DOCSLIB.ORG

Wo 2010/011605 A2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Wo 2010/011605 A2 (12) INTERNATIONALAPPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 28 January 2010 (28.01.2010) WO 2010/011605 A2 (51) International Patent Classification: Avenue, San Diego, CA 92107 (US). TRAMMEL, An- A61K 9/06 (2006.01) A61K 9/16 (2006.01) drew, M. [US/US]; 12485 South Alden Circle, Olathe, A61P 27/16 (2006.01) A61K 47/34 (2006.01) KS 66062 (US). DURON, Sergio, G. [US/US]; 1605 ,„,. (21) v ' (22) (25) (26) (30) 94304 (US). for every AG, AL, AM, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (71) LT, LU, LY, MA, MD, MZ, NA, NG, NI, TM, TN, TR, TT, (72) Inventors; and (84) Designated States (unless otherwise indicated, for every (75) Inventors/Applicants (for US only): LICHTER, Jay kind of regional protection available): ARIPO (BW, GH, [US/US]; P.O. Box 676244, Rancho Santa Fe, CA 92067 GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (US). VOLLRATH, Benedikt [DE/US]; 4704 Niagara ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, [Continued on next page] (54) Title: CONTROLLED-RELEASE OTIC STRUCTURE MODULATING AND INNATE IMMUNE SYSTEM MODULAT ING COMPOSITIONS AND METHODS FOR THE TREATMENT OF OTIC DISORDERS (57) Abstract: Disclosed herein are compositions and methods for the treatment of otic disorders with otic structure modulating compositions administered locally to an individual afflicted with an otic disorder, through direct application of these compositions and compositions onto or via perfusion into the targeted auris structure(s). TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, Published: ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, -,; - i i u uv i MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, yn ύ umt f ° arch report andA to be repubhshedA TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Upon °fthat 4 8-2(g)) ML, MR, NE, SN, TD, TG). CONTROLLED-RELEASE OTIC STRUCTURE MODULATING AND INNATE IMMUNE SYSTEM MODULATING COMPOSITIONS AND METHODS FOR THE TREATMENT OF OTIC DISORDERS CROSS-REFERENCE [0001] This application claims the benefit of U.S. Provisional Application No. 61/082,450, filed 21- July-2008; U.S. Provisional Application No. 61/091,205, filed 22-August-2008; U.S. Provisional Application No. 61/094,384, filed 04-September-2008; U.S. Provisional Application No. 61/101,1 12, filed 29-September-2008; U.S. Provisional Application No. 61/108,845, filed 27-October-2008; U.S. Provisional Application No. 61/140,033, filed 22-December-2008; U.S. Provisional Application No. 61/156,771, filed 02-March-2009; and U.S. Provisional Application No. 61/091,200, filed 22-August-2008; all of which are incorporated by reference herein in their entirety. BACKGROUND OF THE INVENTION [0002] Vertebrates have a pair of ears, placed symmetrically on opposite sides of the head. The ear serves as both the sense organ that detects sound and the organ that maintains balance and body position. The ear is generally divided into three portions: the outer ear, auris media (or middle ear) and the auris interna (or inner ear). SUMMARY OF THE INVENTION [0003] Described herein, in certain embodiments, are compositions, compositions, manufacturing methods, therapeutic methods, uses, kits, and delivery devices for the controlled-release of an otic structure modulating agent or innate immune system modulating agent to at least one structure or region of the ear. Disclosed herein, in certain embodiments, are controlled-release compositions for delivering an otic structure modulating agent or innate immune system modulating agent to the ear. In some embodiments, the target portion of the ear is the middle ear (or auris media). In some embodiments, the target portion of the ear is the inner ear (or auris interna). In other embodiments, the target portion of the ear is both the auris media