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American journal of obstetrics and gynecology2005; 192(5); 1741-1751; doi: 10.1016/j.ajog.2004.10.639

The effects of hormone replacement on the biomechanical properties of the uterosacral and round ligaments in the monkey model.

Abstract: The purpose of this study was to determine effects of ovariectomy (OVX) and conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA), or ethinyl estradiol plus norethindrone acetate (EE/NA) on biomechanics of uterosacral (USL) and round (RL) ligaments in postmenopausal (PMP) monkeys. Methods: This was a randomized, triple blind, placebo-controlled study. OVX monkeys received 12 months no treatment (Pbo) (n = 19), CEE/MPA (n = 19), or EE/NA (n = 21). USL and RL step strains and stress-relaxation data were curve-fitted, giving strain-dependent tensile modulus (TM) from 0% to 30%. Results: (1) USL: TM for both treatment groups was greater than Pbo for strains from 0% to 12% (P < .04). (2) RL: TM for both treatment groups was smaller than Pbo for strains from 12% to 30% (P < .05). No differences were found between treatment regimens. Conclusions: CEE/MPA and EE/NA both affect functional biomechanical properties by increasing tensile stiffness in the USL and decreasing it in the RL.
Publication Date: 2005-05-20 PubMed ID: 15902188DOI: 10.1016/j.ajog.2004.10.639Google Scholar: Lookup
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Summary

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The study investigates how hormonal treatments affect the physical properties of two ligaments in postmenopausal monkeys: uterosacral and round ligaments. Researchers found that both types of hormone treatment increased tensile stiffness, a measure of a material’s resistance to deformation, in the uterosacral ligament and decreased it in the round ligament.

Experiment Overview

  • The research aimed to determine the effects of hormone replacement on the biomechanical traits of two monkey ligaments – the round (RL) and uterosacral (USL). These ligament changes were analysed following ovariectomy (OVX—a surgical removal of the ovaries) which effectively induced a postmenopausal state.
  • The hormones used in the study were conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA) and ethinyl estradiol plus norethindrone acetate (EE/NA), both widely used in hormone replacement therapy in humans.
  • Postmenopausal monkeys were divided into three groups: those that received no treatment at all (placebo), those that received CEE/MPA, and those that received EE/NA.

Results and Findings

  • Data collected from step strains and stress-relaxation trials was curve-fitted for both RL and USL, which determined strain-dependent tensile modulus (TM) values across a 0% to 30% range. The tensile modulus measures an object’s resistance to deformation.
  • For the USL, the tensile modulus was found to be greater in both hormone treatment groups when compared to the placebo group for strains from 0% to 12%. The higher the tensile modulus, the more the ligament resists stretching and deformation.
  • Contrarily, in the RL, the tensile modulus in the hormone treatment groups was smaller than in the placebo group for strains from 12% to 30%. The decrease in the tensile modulus indicates lower resistance to stretching or deformation.
  • Interestingly, the researchers found no significant difference between the effects of the two different hormone treatments (CEE/MPA and EE/NA) on the ligaments’ biomechanics.

Conclusion

  • The study concludes that both CEE/MPA and EE/NA affect the functional biomechanical properties of the round and the uterosacral ligaments in postmenopausal monkeys. Both hormone replacements resulted in increased tensile stiffness in the uterosacral ligament and decreased tensile stiffness in the round ligament.
  • This research might have implications in determining the effects of hormone replacement therapy in postmenopausal women and could serve as the basis for future research on pelvic organ prolapse and other related diseases.

