[Problems of dose finding: sexual hormones (author's transl)].
1. Reproduction processes are differently regulated in different species. The gestagen/estrogen ratio is of paramount importance for the evaluation of gestagens. Steroids possessing inherent estrogenicity might act as estrogens in, e.g., rodents like rats and mice, but might be active as gestagens in women (e.g. norethinodrel). 2. There is a good and partly significant correlation between the activity of various gestagens in a number of experimental test models and clinical trials. The same is true for the antiovulatory activity of various gestagens in rats and women. Oral rat tests, however, are not relevant. Receptor tests are not at all suitable for dose finding. 3. Erroneously dissociated peripheral and central (inhibition of ovulation) activity of gestagens are found only if different animal species are used (e.g., test on gonadotropin inhibition in rats, gestagen test in rabbits). This is not the case if both kinds of tests are done in one species (e.g., ovulation inhibition test in rats and test on the peripheral progestational activity in rats). 4. As far as the combined oral contraceptives containing estrogens and gestagens are concerned, it seems that both components are involved in the inhibition of ovulation in rats and women. There is additive synergism. 5. Conclusions concerning the activity and duration of effect in the clinic can be drawn from the intensity and duration of the progestational effect in rabbits. 6. The oral and subcutaneous activity of estrogens in different tests in rats and mice is in parts very well correlated. This is also true for the antiovulatory activity. 7. Comparison of the estrogenic activity of ethinyl estradiol and mestranol in rats, mice and women still leaves the question unanswered whether ethinyl estradiol is more potent than mestranol. 8. Certain conclusions regarding the depot effect in the clinic can be drawn from the duration of the estrogenic activity in the Allen-Doisy test. This test is at least suitable for the selection of the optimal depot estrogen. 9. As concerns androgens, clinical dose finding is so difficult because there are no or only poor clinical parameters for androgenicity. The oral evaluation of androgens in rats and mice provides no evidence for whether or not an androgen is orally active in men. Frequently, one can only resort to conclusions form analogy. 10. The duration of androgenic activity in rats allows certain conclusions to be drawn regarding the duration of activity in men. Dose finding, however, is difficult. 11. Steroids in which the anabolic and androgenic activity in the levator ani muscle/accessory sexual gland test are dissociated (anabolics) do also show dissociation of these two partial activities in the clinic. 12. The levator ani muscle/accessory sexual gland test in rats allows also conclusions to be drawn as to the depot activity in the clinic. 13...
D045930:Anabolic Agents / Q000008:administration & dosage; D000728:Androgens / Q000008:administration & dosage; D000818:Animals; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage; D003534:Cyproterone / Q000008:administration & dosage; D003692:Delayed-Action Preparations; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D005835:Genitalia / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D010060:Ovulation / Q000187:drug effects; D011247:Pregnancy; D045167:Progesterone Congeners / Q000008:administration & dosage; D011817:Rabbits; D051381:Rats; D012098:Reproduction / Q000187:drug effects; D013045:Species Specificity
D045930:Anabolic Agents; D000728:Androgens; D003277:Contraceptives, Oral, Combined; D003692:Delayed-Action Preparations; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D045167:Progesterone Congeners; D003534:Cyproterone
Probleme der Dosisfindung: Sexualhormone