Androgens and Bone

Total Page:16

File Type:pdf, Size:1020Kb

Androgens and Bone 0163-769X/04/$20.00/0 Endocrine Reviews 25(3):389–425 Printed in U.S.A. Copyright © 2004 by The Endocrine Society doi: 10.1210/er.2003-0003 Androgens and Bone DIRK VANDERSCHUEREN, LIESBETH VANDENPUT, STEVEN BOONEN, MARIE K. LINDBERG, ROGER BOUILLON, AND CLAES OHLSSON Laboratory for Experimental Medicine and Endocrinology (D.V., L.V., S.B., R.B.), and Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine (S.B.), Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; and Division of Endocrinology, Department of Internal Medicine (M.K.L., C.O.), Sahlgrenska University Hospital, SE-41345 Go¨teborg, Sweden Loss of estrogens or androgens increases the rate of bone chondral bone formation, whereas they induce epiphyseal clo- remodeling by removing restraining effects on osteoblasto- sure at the end of puberty. Androgen action on the growth genesis and osteoclastogenesis, and also causes a focal imbal- plate is, however, clearly mediated via aromatization in es- ance between resorption and formation by prolonging the trogens and interaction with ER␣. Androgens increase radial lifespan of osteoclasts and shortening the lifespan of osteo- growth, whereas estrogens decrease periosteal bone forma- blasts. Conversely, androgens, as well as estrogens, maintain tion. This effect of androgens may be important because bone cancellous bone mass and integrity, regardless of age or sex. strength in males seems to be determined by relatively higher Although androgens, via the androgen receptor (AR), and es- periosteal bone formation and, therefore, greater bone dimen- trogens, via the estrogen receptors (ERs), can exert these ef- sions, relative to muscle mass at older age. Experiments in fects, their relative contribution remains uncertain. Recent mice again suggest that both the AR and ER␣ pathways are studies suggest that androgen action on cancellous bone de- involved in androgen action on radial bone growth. ER␤ may pends on (local) aromatization of androgens into estrogens. mediate growth-limiting effects of estrogens in the female but However, at least in rodents, androgen action on cancellous does not seem to be involved in the regulation of bone size in bone can be directly mediated via AR activation, even in the males. absence of ERs. In conclusion, androgens may protect men against osteo- Androgens also increase cortical bone size via stimulation porosis via maintenance of cancellous bone mass and expan- of both longitudinal and radial growth. First, androgens, like sion of cortical bone. Such androgen action on bone is medi- estrogens, have a biphasic effect on endochondral bone for- ated by the AR and ER␣.(Endocrine Reviews 25: 389–425, 2004) mation: at the start of puberty, sex steroids stimulate endo- I. Introduction A. The rodent as a model for the study of skeletal andro- II. General Aspects of Androgen Action gen action A. Androgen metabolism B. Skeletal consequences of gonadectomy in rodents B. Mechanism of action of androgens C. Skeletal effects of androgen replacement in rodents C. Nongenomic effects of sex steroids D. Skeletal effects of selective modulation of estrogen and D. Expression of androgen and estrogen receptors in the androgen action in rodents skeleton E. Skeletal effects of selective manipulation of androgen III. Effects of Androgens in Vitro on Skeletal Cells and estrogen action in transgenic mice A. Growth plate chondrocytes F. Skeletal effects of androgen resistance in rodents B. Osteoblasts/osteocytes G. Animal data in support of a dual mode of androgen C. Osteoclasts action on the skeleton IV. Effects of Androgens on the Rodent Skeleton V. Indirect Mechanisms of Action of Androgens with Skeletal Implications A. Androgens, body growth, and body composition Abbreviations: AF, Activation function; ANDRKO, AR knockout; AR, androgen receptor; ArKO, aromatase knockout; BERKO, ER␤ knockout; B. Androgens and the GH-IGF-I axis BMD, bone mineral density; cAIS, complete androgen insensitivity syn- VI. Effects of Androgens on the Human Skeleton drome; DERKO, double ER knockout; DHEA, dehydroepiandrosterone; A. Skeletal consequences of castration, male hypogonad- DHEA-S, DHEA sulfate; DHT, 5␣-dihydrotestosterone; DPA, dual pho- ism, and androgen resistance in men ton absorptiometry; DXA, dual energy x-ray absorptiometry; E2, estra- B. Skeletal effects of androgens in women ␣ ␤ ␤ diol; ER, estrogen receptor; ERKO, ER knockout; 17 -HSD, 17 -hy- C. Skeletal effects of androgen replacement droxysteroid dehydrogenase; IGFBP, IGF binding protein; IHH, isolated hypogonadotropic hypogonadism; KS, Klinefelter’s syndrome; LBD, D. Skeletal effects of selective modulation of androgen and ligand-binding