Effects of preoperative local estrogen in postmenopausal women with prolapse

A randomized trial

David D. Rahn, Meadow M. Good, Shayzreen M. Roshanravan, Haolin Shi, Joseph I. Schaffer, Ravinder J. Singh, R. Ann Word

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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), where as 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.

Design: This was 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.

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.

Original languageEnglish (US)
Pages (from-to)3728-3736
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number10
DOIs
StatePublished - Oct 1 2014

Fingerprint

Prolapse
Estrogens
Collagen
Connective Tissue
Pelvic Organ Prolapse
Mucous Membrane
Repair
Estrone
Tissue
Surgery
Estradiol
Placebos
Conjugated (USP) Estrogens
Messenger RNA
Pelvic Floor
Biopsy
Macrophages
Pancreatic Elastase
Liquid chromatography
Enzyme activity

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Effects of preoperative local estrogen in postmenopausal women with prolapse : A randomized trial. / Rahn, David D.; Good, Meadow M.; Roshanravan, Shayzreen M.; Shi, Haolin; Schaffer, Joseph I.; Singh, Ravinder J.; Word, R. Ann.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 10, 01.10.2014, p. 3728-3736.

Research output: Contribution to journalArticle

Rahn, David D. ; Good, Meadow M. ; Roshanravan, Shayzreen M. ; Shi, Haolin ; Schaffer, Joseph I. ; Singh, Ravinder J. ; Word, R. Ann. / Effects of preoperative local estrogen in postmenopausal women with prolapse : A randomized trial. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 10. pp. 3728-3736.
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abstract = "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), where as 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.Design: This was 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.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.",
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T2 - A randomized trial

AU - Rahn, David D.

AU - Good, Meadow M.

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AU - Shi, Haolin

AU - Schaffer, Joseph I.

AU - Singh, Ravinder J.

AU - Word, R. Ann

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N2 - 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), where as 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.Design: This was 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.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.

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