and the auris interna. In some embodiments, the controlled-release compositions further comprise a rapid or immediate release component for delivering an otic structure modulating agent or innate immune system modulating agent to the targeted auris structure. All compositions comprise excipients that are auris-acceptable. [0004] Also disclosed herein, in certain embodiments, are compositions and devices for the treatment of otic disorders, said compositions and devices comprising an otic structure modulating agent or innate immune system modulating agent. Further disclosed herein, in certain embodiments, are methods for the treatment of otic disorders by administration of a controlled-release composition comprising an otic structure modulating agent or innate immune system modulating agent to an individual in need thereof. In some embodiments, the otic disorder is otitis externa, otitis media, mastoiditis, sensorineural hearing loss, ototoxicity, endolymphatic hydrops, labyrinthitis, Meniere's disease, Meniere's syndrome, microvascular compression syndrome, vestibular neuronitis, acoustic trauma, presbycusis, cholesteatoma, otosclerosis, Scheibe syndrome, Mondini-Michelle syndrome, Waardenburg's syndrome, Michel syndrome, Alexander's ear deformity, hypertelorism, Jervell- Lange Nielson syndrome, Refsum's syndrome, Usher's syndrome, or combinations thereof. In some embodiments, the otic disorder is otitis externa, otitis media, mastoiditis, AIED, Ramsay Hunt's, reperfusion injury, labyrinthitis ossificans or combinations thereof. [0005] The auris compositions and therapeutic methods described herein have numerous advantages that overcome the previously -unrecognized limitations of compositions and therapeutic methods described in prior art. Sterility [0006] The environment of the inner ear is an isolated environment. The endolymph and the perilymph are static fluids and are not in contiguous contact with the circulatory system. The blood - labyrinth - barrier (BLB), which includes a blood-endolymph barrier and a blood-perilymph barrier, consists of tight junctions between specialized epithelial cells in the labyrinth spaces (i.e., the vestibular and cochlear spaces). The presence of the BLB limits delivery of active agents (e.g., otic structure modulating agent or innate immune system modulating agents) to the isolated microenvironment of the inner ear. Auris hair cells are bathed in endolymphatic or perilymphatic fluids and cochlear recycling of potassium ions is important for hair cell function. When the inner ear is infected, there is an influx of leukocytes and/or immunoglobulins (e.g. in response to a microbial infection) into the endolymph and/or the perilymph and the ionic composition of inner ear fluids is upset by the influx of leukocytes and/or immunoglobulins. In certain instances, a change in the ionic composition of inner ear fluids results in hearing loss, loss of balance and/or ossification of auditory structures. In certain instances, trace amounts of pyrogens and/or microbes trigger infections and related physiological changes in the isolated microenvironment of the inner ear. [0007] Due to the susceptibility of the inner ear to infections, auris compositions require a level of sterility that has not been recognized hitherto in prior art. Provided herein are auris compositions that are sterilized with stringent sterility requirements and are suitable for administration to the middle and/or inner ear. In some embodiments, the auris compatible compositions described herein are substantially free of pyrogens and/or microbes. Compatibility with Inner Ear Environment [0008] Described herein are otic compositions with an ionic balance that is compatible with the perilymph and/or the endolymph and does not cause any change in cochlear potential. In specific embodiments, osmolarity/osmolality of the