Division of Obstetrics and Gynaecology, Department of Women's and Children's Health, Karolinska University Hospital/Karolinska Institutet, SE-17176 Stockholm, Sweden.
Hum Reprod. 2010 Apr;25(4):874-83. doi: 10.1093/humrep/deq007. Epub 2010 Feb 6.
The standard regimen of the levonorgestrel-only pill (1.5 mg either in a single dose or in a dose of 0.75 mg twice, 12 h apart) administered orally for emergency contraception (EC) has been shown to have no effect on endometrial development and markers of endometrial receptivity. We aimed to explore whether repeated oral and single vaginal administration of levonorgestrel affect the endometrium and thus potentially increase the EC efficacy, compared with the standard regimen.
Endometrial biopsies were taken from non-smoking, healthy women with proven fertility on cycle days LH + 6 to LH + 8 in control and levonorgestrel treatment cycles (each woman serving as her own control). Levonorgestrel was administered either orally (0.75 mg x 4, at 24 h intervals on LH + 1 to LH + 4; n = 8) or vaginally (a single dose of 1.5 mg on LH + 2; n = 7). Immunohistochemistry and real-time RT-PCR was performed to compare the levels of protein and mRNA for sex steroid receptors, interleukin-1beta, leukaemia inhibitory factor (LIF), vascular endothelial growth factor, cyclooxygenase-2, tumour necrosis factor-alpha, integrin alpha(v)beta(3) and mucin 1 in endometrial cells.
Following the repeated oral treatment, the immunoreactivity of both progesterone receptor (PR)-A and PR-B declined in glandular epithelium (P = 0.03 and P = 0.02, respectively), whereas stromal immunoreactivity and mRNA expression of LIF increased compared with control (P < 0.001 and P = 0.03, respectively). However, vaginal levonorgestrel did not cause any significant endometrial changes.
The two regimens of levonorgestrel caused either only minor or no alterations in markers of endometrial receptivity. New agents targeting the endometrial development should be explored in order to increase EC efficacy.
左炔诺孕酮仅避孕药（1.5 毫克，无论是在单剂量或 0.75 毫克的剂量，两次，12 小时）口服紧急避孕（EC）已被证明对子宫内膜发育和子宫内膜容受性标志物没有影响。我们旨在探索口服和阴道单次重复给予左炔诺孕酮是否会影响子宫内膜，从而可能提高 EC 的疗效，与标准方案相比。
从非吸烟、生育能力正常的妇女的子宫内膜活检中进行，在控制和左炔诺孕酮治疗周期的 LH + 6 至 LH + 8 天（每个妇女作为自己的对照）。左炔诺孕酮口服（0.75 毫克×4，在 LH + 1 至 LH + 4 的 24 小时间隔；n = 8）或阴道（LH + 2 单次剂量 1.5 毫克；n = 7）。进行免疫组织化学和实时 RT-PCR 比较孕激素受体、白细胞介素-1β、白血病抑制因子（LIF）、血管内皮生长因子、环氧化酶-2、肿瘤坏死因子-α、整合素 α（v）β（3）和粘蛋白 1 在子宫内膜细胞中的蛋白和 mRNA 水平。
口服重复治疗后，孕激素受体（PR）-A 和 PR-B 的免疫反应在腺上皮中均下降（P = 0.03 和 P = 0.02），而基质免疫反应和 LIF 的 mRNA 表达与对照组相比增加（P <0.001 和 P = 0.03）。然而，阴道左炔诺孕酮不会引起任何明显的子宫内膜变化。
两种左炔诺孕酮方案仅引起子宫内膜接受性标志物的轻微或无改变。应该探索新的靶向子宫内膜发育的药物，以提高 EC 的疗效。
