Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial.

CONTEXT

Pelvic organ prolapse (POP) increases in prevalence with age; recurrence after surgical repair is common.

OBJECTIVE

The objective of the study was to determine the effects of local estrogen treatment on connective tissue synthesis and breakdown in the vaginal wall of postmenopausal women planning surgical repair of POP.

DESIGN

This was a randomized trial.

SETTING

The study was conducted at an academic tertiary medical center.

PATIENTS OR OTHER PARTICIPANTS

Postmenopausal women with a uterus and symptomatic anterior and/or apical prolapse at stage 2 or greater participated in the study.

INTERVENTION

Estrogen (Premarin) or placebo cream for 6 weeks preoperatively was the intervention.

MAIN OUTCOME MEASURES

Full-thickness anterior apical vaginal wall biopsies were obtained at the time of hysterectomy and analyzed for mucosa and muscularis thickness, connective tissue synthesis, and degradation. Serum levels of estrone and 17β-estradiol were analyzed at baseline and the day of surgery using highly sensitive liquid chromatography-tandem mass spectrometry.

RESULTS

Fifteen women per group (n = 30 total) were randomized; 13 per group underwent surgery. Among drug-adherent participants (n = 8 estrogen, n = 13 placebo), epithelial and muscularis thickness was increased 1.8- and 2.7-fold (P = .002 and P =.088, respectively) by estrogen. Collagen types 1α1 and 1α2 mRNA increased 6.0- and 1.8-fold in the vaginal muscularis (P < .05 for both); collagen type Ia protein increased 9-fold in the muscularis (P = .012), whereas collagen III was not changed significantly. MMP-12 (human macrophage elastase) mRNA was suppressed in the vaginal mucosa from estrogen-treated participants (P = .011), and matrix metalloprotease-9 activity was decreased 6-fold in the mucosa and 4-fold in the muscularis (P = .02). Consistent with menopausal norms, serum estrone and 17β-estradiol were low and did not differ among the two groups.

CONCLUSIONS

Vaginal estrogen application for 6 weeks preoperatively increased synthesis of mature collagen, decreased degradative enzyme activity, and increased thickness of the vaginal wall, suggesting this intervention improves both the substrate for suture placement at the time of surgical repair and maintenance of connective tissue integrity of the pelvic floor.