FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Biol Reprod / Effects of vaginal conjugated equine estrogens and ospemifen...
Biology of reproduction2017; 96(1); 81-92; doi: 10.1095/biolreprod.116.144428

Effects of vaginal conjugated equine estrogens and ospemifene on the rat vaginal wall and lower urinary tract.

Abstract: Although the positive effects of vaginal estrogens and the selective estrogen receptor modulator, ospemifene (OS), on the vaginal epithelium are well recognized, less is known regarding the effects of these therapies on the lower urinary tract or vaginal muscularis. Clinical evidence suggests that vaginally administered estrogen may improve overactive bladder-related symptoms. The objective of this study was to compare the effects of OS, vaginal conjugated equine estrogens (CEE), or both on the vaginal wall and lower urinary tract in a rat model of menopause. Contractile force of the bladder neck, dome, and external urethral sphincter at optimal field stimulation did not differ significantly among treatment groups. Pharmacologic responses to atropine, carbachol, and potassium chloride were similar among groups. Vaginal epithelial thickness and differentiation were differentially regulated by CEE or OS. Ospemifene altered epithelial differentiation pathways in vaginal epithelium in a unique way, and these effects were additive with local CEE. Unless contraindicated, the beneficial effects of vaginal CEE on the vaginal wall outweigh those of OS.
© The Authors 2016. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.
Get Full Text
Publication Date: 2017-04-11 PubMed ID: 28395337PubMed Central: PMC6366548DOI: 10.1095/biolreprod.116.144428Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study is investigating the impact of vaginal conjugated equine estrogens and the drug ospemifene on the vaginal wall and lower urinary tract, and it suggests that the hormonal treatment may have more benefits than ospemifene for post-menopausal women, unless contraindicated.

Objective of the Study

  • The main objective of this research was to explore and compare the impacts of ospemifene and vaginal conjugated equine estrogens on the vaginal wall and the lower urinary tract. The research is carried out using a rat model simulating post-menopausal conditions.

Research Methodology

  • The team studied the effects of ospemifene, vaginal conjugated equine estrogens, and their combination on the rat model. The researchers looked at three important regions: the bladder neck, the dome, and the external urethral sphincter with optimal field stimulation.
  • They also analyzed pharmacological responses towards different drugs such as atropine, carbachol, and potassium chloride. These drugs are commonly used to check the functionality and responsiveness of muscular and neural actions in the urinary tract.
  • The effects on vaginal epithelial thickness and differentiation were also monitored and compared amongst the treatments.

Results

  • The study found that the contractile force of the key regions in the urinary tract system did not vary significantly among different treatment groups. This indicates that neither vaginal conjugated equine estrogens nor ospemifene had a profound impact on the contraction strength.
  • The pharmacological responses to atropine, carbachol, and potassium chloride were also found to be similar among the various groups. This result suggests that none of the treatments notably altered the functional and neural reactions to these drugs.
  • However, the treatments did have varying effects on the thickness and differentiation of vaginal epithelial cells. Ospemifene was found to have a distinct impact on cell differentiation pathways in the vaginal epithelium. Interestingly, when combined with local vaginal conjugated equine estrogens, ospemifene’s effects were enhanced.

Conclusion

  • The research concludes that among the treatments tested, local vaginal conjugated equine estrogens had a more beneficial impact on the vaginal wall compared to ospemifene. Therefore, unless contraindicated, usage of vaginal conjugated equine estrogens were recommended over ospemifene in postmenopausal women.

