAL Call Number: 41.8 V641
Descriptors: megestrol, cats, oral administration, female.

Geil, R.G. and J.K. Lamar (1977). FDA studies of estrogen, progestogens, and estrogen/progestogen combinations in the dog and monkey. Journal Of Toxicology And Environmental Health 3(1-2): 179-193. ISSN: 0098-4108.
NAL Call Number: RA565.A1J6
Abstract: A study begun by a drug company and taken over by the FDA (Food and Drug Administration) in 1970 attempted to assess the role of oral contraceptives in tumorigenesis and clotting abnormalities in animals. The study used ethynerone (MK 665) + mestranol; chloroethynyl norgestrel (Wy-4355) + mestranol; anagestone acetate + mestranol; ethynerone, and; mestranol administered at levels up to 25 times the human use level to female beagle dogs and 50 times the human use level to female rhesus monkeys. No behavioral changes related to compound or dose were observed in either species. Both species exhibited pharmacologic effects of hormone administration. Inhibition of the estrous cycle and vulvar enlargement were seen in all dosed dogs. Both species exhibited a dose-dependent, nonprogressive decrease in hemoglobin and hematocrits, with the anagestone acetate-mestranol combination showing the greatest effect. More nodules developed in the mammary glands of dogs who received the progestogen-mestranol combinations and who received ethynerone alone than control dogs. The 3 progestogen-mestranol combination showed the greatest tumorigenic effect as expressed by the number of dogs affected and by numbers of mammary nodules. This effect was dose-dependent for the ethynerone-mestranol and chloroethynyl norgestrel-mestranol combinations, but for the anagestone acetate-mestranol combination was maximal at the lower dose. A small number of dogs that received each progestogen-mestranol combination developed clinically malignant tumors; control dogs or dogs that received only mestranol or ethynerone were unaffected. In contrast, none of the drugs was associated with an increased incidence of mammary nodules in the monkeys. Some monkeys that received each drug showed ductal epithelial hyperplasia in mammary gland biopsies. Diabetes mellitus occurred in 10 dogs from the chloroethynyl norgestrel-mestranol and anagestone acetate-mestranol groups and in 3 monkeys from the ethynerone-mestranol high dose and anagestone acetate-mestranol high dose groups. Generalized cystic hyperplasia of the gallbladder mucosa was seen in a small number of dogs from the anagestone acetate-mestranol group. The suitability of the dog as test species for the tumorigenic and carcinogenic study of oral contraceptives is indicated.
Descriptors: alopecia, laboratory animals, clinical research, contraception, contraceptive methods, estrogen, progestin, mestranol, oral contraceptives.

Goldzieher, J.W., C.B. Chenault, A. de la Pena, T.S. Dozier, and D.C. Kraemer (1977). Comparative studies of the ethynyl estrogens used in oral contraceptives: effects with and without progestational agents on plasma cortisol and cortisol binding in humans, baboons, and beagles. Fertility and Sterility 28(11): 1182-1190. ISSN: 0015-0282.
NAL Call Number: 448.8 F41
Descriptors: comparative study, dogs, ethinyl estradiol, animal models, hydrocortisone, megestrol, mestranol, norethindrone, norgestrel, oral contraceptives.

Hassan, T., R.E. Falvo, V. Chandrashekar, B.D. Schanbacher, and C. Awoniyi (1985). Active immunization against LHRH in the male mongrel dog. Biology of Reproduction 32(Suppl. 1): 222. ISSN: 0006-3363.
NAL Call Number: QL876.B5
Descriptors: LHRH, immunocontraception, dogs.

Horoz, H., C.S. Konuk, K. Gurbulak, G. Kasikci, M.E.C. Sonmez, and A. Gurel (2000). The effect of intrauterine device (IUD) administration on fertility, serum progesterone, oestradiol 17 beta and uterine endometrium during the induced estrus cycle in the bitch. Veteriner Fakultesi Dergisi Istanbul 26(2): 325-335. ISSN: 0378-2352.
Descriptors: bitches, clinical aspects, endometritis, endometrium, estradiol, female infertility, intrauterine devices, oestrous cycle, oestrus, progesterone, pyometra, dogs.
Language of Text: Turkish.

Hubler, M. and S. Arnold (2000). Verhinderung der Trächtigkeit bei Hündinnen mit dem Progesteronantagonisten Aglépristone (Alizine) [Prevention of pregnancy in bitches with the progesterone antagonist anglepristone (Alizone)]. Schweizer Archiv Fur Tierheilkunde 142(7): 381-386. ISSN: 0036-7281.
NAL Call Number: 41.8 SCH9
Abstract: A study was carried out between April 1997 and October 1998 to determine the effect of the progesterone antagonist, Aglépristone (Alizine), for the prevention of pregnancy. 93 bitches were treated, because of mismating, with Aglépristone. The owners were then contacted 2 weeks and 6 to 12 months after treatment to gather any information on effects noted over this period. The major questions were, was pregnancy prevented and if so what side effects were observed, if any, and whether any metropathies were diagnosed. Also noted was the beginning of the next heat and, if the bitch was mated, the fertility rate. Pregnancy was seen in only one bitch. In 51 bitches minor side effects, either singularly or in combination, such as a transient itch, vaginal discharge, reduced appetite, tiredness or attachment were observed. The fertility was not influenced by the treatment and the incidence of metropathies was unchanged.
Descriptors: contraception, contraceptive agents, dogs , estrenes, female, hormone antagonists, pregnancy, progesterone.
Language of Text: German.

Inaba, T., T. Umehara, J. Mori, R. Torii, H. Tamada, and T. Sawada (1996). Reversible suppression of pituitary-testicular function by a sustained-release formulation of a GnRH agonist (leuprolide acetate) in dogs. Theriogenology 46(4): 671-677. ISSN: 0093-691X.
NAL Call Number: QP251.A1T5
Descriptors: GnRH, LH, testosterone, semen, dog, testis function, contraception, leuprorelin, gonadorelin agonist.

