Endocrinology: Immunohistochemical sex steroid receptor distribution in endometrium from long-term subdermal levonorgestrel users and during the normal menstrual cycle

Abstract

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) distribution in levonorgestrel-treated endometrial biopsies from 31 subjects recruited in Jakarta, Indonesia, and to compare the sex steroid receptor immunostaining with that of endometrium from 58 normally cycling women from Melbourne, Australia. Sex steroid receptor immunoreactivity was additionally compared with days of exposure to subdermal levonorgestrel, serum oestradiol and progesterone levels and days of bleeding during a 90-day reference period. An immunohistochemical technique with an alkaline phosphatase anti-alkaline phosphatase (APAAP) detection 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 endometrium at all stages across the cycle. No significant correlations were demonstrated between sex steroid receptor immunostaining and days of exposure to subdermal levonorgestrel, serum oestradiol or progesterone concentrations or days of bleeding during a 90-day reference period. Whether the elevated stromal PR immunostaining in Norplant-treated endometrium 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 functional PR.