domain; OPG, osteoprotegerin; orch, orchidectomized or estrogen action in men orchidectomy; ovx, ovariectomized or ovariectomy; PCOS, polycystic VII. General Conclusions ovary syndrome; pQCT, peripheral QCT; QCT, quantitative computed tomography; RANK, receptor activator of nuclear factor ␬B; RANKL, RANK ligand; SERM, selective ER modulator; SPA, single photon absorp- I. Introduction tiometry; T, testosterone; Tfm, testicular feminized male. Endocrine Reviews is published bimonthly by The Endocrine Society NDROGENS INDUCE MALE sexual differentiation (http://www.endo-society.org), the foremost professional society serving A before birth and sexual maturation during puberty; in the endocrine community. adult men, they maintain the function of the male genital 389 Downloaded from edrv.endojournals.org on September 19, 2005 390 Endocrine Reviews, June 2004, 25(3):389–425 Vanderschueren et al. • Androgens and Bone system, including spermatogenesis. However, the role of but this is due to a greater bone volume and not to a greater androgens in other target organs—including muscle tissue; volumetric density. The greater areal bone mineral density the cardiovascular, central nervous, and immune systems; (BMD) in males is thus only an artifact of the dual energy and bone—is less well-established (1). x-ray absorptiometry (DXA) software by expression of bone In the early 1940s, Albright and Reifenstein were among mass as projected areal (grams per square centimeter) instead the first to refer to the antiosteoporotic and anabolic prop- of true or volumetric density (grams per cubic centimeter). erties of androgens (2). From a public health perspective, In the current review, we will focus on the potential mech- osteoporosis is a greater problem in women than in men (3). anisms through which androgens may prevent bone loss, This explains why most research efforts to explore skeletal increase bone mass (size), and improve bone strength. effects of sex steroids have been devoted to estrogens. More- In this manuscript, in vitro, experimental animal data and over, androgens may be converted into estrogens via the clinical human data with respect to skeletal androgen action P450 aromatase enzyme complex and may therefore act as will be reviewed in an attempt to define the possible impact prohormones for estrogens. In this respect, there is increasing of androgen action [through the estrogen receptor (ER) and evidence that at least part of the effects of androgens in men AR pathways] on different aspects of skeletal homeostasis can be explained by their aromatization into estrogens (4, 5). during growth and aging. Recent clinical and experimental Epiphyseal closure at the end of puberty, for example, is now data have indeed provided evidence that at least some of the generally accepted to be estrogen-dependent in both genders skeletal androgen actions are not solely ER-dependent. Fur- (6). In recent years, a specific role of androgens in skeletal thermore, we will discuss potential indirect nonbone cell- homeostasis has even been questioned, although androgen mediated effects of androgens on the skeleton. receptors (ARs) in bone cells and AR-mediated actions on Finally, the potential clinical benefits of androgen replace- bone have been documented for more than a decade (7, 8). ment in the context of male hypogonadism as well as in The aim of this review is to address the question whether different patient groups will be discussed. Recent studies and how (through which receptors and/or pathways) an- have explored different modes of action of androgens via the drogens may affect bone strength and provide protection AR and ER pathways and may ultimately contribute to the against osteoporosis. The clinical relevance of this question potential use of selective AR or ER modulators in selected results from the recognition that, even in men, fractures due male target populations. to skeletal fragility represent a huge public health problem. Elderly men maintain cancellous bone integrity in com- parison with postmenopausal women, although their bone II. General Aspects of Androgen Action trabeculae become thinner. From a biomechanical perspec- A. Androgen metabolism tive, compromised bone strength in men is the result of gender-related differences in the loss of bone mass during Androgens are C-19 steroids secreted primarily from the aging and, even more importantly, in the accumulation of testes and the adrenals. The synthesis and metabolism of sex bone mass during childhood and adolescence (9) (Table 1). steroids have been extensively reviewed in several recent During puberty, men develop a bigger bone size than publications (4, 12). Therefore, we will just briefly mention women, due to increased periosteal apposition. In females, the major pathways to facilitate the interpretation of exper- on the other hand, estrogens
