The effect of levonorgestrel administered in large doses at different stages of the cycle on ovarian function and endometrial morphology.
In a pharmacokinetic study, levonorgestrel (L-NOG) 0.75 mg was administered orally to 10 swedish women in the early follicular phase of the menstrual cycle. L-NOG levels were measured after L-NOG administration. A peak level of 16 nmol/l was reached after 2 hours, T 1/2 was estimated to be 14.5 hours (8.5-18.5) in the 24-48-hour interval after dosing. Seventy-two women (in Stockholm, Bombay and Shanghai) were assigned to 4 treatment groups and studied during a control cycle, a treatment cycle and a posttreatment cycle when 0.75 mg L-NOG was administered orally for 4 days in the follicular phase, periovulatory period or luteal phase. Peripheral blood was drawn 3 times weekly during the entire study for the assay of estradiol and progesterone. In 22 women in Stockholm, an endometrial biopsy was obtained on cycle day 20-22 in all 3 cycles studied. When L-NOG was administered on periovulatory days 9, 11, 13, and 15, 3 women showed follicular activity only, 7 exhibited follicular activity followed by insufficient luteal function and 7 women ovulated normally. When L-NOG was administered on periovulatory days 11, 12, 16 and 19, 7 women ovulated during treatment, 6 women exhibited follicular activity followed by insufficient luteal function and 5 exhibited follicular activity only. When L-NOG was administered in the follicular or luteal phase, no effect on ovarian function was seen. No significant prolongation of the cycle lengths was seen when L-NOG was taken during the follicular phase. Only minor effects in the endometrium were observed during treatment.
Landgren
B M
BM
Department of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden.
Johannisson
E
E
Aedo
A R
AR
Kumar
A
A
Shi
Y E
YE
D000328:Adult; D004717:Endometrium / Q000187:drug effects*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005498:Follicular Phase / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D016912:Levonorgestrel; D008183:Luteal Phase / Q000187:drug effects; D009644:Norgestrel / Q000493:pharmacokinetics / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects*; D010060:Ovulation / Q000187:drug effects
D009644:Norgestrel; D004958:Estradiol; D016912:Levonorgestrel; D005640:Follicle Stimulating Hormone