DOCSLIB.ORG

Potential Mechanisms of Action of Kaempferol in the Prevention

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Potential Mechanisms of Action of Kaempferol in the Prevention POTENTIAL MECHANISMS OF ACTION OF KAEMPFEROL IN THE PREVENTION OF BREAST CANCER A Dissertation Presented to the Faculty of the Graduate School of Cornell University in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Jinzhou Li August 2015 © 2015 Jinzhou Li POTENTIAL MECHANISMS OF ACTION OF KAEMPFEROL IN THE PREVENTION OF BREAST CANCER Jinzhou Li, Ph.D. Cornell University 2015 Epidemiological studies have shown that regular consumption of fruits and vegetables could reduce the risk of cancer. Phytochemicals in fruits and vegetables have been suggested to be responsible for their health benefits. Asparagus and one of its major phytochemical, Kaempferol, have been reported to have anti-cancer activities. However, the mechanisms of the anticancer activities are not completely understood. Seven varieties of asparagus were compared for their antioxidant content, antioxidant activities, and anticancer activities. The results showed that asparagus are rich in phenolic and flavonoids. They also show antioxidant activities in chemical assays and in vitro assays. Asparagus possesses potent anticancer abilities in inhibiting proliferation of HepG2 human liver cancer cells. Among the different varieties, Apollo has the highest phenolic content, flavonoid content, antioxidant activities, and anticancer activities. We further studied kaempferol’s effects in breast cancer cells growth and metastasis. The anti-proliferative activity and cytotoxicity of kaempferol against MCF-7 human breast cancer cells were measured by the methylene blue assay. All the key proteins regulating cell proliferation through signaling transduction pathways were determined by Western blot assay. Kaempferol exhibited potent anti-proliferative activity against MCF-7 human breast cancer cells in a dose-dependent manner. No cytotoxicity was observed at the concentrations tested. Kaempferol significantly down-regulated expression of PCNA, CDK-4, Cyclin D1, and estrogen-receptor alpha, and up-regulated expression of p21, and p-p53 in MCF-7 human breast cancer cells in dose-dependent manners when compared to the control. Kaempferol specifically inhibited estradiol-induced cell proliferation in MCF-7 human breast cancer cells. Kaempferol also exhibited anti-proliferative activity against MDA-MB-231 human breast cancer cells in a dose-dependent manner. No cytotoxicity was observed at concentrations below 100 µM in MDA-MB-231 cells. Kaempferol significantly inhibited MDA-MB-231 human breast cancer cell migration observed by scratch assay. The activity of MMP-2, a critical enzyme for cancer cell metastasis, was assessed by zymography assay, and it was dramatically inhibited in a dose-dependent manner. Cell transformations studied by soft agar assay were also inhibited by kaempferol in a dose-dependent manner. In conclusion, we demonstrated that asparagus and kaempferol exhibited anticancer activities through effects on antioxidant activity, cancer cell proliferation, migration and metastasis. These data are important in understanding the protective effects of fruits and vegetables in the prevention of breast cancer. BIOGRAPHIC SKETCH Jinzhou Li was born in Yongnian, Hebei, China. Currently he is a Ph.D. candidate in Dr. Rui Hai Liu’s lab studying health benefits of phytochemicals in fruits and vegetables. He received his B.E. degree in Food Science and Engineering at Tianjin University in China in 2005. He received his M.S. degree in Human Nutrition at Columbia University in 2010. Prior to join the PhD program, Jinzhou has interned in Nanjing University Organic Food Research and Development Institute with Professor Wenlong He to study organic agriculture practice and policy. During his stay at Cornell, Jinzhou joined the IFT product development team and won the second place in final 2011. Jinzhou had co-captained several trips for Cornell students doing project in China organized by smart program. He also worked as a vice president in Cornell China Association for the Promotion of Agriculture. He has helped organize the Cornell-China forum in 2012 and 2014. He also helped his family business set up a branch in the US, and successfully marketed the products to US market. Jinzhou’s interest in Food Science comes from his experience in his family food business, which is doing organic vegetables and fruits growing, processing, and exporting. Involved in the family business these years, Jinzhou feels amazed that running the business can make profit and take the social responsibility at the same time. He also realized that only with a wide knowledge about food science and technology, the company can sustainably develop for a long time. Now as Jinzhou is getting his PhD degree, he is excited