The relevance of the pharmacologic properties of a progestational agent to its clinical effects as a combination oral contraceptive.
Levonorgestrel (LNg) is known for its marked progestational/contraceptive activity. As shown in animal experiments, however, high doses of LNg are required to elicit an androgenic response; in contrast, considerably lower doses of LNg are required for antiovulatory (contraceptive) action. Thus, a large dose separation exists between androgenic and contraceptive activity. When LNg is combined with an estrogen, as in the contraceptive formulations, the androgenic response is attenuated or negated. The results of recent clinical trials have demonstrated that the androgenic activity of LNg is not expressed at contraceptive doses, particularly when LNg is combined with ethinyl estradiol (EE), as in the low-dose monophasic/triphasic formulations (monophasic [Nordette]: 150 mcg LNg/30 mcg EE; triphasic [Triphasil/Trinordiol]: six days, 50 mcg LNg/30 mcg EE; five days, 75 mcg LNg/40 mcg EE; ten days, 125 mcg LNg/30 mcg EE). Clinical evidence from several trials confirms that sex hormone-binding globulin levels are increased, plasma androgen levels are decreased, and acne is markedly improved with the use of Triphasil and Nordette, suggesting a non-androgenic profile.
Upton
G V
GV
Clinical Research and Development, Wyeth-Ayerst Research, Philadelphia, Pennsylvania 19101.
Corbin
A
A
D000152:Acne Vulgaris / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016912:Levonorgestrel; D008297:Male; D015337:Multicenter Studies as Topic; D009644:Norgestrel / Q000494:pharmacology*; D009929:Organ Size; D010060:Ovulation / Q000187:drug effects*; D045167:Progesterone Congeners / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000187:drug effects; D012738:Sex Hormone-Binding Globulin / Q000096:biosynthesis
D000728:Androgens; D003277:Contraceptives, Oral, Combined; D045167:Progesterone Congeners; D012738:Sex Hormone-Binding Globulin; D009644:Norgestrel; D016912:Levonorgestrel