Recommended publications
  • (12) United States Patent (10) Patent No.: US 7,871,995 B2 Bunschoten Et Al
    US00787 1995 B2 (12) United States Patent (10) Patent No.: US 7,871,995 B2 Bunschoten et al. (45) Date of Patent: *Jan. 18, 2011 (54) DRUG DELIVERY SYSTEM COMPRISINGA (52) U.S. Cl. ....................................... 514/171; 514/182 TETRAHYDROXYLATED ESTROGEN FOR (58) Field of Classification Search ................. 514/171, USE IN HORMONAL CONTRACEPTION 514f182 See application file for complete search history. (75) Inventors: Evert Johannes Bunschoten, Heesch (NL); Herman Jan Tijmen Coelingh (56) References Cited Bennink, Driebergen (NL); Christian U.S. PATENT DOCUMENTS Franz Holinka, New York, NY (US) 3,440,320 A 4, 1969 Sackler et al. O O 3,797.494. A 3, 1974 Zaffaroni (73) Assignee: Pantarhei Bioscience B.V., Al Zeist 4,460.372 A 7/1984 Campbell et al. (NL) 4,573.996 A 3/1986 Kwiatek et al. 4,624,665 A 1 1/1986 Nuwayser (*) Notice: Subject to any disclaimer, the term of this 4,722,941 A 2f1988 Eckert et al. patent is extended or adjusted under 35 4,762,717 A 8/1988 Crowley, Jr. U.S.C. 154(b) by 1233 days. 4.937,238 A 6, 1990 Lemon 5,063,507 A 1 1/1991 Lindsey et al. This patent is Subject to a terminal dis- 5,130,137 A 7/1992 Crowley, Jr. claimer. 5,211,952 A 5/1993 Spicer et al. 5,223,261 A 6/1993 Nelson et al. 5,340,584 A 8/1994 Spicer et al. (21) Appl. No.: 10/478,357 5,340,585 A 8/1994 Pike et al. 1-1. 5,340,586 A 8, 1994 Pike et al.
    [Show full text]
  • Mifepristone
    1. NAME OF THE MEDICINAL PRODUCT Mifegyne 200 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 200-mg mifepristone. For the full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM Tablet. Light yellow, cylindrical, bi-convex tablets, with a diameter of 11 mm with “167 B” engraved on one side. 4. CLINICAL PARTICULARS For termination of pregnancy, the anti-progesterone mifepristone and the prostaglandin analogue can only be prescribed and administered in accordance with New Zealand’s abortion laws and regulations. 4.1 Therapeutic indications 1- Medical termination of developing intra-uterine pregnancy. In sequential use with a prostaglandin analogue, up to 63 days of amenorrhea (see section 4.2). 2- Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester. 3- Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester). 4- Labour induction in fetal death in utero. In patients where prostaglandin or oxytocin cannot be used. 4.2 Dose and Method of Administration Dose 1- Medical termination of developing intra-uterine pregnancy The method of administration will be as follows: • Up to 49 days of amenorrhea: 1 Mifepristone is taken as a single 600 mg (i.e. 3 tablets of 200 mg each) oral dose, followed 36 to 48 hours later, by the administration of the prostaglandin analogue: misoprostol 400 µg orally or per vaginum. • Between 50-63 days of amenorrhea Mifepristone is taken as a single 600 mg (i.e. 3 tablets of 200 mg each) oral dose, followed 36 to 48 hours later, by the administration of misoprostol.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,723,320 B2 Bunschoten Et Al
    US007723320B2 (12) United States Patent (10) Patent No.: US 7,723,320 B2 Bunschoten et al. (45) Date of Patent: May 25, 2010 (54) USE OF ESTROGEN COMPOUNDS TO DE 23,36434. A 4, 1975 INCREASE LIBDO IN WOMEN WO WO96 O3929 A 2, 1996 (75) Inventors: Evert Johannes Bunschoten, Heesch OTHER PUBLICATIONS (NL); Herman Jan Tijmen Coelingh Bennink, Driebergen (NL); Christian Holinka CF et al: “Comparison of Effects of Estetrol and Taxoxifen Franz Holinka, New York, NY (US) with Those of Estriol and Estradiol on the Immature Rat Uterus'; Biology of Reproduction; 1980; pp. 913-926; vol. 22, No. 4. (73) Assignee: Pantarhei Bioscience B.V., Al Zeist Holinka CF et al; "In-Vivo Effects of Estetrol on the Immature Rat (NL) Uterus'; Biology of Reproduction; 1979: pp. 242-246; vol. 20, No. 2. Albertazzi Paola et al.; "The Effect of Tibolone Versus Continuous Combined Norethisterone Acetate and Oestradiol on Memory, (*) Notice: Subject to any disclaimer, the term of this Libido and Mood of Postmenopausal Women: A pilot study': Data patent is extended or adjusted under 35 base Biosis "Online!; Oct. 31, 2000: pp. 223-229; vol. 36, No. 3; U.S.C. 154(b) by 1072 days. Biosciences Information Service.: Philadelphia, PA, US. Visser et al., “In vitro effects of estetrol on receptor binding, drug (21) Appl. No.: 10/478,264 targets and human liver cell metabolism.” Climacteric (2008) 11(1) Appx. II: 1-5. (22) PCT Filed: May 17, 2002 Visser et al., “First human exposure to exogenous single-dose oral estetrol in early postmenopausal women.” Climacteric (2008) 11(1): (86).
