title: Studies on a vaginal ring releasing levonorgestrel at an initial rate of 27 micrograms/24 h when used alone or in combination with transdermal systems releasing estradiol.
abstract: Vaginal rings releasing levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24h were studied in a group of 24 normally menstruating women during three months (i.e., during three four-week segments). Each segment consisted of three weeks with the vaginal rings in situ followed by a treatment-free period of one week. The women were divided into three groups (8 subjects each). The first group received vaginal rings only, the second and third groups were treated, in addition, with transdermal systems (patches) releasing estradiol at a rate of 50 and 100 micrograms/24h, respectively. Peripheral blood samples were withdrawn three times weekly (Monday, Wednesday and Friday) during a pretreatment cycle and during the following three months of treatment. The levels of L-NOG, estradiol and progesterone were analyzed by radioimmunoassay techniques. In all subjects, endometrial biopsies were taken in a control cycle and during the last days with vaginal rings in situ in segments II and III. The treatment with estradiol did not significantly influence L-NOG levels. Considerable differences in the L-NOG levels between the subjects of the same group were observed. Fluctuation in ovarian reaction within groups was also large. Nevertheless, estradiol noticeably increased the proportion of anovulatory cycles; the total number of anovulatory segments was 5, 9 and 19 (out of 24) in the groups "No estradiol", "50 micrograms/24h estradiol" and "100 micrograms/24h estradiol", respectively. A morphometric study of the endometrium indicated a significant decrease in the diameter of glands. This change was due to L-NOG alone, but it seemed to be accentuated by the exogenous estradiol. The occurrence of glandular mitoses increased in both groups receiving estradiol in a dose-dependent manner, indicating an increased endometrial proliferation. The treatment with estradiol did not significantly alter the bleeding pattern.
authors.affiliation: Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden.
authors.forename: B M
authors.initials: BM
authors.lastname: Landgren
authors.forename: A R
authors.initials: AR
authors.lastname: Aedo
authors.forename: E
authors.initials: E
authors.lastname: Johannisson
authors.forename: S Z
authors.initials: SZ
authors.lastname: Cekan
mesh_terms: D000279:Administration, Cutaneous; D000282:Administration, Intravaginal; D000328:Adult; D003274:Contraceptive Devices, Female; D004717:Endometrium / Q000033:anatomy & histology / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010053:Ovary / Q000187:drug effects / Q000502:physiology; D010060:Ovulation / Q000187:drug effects; D011374:Progesterone / Q000097:blood
chemical_list: D011374:Progesterone; D004958:Estradiol; D016912:Levonorgestrel