to make full use of his knowledge gained at Cornell to develop the business and help more people. ACKNOWLEDGEMENT First I would like to thank the unconditional love from my family, without their support I cannot reach this far. I want to thank my mother, my father, my wife, and my babies. They give me courage and motivation. Because of them, I become fearless when I face challenge. I know no matter what happen to me, they will be there with me. Their love brings happiness to my life and work. I want to thank my lab mates. They have helped me a lot for my research and PhD life. I want to thank Xue, Ran, Xinbo, Dan, Gu, Hao, Ningbo, Caroline, Hongyu, Xi and all other people in my lab. They give me helpful advices for my project. We discuss to solve the problem together. They are all talent people and inspired me. I really enjoyed the five years when I stayed with them. I want to thank my friends, who always get my back. My friends Sen, Jie, Boteng and others are always there when I want to share my happiness and sadness with. And when I need some help, they just do it without any hesitate. I want to thank my aunt; she helps us taking care of the babies, so life will not be too stressful. I want to thank the people who have helped my experiment. Sungsoo Yoo and Zeping Zhao showed me some experiment techniques step by step with patience. I would like to thank Professor Jane Pleasant, Jennifer nelson, and Brian Henehan for help me edit my dissertation. There are also many other people gave me unreserved advices for my project even they do not know me. I want to thank my minor advisor Dr. Miller and Dr. Gomez. They not only gave me very helpful advices on my minor field, but also very patiently discuss with me about my career path. In the end, I want give my appreciation to my advisor Dr. Rui Hai Liu and his wife Dr. Li. Dr, Liu has given me huge understanding and flexibility. Without his support I cannot harvest so many things in my study, family, and business. I have learned a lot from him. Dr. Li is like my family member. My heart always feels warmth when I stay in Ithaca. Thank all the people in my life. TABLE OF CONTENTS CHAPTER ONE INTRODUCTION .................................................................................................. 1 1.1 Fruits and vegetables in cancer prevention ........................................................................................ 1 1.1.1 Cancer background and statistics ..................................................................................................... 1 1.1.2 Consumption of fruits and vegetables for cancer prevention: epidemiology evidence.......... 2 1.2 Phytochemicals for cancer prevention ................................................................................................ 3 1.2.1 Phytochemicals ..................................................................................................................................... 3 1.2.2 Intake in the US, bioavailability and absorption ............................................................................ 4 1.2.3 Different phytochemicals for cancer prevention ........................................................................... 5 1.2.4 Phytochemical synergy and whole foods benefits for cancer prevention ............................... 16 1.3 Asparagus and its health benefits ...................................................................................................... 19 1.3.1 General introduction ......................................................................................................................... 19 1.3.2 Asparagus nutrition composition and phytochemicals .............................................................. 20 1.3.3 Bioactive compounds of asparagus ................................................................................................. 22 1.4 Kaempferol ........................................................................................................................................... 24 1.4.1 Chemistry of kaempferol ................................................................................................................... 24 1.4.1.1 Structure and derivatives ................................................................................................................ 24 1.4.2 Anticancer activities of Kaempferol................................................................................................ 28 1.5 Potential mechanisms of action .......................................................................................................... 30 1.5.1 Antioxidant effects and Redox regulation ..................................................................................... 30 1.5.2 Antiproliferation and cell cycle arrest ..........................................................................................
