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• W2019325336 abstract "Eight normally menstruating women were provided with vaginal devices releasing levonorgestrel (NOG)4) at a constant rate of 20 micrograms/24 h. On day 71 or 72 following the insertion of the device, oral doses of 50 micrograms of ethinyl estradiol (EE) were administered daily for one week. Peripheral blood samples were drawn three times weekly during a pretreatment (control) cycle and from day 29 of the treatment period. The levels of progesterone (P), estradiol (E2) and NOG were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by a steady state polyacrylamide gel electrophoresis and the percentage of binding of NOG, testosterone (T) and E2 by equilibrium dialysis of diluted plasma. An endometrial smear and a biopsy were taken from each subject on 3 occasions, viz. during the control cycle (cycle day 20-22), during the period with the NOG-releasing device in situ (44-50 days after the insertion of the device), and on the 7th day of concomitant EE administration.8 normally menstruating women were provided with vaginal devices releasing levonorgestrel (NOG) at a constant rate of 20 mcg/24 hours. On day 71 or 72 following device insertion, oral doses of 50 mcg ethinyl estradiol (EE) were administered daily for 1 week. Peripheral blood samples were drawn 3 times weekly during a pretreatment (control) cycle and from day 29 of the treatment period. Levels of progesterone (P), estradiol (E2), and NOG were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by a steady state polyacrylamide gel electrophoresis and the percentage of binding of NOG, testosterone (T), and E2 by equilibrium dialysis of diluted plasma. An endometrial smear and a biopsy were taken from each subject on 3 occasions: during the control cycle (cycle day 20-22), during the period with the NOG-releasing device in situ (44-50 days after device insertion), and on the 7th day of concomitant EE administration. In 4 of 8 subjects studied, ovarian function was not suppressed by NOG. Levels of SHBG in the individual subject were unrelated to the degree of suppression of ovarian function. The mean levels of SHBG exhibited a significant (15%; P0.001) decrease during NOG administration and a marked (almost 3-fold) increase during EE administration. This increase was paralleled by a similar rise in NOG levels. The 1/2-life of NOG was calculated to be 6.7 days and that of SHBG approximately 10 days. A similar pattern to that of SHBG, i.e., decrease during exposure to NOG and a marked increase during the concomitant EE administration, was observed as far as the percentage of bound NOG, T, and E2 were concerned. The increase in total NOG levels during EE administration is interpreted as a consequence of a parallel increase in SHBG levels protecting NOG against metabolic degradation and/or rapid elimination. The results of the simultaneous measurements of total and bound NOG suggest that the concentration of unbound NOG also increases during EE administration. The small amounts of NOG continuously released from the vaginal devices influenced endometrial morphology independently of their effect on ovarian function. The diameter of the endometrial glands was significantly diminished (P0.01) and the concomitant administration of EE did not interfere with this effect. A significant increase (P0.05) was observed in the number of plasmolemmal vesicles during the combined treatment with NOG and EE and a significant decrease (P0.001) in DNA/cell nucleus was found 10 weeks after the start of NOG administration. The administration of EE did not interfere with this latter effect. The vaginal administration of NOG reduced the nucleic acid synthesis of the endometrium irrespective of its effect on ovarian function or of concomitant EE administration. It is concluded that EE in the regimen used does not exert a significant stimulatory effect on endometrial proliferation in the presence of constant low levels of NOG." @default.
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• W2019325336 date "1983-07-01" @default.
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• W2019325336 title "Pharmacodynamic effects of ethinyl estradiol in women using vaginal devices releasing small doses of levonorgestrel at a constant rate" @default.
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• W2019325336 doi "https://doi.org/10.1016/s0010-7824(83)80003-1" @default.
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