Endometrial morphology during hormone replacement therapy with estradiol gel combined to levonorgestrel-releasing intrauterine device or natural progesterone

Abstract

Objectives: To evaluate endometrial responses to three different forms of amenorrhea-inducing HRT in postmenopausal women.

Material and methods: Fifty-one postmenopausal women completing a one-year HRT trial with percutaneous estradiol gel containing 1.5 mg estradiol daily combined with a levonorgestrel-releasing intrauterine device (LNG-IUD) (n=18), or natural progesterone 100 mg daily orally (n= 19) or vaginally (n=15) during 1-25 calendar days of each month. Endometrial thickness and uterine size were measured by transvaginal ultrasound, and endometrial cytology/histology was assessed from specimens taken by needle aspiration before the study and at 12 months.

Results: Before medication, the median endometrial thickness was 2.0 mm in the LNG-IUD group, 2.4 mm in the oral P group and 2.5 mm in the vaginal P group. At 12 months of therapy the respective values, 3.0, 2.7 and 2.4 mm, did not differ significantly from the initial values. LNG-IUD induced epithelial atrophy in all women, which was accompanied by stromal decidualization in 12 women. On the contrary, only four women in the oral P group and five women in the vaginal P group had an inactive or atrophic endometrium. The remaining cases were dominated by proliferative features. No hyperplasia was seen in any of the groups.

Conclusion: LNG-IUD appeared to be an effective method of counteracting the stimulatory effect of estrogen on the endometrium, whereas natural progesterone given orally or vaginally was not sufficiently effective in this function at the doses used. The vaginal and oral administrations of progesterone did not differ from each other in this respect.

PIP: This study evaluated the endometrial morphological response to the levonorgestrel-releasing IUD (LNG-IUD) and to natural progesterone administered orally or vaginally in postmenopausal women using percutaneous estradiol gel on a daily basis. The study employed 51 postmenopausal women who completed a 1-year hormone replacement therapy trial of 1.5 mg estradiol daily combined with a LNG-IUD (n = 18), 100 mg oral progesterone (n = 19), or 100 mg vaginal progesterone (n = 15) during 1-2 calendar days of each month. Using a transvaginal ultrasound, endometrial thickness was measured prior to and 12 months after the study. Prior to the study, endometrial thickness was 2.0, 2.4, and 2.5 mm for the LNG-IUD, oral progesterone, and vaginal progesterone groups, respectively. During the transvaginal ultrasound (after 12 months) the respective values were 3.0, 2.7, and 2.4 mm, respectively, which was considered normal among postmenopausal women. 12 of the women who were administered the LNG-IUD were found to have epithelial atrophy accompanied by stromal decidualization. On the other hand, 4 women in the oral progesterone and 14 in the vaginal progesterone groups were found to have inactive or atrophic endometrium. Proliferative features dominated the remaining cases, while hyperplasia was not observed in any of the cases. This study confirms the efficacy of the LNG-IUD in suppressing the stimulatory effect of estrogen on the endometrium, while oral and vaginal progesterone were not sufficiently effective at the doses used.