Load more

Recommended publications
  • Role of Synthetic and Natural Inhibitors
    Biochimica et Biophysica Acta 1845 (2014) 136–154 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbacan Review Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors Kodappully Sivaraman Siveen a,1, Sakshi Sikka a,b,1,RohitSuranaa,b, Xiaoyun Dai a, Jingwen Zhang a, Alan Prem Kumar a,b,c,d, Benny K.H. Tan a, Gautam Sethi a,b,⁎, Anupam Bishayee e,⁎⁎ a Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore b Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore c School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia, Australia d Department of Biological Sciences, University of North Texas, Denton, TX, USA e Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA, USA article info abstract Article history: Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors Received 15 August 2013 that mediate intracellular signaling that is usually generated at cell surface receptors and thereby transmit it to Received in revised form 24 December 2013 the nucleus. Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human Accepted 27 December 2013 tumors, including hematological malignancies (leukemias, lymphomas, and multiple myeloma) as well as Available online 2 January 2014 diverse solid tumors (such as head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers). There is strong evidence to suggest that aberrant STAT3 signaling promotes initiation and progression of human Keywords: STAT3 cancers by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis.
    [Show full text]
  • Potential of Guggulsterone, a Farnesoid X Receptor Antagonist, In
    Exploration of Targeted Anti-tumor Therapy Open Access Review Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer Sosmitha Girisa , Dey Parama , Choudhary Harsha , Kishore Banik , Ajaikumar B. Kunnumakkara* Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India *Correspondence: Ajaikumar B. Kunnumakkara, Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India. [email protected]; [email protected] Academic Editor: Gautam Sethi, National University of Singapore, Singapore Received: August 8, 2020 Accepted: September 14, 2020 Published: October 30, 2020 Cite this article: Girisa S, Parama D, Harsha C, Banik K, Kunnumakkara AB. Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer. Explor Target Antitumor Ther. 2020;1:313-42. https://doi.org/10.37349/ etat.2020.00019 Abstract Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains a serious concern due to the limitations associated with currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. The importance of medicinal plants as primary healthcare has been well-known from time immemorial against various human diseases, including cancer. Commiphora wightii that belongs to Burseraceae family is one such plant which has been used to cure various ailments in traditional systems of medicine.
    [Show full text]
  • Cancer Risk an Unfortunate Truth
    Breast Cancer May 2013 Issue 30 RO F ACTs, MYTHs, VI N Cancer Risk N M an E E CHOICEs N and T unfortunate(excerpts from truth P Anand et al, 2008) GENES diet is linked to cancer deaths in as many as 70% of colorectal cancer cases. How diet contributes to cancer is not fully understood. Most carcinogens that are ingested, such as nitrates, nitrosamines, pesticides, and dioxins, come from food or food additives or from cooking. INDEX Various phytochemicals have been identified in RESEARCH PARTNERS fruits, vegetables, spices, and grains that exhibit chemopreventive potential, and numerous studies Cancer risk.....................................1 have shown that a proper diet can help protect Addictive junk food......,..................7 against cancer. Although all cancers are a result of multiple COMMUNITY PARTNERS mutations, these mutations are due to interaction with the environment. Coffee Talks..................................8 Sunchokes.......................................9 Up to 10% of total cancer cases may be Crossword puzzle.........................10 induced by radiation, both ionizing and nonionizing, typically from radioactive substances and ultraviolet Nutrient Density............................12 (UV), pulsed electromagnetic fields. Yoga Pose......................................13 Junk food and brain activity......14 Heavy consumption of red meat is a risk factor Just 4 fun.......................................15 for colorectal, prostate, bladder, breast, gastric, pancreatic, and oral cancers. Contacts Inflammation may
    [Show full text]
  • Switchgrass Metabolomics Reveals Striking Genotypic And
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.01.127720; this version posted June 1, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Short title: Specialized Metabolite Diversity 2 3 Title: Switchgrass metabolomics reveals striking genotypic and developmental differences in 4 saponins 5 6 Author for contact: 7 Robert Last, Department of Biochemistry and Molecular Biology, Michigan State University, 8 603 Wilson RD, East Lansing, MI 48823 USA, email: [email protected], telephone: (517) 432- 9 3278, ORCID ID: 0000-0001-6974-9587 10 11 Xingxing Lia, b, A. Daniel Jonesa, b and Robert L. Lasta, b, c * 12 13 aDepartment of Biochemistry and Molecular Biology, Michigan State University, MI 48824; 14 b DOE Great Lakes Bioenergy Research Center, Michigan State University, MI 48824. 15 cDepartment of Plant Biology, Michigan State University, MI 48824 16 17 ORCID ID: 0000-0002-7725-0329 (X. L.); 0000-0002-7408-6690 (A.D.J.); 0000-0001-6974- 18 9587 (R.L.L.) 19 20 One sentence summary: Switchgrass structurally diverse steroidal saponins and phenolics vary in 21 abundance and structures in a tissue- and ecotype-specific manner. 22 23 *Corresponding author: [email protected] 24 25 List of author contributions: 26 X.L. Conceived and performed research, created figures and tables and wrote manuscript 27 A.D.J. Conceived of experimental approaches, provided technical input, reviewed data, edited 28 manuscript 29 R.L.L Conceived of experimental approaches, wrote and edited manuscript 30 31 Funding information: 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.01.127720; this version posted June 1, 2020.
