Rahn David D, Good Meadow M, Roshanravan Shayzreen M, Shi Haolin, Schaffer Joseph I, Singh Ravinder J, Word R Ann
Department of Obstetrics and Gynecology (D.D.R., M.M.G., S.M.R., H.S., J.I.S., R.A.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032; and Department of Laboratory Medicine and Pathology (R.J.S.), Mayo Clinic, Rochester, Minnesota 55905.
J Clin Endocrinol Metab. 2014 Oct;99(10):3728-36. doi: 10.1210/jc.2014-1216. Epub 2014 Jun 20.
Pelvic organ prolapse (POP) increases in prevalence with age; recurrence after surgical repair is common.
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.
This was a randomized trial.
The study was conducted at an academic tertiary medical center.
Postmenopausal women with a uterus and symptomatic anterior and/or apical prolapse at stage 2 or greater participated in the study.
Estrogen (Premarin) or placebo cream for 6 weeks preoperatively was the intervention.
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.
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.
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.
盆腔器官脱垂（POP）的患病率随年龄增长而增加；手术修复后复发很常见。
本研究的目的是确定局部雌激素治疗对计划进行POP手术修复的绝经后女性阴道壁结缔组织合成和分解的影响。
这是一项随机试验。
该研究在一家学术性三级医疗中心进行。
患有子宫且有症状的前壁和/或顶部脱垂达到2期或更严重程度的绝经后女性参与了该研究。
术前使用雌激素（倍美力）或安慰剂乳膏，为期6周。
在子宫切除时获取全层前顶部阴道壁活检组织，分析其黏膜和肌层厚度、结缔组织合成及降解情况。使用高灵敏度液相色谱 - 串联质谱法在基线和手术当天分析血清雌酮和17β - 雌二醇水平。
每组随机分配15名女性（共30名）；每组13名接受手术。在依从药物治疗的参与者中（雌激素组8名，安慰剂组13名），雌激素使上皮和肌层厚度分别增加了1.8倍和2.7倍（P分别为0.002和0.088）。阴道肌层中I型胶原蛋白α1和α2 mRNA分别增加了6.0倍和1.8倍（两者P均<0.05）；肌层中I型胶原蛋白蛋白增加了9倍（P = 0.012），而III型胶原蛋白无显著变化。雌激素治疗参与者的阴道黏膜中MMP - 12（人巨噬细胞弹性蛋白酶）mRNA受到抑制（P = 0.011），黏膜中基质金属蛋白酶 - 9活性降低了6倍，肌层中降低了4倍（P = 0.02）。与绝经标准一致，两组血清雌酮和17β - 雌二醇水平较低且无差异。
术前6周应用阴道雌激素可增加成熟胶原蛋白的合成，降低降解酶活性，并增加阴道壁厚度，表明该干预措施既能改善手术修复时缝线放置的基质，又能维持盆底结缔组织的完整性。