Cite This Article

APA
Maldonado PA, Montoya TI, Acevedo JF, Keller PW, Word RA. (2017). Effects of vaginal conjugated equine estrogens and ospemifene on the rat vaginal wall and lower urinary tract. Biol Reprod, 96(1), 81-92. https://doi.org/10.1095/biolreprod.116.144428

Publication

Biology of reproduction
ISSN: 1529-7268
NlmUniqueID: 0207224
Country: United States
Language: English
Volume: 96
Issue: 1
Pages: 81-92

Researcher Affiliations

Maldonado, P Antonio
    Montoya, T Ignacio
      Acevedo, Jesus F
        Keller, Patrick W
          Word, R Ann

            MeSH Terms

            • Administration, Intravaginal
            • Administration, Oral
            • Animals
            • Drug Evaluation, Preclinical
            • Estrogens / pharmacology
            • Estrogens / therapeutic use
            • Estrogens, Conjugated (USP) / pharmacology
            • Estrogens, Conjugated (USP) / therapeutic use
            • Female
            • Menopause
            • Random Allocation
            • Rats, Sprague-Dawley
            • Tamoxifen / analogs & derivatives
            • Tamoxifen / pharmacology
            • Tamoxifen / therapeutic use
            • Urethra / drug effects
            • Urinary Bladder / drug effects
            • Vagina / drug effects