Jochle, W. and M. Jochle (1975). Reproductive and behavioral control in the male and female cat with progestins: long-term field observations in individual animals. Theriogenology 3(5): 179-185. ISSN: 0093-691X.
NAL Call Number: QP251.A1T5
Descriptors: cats, chlormadinone acetate, comparative study, estrus, female, megestrol, pregnancy, progestins, sexual behavior, social dominance.

Johnson, A.N. (1989). Comparative aspects of contraceptive steroids--effects observed in beagle dogs. Toxicologic Pathology 17(2): 389-95. ISSN: 0192-6233.
Abstract: The effects of oral contraceptives have been studied in the beagle bitch for periods up to 7 yr. High doses of these potent estrogen: progestogen (E:P) combinations have been shown to promote tumors in the mammary glands, smooth muscle of the tubular genitalia, and occasionally in the transitional epithelium of the neck/trigone area of the urinary bladder. The contraceptive formulations used in humans are balanced with an E:P ratio of about 1:5 to 1:80 to produce a desired decidual response in the uterus. The corresponding ratio for producing the decidual reaction in the dog is 1:1,000 to 1:3,000 with the result that the dog is grossly overdosed with estrogens when given the human formulation at the usual multiples of up to 25 times the human dose. Smooth muscle tumors of the tubular reproductive tract are common sequelae to estrogen overstimulation in the dog and are known to occur in other species, including the humans. The dog also has major differences in hormonal control and sensitivity when compared to humans. Progestogens stimulate synthesis and release of growth hormone (GH) in dogs which in turn is the major stimulant (with progestogens) of mammary growth and tumors. Evidence is accumulating which indicates that most if not all progestogens can produce mammary tumors in the dog if given by the correct route and at high enough dosage. In contrast, GH in humans is not increased nor does it have any significant mammotrophic role. Mammary tumors in dogs related to oral contraceptives are now widely considered to be irrelevant as a model or predictor for human tumors. Transitional cell tumors in the urinary bladder seem to be a species specific phenomenon seen on occasion in the dog, but not in the rat, monkey, or human. The usual location in the neck/trigone area may be related to the embryologic origin of this portion of the bladder, which derives from tissues more closely related to the genital organs than does the rest of the bladder.
Descriptors: contraceptives, oral, hormonal toxicity, dogs, neoplasms chemically induced.

Kwapien, R.P., R.C. Giles, R.G. Geil, and H.W. Casey (1977). Basaloid adenomas of the mammary gland in beagle dogs administered investigational contraceptive steroids. Journal of the National Cancer Institute 59(3): 933-940. ISSN: 0027-8874.
NAL Call Number: 176.622 J82
Descriptors: adenomas, oral contraceptives, mammary tumors, light microscopy, progestins, estrogens, mestranol, dogs.

Kwapien, R.P., R.C. Giles, R.G. Geil, and H.W. Casey (1980). Malignant mammary tumors in beagle dogs dosed with investigational oral contraceptive steroids. Journal of the National Cancer Institute 65(1): 137-144. ISSN: 0027-8874.
NAL Call Number: 176.622 J82
Abstract: Of 172 beagle dogs administered investigational oral contraceptive steroids for 2.4-5.2 yr, 9 developed malignant mammary tumors. At necropsy their ages varied from 41-70 mo., with a mean age of 4.9 yr. The malignant tumors were observed in 1 dog that received ethynerone plus mestranol at 1.05 mg/kg per day and in 4 dogs that received chlorethynyl norgestrel plus menstranol at 1.05 mg/kg per day. Also, 4 dogs that received anagestone acetate plus menstranol at 0.44 or 1.10 mg/kg per day developed malignant mammary tumors. Malignant tumors were not seen in 33 dogs administered mestranol at 0.02 and 0.05 mg/kg per day for 7 yr or in 18 dogs given ethynerone without mestranol at 1.00 mg/kg per day for 5 yr. No malignant tumors were observed in 18 control dogs maintained for 7 yr without treatment. Three dogs had single malignant mammary nodules, 3 dogs had 2 malignant nodules, 2 dogs had 4-6 malignant nodules and 1 dog in the treatment group given high dosages of ethynerone plus mestranol had 14 mammary nodules composed of fibrosarcoma. The malignant tumors were histologically classified as 5 anaplastic carcinomas, 2 solid carcinomas, 1 tubular adenocarcinoma, 1 squamous cell carcinoma and 1 fibrosarcoma. Most dogs had only 1 histologic type of cancer (8/9 dogs); 1 dog had carcinomas of both solid and anaplastic types involving different glands. Metastases were present in 5 dogs and most often involved regional lymph nodes and lung.
Descriptors: adenocarcinoma, carcinogens, oral contraceptives, dogs, fibrosarcoma, lung neoplasms, mammary tumors, mestranol, norgestrel, norpregnadienes, pregnenes.

McDonald, M. (1980). Contraceptives for feral cats. The Veterinary Record 106(18-20): 418. ISSN: 0042-4900.
NAL Call Number: 41.8 V641
Descriptors: animal population groups, feral cats, oral contraceptives, population control, poisoning.

