IMMUNOHISTOCHEMICAL SEX STEROID-RECEPTOR DISTRIBUTION IN ENDOMETRIUM FROM LONG-TERM SUBDERMAL LEVONORGESTREL USERS AND DURING THE NORMAL MENSTRUAL-CYCLE

The bleeding problems experienced by users of subdermal levonorgestrel implants (Norplant) remain unexplained. The aim of the present study was to investigate the oestrogen (ER) and progesterone receptor (PR) d istribution in levonorgestrel-treated endometrial biopsies from 31 sub jects recruited in Jakarta, Indonesia, and to compare the sex steroid receptor immunostaining with that of endometrium from 58 normally cycl ing women from Melbourne, Australia. Sex steroid receptor immunoreacti vity was additionally compared with days of exposure to subdermal levo norgestrel, serum oestradiol and progesterone levels and days of bleed ing during a 90-day reference period. An immunohistochemical technique with an alkaline phosphatase anti-alkaline phosphatase (APAAP) detect ion system for use in formalin-fixed paraffin wax embedded endometrial tissue was employed. Significantly greater mean immunostaining scores of stromal PR were observed in Norplant compared with control endomet rium at all stages across the cycle. No significant correlations were demonstrated between sex steroid receptor immunostaining and days of e xposure to subdermal levonorgestrel, serum oestradiol or progesterone concentrations or days of bleeding during a 90-day reference period. W hether the elevated stromal PR immunostaining in Norplant-treated endo metrium is a consequence of increased synthesis or reduced turnover of receptor remains unclear. As yet it is undetermined whether increased PR immunoreactivity corresponds to an increase in number of functiona l PR.