            Grant Funding

            • R01 AG028048 / NIA NIH HHS

            References

            This article includes 54 references
            1. Santoro N, Komi J. Prevalence and impact of vaginal symptoms among postmenopausal women.. J Sex Med 2009 Aug;6(8):2133-42.
              pubmed: 19493278doi: 10.1111/j.1743-6109.2009.01335.xgoogle scholar: lookup
            2. Winneker RC, Harris HA. Progress and prospects in treating postmenopausal vaginal atrophy.. Clin Pharmacol Ther 2011 Jan;89(1):129-32.
              pubmed: 20944561doi: 10.1038/clpt.2010.161google scholar: lookup
            3. Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, Word RA. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial.. J Clin Endocrinol Metab 2014 Oct;99(10):3728-36.
              pmc: PMC4184065pubmed: 24947034doi: 10.1210/jc.2014-1216google scholar: lookup
            4. Zheng Y, Zhu M, Srinivasan S, Nwachukwu JC, Cavett V, Min J, Carlson KE, Wang P, Dong C, Katzenellenbogen JA, Nettles KW, Zhou HB. Development of selective estrogen receptor modulator (SERM)-like activity through an indirect mechanism of estrogen receptor antagonism: defining the binding mode of 7-oxabicyclo[2.2.1]hept-5-ene scaffold core ligands.. ChemMedChem 2012 Jun;7(6):1094-100.
              pmc: PMC4301955pubmed: 22517684doi: 10.1002/cmdc.201200048google scholar: lookup
            5. Gennari L, Merlotti D, Valleggi F, Nuti R. Ospemifene use in postmenopausal women.. Expert Opin Investig Drugs 2009 Jun;18(6):839-49.
              pubmed: 19466874doi: 10.1517/13543780902953715google scholar: lookup
            6. Gennari L, Merlotti D, Valleggi F, Martini G, Nuti R. Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development.. Drugs Aging 2007;24(5):361-79.
              pubmed: 17503894doi: 10.2165/00002512-200724050-00002google scholar: lookup
            7. Rutanen EM, Heikkinen J, Halonen K, Komi J, Lammintausta R, Ylikorkala O. Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women: a double-blind, randomized trial.. Menopause 2003 Sep-Oct;10(5):433-9.
              pubmed: 14501605doi: 10.1097/01.GME.0000063609.62485.27google scholar: lookup
            8. Komi J, Lankinen KS, Härkönen P, DeGregorio MW, Voipio S, Kivinen S, Tuimala R, Vihtamäki T, Vihko K, Ylikorkala O, Erkkola R. Effects of ospemifene and raloxifene on hormonal status, lipids, genital tract, and tolerability in postmenopausal women.. Menopause 2005 Mar;12(2):202-9.
              pubmed: 15772568doi: 10.1097/00042192-200512020-00015google scholar: lookup
            9. Portman DJ, Bachmann GA, Simon JA. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy.. Menopause 2013 Jun;20(6):623-30.
              pubmed: 23361170doi: 10.1097/gme.0b013e318279ba64google scholar: lookup
            10. Wurz GT, Read KC, Marchisano-Karpman C, Gregg JP, Beckett LA, Yu Q, Degregorio MW. Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice.. J Steroid Biochem Mol Biol 2005 Nov;97(3):230-40.
              pubmed: 16153821doi: 10.1016/j.jsbmb.2005.06.027google scholar: lookup
            11. Unkila M, Kari S, Yatkin E, Lammintausta R. Vaginal effects of ospemifene in the ovariectomized rat preclinical model of menopause.. J Steroid Biochem Mol Biol 2013 Nov;138:107-15.
              pubmed: 23665515doi: 10.1016/j.jsbmb.2013.04.004google scholar: lookup
            12. Montoya TI, Maldonado PA, Acevedo JF, Word RA. Effect of vaginal or systemic estrogen on dynamics of collagen assembly in the rat vaginal wall.. Biol Reprod 2015 Feb;92(2):43.
              pmc: PMC4326728pubmed: 25537371doi: 10.1095/biolreprod.114.118638google scholar: lookup
            13. Ellington DR, Szychowski JM, Malek JM, Gerten KA, Burgio KL, Richter HE. Combined Tolterodine and Vaginal Estradiol Cream for Overactive Bladder Symptoms After Randomized Single-Therapy Treatment.. Female Pelvic Med Reconstr Surg 2016 Jul-Aug;22(4):254-60.
              pmc: PMC4919279pubmed: 26945271doi: 10.1097/SPV.0000000000000256google scholar: lookup
