Possible significance of degeneration and decreased expression of progesterone receptor in postmenopausal uterine leiomyoma

Abstract

Background: The growth of uterine leiomyomas is dependent on the levels of sex steroid hormones, and they usually shrink after menopause. However, there are cases in which leiomyomas continue to grow and/or surgery is required after menopause. In addition to estrogen, progesterone has recently been implicated in leiomyoma enlargement, but its relevance to postmenopausal leiomyoma remains unknown. Therefore, we investigated whether hormone receptor expression is associated with postmenopausal leiomyoma enlargement and characterized pathological findings of postmenopausal leiomyoma, which have not been clarified yet.

Methods: Nine cases that required total hysterectomy for leiomyomas after menopause were examined. Surgeries were conducted because of pelvic pressure, pelvic pain, suspected malignancy, or growing leiomyoma. Six cases of leiomyomas being incidentally found during total hysterectomy for postmenopausal uterine prolapse, and six patients who underwent hysterectomy for leiomyomas before menopause, were examined as controls. We evaluated the expression of estrogen receptor, progesterone receptor B, and progesterone receptor AB by immunohistochemical staining among the cases. We also analyzed the pathological findings of leiomyomas.

Results: In postmenopausal leiomyomas, the expression of progesterone receptor was higher than that in the adjacent myometrium. Compared with premenopausal leiomyomas, the expression of progesterone receptor decreased. Postmenopausal leiomyomas that required surgery did not show elevated sex steroid hormone receptor expression, compared with the leiomyomas that did not require surgery. The degeneration frequency of leiomyomas was 92% in the group that underwent surgery for postmenopausal leiomyomas, 65% in the group that underwent surgery for reasons other than the presence of leiomyomas after menopause, and 47% in the group operated for leiomyomas before menopause.

Conclusions: These results suggest that sex steroid hormones are unlikely to be associated with the growth of leiomyomas after menopause. Since leiomyoma degeneration with increased extracellular matrix is likely to occur in postmenopausal women, the degeneration of leiomyomas may be the main mechanism for the growth of postmenopausal leiomyomas.

Keywords: Degeneration; Estrogen receptor; Menopause; Progesterone receptor; Uterine leiomyoma.

Fig. 1

Immunohistochemical staining of ER, PRAB, and PRB in endometria of postmenopausal and premenopausal women. Results for a postmenopausal woman (age: 65 years, 15 years post menopause, underwent hysterectomy for pelvic organ prolapse) and premenopausal woman (age: 43 years) are shown. All slides were stained strongly, with the Allred score being TS 8. ER, estrogen receptor; PRAB, progesterone receptor AB; PRB progesterone receptor B

Fig. 2

Representative images of slides for each Allred score. PS, proportion score (0–5); IS, intensity score (0–3); TS, total score (0, 2–8); original magnification 400×

Fig. 3

Degeneration images (myxoid, edematous and hyaline) of H&E staining. Original magnification 40×

Fig. 4

Expression of hormone receptors in leiomyomas of each group. Hormone receptor expression in leiomyomas showed no significant difference in the Allred score of ER, PRAB, and PRB between groups A and B. Groups A and B had lower expression of PRAB compared to that in group C. Group A: postmenopausal women who underwent surgery for leiomyoma; group B: postmenopausal women incidentally complicated with leiomyoma who underwent hysterectomy; group C: premenopausal women who underwent hysterectomy for leiomyoma without hormonal treatment. Original magnification 400×

Fig. 5

Hormone receptor expression in postmenopausal myometrium and leiomyoma. Expression of PRAB and PRB was significantly higher in leiomyomas than in the adjacent myometrium. Original magnification 400×