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
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
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, estrus, pharmacokinetics
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.
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, antiestrogen
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
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): 908-913. 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: oral contraceptives, adverse effects,
eye-drug effects, body weight, cataract, corneal opacity, dogs, ethynodiol
diacetate, fundus oculi, crystalline, mestranol, norethynodrel, papilledema,
retinal vessels, thrombosis
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 (
Descriptors: oral contraceptives, estrus, injections,
dogs, levonorgestrel, endomedrial effects, progestogen
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.
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, animal models,
hydrocortisone, megestrol, mestranol, norethindrone, norgestrel, oral
contraceptives
Hubler, M. and S.
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
Note: 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
Lacoste, D., R. St-Arnaud, S. Caron, A. Belanger, and F. Labrie (1988). The
rise in testicular androgens during the first days of treatment with an LHRH
agonist in the dog can be blocked by aminoglutethimide or ketoconazole. Journal
of Steroid Biochemistry 31(6): 963-970.
ISSN: 0022-4731.
NAL Call Number: QD426.A1J6
Descriptors: luteinizing hormone releasing hormone,
androgens, aminoglutethimide, ketoconazole, receptors, agonists, effects on,
serum levels, inhibition, dogs
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, estrus 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
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):
1303-11. 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
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
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.
URL: http://www.ivis.org
Descriptors: progestins, dogs, cats, estrus cycle
suppression, suppression of sexual behaviors, side effects, contraception,
non-contraceptive uses, medroxyprogesterone acetate (MPA), melengesterol acetate
(MGA), megestrol acetate (MA)
Sabeur, K., B.A. Ball, T.M. Nett, H.H. Ball, and I.K. Liu (2003). Effect
of GnRH conjugated to pokeweed antiviral protein on reproductive function in
adult male dogs. Reproduction 125(6): 801-806. ISSN: 1470-1626.
NAL Call Number: QP251.J75
Abstract: This study evaluated the effect of a GnRH
analogue conjugated to the cytotoxin, pokeweed antiviral protein (PAP), on
reproductive function in adult, male dogs. Four dogs received 0.0042 mg
GnRH-PAP kg(-1) hourly for 36 h, and four other dogs received 0.1 mg GnRH-PAP
kg(-1) as one bolus injection daily for three consecutive days. One dog
received a single bolus (0.1 mg x kg(-1)). Three adult male dogs received GnRH
without the PAP conjugate, as controls. Twenty-five weeks after the initial
treatment, all treated dogs received 0.1 mg GnRH-PAP kg(-1) as a single
administration, whereas dogs in the control group received 0.0045 mg kg(-1) of
the GnRH analogue. Serum concentrations of testosterone and LH were determined
by radioimmunoassay, and testis size was measured for 9 months after treatment.
Stimulation tests (5 microg GnRH kg(-1)) were used to evaluate LH release (-15,
0, 30, 60, 90, 120 min), which was assessed by measuring area under the curve.
Serum testosterone concentrations were significantly lower (P<0.05) after
treatment in the bolus and hourly groups than in the control group.
Testosterone concentrations fell to less than 50 pg x ml(-1) in three of four
dogs in the bolus group and one of four dogs in the hourly group by week 8-9
after treatment. Basal LH was lower (P<0.05) in the bolus and hourly groups
than in the control group between weeks 0 and 33 after treatment. Treatment
with GnRH-PAP reduced (P<0.05) LH release after GnRH stimulation in the
bolus and hourly groups compared with the control group. Testis volume was
lower (P<0.05) in all treated versus control dogs. In conclusion,
administration of the conjugate GnRH-PAP at a 25 week interval resulted in a
major disruption of reproductive parameters in male dogs; this effect was
maintained for 11-12 weeks after a second injection of GnRH-PAP.
Descriptors: contraception, dogs, gonadorelin, GnRH
analogue, testosterone, testis volume
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
Note: Language of text: Dutch.
Schaefers-Okkens, A.C. and H.S. Kooistra (1996). Progestageen gebruik.
[Use of progestagens]. Tijdschrift voor Diergeneeskunde 121(11):
335-337. ISSN: 0040-7453.
Descriptors: animals, comparative study, contraceptive
agents, dogs, estrus, female, medroxyprogesterone 17-acetate, progestins
Note: 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
Shafik, A. (1994). Prolactin injection, a new contraceptive method:
experimental study. Contraception 50(2): 191-199. ISSN: 0010-7824.
NAL Call Number: RG136.A1C6
Abstract: "Prolactin injection" is presented
as a new contraceptive method. The method was tested in dogs. The dogs in the
test group were injected with prolactin (PRL) in a dose of 600 micrograms/kg of
body weight weekly for 6 months. During this period, the testicles, semen, reproductive
hormones, renal function, and serum sodium and potassium were examined
periodically. Testicular biopsy was obtained after 3 and 6 months of PRL
injection. These investigations were repeated during the 6 months following
withdrawal of the drug. Sperm count decreased to azoospermia in 3 months after
PRL administration with decrease of sperm motility and increase of abnormal
forms. Testicular biopsy showed degenerated seminiferous tubules. Reproductive
hormones, renal function, and serum sodium and potassium revealed insignificant
change (P > 0.05). Dog mating during the period of PRL administration
induced no pregnancy. After 3 months of drug withdrawal, the sperm count
normalized and dog mating produced pregnancy; offsprings showed no anomalies. The
study demonstrates that PRL administration has the potential to be developed as
a reversible male contraceptive.
Descriptors: reversible male contraception, intramuscular
injection, dogs, prolactin (PRL), antispermatogenic agents, reduction in sperm count
and motility
Snowball, S. and W.
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
Stovring, M., L. Moe, and E. Glattre (1997). A population-based
case-control study of canine mammary tumours and clinical use of medroxyprogesterone
acetate. Acta Pathologica, Microbiologica et Immunologica Scandinavica
105(8): 590-596. ISSN: 0903-4641.
NAL Call Number: QR1.A6
Abstract: We investigated whether or not an association
could be found between mammary tumours and prior clinical use of
medroxyprogesterone acetate (MPA) in bitches. A population-based retrospective
age-matched case-control study was designed based on interviews with the owners
of the bitches. The proportion of bitches with diagnosed mammary tumours (group
Descriptors: medroxyprogesterone acetate, mammary tumor
development, female contraceptive agents, dogs
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, Suppl. 3):
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
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, mammary changes, tumorigenesis, animal models
Wright, P.J., T. Stelmasiak, D. Black, and D. Sykes (1979). Medroxyprogesterone
acetate and reproductive processes in male dogs. Australian Veterinary
Journal 55(9): 437-438. ISSN:
0005-0423.
NAL Call Number: 41.8 Au72
Abstract: The treatment of normal male dogs with a
depot preparation of medroxyprogesterone acetate (4 mg/kg) for 7 weeks reduced
peripheral testosterone levels by 58%. No effects on testicular size and
consistency, semen quality or libido were found.
Descriptors: libido, semen quality, testosterone levels,
testis, medroxyprogesterone acetate, dogs, male, drug effects on reproduction
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
Descriptors: deslorelin, contraceptive implants, dogs,
plasma progesterone concentration, progestin, pregnancy