            14. Nelken RS, Ozel BZ, Leegant AR, Felix JC, Mishell DR Jr. Randomized trial of estradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder.. Menopause 2011 Sep;18(9):962-6.
              pubmed: 21532512doi: 10.1097/gme.0b013e3182104977google scholar: lookup
            15. Zullo MA, Plotti F, Calcagno M, Palaia I, Muzii L, Manci N, Angioli R, Panici PB. Vaginal estrogen therapy and overactive bladder symptoms in postmenopausal patients after a tension-free vaginal tape procedure: a randomized clinical trial.. Menopause 2005 Jul-Aug;12(4):421-7.
              pubmed: 16037757doi: 10.1097/01.GME.0000148645.93603.62google scholar: lookup
            16. Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women.. Am J Obstet Gynecol 1999 May;180(5):1072-9.
              pubmed: 10329858doi: 10.1016/s0002-9378(99)70597-1google scholar: lookup
            17. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections.. N Engl J Med 1993 Sep 9;329(11):753-6.
              pubmed: 8350884doi: 10.1056/NEJM199309093291102google scholar: lookup
            18. Mannino CA, South SM, Inturrisi CE, Quinones-Jenab V. Pharmacokinetics and effects of 17beta-estradiol and progesterone implants in ovariectomized rats.. J Pain 2005 Dec;6(12):809-16.
              pubmed: 16326369doi: 10.1016/j.jpain.2005.07.007google scholar: lookup
            19. López-Belmonte J, Nieto C, Estevez J, Delgado JL, del Prado JM. Comparative uterine effects on ovariectomized rats after repeated treatment with different vaginal estrogen formulations.. Maturitas 2012 Aug;72(4):353-8.
              pubmed: 22683083doi: 10.1016/j.maturitas.2012.05.007google scholar: lookup
            20. Rahn DD, Ruff MD, Brown SA, Tibbals HF, Word RA. Biomechanical properties of the vaginal wall: effect of pregnancy, elastic fiber deficiency, and pelvic organ prolapse.. Am J Obstet Gynecol 2008 May;198(5):590.e1-6.
              pmc: PMC2760217pubmed: 18455541doi: 10.1016/j.ajog.2008.02.022google scholar: lookup
            21. Miller EJ, Rhodes RK. Preparation and characterization of the different types of collagen.. Methods Enzymol 1982;82 Pt A:33-64.
              pubmed: 7078441doi: 10.1016/0076-6879(82)82059-4google scholar: lookup
            22. Wai CY, Liehr P, Boreham MK, Schaffer JI, Word RA. Effect of periurethral denervation on smooth muscles of the lower urinary tract.. Am J Obstet Gynecol 2004 Dec;191(6):1950-60.
              pubmed: 15592277doi: 10.1016/j.ajog.2004.06.091google scholar: lookup
            23. Wai CY, Liehr P, Tibbals HF, Sager M, Schaffer JI, Word RA. Effect of periurethral denervation on function of the female urethra.. Am J Obstet Gynecol 2003 Dec;189(6):1637-45.
              pubmed: 14710091doi: 10.1016/s0002-9378(03)00901-3google scholar: lookup
            24. Feng Q, O'Malley BW. Nuclear receptor modulation--role of coregulators in selective estrogen receptor modulator (SERM) actions.. Steroids 2014 Nov;90:39-43.
              pmc: PMC4192004pubmed: 24945111doi: 10.1016/j.steroids.2014.06.008google scholar: lookup
            25. Blakeman PJ, Hilton P, Bulmer JN. Oestrogen and progesterone receptor expression in the female lower urinary tract, with reference to oestrogen status.. BJU Int 2000 Jul;86(1):32-8.
              pubmed: 10886079doi: 10.1046/j.1464-410x.2000.00724.xgoogle scholar: lookup
            26. Iosif CS, Batra S, Ek A, Astedt B. Estrogen receptors in the human female lower uninary tract.. Am J Obstet Gynecol 1981 Dec 1;141(7):817-20.
              pubmed: 7198384doi: 10.1016/0002-9378(81)90710-9google scholar: lookup
            27. Smith P. Estrogens and the urogenital tract. Studies on steroid hormone receptors and a clinical study on a new estradiol-releasing vaginal ring.. Acta Obstet Gynecol Scand Suppl 1993;157:1-26.
              pubmed: 8393609
            28. Krause M, Wheeler TL 2nd, Snyder TE, Richter HE. Local Effects of Vaginally Administered Estrogen Therapy: A Review.. J Pelvic Med Surg 2009 May;15(3):105-114.
              pmc: PMC3252029pubmed: 22229022doi: 10.1097/SPV.0b013e3181ab4804google scholar: lookup
