Effects of oral and vaginal administration of levonorgestrel emergency contraception on markers of endometrial receptivity.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Obstetrics and Gynaecology, Department of Women's and Children's Health, Karolinska University Hospital/Karolinska Institutet, SE-17176 Stockholm, Sweden.
C-X
CX
Meng
L
L
Marions
B
B
Byström
K
K
Gemzell-Danielsson
D000282:Administration, Intravaginal; D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D044363:Contraception, Postcoital / Q000379:methods*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism; D016912:Levonorgestrel / Q000008:administration & dosage*; D007986:Luteinizing Hormone / Q000652:urine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D003271:Contraceptive Agents, Female; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D016912:Levonorgestrel; D007986:Luteinizing Hormone