Intrauterine and subdermal progestin administration in postmenopausal hormone replacement therapy

To compare the effects of intrauterine and subdermal administration of levonorgestrel on control of bleeding and on the endometrium in postmenopausal hormone replacement therapy.

Nineteen women started continuous oral E2 valerate therapy (2 mg daily) together with continuous parenteral progestin therapy. The subjects randomly received either a subdermal levonorgestrel-releasing implant (n = 9) or an intrauterine device (IUD) releasing levonorgestrel (n = 10).

Serum concentrations of estrone, E2, FSH, sex hormone-binding globulin (SHBG) and levonorgestrel were followed. Endometrial biopsies and transvaginal ultrasonography were used to evaluate the endometrium. The subjects kept daily records of bleeding. The observation time was 1 year.

Serum concentrations of the hormones mentioned above and SHBG were similar in both groups during the observation time, but the patterns of bleeding differed. In the IUD group there were 0.9 days (mean, range 0 to 4 days) of spotting and no days of bleeding during the last month of the follow-up year. In the implant group there were 8 days (mean, range 0 to 25 days) of spotting and 3.4 days (mean, range 0 to 14 days) of bleeding. In histological examination there was uniform atrophy in the endometrial samples from the IUD group, and a weak or absent progestin effect in the implant group.

In spite of similar serum levonorgestrel concentrations, local intrauterine administration of levonorgestrel resulted in better control of bleeding and in more effective endometrial suppression than subdermal administration.