McRae, G.I., B.B. Roberts, A.C. Worden, A. Bajka, and B.H. Vickery (1985). Long-term reversible suppression of oestrus in bitches with nafarelin acetate, a potent LHRH agonist. Journal of Reproduction and Fertility 74(2): 389-397. ISSN: 0022-4251.
NAL Call Number: 442.8 J8222
Abstract: Adult cyclic beagle bitches were treated for up to 18 months with nafarelin acetate via subcutaneously implanted osmotic pumps, starting during the first week of a pro-oestrous vaginal discharge. The imminent ovulation appeared to be unaffected by treatment, but doses of 8 or 32 micrograms analogue/day reduced the integrated luteal progesterone values. No new oestrus was detected in 3 bitches during 18 months of treatment with 32 micrograms/day, which resulted in mean plasma levels of 0.4 ng analogue/ml. A return to oestrus was observed in all 3 bitches between 3 and 18 weeks after cessation of treatment: 2 of the bitches mated at those times and produced normal litters. Another 2 bitches were similarly treated with 32 micrograms analogue/day; they were mated at the oestrus at start of treatment and dosing was continued for about 63 days. One of the bitches conceived and produced a normal litter. Nafarelin acetate treatment begun during anoestrus resulted in an induced heat 1-2 weeks after the start of treatment. The induced heat consisted of pro-oestrous vaginal discharge, oestrous vaginal cytology, and ovulation (judged by increased circulating levels of progesterone). Three bitches mated at the induced heat and treated for the normal duration of gestation did not litter. Nafarelin treatment of 3 bitches before puberty did not induce signs of oestrus and prevented the occurrence of oestrus through 18 months of treatment. The first oestrus in these bitches occurred 3.5-4 months after cessation of treatment, but mating at that time did not result in pregnancy. These studies have established the feasibility of and dosage requirement for the use of the LHRH agonist as a contraceptive in the bitch.
Descriptors: contraception, oestrus suppression, LHRH agonist, dogs.

Munson, L., J.E. Bauman, C.S. Asa, W. Jochle, and T.E. Trigg (2001). Efficacy of the GnRH analogue deslorelin for suppression of oestrous cycles in cats. Journal of Reproduction and Fertility 57(Suppl.): 269-273. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Abstract: The aim of this study was to develop a method for long-term but reversible inhibition of oestrous cycles in female cats by downregulation of GnRH receptors with deslorelin released from a long-acting implant. In a blind study with mature cats (n = 20), a 6 mg deslorelin implant was administered s.c. to ten cats and a placebo implant was administered to ten cats. Occurrence of oestrus and general health were observed daily, and individual faecal samples were collected at 3 day intervals for 14 months and analysed for oestradiol content. All the placebo-treated queens continued to undergo normal oestrous cycles during the study. Oestrus was accompanied by peaks in oestradiol concentrations of > or = 20 ng g-1 faeces. Treatment with deslorelin initially stimulated oestradiol release, which accompanied treatment-induced ovulations. Thereafter, oestradiol concentrations decreased to 1-10 ng g-1 faeces and remained low for extended periods. Observations of small increases in oestradiol concentrations in one cat led to a second treatment with 6 mg deslorelin in five cats on day 155 after first treatment. Faecal oestradiol concentrations remained < 20 ng g-1 faeces in the five single treatment cats for 8.0, 8.5, 11.0 and 14.0 (two cats) months. Cats receiving two implants had the first oestradiol peak > 20 ng g-1 faeces after treatment at 7.5, 11.0 (two cats), 11.5 and 14.0 months. After 14 months, two cats had returned to normal cyclic activity, two had irregular small oestrogen peaks and six showed no cyclic activity. For months 2-5, 6-10 and 11-14, oestrogen values in treated cats were significantly different from control values (P < 0.001, 0.05 and 0.02, respectively). Differences in oestrogen concentration between control cats and cats that were treated twice were significant (P < 0.001) during months 6-10 only. The general health of treated cats was unchanged throughout the study. These results confirm that deslorelin can effectively suppress ovarian activity in domestic cats, but that the duration of suppression varies among individuals.
Descriptors: female cats, contraceptive agents, estradiol, gonadorelin, estrus detection, inhibition of estrus, drug implants, deslorelin.

Murakoshi, M., R. Ikeda, M. Tagawa, T. Iwasaka, and T. Nakayama (2000). Histopathological study of female beagle dogs for four year treatment with subcutaneous implantation of chlormadinone acetate (CMA). The Tokai Journal of Experimental and Clinical Medicine 25(3): 87-91. ISSN: 0385-0005.
Abstract: The histopathological changes related to chlormadinone acetate (CMA) implantation were examined using female beagle dogs given 10mg/kg for four years. All control animals showed sign of estrus during the experiment, with periods of anestrus of normal duration. In contrast, estrus was completely inhibited in the CMA-implanted animals. Histopathologically, uterine sections from the CMA-implanted animals showed cystic glandular hyperplasia, but no histologic evidence of endometritis, myometritis, and pyometra was found. In the ovaries of the CMA-implanted animals, developing ovarian follicles were observed but no mature follicles were noted in addition to an absence of corpus luteum. No remarkable changes were observed in the liver, adrenal, mammary gland, gallbladder and implanted site. Furthermore, the intensity of staining and number and size of ACTH-and LH-positive cells in the pituitary sections of CMA-implanted animals were not different from control animals. It was concluded, therefore, that subcutaneous implantation of CMA is a potential drug-delivery system for reducing changes due to antigonadotropic and glucocorticoid-like activities and characteristic histopathological changes in the uterus due to progestagenic activity.
Descriptors: chlormadinone acetate implants, contraceptive agents, dogs, physiological effects, drug implants.

Nelson, L.W., J.A. Botta Jr, and J.H. Weikel Jr (1973). Estrogenic activity of norethindrone in the immature female beagle. Research Communications in Chemical Pathology and Pharmacology 5(3): 879-882. ISSN: 0034-5164.
NAL Call Number: RM1.R4
Descriptors: cervix uteri, dogs, estradiol, female, mammary glands, norethindrone, ovary, progesterone, uterus, vagina.