Cite This Article

APA
Vardy MD, Gardner TR, Cosman F, Scotti RJ, Mikhail MS, Preiss-Bloom AO, Williams JK, Cline JM, Lindsay R. (2005). The effects of hormone replacement on the biomechanical properties of the uterosacral and round ligaments in the monkey model. Am J Obstet Gynecol, 192(5), 1741-1751. https://doi.org/10.1016/j.ajog.2004.10.639

Publication

ISSN: 0002-9378
NlmUniqueID: 0370476
Country: United States
Language: English
Volume: 192
Issue: 5
Pages: 1741-1751

Researcher Affiliations

Vardy, Michael D
  • Columbia College of Physicians & Surgeons, New York, NY, USA. Michael.Vardy@ehmc.com
Gardner, Thomas R
    Cosman, Felicia
      Scotti, Richard J
        Mikhail, Magdy S
          Preiss-Bloom, A Orahn
            Williams, J Koudy
              Cline, J Mark
                Lindsay, Robert

                  MeSH Terms

                  • Animals
                  • Biomechanical Phenomena
                  • Drug Synergism
                  • Elasticity / drug effects
                  • Estrogens / pharmacology
                  • Estrogens, Conjugated (USP) / pharmacology
                  • Ethinyl Estradiol / pharmacology
                  • Female
                  • Hormones / pharmacology
                  • Ligaments / drug effects
                  • Ligaments / physiology
                  • Macaca fascicularis
                  • Medroxyprogesterone Acetate / pharmacology
                  • Norethindrone / analogs & derivatives
                  • Norethindrone / pharmacology
                  • Norethindrone Acetate
                  • Ovariectomy
                  • Round Ligament of Uterus / drug effects
                  • Round Ligament of Uterus / physiology
                  • Tensile Strength / drug effects
                  • Uterus

                  Grant Funding

                  • R01 AG 17864 / NIA NIH HHS

                  Citations

                  This article has been cited 9 times.
                  1. Donaldson K, De Vita R. Ex Vivo Uniaxial Tensile Properties of Rat Uterosacral Ligaments.. Ann Biomed Eng 2023 Apr;51(4):702-714.
                    doi: 10.1007/s10439-023-03135-ypubmed: 36652028google scholar: lookup
                  2. Gharibeh N, Aghebati-Maleki L, Madani J, Pourakbari R, Yousefi M, Ahmadian Heris J. Cell-based therapy in thin endometrium and Asherman syndrome.. Stem Cell Res Ther 2022 Jan 28;13(1):33.
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                  3. Donaldson K, Huntington A, De Vita R. Mechanics of Uterosacral Ligaments: Current Knowledge, Existing Gaps, and Future Directions.. Ann Biomed Eng 2021 Aug;49(8):1788-1804.
                    doi: 10.1007/s10439-021-02755-6pubmed: 33754254google scholar: lookup
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                    doi: 10.1097/GME.0000000000001209pubmed: 30300297google scholar: lookup
                  5. Baah-Dwomoh A, Alperin M, Cook M, De Vita R. Mechanical Analysis of the Uterosacral Ligament: Swine vs. Human.. Ann Biomed Eng 2018 Dec;46(12):2036-2047.
                    doi: 10.1007/s10439-018-2103-xpubmed: 30051246google scholar: lookup
                  6. Easley DC, Abramowitch SD, Moalli PA. Female pelvic floor biomechanics: bridging the gap.. Curr Opin Urol 2017 May;27(3):262-267.
                    doi: 10.1097/MOU.0000000000000380pubmed: 28267057google scholar: lookup
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                    doi: 10.1007/s00192-012-1861-5pubmed: 22751993google scholar: lookup
                  8. Epstein LB, Graham CA, Heit MH. Correlation between vaginal stiffness index and pelvic floor disorder quality-of-life scales.. Int Urogynecol J Pelvic Floor Dysfunct 2008 Jul;19(7):1013-8.
                    doi: 10.1007/s00192-007-0551-1pubmed: 18217178google scholar: lookup
                  9. Rizk DE, Fahim MA, Hassan HA, Al-Marzouqi AH, Ramadan GA, Al-Kedrah SS, Al-Ghafri LS. The effect of ovariectomy on biomarkers of urogenital ageing in old versus young adult rats.. Int Urogynecol J Pelvic Floor Dysfunct 2007 Sep;18(9):1077-85.
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