present compositions is adjusted, for example, by the use of appropriate salt concentrations (e.g., concentration of sodium salts) or the use of tonicity agents that render the compositions endolymph-compatible and/or perilymph-compatible (i.e. isotonic with the endolymph and/or perilymph). In some instances, the endolymph-compatible and/or perilymph- compatible compositions described herein cause minimal disturbance to the environment of the inner ear and cause minimum discomfort (e.g., vertigo) to a subject (e.g., a human) upon administration. Further, the compositions comprise polymers that are biodegradable and/or dispersible, and/or otherwise non-toxic to the inner ear environment. In some embodiments, the compositions described herein are free of preservatives and cause minimal disturbance (e.g., change in pH or osmolarity, irritation) in auditory structures. In some embodiments, the compositions described herein comprise antioxidants that are non-irritating and/or non-toxic to otic structures. Dosing Frequency [0009] The current standard of care for auris compositions requires multiple administrations of drops or injections (e.g. intratympanic injections) over several days (e.g., up to two weeks), including schedules of receiving multiple injections per day. In some embodiments, auris compositions described herein are controlled-release compositions and are administered at reduced dosing frequency compared to the current standard of care. In certain instances, when an auris composition is administered via intratympanic injection, a reduced frequency of administration alleviates discomfort caused by multiple intratympanic injections in individuals undergoing treatment for a middle and/or inner ear disease, disorder or condition. In certain instances, a reduced frequency of administration of intratympanic
Load more

Recommended publications
  • Universidade Estadual De Campinas Faculdade De Engenharia De Alimentos Naice Eleidiane Santana Monteiro Evaluation of Probiotics
    UNIVERSIDADE ESTADUAL DE CAMPINAS FACULDADE DE ENGENHARIA DE ALIMENTOS NAICE ELEIDIANE SANTANA MONTEIRO EVALUATION OF PROBIOTICS ON INFLUENCE IN THE ABSORPTION AND PRODUCTION OF SOY ISOFLAVONES METABOLITES IN MENOPAUSAL WOMEN WITH CLIMATERIC SYMPTOMATOLOGY AVALIAÇÃO DA INFLUÊNCIA DE PROBIÓTICOS NA ABSORÇÃO E PRODUÇÃO DE METABÓLITOS DE ISOFLAVONAS DA SOJA EM MULHERES MENOPAUSADAS COM SINTOMATOLOGIA CLIMATÉRICA CAMPINAS 2018 NAICE ELEIDIANE SANTANA MONTEIRO EVALUATION OF PROBIOTICS ON INFLUENCE IN THE ABSORPTION AND PRODUCTION OF SOY ISOFLAVONES METABOLITES IN MENOPAUSAL WOMEN WITH CLIMATERIC SYMPTOMATOLOGY AVALIAÇÃO DA INFLUÊNCIA DE PROBIÓTICOS NA ABSORÇÃO E PRODUÇÃO DE METABÓLITOS DE ISOFLAVONAS DA SOJA EM MULHERES MENOPAUSADAS COM SINTOMATOLOGIA CLIMATÉRICA Thesis presented to School of Food Engineering of University of Campinas as part of the requirements for PhD in Food and Nutrition in Experimental Nutrition and Applied to Food Technology area. Tese apresentada à Faculdade de Engenharia de Alimentos da Universidade Estadual de Campinas como parte dos requisitos exigidos para a obtenção do título de Doutora em Alimentos e Nutrição na Área de Nutrição Experimental e aplicada à Tecnologia de Alimentos. ORIENTADOR: GABRIELA ALVES MACEDO COORIENTADOR: ADRIANA ORCESI PEDRO CAMPANA ESTE EXEMPLAR CORRESPONDE A VERSÃO FINAL DA TESE DEFENDIDA PELA ALUNA NAICE ELEIDIANE SANTANA MONTEIRO, E ORIENTADA PELA PROFª. DRª. GABRIELA ALVES MACEDO. CAMPINAS 2018 BANCA EXAMINADORA DA DEFESA DE DOUTORADO NAICE ELEIDIANE SANTANA MONTEIRO MEMBROS: 1. PROF. DR. GABRIELA ALVES MACEDO - PRESIDENTE - (UNIVERSIDADE ESTADUAL DE CAMPINAS) 2. PROF. DR. ANA LUCIA TASCA GOIS RUIZ (UNIVERSIDADE ESTADUAL DE CAMPINAS) 3. PROF. DR. JOELISE DE ALENCAR FIGUEIRA ANGELOTTI (UNIVERSIDADE FEDERAL DE ALFENAS) 4. PROF. DR. LOUISE EMY KUROZAWA (UNIVERSIDADE ESTADUAL DE CAMPINAS) 5.