Nelson, L.W., J.H. Weikel Jr., and F.E. Reno (1973). Mammary nodules in dogs during four years' treatment with megestrol acetate or chlormadinone acetate. Journal of the National Cancer Institute 51(4): 1303-1311. ISSN: 0027-8874.
Abstract: A 7 year study of megestrol and chlormadinone in female dogs is in progress. This report characterized histopathologically 60 mammary nodules during the first 4 years of the study. 100 purebred female beagles, 6-12 months of age, were randomly assigned to 5 equal groups. One group was used as a control. Oral doses were .01, .10, and .25 mg/kg/day of megestrol acetate in coconut oil in capsules and of chlormadinone acetate .25 mg/kg/day in lactose tablets. These doses were 1, 10, and 25 times the projected dose of megestrol for humans and about 25 times the human dose of chlormadinone. After 2 years 4 dogs from each group were necropsied. One high-dose megestrol-treated and 1 chlormadinone-treated dog had benign mixed mammary tumors. Palpable nodules were first observed at 16 months in the chlormadinone-treated dogs, at 18 months in dogs given the high dose megestrol and at 27 months in the dogs treated with middle-dose megestrol. Transitory nodules were found in 4 control dogs after 21 months and in low dose megestrol-treated dogs at 26 months. Of 38 grossly detected nodules evaluated microscopically from the megestrol-treated dogs 27 were nodular hyperplasia, 5 were benign mixed mammary tumors, 3 were ductal dialatations, 1 was a lymph node, 1 was fat necrosis and 1 was the umbilicus. Of 22 nodules from the chlormadinone-treated dogs 12 were nodular hyperplasia, 4 benign mixed mammary tumors, 1 chondromucoid degeneration and 1 adenocarcinoma with widespread metastases. 3 nodules were lymph nodes and 1 other had no mammary tissue. Involutions, regression and sclerosis of many areas of nodular hyperplasia were evident at 4 years. Thus of the 60 nodules evaluated during the first 4 years of the study 50 were non-neoplastic and 10 were neoplastic. It is considered that the 1 adenocarcinoma may have been spontaneous and not a treatment-related neoplasm. A precursor stage through nodular hyperplasia apparently did not occur.
Descriptors: adenocarcinoma, chlormadinone, contraceptives, mammary glands, drug effects, megestrol, adenocarcinoma, chlormadinone acetate, dogs, hyperplasia.

Okkens, A.C., J.E. Eigenmann, and G.C. vd Weyden (1981). Preventie van loopsheid en/of dracht bij de hond door andere methoden dan ovario-hysterectomie. [Prevention of oestrus and/or pregnancy in dogs by methods other than ovariohysterectomy (author's transl)]. Tijdschrift Voor Diergeneeskunde 106(23): 1215-1225. ISSN: 0040-7453.
NAL Call Number: 41.8 T431
Abstract: The present paper is based on findings reported in the literature and concerned with various possible methods of preventing heat and/or pregnancy without resorting to ovariohysterectomy. The drugs used to suppress and prevent oestrus, such as progestagens, testosterone and 19-nortestosterone derivates, are reviewed, the mechanism of action, mode of administration and advantages and disadvantages being discussed. Progestagens are particularly found to affect the uterus (CEH) and mammary glands (increased incidence of mammary tumours), and they may also induce diabetes mellitus and acromegaly. On the other hand, the untoward side-effects of 19-nortestosterone derivatives are found to be mainly due to their androgenic action, resulting in enlargement of the clitoris, vaginitis, changes of behaviour and masculinization of puppies when the drug is administered during pregnancy. Subsequently, those mechanical and surgical procedures which are less commonly employed, are discussed. The pros and cons of the various methods and drugs as well as the possible causes of the difference in gestagenic effect of a number of progestational agents are discussed in greater detail.
Descriptors: contraception, contraceptive agents, dogs, estrus, female, pregnancy, progestins, testosterone.
Language of Text: Dutch.

Owen, L.N. and M.H. Briggs (1976). Contraceptive steroid toxicology in the beagle dog and its relevance to human carcinogenicity. Current Medical Research and Opinion 4(5): 309-329. ISSN: 0300-7995.
Abstract: Problems associated with the use of the Beagle dog in chronic toxicological studies of contraceptive steroids are described. A short review is presented on the occurrence of spontaneous tumours in dogs and in bitches of various breeds. The current status of knowledge of canine reproductive hormones and endocrinology is outlined, together with effects of contraceptive steroids. The pathology and histological classification of spontaneous and induced mammary neoplasia in the dog is discussed and compared with breast cancer in women. A series of recommendations are included for future research in this field which it is hoped may resolve some of the outstanding issues and lead to a more suitable toxicological model for contraceptive steroids. Many scientists have criticized the mandatory use of dogs for studies of the chronic toxicity of synthetic steroidal contraceptive hormones. The estimated annual incidence rates for cancer of all sites in dogs is 381.2/100,000 dogs. The estimated relative risk (R) value for the occurrence of tumors in the Beagle breed is 0.9; for malignant tumors, the R value in the Beagle is 0.8. A review of the hormonal potency of various contraceptive steroids in the Beagles indicates that progestogenic compounds generally produce a much lower progestational activity in dogs than in women, and the the predominant hormonal action of norethisterone in dogs is estrogenicity rather than progestogenicity. This weak activity for the canine species may account for some of the toxicological findings for norethisterone and related compounds in the Beagle. It is also possible that there are species differences in the relative affinities of estrogen and progesterone receptors for contraceptive steroids. Studies on long-term administration to female Beagle dogs suggest that the nodules found in the mammary gland are not histologically comparable to mammary tumors found in the human female although there is a superficial morphological resemblance to some forms of human mammary dysplasia. Several authors suggest that the results of testing progestational compounds in Beagles are unlikely to be indicative of a potential hazard to the human female. In testing megestrol acetate, it is suggested that the unique sensitivity of the canine females to megestrol acetate is exemplified by intense mammary development at dose levels 10 times the human oral contraceptive level. In contrast, daily dose levels of 500 mg/day in women as a palliative for endometrial cancer have been used with no serious side effects or mammary enlargement. Also the canine mammary gland produces certain pathological changes following administration of natural or synthetic progesterones in a way not readily seen in other species. Possible alternative models (cat, pig) for contraceptive steroid toxicological studies and recommendations for future research are discussed.
Descriptors: contraceptive agents, disease models, dogs, breast neoplasms, cats, chlormadinone acetate toxicity, pituitary analysis, mammary glands, mammary neoplasms, megestrol toxicity.

