Endometrial and vaginal response to three different oestrogen preparations administered by the transdermal and oral routes

Abstract

In a randomized, cross-over study endometrial and vaginal response to transdermal 17β-oestradiol (TTS-oestradiol 50 μg) and two forms of oral oestrogen replacement therapy (conjugated oestrogens 1.25 mg and oestradiol valerate 2 mg) were studied in 13 peri-menopausal and post-menopausal women. Five (5) of the women exhibited periodic ovarian function as evidenced by peripheral oestradiol and progesterone levels and were considered to be peri-menopausal. In the post-menopausal group of 8 women the bleeding pattern was more regular than among the peri-menopausal women. In the case of the post-menopausal group the number of days on which spotting and bleeding occurred was significantly lower during the administration of TTS-oestradiol than during treatment with conjugated oestrogens. This finding was paralleled by a significantly higher karyopyknotic index in the vaginal epithelium and significantly increased deoxyribonucleic acid (DNA) synthesis in the endometrial cells during treatment with equine oestrogens. No significant difference was seen in these indices when the effect of TTS-oestradiol was compared with that of oestradiol valerate. The study results in the post-menopausal group suggested a relationship between the intensity of the oestrogen treatment and not only the proliferation and maturation of the oestrogen target-organ cells but also the number of days on which bleedling occurred. It was concluded that a clear distinction needs to be made between peri-menopausal and post-menopausal women. In the present study the irregular ovarian activity among the peri-menopausal subjects precluded an unbiased assessment of the exogenous oestrogens. It is also likely that exogenous oestrogens exert a cumulative action with oestrogen secreted endogenously, interfere with the physiological events at the target organ level and induce uncontrollable endometrial bleeding. The complete cessation of ovarian activity may therefore have to be established before exogenous oestrogens are administered to climacteric patients.