    [Show full text]
  • Role of Progestogen in Hormone Therapy for Postmenopausal Women: Position Statement of the North American Menopause Society
    Menopause: The Journal of The North American Menopause Society Vol. 10, No. 2, pp. 113-132 DOI: 10.1097/01.GME.0000055879.45975.92 © 2003 The North American Menopause Society ࠗϱ Text printed on acid-free paper. POSITION STATEMENT Role of progestogen in hormone therapy for postmenopausal women: position statement of The North American Menopause Society ABSTRACT Objective: To create an evidence-based position statement regarding the role of progestogen in postmenopausal hormone therapy (estrogen plus a progestogen, or EPT) for the management of menopause-related symptoms. Design: NAMS followed the general principles established for evidence-based guidelines to create this document. Clinicians and researchers acknowledged to be experts in the field of post- menopausal hormone therapy were enlisted to review the evidence obtained from the medical literature and develop a position statement for approval by the NAMS Board of Trustees. Results: The primary role of progestogen in postmenopausal hormone therapy is endometrial protection. Unopposed estrogen therapy (ET) is associated with a significantly increased risk of endometrial hyperplasia and adenocarcinoma. Adding the appropriate dose and duration of pro- gestogen to ET has been shown to lower that risk to the level found in never-users of ET. The clinical goal of progestogen in EPT is to provide endometrial protection while maintaining estrogen benefits and minimizing progestogen-induced side effects, particularly uterine bleeding. EPT dis- continuance correlates with uterine bleeding—women with more days of amenorrhea have higher rates of continuance. All US Food and Drug Administration-approved progestogen formulations will provide endometrial protection if the dose and duration are adequate.
    [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]
  • WHO Monographs on Selected Medicinal Plants. Volume 3
    WHO monographs on WHO monographs WHO monographs on WHO published Volume 1 of the WHO monographs on selected medicinal plants, containing 28 monographs, in 1999, and Volume 2 including 30 monographs in 2002. This third volume contains selected an additional collection of 32 monographs describing the quality control and use of selected medicinal plants. medicinal Each monograph contains two parts, the first of which provides plants selected medicinal plants pharmacopoeial summaries for quality assurance purposes, including botanical features, identity tests, purity requirements, Volume 3 chemical assays and major chemical constituents. The second part, drawing on an extensive review of scientific research, describes the clinical applications of the plant material, with detailed pharmacological information and sections on contraindications, warnings, precautions, adverse reactions and dosage. Also included are two cumulative indexes to the three volumes. The WHO monographs on selected medicinal plants aim to provide scientific information on the safety, efficacy, and quality control of widely used medicinal plants; provide models to assist Member States in developing their own monographs or formularies for these and other herbal medicines; and facilitate information exchange among Member States. WHO monographs, however, are Volume 3 Volume not pharmacopoeial monographs, rather they are comprehensive scientific references for drug regulatory authorities, physicians, traditional health practitioners, pharmacists, manufacturers, research scientists
    [Show full text]
  • Progesterone in Peri- and Postmenopause: a Review Progesteron in Der Peri-Und Postmenopause – Ein Überblick