Palmer, C.W. and K. Post (2002). Prevention of pregnancy in the dog with a combination of prostaglandin F2 alpha and bromocriptine. The Canadian Veterinary Journal: La Revue Veterinaire Canadienne 43(6): 460-462. ISSN: 0008-5286.
NAL Call Number: 41.8 R3224
Abstract: Fifteen mated bitches were given prostaglandin F2 alpha (PGF2 alpha) [250 micrograms/kg body weight] and bromocriptine (10 micrograms/kg BW) twice daily from days 6 to 10 of diestrus. Progesterone concentrations declined during treatment. None of the bitches whelped. Daily treatment with PGF2 alpha and bromocriptine for 5 d appears to induce luteolysis and prevent early pregnancy.
Descriptors: abortifacient agents, bromocriptine, methods of contraception, corpus luteum, hormone antagonists.

Pineda, M.H. and L.C. Faulkner (1974). Immunologic control of reproduction in dogs. Canine Practice 1(2): 11. ISSN: 0094-4904.
NAL Call Number: SF991.A1C3
Descriptors: laboratory animals, antibodies, chorionic gonadotropin, immunologic contraception, endocrine system, gonadotropins, luteinizing hormone.

Riesenbeck, A., R. Klein, and B. Hoffmann (2002). Downregulation, a new and reversible approach to eliminate testicular function in the dog. Der Praktische Tierarzt 83(6): 512-520. ISSN: 0032-681X.
NAL Call Number: 41.8 P882
Descriptors: downregulation, castration, dog, gonadotropin releasing hormone, prostatic hypertrophy, immunization, ovarian.

Romagnoli, S. and P. Concannon (2003). Clinical use of progestins in bitches and queens: a review. In: P. Concannon, G. England, J. Verstegen and C. Linde-Forsberg (editors), Recent Advances in Small Animal Reproduction, International Veterinary Information Service: Ithaca, NY.
Descriptors: progestins, dogs, cats, estrus cycle suppression, suppression of sexula behaviors, side effects, contraception, non-contraceptive uses, medroxyprogesterone acetate (MPA), melengesterol acetate (MGA), megestrol acetate (MA).

Sandow, J., W. von Rechenberg, C. Baeder, and K. Engelbart (1980). Antifertility effects of an LH-RH analogue in male rats and dogs. International Journal Of Fertility 25(3): 213-221. ISSN: 0020-725X.
NAL Call Number: 442.8 In83
Abstract: The antifertility effects of a highly active LH-RH analogue, D-Ser(Bu)6-LH-RH(1-9)nonapeptide-ethylamide (buserelin) were studied in male rats and dogs. Pituitary-testicular function was not impaired by a "physiological" dose of 5 ng/rat; this dose gave reproducible LH release during chronic administration. At higher dose testicular LH receptors and responsiveness to HCG were diminished in intact prepubertal and adult rats. Pituitary inhibition was independent of gonadal or adrenal steroid feedback, and hypothalamic LH-RH as well as pituitary LH and FSH were reduced by 4 weeks treatment of castrate/adrenalectomized rats with 50 ng buserelin. In male dogs, a dose of 2.5 micrograms/kg sc reduced serum testosterone to 6% of controls within 8 weeks of treatment. Treatment was continued for 6 months and testicular involution was found to be reversible within 8 weeks of stopping treatment. LH-RH analogues at "supraphysiological" doses can be used as antifertility agents, but suppression of sexual activity in male dogs under treatment indicates that loss of libido will be a problem.
Descriptors: adrenalectomy, buserelin, castration, dogs, drug effects on fertility, rats, gonadorelin, luteinizing hormone, testosterone.

Schaefers-Okkens, A.C. and H.S. Kooistra (1996). Anticonceptiepillen voor de poes. [Contraceptive tablets for the cat]. Tijdschrift Voor Diergeneeskunde 121(7): 207. ISSN: 0040-7453.
NAL Call Number: 41.8 T431
Descriptors: cats, oral contraceptives, estrus effects, progestins.
Language of Text: Dutch.

Schaefers-Okkens, A.C. and H.S. Kooistra (1996). Progestageen gebruik [Use of progestagens]. Tijdschr Diergeneeskd 121(11): 335-337. ISSN: 0040-7453.
Descriptors: animals, comparative study, contraceptive agents, dogs, estrus, female, medroxyprogesterone 17-acetate, progestins.
Language of Text: Dutch.