    [Show full text]
  • Interaction Between the Effects of the Selective Estrogen Modulator Femarelle and a Vitamin D Analog in Human Umbilical Artery V
    Journal of Steroid Biochemistry and Molecular Biology xxx (xxxx) xxx–xxx Contents lists available at ScienceDirect Journal of Steroid Biochemistry and Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb Interaction between the effects of the selective estrogen modulator femarelle and a vitamin D analog in human umbilical artery vascular smooth muscle cells ⁎ Dalia Somjen , Esther Knoll, Orli Sharon, Ariel Many, Naftali Stern Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, 64239, Israel ARTICLE INFO ABSTRACT Keywords: To further investigate the interaction between vitamin D system and estrogen-mimetic compounds in the human Vascular smooth muscle cells vasculature we studied the effect of the “less- calcemic” analog of 1,25(OH)2D3 (1,25D); JK 1624F2-2 (JKF) in Femarelle the presence of selective estrogen modulator femarelle (F), the phytoestrogen daidzein (D) and estradiol-17b (E2) 1,25D on 3[H] thymidine incorporation (DNA synthesis) and creatine kinase specific activity (CK) in human umbilical JKF artery vascular smooth muscle cells (VSMC). F, D and E , stimulated DNA synthesis at low concentrations, and 1OHase 2 inhibited it at high concentrations. All estrogen-related compounds increased CK dose- dependently. Daily treatment with JKF (1 nM for 3 days) resulted in decreased DNA synthesis, increased CK and up- regulation of the stimulation of DNA synthesis by low estrogen-related hormones whereas D- and E2- mediated inhibition of cell proliferation was abolished by JKF. In contrast, inhibition of cell proliferation by F could not be blocked by JKF. JKF also up-regulated the stimulatory effects on CK by F, E2 and D.
    [Show full text]
  • Hormonal and Non-Hormonal Management of Vasomotor Symptoms: a Narrated Review
    Central Journal of Endocrinology, Diabetes & Obesity Review Article Corresponding authors Orkun Tan, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology Hormonal and Non-Hormonal and Infertility, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd. Dallas, TX 75390 and ReproMed Fertility Center, 3800 San Management of Vasomotor Jacinto Dallas, TX 75204, USA, Tel: 214-648-4747; Fax: 214-648-8066; E-mail: [email protected] Submitted: 07 September 2013 Symptoms: A Narrated Review Accepted: 05 October 2013 Orkun Tan1,2*, Anil Pinto2 and Bruce R. Carr1 Published: 07 October 2013 1Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology Copyright and Infertility, University of Texas Southwestern Medical Center, USA © 2013 Tan et al. 2Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, ReproMed Fertility Center, USA OPEN ACCESS Abstract Background: Vasomotor symptoms (VMS; hot flashes, hot flushes) are the most common complaints of peri- and postmenopausal women. Therapies include various estrogens and estrogen-progestogen combinations. However, both physicians and patients became concerned about hormone-related therapies following publication of data by the Women’s Health Initiative (WHI) study and have turned to non-hormonal approaches of varying effectiveness and risks. Objective: Comparison of the efficacy of non-hormonal VMS therapies with estrogen replacement therapy (ERT) or ERT combined with progestogen (Menopausal Hormone Treatment; MHT) and the development of literature-based guidelines for the use of hormonal and non-hormonal VMS therapies. Methods: Pubmed, Cochrane Controlled Clinical Trials Register Database and Scopus were searched for relevant clinical trials that provided data on the treatment of VMS up to June 2013.
