The most common side-effect and reason for discontinuation with Norplant use is bleeding disturbance. The aim of this study was to investigate whether the 6 week application of a patch which released 100 micrograms/day oestradiol would reduce the number of abnormal bleeding days or eliminate the problem. Another objective was to find out the correlation between the bleeding pattern and endometrial concentrations of oestrogen receptor (ER) and progesterone receptor (PR). Of 98 Norplant users, 34 patients had normal bleeding patterns and 64 patients had abnormal bleeding patterns. An oestradiol patch or a placebo patch were randomly used to treat 33 and 31 women with abnormal bleeding respectively. There was a clinical improvement in the oestradiol group compared with the placebo group, although this was not statistically significant. There were no correlations between PR and ER concentration and the serum oestradiol, progesterone, levonorgestrel and sex hormone-binding globulin concentrations. Significantly increased mean immunostaining scores of stromal PR were observed in those Norplant users whose endometrium had an atrophic histological appearance. The serum oestradiol concentration did not show a significant change after treatment with the oestradiol patch compared with the placebo patch.
PIP: The potential of an estradiol patch (100 mcg/day for 6 weeks) to reduce the menstrual disturbances associated with progestogen-only contraception was investigated in 98 Norplant users. Of the 64 subjects reporting abnormal bleeding, 33 were given an estradiol patch and 31 received a placebo patch; the 34 Norplant users with normal bleeding patterns served as controls. Clinical improvement was recorded in 23 estradiol patch and 13 placebo patch subjects, a nonsignificant difference. Ovarian activity, demonstrated by fluctuating high levels of estrogen, occurred in most Norplant users, but without ovulation. Serum levonorgestrel concentrations ranged from 1000 to 1500 pmol/l, with no significant differences according to group. Sex hormone-binding globulin (SHBG) levels were low (range, 20-50 nmol/l), again with no significant group differences. Both levonorgestrel and SHBG concentrations were steadier in women with normal bleeding patterns. Histology revealed that endometrial specimens from Norplant users were more atrophic than proliferative. Significantly increased mean immunostaining scores of stromal progesterone receptor were noted in Norplant users whose endometrium appeared atrophic. Also observed were low estrogen receptor concentrations in both glandular and stromal compartments. Overall, these findings suggest that progestogen-related bleeding abnormalities are related to the bioavailability of estrogen and progesterone receptors in the endometrium rather than histological changes.