Selman, P.J., E. van Garderen, J.A. Mol, and T.S. van den Ingh (1995). Comparison of the histological changes in the dog after treatment with the progestins medroxyprogesterone acetate and proligestone. The Veterinary Quarterly 17(4): 128-133. ISSN: 0165-2176.
NAL Call Number: SF601.V46
Abstract: Administration of progestins in the dog may result in overproduction of growth hormone, suppression of the hypothalamic-pituitary-adrenocortical axis, and insulin resistance. In this paper we present a comparison of the histological findings in control dogs and dogs treated with either medroxyprogesterone acetate (MPA) or proligestone (PROL). Depot preparations of MPA or PROL were administered (SC) at 3-week intervals in two groups of seven ovariohysterectomized beagle dogs, after which three dogs of each group were killed. After a 6-month period without hormone treatment during which recovery was studied, the remaining dogs received five additional injections at the same interval and were subsequently killed. Tissue samples of four intact female beagle dogs served as controls. Progestin treatment resulted in atrophy of the adrenal cortex. In both MPA- and PROL-treated dogs, the thickness of the combined zona fasciculata and reticularis was significantly smaller than in control animals. In the mammary glands of progestin-treated dogs there were well developed alveoli and normal ducts adjacent to foci of hyperplastic ductular epithelium. Five dogs in each treatment group had developed benign mammary tumours which varied from simple tubular and papillary adenomas to benign complex and mixed tumours, whereas no mammary tumours were observed in the control animals. In each treatment group, steroid-induced hepatopathy was observed in the liver of three dogs. Vacuolation of the cells of the islets of Langerhans and the epithelium of the intercalated ducts was present in two dogs of each treatment group and was only observed after the second series of progestin administrations. Incidental findings included chronic pyelonephritis, aspecific dermatitis, and mucinous dysplasia of the gall bladder. No abnormalities were found in sections of spleen, lung, brain, or pituitary gland. There were no significant differences in the frequencies of the various abnormalities between MPA- and PROL-treated dogs. Our findings correspond with the clinical and biochemical results after treatment of dogs with MPA and PROL. The high incidence of mammary tumours might be associated with our recent finding that in the dog progestins induce ectopic production of growth hormone in the mammary gland. The dog might be a good model for further studies on hormonally induced breast cancers.
Descriptors: medroxyprogesterone acetate (MPA), proligestone (PROL), comparative study, contraceptive agents, hysterectomy, ovariectomy, adverse effects of progesterone and derivatives, dogs.

Snowball, S. and W. Taylor (1986). The effect of a progestin-only oral contraceptive on biliary lipid composition in the cat. Journal of Steroid Biochemistry 25(6): 1007-1011. ISSN: 0022-4731.
NAL Call Number: QD426.A1J6
Abstract: Following a control period of 5 weeks, 3 female cats with chronic gastric and duodenal fistulae were given 37.5 micrograms of the progestin D-norgestrel for 15 weeks. The study was continued for 8 weeks after withdrawal of treatment. Bile was collected via the duodenal fistula at 7-10 day intervals. During treatment the combined molar percentage of biliary cholesterol of all cats (4.2 +/- 0.4, n = 34) was significantly lower than during the control period (8.2 +/- 1.3, n = 11) [P = 0.001], and remained depressed after treatment withdrawal (5.5 +/- 1.0, n = 11) [P = 0.02]. The molar percentage of phospholipids remained unchanged in all animals, and that of total bile acids increased during treatment in one animal. As assessed by triangular coordinate plotting, the bile of each animal became less saturated with cholesterol during norgestrel administration. These results support the concept that the oestrogen component may be a major factor in the development of increased biliary cholesterol saturation in users of mixed-type oral contraceptives.
Descriptors: oral contraceptives, cats, bile acids and salts, norgestrel, cholesterol.

Stolla, R. (1970). Ovulationshemmer in der Veterinärmedizin und in der Tierzucht? [Contraceptives in veterinary medicine and breeding] . Munchener Medizinische Wochenschrift 112(7): 305. ISSN: 0027-2973.
Descriptors: breeding, cats, contraception, oral contraceptives, dogs , estrus, female, pregnancy.
Language of Text: German.

Sundaram, K. (1984). Use of LHRH agonists and antagonists in male contraception: a review. Contraception 29(2): 163-170. ISSN: 0010-7824.
NAL Call Number: RG136.A1C6
Abstract: Agonists and antagonists of LHRH have been shown to inhibit testicular function in animals and are considered to offer potential for nonsteroidal contraception. In men, they offer one of the few promising approaches to reversible suppression of spermatogenesis. They do, however, also depress testosterone synthesis, thus causing loss of libido, necessitating the administration of supplemental androgens.
Descriptors: oral contraceptives, male contraception, inhibition of testicular function, nonsteroidal contraception, reversible suppression of spermatogenesis, testosterone, animals, humans.

Tremblay, Y. and A. Belanger (1984). Reversible inhibition of gonadal functions by a potent gonadotropin-releasing hormone agonist in adult dog. Contraception 30(5): 483-497. ISSN: 0010-7824.
NAL Call Number: RG136.A1C6
Abstract: This study examines the recovery of spermatogenesis, testicular and plasma steroidogenesis and prostatic steroid content 26 weeks following cessation of daily treatment for 16 weeks with [D-Tryp6]LHRH ethylamide (LHRH-A) in the adult dog. While administration of LHRH agonist resulted in testicular and prostatic weight reductions of 40-60%, a complete recovery is observed 26 weeks after cessation of treatment. The number of sperm in LHRH-A-treated dogs declined rapidly in the first 4 weeks, after which no ejaculation or erection is observed in these animals. Spermatogenesis completely recovered four months following cessation of treatment. While testicular steroidogenesis is completely inhibited during the treatment with the agonist peptide, normal levels of testicular steroids are observed with the exception of 17-hydroxypregnenolone, dehydroepiandrosterone and androst-5-ene-3 beta,17 beta-diol which are elevated above control levels and, furthermore, an accumulation of these delta 5-steroids is also observed in the prostate after the end of treatment. Our data strongly suggest that chronic administration of an LHRH agonist may induce, after cessation of treatment, an overproduction of testicular steroids.
Descriptors: LHRH agonist, spermatogenesis, testosterone, andogens, dogs.

