On the mechanisms of action of short-term levonorgestrel administration in emergency contraception

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 (P4) 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 P 4 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. © 2001 Elsevier Science Inc. All rights reserved.

Original research article On the mechanisms of action of short-term levonorgestrel administration in emergency contraception

Metabolism of levonorgestrel, norethindrone, and structurally related contraceptive steroids

SUMMARY
Plasma sex hormone binding globulin capacity (SHBC) measurements were evaluated in 125 women with a pre-treatment mean value of 41 ± 17 nmol/l SHBG and during 3 to 36 cycles of either combination oestrogen and progestagen oral contraceptives (OC) or low progestagen‘mini’pills. An oestrogenic effect or significant elevation of SHBC was noted on combination OC or ethiriyl oestradiol with megestrol acetate, comparable with pregnancy levels (305 t 47 nmol/l SHBC or Volidan), whilst megestrol acetate alone (500 μg) caused a smaller but still significant rise of SHBG. Combination of ethinyl oestradiol with norethisterone acetate (Minovlar Loestrin) produced increased SHBG but ethinyl oestradiol combined with d-norgestrel (Ovranette) caused no change in mean SHBG. An androgenic effect or significant lowering of mean SHBG to 24 ± 11 nmol/l in women on dl-norgestrel (75 μg) and a decrease of mean SHBG on norethisterone (350 μg) daily indicated that these 19-norderivatives are contraindicated in women with low pre-treatment levels of SHBG or any clinical manifestation or history of androgenic hyperactivity. Combined OC preparations causing some elevation of SHBG might be preferable. Conversely women with a high pre-treatment SHBG level might be more suited to combination OC with d-norgestrel or the 19-norprogestagen‘mini’pills. The characteristic response to SHBC for the group of oral contraceptives used was maintained throughout medication but on discontinuing the SHBC levels returned to pre-treatment values.

George Greenspan

Papers

Biological effects of racemic and resolved 13β-ethyl-4-gonen-3-ones