Clinical performance and endocrine profiles of contraceptive vaginal rings releasing 3-keto-desogestrel and ethinylestradiol.
The clinical performance and endocrine profiles of contraceptive vaginal rings (CVR) with an in vitro daily release rate of 15 micrograms of ethinylestradiol combined with 75, 100 or 150 micrograms 3-keto-desogestrel were evaluated. Two studies were performed; one with 11 volunteers, consisting of a control cycle, a cycle with an oral preparation (Marvelon), followed by two CVR treatment cycles, and a second study with 12 volunteers, having the same design but one CVR treatment cycle. A dose-response relationship was seen in the endocrine and clinical performance of the CVR. With CVR 75/15, ovulation occurred in two subjects, and increases in serum estradiol concentrations were seen in two additional subjects. With CVR 100/15, slight estradiol increases were seen in four subjects, but progesterone remained low. With CVR 150/15, both estradiol and progesterone serum concentrations remained low. With CVR 75/15 extra bleeding was common, but with CVR 150/15 this did not occur. No major side effects occurred, and no abnormal Papanicolaou smears or histological findings of the endometrium were found. All volunteers completed all cycles, and the three-week CVR use was generally well accepted. In conclusion, the release rate of CVR 75/15 was insufficient. A vaginal ring with a daily release rate between 100 and 150 micrograms of 3-keto-desogestrel in combination with 15 micrograms of ethinylestradiol seems suitable for contraceptive purposes, and will be further tested in larger clinical studies.
Apter
D
D
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Cacciatore
B
B
Stenman
U H
UH
Alapiessa
U
U
Assendorp
R
R
D000328:Adult; D000735:Androstenedione / Q000097:blood; D003274:Contraceptive Devices, Female; D003687:Dehydroepiandrosterone / Q000097:blood; D017135:Desogestrel; D013196:Dihydrotestosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects; D009652:Norpregnenes / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D011372:Progestins / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood
D009652:Norpregnenes; D011372:Progestins; D013196:Dihydrotestosterone; C044815:etonogestrel; D013739:Testosterone; D000735:Androstenedione; D004997:Ethinyl Estradiol; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol; D017135:Desogestrel