    [Show full text]
  • Applying SERMS to Advance the Management of Menopause
    Applying SERMS to Advance the Management of Menopause Lila Nachtigall, MD NCMP Professor of Ob/Gyn NYU School of Medicine Disclosures I have nothing to disclose SERMs •Selective •Estrogen •Receptor •Modulators The Dynamics of Estrogen & Estrogen Receptors ▪ Estrogen regulates the growth, development, and physiology of the reproductive system ▪ The biological functions of estrogen are mediated by binding to Estrogen Receptors (ER) which our found in most of the female body’s tissues ▪ In each target tissue the ERs have specific characteristics, providing a certain response within the tissue Short & Long-Term Effect of Hormone Depletion Brain & nervous system Skin Heart Breast Reproductive Tract Urinary System • ERs are found in most Bone of the female body’s tissues • Tremendous impact on • Estrogen decline affects short & long term QoL of all tissues women Effect of estrogen depletion in the Brain & Nervous System • Estrogen affects the autonomic control, the emotional state, and higher brain functions; • Reduction in estrogen levels leads to: – Mood swings – Memory loss – Problems focusing – Irritability – Fatigue – Hot flashes & night sweats – Stress & Anxiety – Depression – Decreased libido KNDy Neurons Szeliga A,Gennazzani AD Gynecological Endocrinology, 34:11, 913-919, DOI: 10.1080/09513590.2018.1480711 Szeliga A,Gennazzani AD Gynecological Endocrinology, 34:11, 913-919, DOI: 10.1080/09513590.2018.1480711 The Need Symptoms/Time Line The decline in estrogen levels in women leads to a chronic hormonal imbalance which accompanies women
    [Show full text]
  • Copyright Undertaking
    Copyright Undertaking This thesis is protected by copyright, with all rights reserved. By reading and using the thesis, the reader understands and agrees to the following terms: 1. The reader will abide by the rules and legal ordinances governing copyright regarding the use of the thesis. 2. The reader will use the thesis for the purpose of research or private study only and not for distribution or further reproduction or any other purpose. 3. The reader agrees to indemnify and hold the University harmless from and against any loss, damage, cost, liability or expenses arising from copyright infringement or unauthorized usage. IMPORTANT If you have reasons to believe that any materials in this thesis are deemed not suitable to be distributed in this form, or a copyright owner having difficulty with the material being included in our database, please contact [email protected] providing details. The Library will look into your claim and consider taking remedial action upon receipt of the written requests. Pao Yue-kong Library, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong http://www.lib.polyu.edu.hk CHARACTERIZATION OF THE TISSUE-SELECTIVITY OF TRADITIONAL CHINESE MEDICINE (TCM)-DERIVED PHYTOESTROGEN AND THE POSSIBLE MECHANISMS INVOLVED ZHOU LIPING Ph.D The Hong Kong Polytechnic University 2017 The Hong Kong Polytechnic University Department of Applied Biology and Chemical Technology Characterization of the Tissue-selectivity of Traditional Chinese Medicine (TCM)-derived Phytoestrogen and the Possible Mechanisms Involved ZHOU Liping A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy September 2016 I Certificate Originality I hereby declare that this thesis is my own work and that, to the best of my knowledge and belief, it reproduces no material previously published or written, nor material that has been accepted for the award of any other degree or diploma, except where due acknowledgement has been made in the text.
