Norethindrone (NET) has been used for cycle programming and may result in attenuated responses to controlled ovarian hyperstimulation. The effects of NET on gonadotropin secretion, its bioavailability to the ovary, and its effect on ovarian steroidogenesis in vivo and in vitro were assessed. Endogenous secretion of luteinizing hormone and follicle-stimulating hormone was attenuated by 59% and 50%, respectively, after 2 weeks of orally administered NET. Twelve hours after a single 10-mg oral dose, significant levels of NET were measured in samples of peripheral (8.8 ± 1.9 ng/mL) and ovarian venous blood (10.5 ± 3.1 ng/mL), follicular fluid (7.1 ± 2.1 ng/mL), and homogenates of ovarian tissue (8.0 ± 0.6 ng/g). Furthermore, NET was detectable in follicular fluid 2 weeks after its withdrawal (863 ± 149 pg/mL). However, there were no effects of NET on follicular fluid levels of estradiol and progesterone in vivo or on luteinized granulosa cell steroidogenesis in vitro. We conclude that when used for cycle programming in in vitro fertilization, NET does not inhibit ovarian steroidogenesis but does affect the hypothalamic-pituitary axis.
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