            29. Simon JA. Identifying and treating sexual dysfunction in postmenopausal women: the role of estrogen.. J Womens Health (Larchmt) 2011 Oct;20(10):1453-65.
              pubmed: 21819250doi: 10.1089/jwh.2010.2151google scholar: lookup
            30. Nappi RE, Davis SR. The use of hormone therapy for the maintenance of urogynecological and sexual health post WHI.. Climacteric 2012 Jun;15(3):267-74.
              pubmed: 22612614doi: 10.3109/13697137.2012.657589google scholar: lookup
            31. Krychman ML. Vaginal estrogens for the treatment of dyspareunia.. J Sex Med 2011 Mar;8(3):666-74.
              pubmed: 21091878doi: 10.1111/j.1743-6109.2010.02114.xgoogle scholar: lookup
            32. Crandall C. Vaginal estrogen preparations: a review of safety and efficacy for vaginal atrophy.. J Womens Health (Larchmt) 2002 Dec;11(10):857-77.
              pubmed: 12626086doi: 10.1089/154099902762203704google scholar: lookup
            33. Sturdee DW, Panay N. Recommendations for the management of postmenopausal vaginal atrophy.. Climacteric 2010 Dec;13(6):509-22.
              pubmed: 20883118doi: 10.3109/13697137.2010.522875google scholar: lookup
            34. Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (REal Women's VIews of Treatment Options for Menopausal Vaginal ChangEs) survey.. J Sex Med 2013 Jul;10(7):1790-9.
              pubmed: 23679050doi: 10.1111/jsm.12190google scholar: lookup
            35. Shulman LP, Portman DJ, Lee WC, Balu S, Joshi AV, Cobden D, Wang Q, Pashos CL. A retrospective managed care claims data analysis of medication adherence to vaginal estrogen therapy: implications for clinical practice.. J Womens Health (Larchmt) 2008 May;17(4):569-78.
              pubmed: 18429700doi: 10.1089/jwh.2007.0407google scholar: lookup
            36. Bertin J, Ouellet J, Dury AY, Pelletier G, Labrie F. Expression of the estrogen receptors and steroidogenic enzymes involved in estradiol formation in the monkey vagina.. Am J Obstet Gynecol 2014 Nov;211(5):499.e1-9.
              pubmed: 24928055doi: 10.1016/j.ajog.2014.06.017google scholar: lookup
            37. Wang XN, Simmons HA, Salatto CT, Cosgrove PG, Thompson DD. Lasofoxifene enhances vaginal mucus formation without causing hypertrophy and increases estrogen receptor beta and androgen receptor in rats.. Menopause 2006 Jul-Aug;13(4):609-20.
              pubmed: 16837883doi: 10.1097/01.gme.0000227337.73738.c9google scholar: lookup
            38. Sun J, Meyers MJ, Fink BE, Rajendran R, Katzenellenbogen JA, Katzenellenbogen BS. Novel ligands that function as selective estrogens or antiestrogens for estrogen receptor-alpha or estrogen receptor-beta.. Endocrinology 1999 Feb;140(2):800-4.
              pubmed: 9927308doi: 10.1210/endo.140.2.6480google scholar: lookup
            39. Kraichely DM, Sun J, Katzenellenbogen JA, Katzenellenbogen BS. Conformational changes and coactivator recruitment by novel ligands for estrogen receptor-alpha and estrogen receptor-beta: correlations with biological character and distinct differences among SRC coactivator family members.. Endocrinology 2000 Oct;141(10):3534-45.
              pubmed: 11014206doi: 10.1210/endo.141.10.7698google scholar: lookup
            40. Sun J, Huang YR, Harrington WR, Sheng S, Katzenellenbogen JA, Katzenellenbogen BS. Antagonists selective for estrogen receptor alpha.. Endocrinology 2002 Mar;143(3):941-7.
              pubmed: 11861516doi: 10.1210/endo.143.3.8704google scholar: lookup
            41. Harrington WR, Sheng S, Barnett DH, Petz LN, Katzenellenbogen JA, Katzenellenbogen BS. Activities of estrogen receptor alpha- and beta-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression.. Mol Cell Endocrinol 2003 Aug 29;206(1-2):13-22.
              pubmed: 12943986doi: 10.1016/s0303-7207(03)00255-7google scholar: lookup
            42. Meyers MJ, Sun J, Carlson KE, Marriner GA, Katzenellenbogen BS, Katzenellenbogen JA. Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues.. J Med Chem 2001 Nov 22;44(24):4230-51.
              pubmed: 11708925doi: 10.1021/jm010254agoogle scholar: lookup