    [Show full text]
  • Kosttilskud Med Planteøstrogener
    VIDENSKAB Kosttilskud med planteøstrogener Anja Olsen1, Cecilie Kyrø1, Peter Schwarz2, Peter Vestergaard3, Øjvind Lidegaard4, Pernille Hermann5, Bente Langdahl6, Jens-Erik Beck Jensen7, Bo Abrahamsen8 & Torben Harsløf6 Planteøstrogener (PØ) er plantestoffer, hvis kemiske ler i forbindelse med medicinsk behandling, særligt an­ STATUSARTIKEL struktur ligner estradiols. PØ kan binde til østrogen­ tiøstrogenbehandling af kvinder, som er blevet opere­ 1) Kost, gener og miljø, receptor­α og ­β og være både antagonistiske og agoni­ ret for brystkræft. Center for Kræft- stiske [1]. I litteraturen er PØ associeret til gavnlige forskning, Kræftens effekter ved en lang række sygdomme. Formålet med PROSTATA Bekæmpelse 2) Medicinsk denne artikel er at beskrive evidensen for brug af PØ i I 2002 blev IF i et review beskrevet som præventiv mod Endokrinologisk Klinik, forhold til sygdomme og gener ved faldende endogen nonmalign prostatahyperplasi uden en overbevisende Rigshospitalet kønshormonproduktion samt at diskutere sikkerheden klinisk baseret evidens [3]. Undersøgelser, som er ud­ 3) Hormon- og ved brug af PØ. ført på aromatase­knockoutmus, der udvikler livslang stofskiftesygdomme, Aalborg Universitets- Der findes generelt tre typer PØ: isoflavonoider prostatavækst, viser dog, at IF sænker niveauerne af te­ hospital (IF), lignaner og coumestaner (Figur 1) [2]. Lignaner stosteron og dihydrotestosteron [4]. I et samtidigt lille 4) Juliane Marie Centret, findes i de fleste fiberrige fødevarer såsom frø, fuldkorn studie på rotter, som var blevet fodret med IF, fandtes Rigshospitalet og grove grøntsager og indgår dermed i den daglige øget østrogenreceptor β (ERβ)­produktion, øget E­cad­ 5) Endokrinologisk Afdeling, Odense kost. IF findes primært i sojabønner både i ukonjugeret herin og mindsket transforming growth factor­ β, og det Universitetshospital form (aglykoner) og som glykosidkonjugater.
    [Show full text]
  • Hormone Therapy for Sexual Function in Perimenopausal and Postmenopausal Women (Review)
    Hormone therapy for sexual function in perimenopausal and postmenopausal women (Review) Nastri CO, Lara LA, Ferriani RA, Rosa-e-Silva ACJS, Figueiredo JBP, Martins WP This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2013, Issue 6 http://www.thecochranelibrary.com Hormone therapy for sexual function in perimenopausal and postmenopausal women (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 5 OBJECTIVES ..................................... 6 METHODS ...................................... 6 RESULTS....................................... 9 Figure1. ..................................... 10 Figure2. ..................................... 12 Figure3. ..................................... 13 Figure4. ..................................... 15 Figure5. ..................................... 17 Figure6. ..................................... 19 Figure7. ..................................... 20 Figure8. ..................................... 22 ADDITIONALSUMMARYOFFINDINGS . 23 DISCUSSION ..................................... 25 AUTHORS’CONCLUSIONS . 27 ACKNOWLEDGEMENTS . 27 REFERENCES ..................................... 27 CHARACTERISTICSOFSTUDIES . 36 DATAANDANALYSES. 77 Analysis 1.1. Comparison
    [Show full text]
  • Washington, Dc September 21-24, 2011
    ABSTRACT BOOK 22ND ANNUAL MEETING Gaylord National on the Potomac WASHINGTON, DC SEPTEMBER 21-24, 2011 Also includes: • Disclosures for all presenters • Speakers’ learning objectives and recommended reading What happens in DC doesn’t have to stay in DC The webcast of the 2011 NAMS Annual Meeting lets you take advantage of the meeting’s educational riches year-round, at your convenience. If you miss part of the meeting or just want to revisit some sessions, this free on-demand webcast is your answer. The webcast will capture all plenary sessions as well as the Pre-Meeting Symposium and let you select individual presentations for targeted viewing. It will be freely available to all through September 15, 2012. It’s a great way to reinforce your learning at your leisure and according to your schedule. The free webcast will be posted soon after the meeting on the NAMS website at: www.menopause.org/meetings/webcast.aspx Stay tuned for webcast launch announcements from NAMS via email blast and Facebook and Twitter postings. Photos used with permission from Microsoft 270 Webcast2011_PreLaunch_Sidebar.indd 1 8/16/11 9:43 AM Contents Key to Abstracts . 4 Invited Speakers’ Abstracts & Learning Objectives . 7 Scientific Session Speakers’ Abstracts . 32 Basic Science Poster Presentations . 40 Clinical Poster Presentations . 44 Disclosure Statement . 67 Key to Disclosures . 68 Disclosures . 69 Invited Speakers’ Recommended Reading . 73 Call for Abstracts 2012 Annual Meeting . Inside Back Cover 3 Key to Abstracts Invited Speakers’ Abstracts Scientific Session Speakers’ Abstracts Speakers Page # Speakers Page # David F . Archer, MD, NCMP . 19 Susan E . Appt, DVM .