    Review 995 Progesterone in Peri- and Postmenopause: A Review Progesteron in der Peri-und Postmenopause – ein Überblick Author P.-A. Regidor1,2 Affiliations 1 Praxis für Frauenheilkunde, München 2 Velvian GmbH, Ismaning Key words Abstract Zusammenfassung l" hormone therapy ! ! l" progesterone Around 14.5 million peri- and postmenopausal Aktuell leben 14,5 Millionen peri- und post- l" menopause women currently live in Germany. Moreover, ap- menopausale Frauen in Deutschland. Gleichzeitig l" menopausal symptoms proximately 450 000 women, each with a life ex- gibt es ungefähr 450 000 neue menopausale Frau- Schlüsselwörter pectancy of around 85 years, reach menopause en pro Jahr, die eine Lebenserwartung von bis zu l" Hormontherapie every year in Germany. The challenge is therefore 85 Jahren haben. Die Herausforderung besteht l" Progesteron to find a therapy with few side effects which daher in einer möglichst nebenwirkungsarmen l" Menopause could improve the quality of life of women with Therapie bei den Frauen mit menopausalen Be- l" Wechseljahresbeschwerden menopausal symptoms. The aim of hormone schwerden, um einer Verschlechterung ihrer Le- therapy (HT) is to remedy hormone deficiencies bensqualität entgegenzuwirken. Ziel einer Hor- using substances that offer the best trade-off montherapie (HT) sollte die Behebung des Hor- between benefits and risks. This is where proges- monmangels sein, wobei Substanzen mit dem terone has a new and important role to play. Pro- besten Nutzen-Risiko-Profil eingesetzt werden Deutschsprachige gesterone is one of the most important gestagens. sollten. Hier spielt Progesteron eine neue und Zusatzinformationen Biologically effective progesterone formulations wichtige Rolle. Beim Progesteron handelt es sich online abrufbar unter: created with micronization techniques have been um den wichtigsten Vertreter der Gestagene.
    [Show full text]
  • Thesis Rests with Its Author
    University of Bath PHD The biotransformation of diosgenin and its precursors extracted from Trigonella foenumgraecum L. seed. Saunders, Roger Award date: 1982 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 08. Oct. 2021 THE BIOTRANSFORMATION OF DIOSGENIN AND ITS PRECURSORS EXTRACTED FROM TRIGONELLA FOENUMGRAECUM L. SEED Submitted by Roger Saunders for the degree of Doctor of Philosophy of the University of Bath 1982 COPYRIGHT "Attention is drawn to the fact that copyright of this thesis rests with its author. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without the prior written consent of the author." "This thesis may not be consulted, photocopied or lent to other libraries without the permission of the author for 5 years from the date of acceptance of the thesis".
    [Show full text]
  • Ep 1039874 B1
    Europäisches Patentamt *EP001039874B1* (19) European Patent Office Office européen des brevets (11) EP 1 039 874 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: A61K 7/06, A61K 38/16, of the grant of the patent: A61K 38/17 08.09.2004 Bulletin 2004/37 (86) International application number: (21) Application number: 98964084.2 PCT/US1998/026955 (22) Date of filing: 18.12.1998 (87) International publication number: WO 1999/032072 (01.07.1999 Gazette 1999/26) (54) COMPOSITIONS AND METHODS FOR TREATMENT OF ALOPECIA ZUSAMMENSETZUNGEN UND VERFAHREN ZUR BEHANDLUNG VON ALOPEZIE COMPOSITIONS ET METHODES DE TRAITEMENT DE L’ALOPECIE (84) Designated Contracting States: (74) Representative: Gowshall, Jonathan Vallance AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU FORRESTER & BOEHMERT MC NL PT SE Pettenkoferstrasse 20-22 80336 München (DE) (30) Priority: 19.12.1997 US 994347 (56) References cited: (43) Date of publication of application: WO-A-97/18239 04.10.2000 Bulletin 2000/40 • DATABASE WPI Week 8750 Derwent (73) Proprietor: Mann, Morris A. Publications Ltd., London, GB; AN 87-350996 Glendale, AZ 85308 (US) XP002099776 & JP 62 252711 A (TAMAKI), 4 November 1987 (72) Inventor: Mann, Morris A. Glendale, AZ 85308 (US) Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid.
