The effects of short-term administration of levonorgestrel (LNG) at different stages
of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium
were investigated. Forty-five surgically sterilized women were studied during two
menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG
taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing
hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C),
or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum
LH were performed from the detection of urinary LH until ovulation. Serum estradiol
(E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition,
an endometrial biopsy was taken at day LH + 9. Eighty percent of participants in Group
A were anovulatory, the remaining (three participants) presented significant shortness
of the luteal phase with notably lower luteal P4 serum concentrations. In Groups B
and C, no significant differences on either cycle length or luteal P4 and E2 serum
concentrations were observed between the untreated and treated cycles. Participants
in Group D had normal cycle length but significantly lower luteal P4 serum concentrations.
Endometrial histology was normal in all ovulatory-treated cycles. It is suggested
that interference of LNG with the mechanisms initiating the LH preovulatory surge
depends on the stage of follicle development. Thus, anovulation results from disrupting
the normal development and/or the hormonal activity of the growing follicle only when
LNG is given preovulatory. In addition, peri- and post-ovulatory administration of
LNG did not impair corpus luteum function or endometrial morphology.