    [Show full text]
  • Alternatives to HRT for the Management of Symptoms of the Menopause
    Alternatives to HRT for the Management of Symptoms of the Menopause Scientific Impact Paper No. 6 September 2010 Alternatives to HRT for the Management of Symptoms of the Menopause This is the second edition of this Opinion Paper, which was originally published in 2006. 1. Background Despite recent encouraging data regarding the safety of traditional hormone replacement therapy (HRT), women and their primary care practitioners continue to be concerned about the purported risks, particularly to the breasts and cardiovascular system. This concern has fuelled continued interest in alternatives to HRT for the management of vasomotor symptoms. The choice of treatment remains confusing and the evidence for efficacy and safety for many of these preparations remains limited. There are a few exceptions where more rigorous randomised trials have been performed in recent years. This Scientific Advisory Committee paper, an update of the publication from four years ago, aims to provide the reader with state-of-the-art knowledge on alternatives to HRT for the management of menopausal symptoms. 2. Lifestyle measures There is some evidence that women who are more active tend to suffer less from the symptoms of the menopause.1 However, evidence from randomised controlled trials concerning the effects of aerobic exercise on vasomotor and other menopausal symptoms is limited.2 The evidence suggests that aerobic exercise can improve psychological health and quality of life in vasomotor symptomatic women. In addition, several randomised controlled trials of middle-aged/menopausal-age women have found that aerobic exercise can result in significant improvements in several common menopause-related symptoms (e.g.
    [Show full text]
  • Tofupill Lacks Peripheral Estrogen-Like Actions in the Rat Reproductive Tract
    Reproductive Toxicology 20 (2005) 261–266 Tofupill lacks peripheral estrogen-like actions in the rat reproductive tract Martha V. Oropeza a, Sandra Orozco b,Hector´ Ponce c, Mar´ıa G. Campos a,∗ a Medical Research Unit in Pharmacology, National Medical Center SXXI, IMSS, Mexico City, Mexico b Medical Research Unit in Neurological Diseases, Specialties Hospital, National Medical Center SXXI, IMSS, Mexico City, Mexico c Universidad Autonoma del Estado de Hidalgo, Campus Ciudad Sahagun, Mexico Received 6 May 2004; received in revised form 16 January 2005; accepted 14 February 2005 Abstract Objective: The objective of this study was to evaluate the estrogenic effect of phytoestrogens contained in a commercial food supplement (Tofupill) on the reproductive tract of ovariectomized rats. Methods: Food supplement (3.4 or 10.2 mg/kg) and conjugated equine estrogens (CEE, 31 or 100 ␮g/kg) were orally administered, daily during 14 days to ovariectomized rats. At the end of treatment, the following determinations were done: dry and wet uterine weight, vaginal epithelium condition, and uterine serotonin-induced contractile response. A group treated with 17␤-estradiol was included as control for serotonin-induced contractile response. Results: Food supplement did not display clear estrogenic effects on vaginal epithelium, uterine weight or myometrial sensitivity to serotonin, whereas high doses of conjugated equine estrogens showed estrogenic action. Conclusions: The present data showed that Tofupill displayed a lower estrogenic effect than conjugated equine estrogens, which are one of the most commonly used hormone replacement therapy for postmenopausal women. However, further studies are needed to evaluate the risk associated to the use of Tofupill as an alternative to hormone replacement therapy for postmenopausal women.