Tremblay, Y., A. Belanger, D. Lacoste, M. Giasson, and F. Labrie (1984). Selective inhibition of spermatogenesis in the presence of normal libido following combined treatment with an LHRH agonist and testosterone in the dog. Contraception 30(6): 585-588. ISSN: 0010-7824.
NAL Call Number: RG136.A1C6
Abstract: In order to maintain libido in dogs treated with an LHRH agonist, animals were administered with testosterone in a gel form for percutaneous adsorption. Histological aspect of testis indicate a complete blockade of spermatogenesis after treatment with the LHRH agonist and the addition of testosterone to these animals did not restore the spermatogenesis. The measurement of testicular steroid levels showed that following LHRH-A administration, the concentration of androgens in testis remained low in the presence or absence of testosterone supplement. However, the prostate weight as well as the volume of ejaculate returned to normal when testosterone was added and this observation can be correlated with the high amount of androgens in prostate. The present study supports the use of LHRH agonist in combination with testosterone as a selective method for inhibition of spermatogenesis in the male.
Descriptors: dogs, LHRH agonist, libido, spermatogenesis inhibition, testosterone administration, contraception.

Trigg, T.E., P.J. Wright, A.F. Armour, P.E. Williamson, A. Junaidi, G.B. Martin, A.G. Doyle, and J. Walsh (2001). Use of a GnRH analogue implant to produce reversible long-term suppression of reproductive function in male and female domestic dogs. Journal of Reproduction and Fertility 57(Suppl.): 255-261. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Abstract: Continuous low-dose administration of a GnRH analogue postpones oestrus in bitches and suppresses reproductive function in dogs. A new drug delivery formulation that could enhance the practicality of this approach for the control of reproduction has been developed. The objective of the present study was to determine whether this method of delivery could, by sustained release of the GnRH analogue deslorelin, act as a reversible anti-fertility agent in domestic male and female dogs for periods exceeding 1 year. Several long-term studies were performed, which monitored reproductive function in 30 dogs and 52 bitches. Suppression of reproductive function in male dogs was dose-related. Spermatogenesis was suppressed for more than a year in 14 of 16 dogs that received doses of > 0.25 mg deslorelin kg-1. In females, postponement of oestrus for periods of up to 27 months was observed, but there was no relationship between the stage of the oestrous cycle at the start of treatment and the duration of efficacy. Treatment-induced effects on fertility were reversible in both sexes. In summary, sustained release deslorelin implants were shown to elicit reversible long-term reproductive control in male and female domestic dogs.
Descriptors: contraceptive implants, male and female dogs, GnRH analogue, deslorelin, anti-fertility, suppression of spermatogenesis, postponement of estrus.

van Os, J.L., P.H. van Laar, E.P. Oldenkamp, and J.S. Verschoor (1981). Oestrus control and the incidence of mammary nodules in bitches, a clinical study with two progestogens. Tijdschrift Voor Diergeneeskunde 106(2): 46-56. ISSN: 0040-7453.
NAL Call Number: 41.8 T431
Abstract: The incidence, size and location of mammary nodules were established in 10 practices in The Netherlands by the clinical examination of bitches in which oestrus was controlled with proligestone (P), 331 animals, or medroxyprogesterone acetate (MAP), 341 animals and in 339 animals never medicated with such compounds. In comparison with the unmedicated control and the P-medicated animals of comparable age the incidence of mammary nodules of all sizes was significantly increased in the MAP-medicated animals. There was no significant difference in nodule incidence between the P-medicated animals and the control animals. Based on the assumption that nodules above a certain size are most likely tumours, these results indicate that oestrus control with MAP stimulates tumour development even in animals medicated for less than four years. The practical value of the reported differences, especially in relation to the subsequent requirement for surgical removal of tumours in bitches, medicated for oestrus control, is discussed.
Descriptors: adverse effects of medrosxyprogesterone acetate, mammary nodules, dogs, female, dog diseases, contraception.

Vickery, B.H. (1985). Comparisons of the potential utility of LHRH agonists and antagonists for fertility control. Journal of Steroid Biochemistry 23(5B): 779-791. ISSN: 0022-4731.
NAL Call Number: QD426.A1J6
Abstract: Prospects for the use of LHRH analogs for human fertility control have been reviewed with particular reference to two highly potent representatives. Nafarelin acetate, the LHRH agonist, has a potency about 200 X that of LHRH and is consistently effective in suppressing gonadal function in females through a desensitization of LHRH receptors in the pituitary. Such agents show promise as ovulation inhibitors for women although concern has been expressed over the dangers of unopposed estrogen or alternatively hypoestrogenemia. Although early studies indicated luteolysis in women and interceptive action in baboons it is now clear that the LHRH agonists will not be useful clinically to terminate pregnancy. Wide species differences in the male response to LHRH agonists exist. Unfortunately azoospermia has not been achieved in men. The LHRH antagonists, typified by [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10]LHRH, require high doses to competitively inhibit responses to endogenous LHRH. Their advantages include a rapid induction of the hypogonadal state with apparently little species or sexual variation in response. Based on animal studies, preferable utility of the antagonists would lie in male contraception and pregnancy interception.
Descriptors: fertility control, human, animal studies, male contraception, LHRH, ovulation inhibitors.

Vickery, B.H., G.I. McRae, J.C. Goodpasture, and L.M. Sanders (1989). Use of potent LHRH analogues for chronic contraception and pregnancy termination in dogs. Journal of Reproduction and Fertility Supplement 39: 175-187. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Descriptors: abortifacient agents, pharmacology, dogs, contraceptive agents, estrus, gonadorelin, nafarelin.

