Problems in evaluating chronic toxicity of contraceptive steroids in dogs.
J Toxicol Environ Health
; 3(1-2): 167-77, 1977 Sep.
Article
in En
| MEDLINE
| ID: mdl-72828
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.
ABSTRACT
PIP The long-term (7-year) effects of oral contraceptive steroids including a combination of norethindrone and ethinyl estradiol, a sequential regimen of dimethisterone and ethinyl estradiol, 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-ethinyl estradiol and dimethisterone-ethinyl estradiol treated dogs. These groups did not have accentuated mammary development or treatment related hyperplastic or neoplastic changes. For dogs given dimethisterone-ethinylestradiol, numerous acnelike 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 tumor, and adenocarcinoma appeared as distinct entitles although constant and intense mammary stimulation may be a common denominator. The relevance of the canine mammary changes to projecting potential tumorigenisis in women is questioned.
Key words
Acne; Alopecia; Animals, Laboratory; Biology; Breast Cancer; Cancer; Clinical Research; Contraception; Contraceptive Agents, Estrogen--administraction and dosage; Contraceptive Agents, Estrogen--side effects; Contraceptive Agents, Female--administraction and dosage; Contraceptive Agents, Female--side effects; Contraceptive Agents, Progestin--administraction and dosage; Contraceptive Agents, Progestin--side effects; Contraceptive Agents--administraction and dosage; Contraceptive Agents--side effects; Contraceptive Methods--side effects; Demographic Factors; Dermatitis; Diabetes Mellitus; Dimethisterone--administraction and dosage; Dimethisterone--side effects; Diseases; Endometrial Effects; Endometrium; Ethinyl Estradiol--administraction and dosage; Ethinyl Estradiol--side effects; Family Planning; Genitalia; Genitalia, Female; Hair Diseases; Histology; Hysterectomy; Longterm Effects; Mammary Gland Effects; Megestrol Acetate--administraction and dosage; Megestrol Acetate--side effects; Neoplasms; Norethindrone--administraction and dosage; Norethindrone--side effects; Oral Contraceptives, Combined; Oral Contraceptives, Phasic; Oral Contraceptives--side effects; Physiology; Population; Population Dynamics; Research Methodology; Time Factors; Urogenital System; Uterus
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Contraceptives, Oral
/
Contraceptives, Oral, Hormonal
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Toxicol Environ Health
Year:
1977
Type:
Article