    [Show full text]
  • Dt56a, a Non-Hormonal Botanical Therapy, As 1St Line Treatment for Menopausal Symptoms
    DT56a, a non-hormonal Botanical Therapy, as 1st Line Treatment for Menopausal Symptoms Prof. Andrea R. Genazzani, MD, PhD, HcD, FRCOG, FACOG President of the International Society of Gynecological Endocrinology (ISGE) President of the European Society of Gynecology (ESG) General Secretary of the International Academy of Human Reproduction (IAHR) University of Pisa, Italy The Dynamics of Estrogen & Estrogen Receptors . Estrogen regulates the growth, development, and physiology of the reproductive system . The biological functions of estrogen are mediated by binding to Estrogen Receptors (ER) which our found in most of the female body’s tissues . In each target tissue the ERs have specific characteristics, providing a certain response within the tissue Bond of Estrogen to Estrogen Receptors . Estrogen serves as the main “building blocks” for ER response, however in most sites it does not work on its own . The specific biochemical environment is formed through co-activators that are found in the different tissues . The bondage of estrogen with the specific co-activator acts as a catalyst in the evolvement of the response according to the age and circumstantial needs of the woman at a specific time: . Puberty / Pregnancy… Reproductive Stage • Normal Estrogen Levels • Contributing Biochemical Catalysts Co-A • Co-activators (Co-A) E2 + co-A • ER response to E2+Co-A – agonistic effect System is Balanced Attachment to ER- agonistic response Estrogen & ER From Pre-Menopause Onwards . The decline in ovarian function at menopause leads to: . Change
    [Show full text]
  • Efficacy and Safety of Dt56a (Femarelle) Compared to Hormone Therapy in Greek Postmenopausal Women
    Labos G., Trakakis E. et al Efficacy and safety of DT56a (Femarelle) compared to hormone therapy in Greek postmenopausal women. J Endocrinol. Invest. 2013; e-pub ahead of print. Efficacy and safety of DT56a (Femarelle) compared to hormone therapy in Greek postmenopausal women George Labos1, Eftixios Trakakis1, Paraskevi Pliatsika2, Areti Augoulea2, Vassilis Vaggopoulos1, George Basios1, George Simeonidis1, Maria Creatsa2, Andreas Alexandrou2, Zoi Iliodromiti2, Dimitrios Kassanos1, Irene Lambrinoudaki2 1 3rd Department of Obstetrics and Gynecology, University of Athens, Attikon Hospital 2 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital Short title: Effect of a unique soybean extract (DT56a) in postmenopausal women Words in abstract: 248 Words in Manuscript: 3,277 Tables: 4 Figures: 1 Corresponding author: Assoc. Professor Irene Lambrinoudaki 27, Themistokleous street, Dionysos GR614578, Athens, Greece Tel: +30 210 6410944 Fax: +30 210 6410325 e-mail: [email protected] 2 Labos G., Trakakis E. et al Efficacy and safety of DT56a (Femarelle) compared to hormone therapy in Greek postmenopausal women. J Endocrinol. Invest. 2013; e-pub ahead of print. ABSTRACT Background: Hormone therapy is the treatment of choice for the alleviation of menopausal symptoms; concerns, however, about its concomitant long term health risks have limited its use. DT56a (Femarelle) is a unique enzymatic isolate of soybeans. The purpose of our study was to evaluate the efficacy and safety of DT56a, compared to hormone therapy (HT), in symptomatic postmenopausal women. Subjects and Methods: 89 postmenopausal women were studied prospectively. Women with climacteric symptoms were randomly assigned to receive either DT56a (n=27) or oral low dose continuous combined HT (n=26).
    [Show full text]