Progestational potency of chlormadinone acetate in the immature beagle bitch: Preliminary report

Hill, R. R.; Averkin, E. G.; Brown, W. Ray; Gagne, William; Segre, Eugene J.

doi:10.1016/s0010-7824(70)80001-4

Cited by 29 publications

(7 citation statements)

References 7 publications

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“…Species and tissue sensitivity, specific endocrinologic profile, and the variable metabolic differences (including biologic half-life) should be considered when evaluating various progestational compounds. The dog is sensitive to progesterone derivatives such as chlormadinone acetate and much less sensitive to 19-nortestosterone derivatives such as norethindrone [12]. Progesterone caused many of the same changes [3] as megestrol acetate and chlormadinone acetate.…”

Section: Discussionmentioning

confidence: 99%

Progestogen-Related Gross and Microscopic Changes in Female Beagles

Nelson

Kelly

1976

Vet Pathol

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Absrruct.Long-term studies of megestrol acetate and chlormadinone acetate in 100 female dogs are in progress. Doses of zero, one, 10 and 25 times the expected human dose of megestrol acetate and 25 times the expected human dose of chlormadinone acetate (on a milligram per kilogram body weight basis) are being given daily. During the first 4 years, eight dogs from each of the five groups were killed. The principal gross findings included enlarged uteri with mucoid material in the lumina, mammary development in dogs given middle and high doses of megestrol acetate and chlormadinone acetate, and thickened gallbladder walls in dogs given high doses of each. Histologic evaluation showed inhibition of ovulation for progestogen-treated dogs and suppression of ovarian follicular development with the high doses. Cystic endometrial hyperplasia was slight in the low-dose dogs and moderate to severe in most of the high-dose dogs; a few also had ulcerative endometritis and pyometra. The mammary glands of dogs given the middle and high doses produced lobules, acini, and secretion exceeding natural metestrus. Slight to marked cystic mucinous hyperplasia occurred in the gallbladders of most dogs given the high doses. Two high-dose megestrol dogs had clinical signs and microscopic pancreatic, renal, and ocular changes indicative of diabetes mellitus.Uterine cystic glandular hyperplasia and pyometra have been known to be related to endocrine imbalances in female dogs for many years [5,6,23]. Similar changes have been produced in the female dog by using naturally occurring hormone progesterone [3,7,8, 201. The causal relationship of cystic glandular hyperplasia to the synthetic progestogen, medroxyprogesterone acetate, is well documented [l, 21. Clinical descriptions of mammary development and secretion are occasionally included in these reports [3,4], but most are for the uterus with no reference to the histologic changes in the other genital organs.

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Section: Discussionmentioning

confidence: 99%

Progestogen-Related Gross and Microscopic Changes in Female Beagles

Nelson

Kelly

1976

Vet Pathol

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“…Certain progestagens used for human contraception have led to mammary gland changes in the dog, including enhanced occurrence of mammary gland neoplasia (Goldzieher & Kraemer, 1972; Wazeter, Geil, Berliner & Lamar, 1973;Hill & Dumas, 1974). The fact that the changes in the mammary gland have been found almost exclusively in the dog, rather than in rats, monkeys and man, has led to the assumption that the pro¬ gestagens concerned are progestationally very active in the dog (Hill, Averkin, Brown, Gagne & Segre, 1970;Graf, El Etreby, Richter, Günzel & Neumann, 1975;Haase, Beier, Hartmann & Elger, 1977), or that the canine mammary and/or anterior pituitary gland is very sensitive to progestagens (Neumann & Elger, 1972). A predominant role of progestagens in the stimulation of prolactin and growth hormone synthesis and/or secretion has therefore been suggested (Neumann & Elger, 1972).…”

Section: Introductionmentioning

confidence: 99%

Serum oestrogen, progesterone and prolactin concentrations in cyclic, pregnant and lactating beagle dogs

Gräf¹

1978

Reproduction

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Summary. No correlations between the three hormones measured were found in any of the reproductive states examined. In 2 out of 8 dogs a negative correlation between serum progesterone and prolactin levels was found at Day 11 and Day 15, respectively (Day 0 = first day of copulation). In all of the 8 animals in which the progesterone and prolactin concentrations were measured in the same samples in late pregnancy, a negatively correlated overall pattern was obtained between both hormone profiles. No correlation between serum oestrogen and prolactin levels was found.It is concluded that the proliferative mammary gland changes which are induced in female dogs during long-term toxicity testing with progestagens are unlikely to be related to prolactin or oestrogen synthesis and/or secretion.

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“…This effect appears to be related to the sensitivity of this species to certain progestins (Hill et al 1970). Also, as pointed out by Nelson and coworkers (1972), the benign mixed mammary tumour which commonly occurs in the dog is rarely seen in other domesticated animals, in other com¬ monly used laboratory animals, or in man.…”

Section: Breast Lesionsmentioning

confidence: 78%

Some Metabolic Actions and Possible Toxic Effects of Hormonal Contraceptives in Animals and Man

Drill¹

1974

Acta Endocrinologica

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Data on contraceptive steroids derived from properly conducted and interpreted animal studies can serve to predict effects that may be expected to occur in women. Important also is the absence of certain effects of the steroids in both animals and man. Since the drugs are for human use it is necessary that adequate clinical studies be conducted to confirm the predictions made regarding effectiveness and safety. Selected topics of importance are discussed to summarize our knowledge in specific areas and to illustrate correlations between the effects of contraceptive steroids in animals and in women.The discovery and development of the first oral contraceptive by our labora¬ tories was the beginning of an extensive biological and clinical evaluation of these substances (Drill 1966). Indeed, the published papers available on oral contraceptives, oestrogens, progestins, and related articles on pregnancy, must now number in the thousands. Many of the publications are concerned with metabolic actions and possible side effects or toxic effects of the contraceptive steroids, but in the time allotted for my presentation this review must neces¬ sarily be limited to certain subjects. The areas of oral contraceptives selected * 4900 Searle Parkway, Skokie, 111., 60076.

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Progestational potency of chlormadinone acetate in the immature beagle bitch: Preliminary report

Cited by 29 publications

References 7 publications

Progestogen-Related Gross and Microscopic Changes in Female Beagles

Progestogen-Related Gross and Microscopic Changes in Female Beagles

Serum oestrogen, progesterone and prolactin concentrations in cyclic, pregnant and lactating beagle dogs

Some Metabolic Actions and Possible Toxic Effects of Hormonal Contraceptives in Animals and Man

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