Von Berky, A.G. and W.L. Townsend (1993). The relationship between the prevalence of uterine lesions and the use of medroxyprogesterone acetate for canine population control. Australian Veterinary Journal 70(7): 249-250. ISSN: 0005-0423.
NAL Call Number: 41.8 Au72
Abstract: The prevalence of uterine disease was established during desexing of 175 bitches in the Torres Strait and Cape York, 42 of which had been treated with injectable medroxyprogesterone acetate (MPA) for oestrus postponement. The prevalence of uterine lesions was 45% for treated bitches, 5% for untreated bitches, and 14.9% for the sample population. A highly significant relationship (P < 0.01) between MPA treatment and uterine lesions was established. A significant association (P < 0.05) between age (> 2 years old) and uterine lesions was found, most likely attributable to a significantly higher proportion (P < 0.01) of MPA-treated bitches in the older population. There was no significant difference in the effect of MPA on the prevalence of uterine lesions between older and younger bitches. There was no effect of parity on the prevalence of uterine lesions.
Descriptors: estrus postponement, medroxyprogesterone acetate, uterine lesions, adverse effects, ovariectomy, dogs.

Weikel, J.H.J., L.W. Nelson, and F.E. Reno (1975). A four-year evaluation of the chronic toxicity of megestrol acetate in dogs. Toxicology And Applied Pharmacology 33(3): 414-426. ISSN: 0041-008X.
NAL Call Number: 391.8 T662
Abstract: A 4-year evaluation of the chronic toxicity of megestrol acetate in dogs is reported. .01, .1 or .25 mg of megestrol acetate/kg/day or .25 mg of chlormadinone acetate/kg/day was administered orally for 4 years t o female beagle dogs. The hormone-treated dogs tended to gain more weig ht than did the controls (controls vs. .25 mg megestrol acetate every month after the 3rd p less than .01). All treated dogs revealed decreased evidence of estrus. Mucoid vaginal discharges were more prevalent among the middle and high dose groups. Mean hemoglobin, packed cell volume and total erythrocyte values were slightly decreased while mean total leucocyte count and erythrocyte sedimentation rates were slightly increased in the middle and high dose groups. Clotting me chanism did not reveal any disturbances. Evidence of diabetes consistin g of bilateral cataracts, elevated serum glucose concentrations and glycosuria after 4 years in 2 of 16 high-dose megestrol acetate and in 6 of 15 chlormadinone acetate-treated dogs was revealed. It is concluded that the effects of megestrol acetate were similar but less severe than those of chlormadinone acetate.
Descriptors: megestrol acetate, dogs, chlormadinone acetate, females, weight gain, vaginal discharge, ovulation, comparison study.

Weikel Jr., J.H. and L.W. Nelson (1977). Problems in evaluating chronic toxicity of contraceptive steroids in dogs. Journal of Toxicology and Environmental Health 3(1-2): 167-177. ISSN: 0098-4108.
NAL Call Number: RA565.A1J6
Abstract: The long-term effects of oral contraceptive steroids including a combination of norethindrone and ethynylestradiol, a sequential regimen of dimethisterone and ethynylestradiol, and daily administration of megestrol acetate were studied in female beagle dogs at dose levels of 1, 10, or 25 times the projected human dose levels. The major findings included cystic endometrial hyperplasia and pyometra requiring hysterectomies and alopecia for the norethindrone-ethynylestradiol and dimethisterone-ethynylestradiol treated dogs. These groups did not have accentuated mammary development or treatment-related hyperplastic or neoplastic changes. For dogs given dimethisterone-ethynylestradiol, numerous acne-like lesions occurred in the skin of the mammary areas. Dogs given the higher dose levels of megestrol acetate had marked mammary stimulation, hyperplastic and neoplastic changes in the mammary glands, and clinical and pathologic changes typical of diabetes mellitus. Mammary changes of nodular hyperplasia, benign mixed tumor, and adenocarcinoma appeared as distinct entities although constant and intense mammary stimulation may be a common denominator. Such mammary changes have not been found in long-term studies in monkeys or rats with megestrol acetate, and the relevance of the canine mammary changes to projecting potential tumorigenesis in women is questioned.
Descriptors: oral contraceptives, norethindrone, ethynylestradiol, megestrol acetate, dogs, complications, alopecia, endomedrial hyperplasia, hysterectomy, mamamary changes, tumorigenesis, animal models.

Wright, P.J., J.P. Verstegen, K. Onclin, W. Jochle, A.F. Armour, G.B. Martin, and T.E. Trigg (2001). Suppression of the oestrous responses of bitches to the GnRH analogue deslorelin by progestin. Journal of Reproduction and Fertility 57(Suppl.): 263-268. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Abstract: Studies were undertaken in Australia and Belgium to determine whether the initial pro-oestrous-oestrous responses of anoestrous bitches to treatment with deslorelin administered in a s.c. implant were inhibited by progestin treatment. Thirty-nine bitches of mixed breeding were treated daily with 2 mg megestrol acetate kg-1 body weight for 21 (group 1, n = 5) or 14 days (group 2, n = 10), or with 1 mg megestrol acetate kg-1 body weight for 14 days (group 3, n = 10). A deslorelin (6 mg) implant was placed s.c. on day 14 (group 1) or day 7 (groups 2 and 3) of treatment. Bitches not treated with progestin also received a deslorelin implant (group 4, n = 9) or were untreated controls (group 5, n = 9). Signs of pro-oestrus-oestrus were not observed in bitches in groups 1, 2 and 5, but were observed in bitches in groups 3 (4/10) and 4 (9/9). Four bitches in group 4 were mated, two of which became pregnant. The pregnancies failed at about day 40 of gestation and were associated with low plasma progesterone concentrations. Treatment with progestin inhibited the pro-oestrous-oestrous responses of bitches to deslorelin.
Descriptors: deslorelin, contraceptive implants, dogs, plasma progesterone concentration, progestin, pregnancy.



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