            43. Stauffer SR, Coletta CJ, Tedesco R, Nishiguchi G, Carlson K, Sun J, Katzenellenbogen BS, Katzenellenbogen JA. Pyrazole ligands: structure-affinity/activity relationships and estrogen receptor-alpha-selective agonists.. J Med Chem 2000 Dec 28;43(26):4934-47.
              pubmed: 11150164doi: 10.1021/jm000170mgoogle scholar: lookup
            44. Smith CL, Nawaz Z, O'Malley BW. Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen.. Mol Endocrinol 1997 Jun;11(6):657-66.
              pubmed: 9171229doi: 10.1210/mend.11.6.0009google scholar: lookup
            45. Iosif CS, Bekassy Z. Prevalence of genito-urinary symptoms in the late menopause.. Acta Obstet Gynecol Scand 1984;63(3):257-60.
              pubmed: 6730943doi: 10.3109/00016348409155509google scholar: lookup
            46. Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women.. Cochrane Database Syst Rev 2012 Oct 17;10(10):CD001405.
              pmc: PMC7086391pubmed: 23076892doi: 10.1002/14651858.CD001405.pub3google scholar: lookup
            47. Simunić V, Banović I, Ciglar S, Jeren L, Pavicić Baldani D, Sprem M. Local estrogen treatment in patients with urogenital symptoms.. Int J Gynaecol Obstet 2003 Aug;82(2):187-97.
              pubmed: 12873780doi: 10.1016/s0020-7292(03)00200-5google scholar: lookup
            48. Cardozo L, Lose G, McClish D, Versi E. A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder.. Acta Obstet Gynecol Scand 2004 Oct;83(10):892-7.
              pubmed: 15453881doi: 10.1111/j.0001-6349.2004.00581.xgoogle scholar: lookup
            49. Long CY, Liu CM, Hsu SC, Chen YH, Wu CH, Tsai EM. A randomized comparative study of the effects of oral and topical estrogen therapy on the lower urinary tract of hysterectomized postmenopausal women.. Fertil Steril 2006 Jan;85(1):155-60.
              pubmed: 16412747doi: 10.1016/j.fertnstert.2005.06.042google scholar: lookup
            50. Hong SK, Yang JH, Kim TB, Kim SW, Paick JS. Effects of ovariectomy and oestrogen replacement on the function and expression of Rho-kinase in rat bladder smooth muscle.. BJU Int 2006 Nov;98(5):1114-7.
              pubmed: 17034613doi: 10.1111/j.1464-410X.2006.06486.xgoogle scholar: lookup
            51. Yoshida J, Aikawa K, Yoshimura Y, Shishido K, Yanagida T, Yamaguchi O. The effects of ovariectomy and estrogen replacement on acetylcholine release from nerve fibres and passive stretch-induced acetylcholine release in female rat bladder.. Neurourol Urodyn 2007;26(7):1050-5.
              pubmed: 17480029doi: 10.1002/nau.20438google scholar: lookup
            52. Birder L, Andersson KE. Urothelial signaling.. Physiol Rev 2013 Apr;93(2):653-80.
              pmc: PMC3768101pubmed: 23589830doi: 10.1152/physrev.00030.2012google scholar: lookup
            53. Blakeman PJ, Hilton P, Bulmer JN. Cellular proliferation in the female lower urinary tract with reference to oestrogen status.. BJOG 2001 Aug;108(8):813-6.
              pubmed: 11510705doi: 10.1111/j.1471-0528.2001.00210.xgoogle scholar: lookup
            54. Silva C, Rey R, Elena Nader-Macías M. Effects of estrogen administration on the colonization capability of lactobacilli and Escherichia coli in the urinary tracts of mice.. Methods Mol Biol 2004;268:387-399.
              pubmed: 15156049doi: 10.1385/1-59259-766-1:387google scholar: lookup

            Citations

            This article has been cited 2 times.
            1. McCracken JM, Calderon GA, Robinson AJ, Sullivan CN, Cosgriff-Hernandez E, Hakim JCE. Animal Models and Alternatives in Vaginal Research: a Comparative Review.. Reprod Sci 2021 Jun;28(6):1759-1773.
              doi: 10.1007/s43032-021-00529-ypubmed: 33825165google scholar: lookup
            2. Florian-Rodriguez M, Chin K, Hamner J, Acevedo J, Keller P, Word RA. Effect of Protease Inhibitors in Healing of the Vaginal Wall.. Sci Rep 2019 Aug 26;9(1):12354.
              doi: 10.1038/s41598-019-48527-0pubmed: 31451729google scholar: lookup
            Subscribe to our newsletter
            Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.