    [Show full text]
  • Post-Menopausal Oestrogen– Progestogen Therapy
    POST-MENOPAUSAL OESTROGEN– PROGESTOGEN THERAPY 1. Exposure Post-menopausal oestrogen–progestogen therapy involves administration of the oestro- gens described in the monograph on ‘Post-menopausal oestrogen therapy’ accompanied by a progestogen or progesterone to women around the time of the menopause, primarily for the treatment of menopausal symptoms but also for the prevention of conditions that become more common after the menopause, such as osteoporosis and ischaemic heart disease. The progestogen can be administered orally or transdermally and either conti- nuously or at various intervals. Intermittent progestogen administration causes withdrawal uterine bleeding, while continuous therapy generally does not. In ‘peri-menopausal hormo- nal therapy’, the components are not specified but are usually oestrogen with or without a progestogen. Annex 2 (Table 5) gives examples of brands of post-menopausal oestrogen– progestogen therapy. Progestogens that can be given in combination with the oestrogens are listed in Annex 1, with their constituents, doses, routes of administration and the names of some countries in which the brands are available; Annex 1 also gives the chemical formulae and some information on indications for use. 1.1 Historical overview The earliest forms of hormones used for the treatment of ovarian failure or after oopho- rectomy were natural extracts of ovarian tissue, placenta and urine from pregnant women and thus contained both oestrogen and progestogen, as well as other substances. Crystalline progesterone was first identified in 1934, and shortly afterwards experimental treatment of women with injected oestrogen and progesterone began (Hirvonen, 1996). In the decades that followed, however, menopausal symptoms were treated mainly with oestrogen alone rather than with combined oestrogen–progestogen therapy.
    [Show full text]
  • Residual Ovarian Activity During Oral Contraception
    RESIDUAL OVARIAN ACTIVITY DURING ORAL CONTRACEPTION RESTERENDE OVARIUM ACTIVITEIT TUDENS ORALE ANTICONCEPTIE RESIDUAL OVARIAN ACTIVITY DURING ORAL CONTRACEPTION RESTERENDE OVARIUM ACTIVITEIT TIJDENS ORALE ANTICONCEPTIE PROEFSCHRIFT TER VERKRIJGING VAN DE GRAAD VAN DOCTOR AAN DE ERASMUS UNIVERSITEIT ROTTERDAM OP GEZAG VAN DE RECTOR MAGNIFICUS PROF.DR.IR. J.H. van BEMMEL EN VOLGENS BESLUIT VAN HET COLLEGE VOOR PROMOTIES DE OPENBARE VERDEDIGING ZAL PLAATSVINDEN OP WOENSDAG 5 FEBRUARI2003 OM 15.45 UUR DOOR ARNE MARIUS VAN HEUSDEN Geboren te BILTHOVEN The work presented in this thesis was performed in the Division of Reproductive Medicine (Head Prof. Dr. B.C.J.M. Fauser), Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, the Netherlands. The author and studies presented in this thesis were supported by 'Stichting Voortplantingsgeneeskunde Rotterdam' and research grants from Organon International and Wyeth Nederland BV. Most of this PhD manuscript has been published previously and has been reproduced with permission from the publishers: van Heusden,A.M. and Fauser,B.C.J.M. (1996) FSH and ovarian function during combined oral contraceptive regimens. In Fauser,B.C.J.M. (ed), FSH action and intraovarian regulation. The Parthenon Publishing Group, London, pp. 211-221. Fauser,B.C.J.M. and van Heusden,A.M. (1997) Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocrine Reviews, 18, 71-106. van Heusden,A.M. and Fauser,B.C.J.M. (1999) Activity of the pituitary-ovarian axis in the pill­ free interval during use of low-dose combined oral contraceptives. Contraception, 59, 237-243. van Heusden,A.M., Killick,S.R., Coelingh Bennink,H.J.
    [Show full text]