    [Show full text]
  • Emergency Contraception: History, Methods, Mechanisms, Misconceptions and a Philosophical Evaluation
    logy & Ob o st ec e tr n i y c s G Gynecology & Obstetrics Goldstuck, Gynecol Obstet (Sunnyvale) 2014, 4:5 DOI: 10.4172/2161-0932.1000224 ISSN: 2161-0932 Review Article Open Access Emergency Contraception: History, Methods, Mechanisms, Misconceptions and a Philosophical Evaluation Norman D Goldstuck* Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town 7505, South Africa *Corresponding author: Norman D Goldstuck, Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town 7505, South Africa, Tel: +27823418200; E-mail: [email protected] Received: Apr 07, 2014; Accepted: May 28, 2014; Published: May 31, 2014 Copyright: © 2014 Goldstuck. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Humans have attempted to disrupt the progression of pregnancy for a very long time. This dates back to the realization that it was a sexual activity which started the reproductive cycle. Folk methods for preventing pregnancy after unprotected sexual activity are physiologically unable to be effective and we now have chemical, mainly hormonal methods, and a mechanical method the intrauterine device which do work in the very early stages before conception can be diagnosed with certainty. These methods are impeded by those who worry that fertilisation of the ovum may have occurred, and that the method may then be abortifacient. Considering that it is possible to easily disrupt an established pregnancy by medical or surgical means depending on the duration, this would be no different than any other means of abortion induction.
    [Show full text]
  • Gynaecology-Changing-Services-For-Changing
    GYNAECOLOGY GYNAECOLOGY Changing Services for Changing Needs Edited by SUE JOLLEY Copyright © 2006 John Wiley & Sons Ltd The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England Telephone (+44) 1243 779777 Email (for orders and customer service enquiries): [email protected] Visit our Home Page on www.wiley.com All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1T 4LP, UK, without the permission in writing of the Publisher. Requests to the Publisher should be addressed to the Permissions Department, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, or emailed to [email protected], or faxed to (+44) 1243 770620. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The Publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the Publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought.
    [Show full text]
  • Selective Progesterone Receptor Modulators in Gynaecological Therapies
    65 1 Journal of Molecular H O D Critchley and SPRMs in gynaecological 65:1 T15–T33 Endocrinology R Chodankar therapies THEMATIC REVIEW 90 YEARS OF PROGESTERONE Selective progesterone receptor modulators in gynaecological therapies H O D Critchley and R R Chodankar MRC Centre for Reproductive Health, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh Bioquarter, Edinburgh, UK Correspondence should be addressed to H O D Critchley: [email protected] This review forms part of a special section on 90 years of progesterone. The guest editors for this section are Dr Simak Ali, Imperial College London, UK, and Dr Bert W O’Malley, Baylor College of Medicine, USA. Abstract Abnormal uterine bleeding (AUB) is a chronic, debilitating and common condition Key Words affecting one in four women of reproductive age. Current treatments (conservative, f abnormal uterine medical and surgical) may be unsuitable, poorly tolerated or may result in loss of fertility. bleeding (AUB) Selective progesterone receptor modulators (SPRMs) influence progesterone-regulated f heavy menstrual bleeding (HMB) pathways, a hormone critical to female reproductive health and disease; therefore, f selective progesterone SPRMs hold great potential in fulfilling an unmet need in managing gynaecological receptor modulators disorders. SPRMs in current clinical use include RU486 (mifepristone), which is licensed (SPRM) for pregnancy interruption, and CDB-2914 (ulipristal acetate), licensed for managing AUB f leiomyoma in women with leiomyomas and in a higher dose as an emergency contraceptive. In this f fibroid article, we explore the clinical journey of SPRMs and the need for further interrogation of this class of drugs with the ultimate goal of improving women’s quality of life.
    [Show full text]
  • Appendix Some Important Pharmacological Agents
    Appendix Some important pharmacological agents Students may feel overwhelmed by the number of drugs pharmacists play a crucial role) grapple with choosing described in pharmacology textbooks. We would empha- which individual drugs to stock in the pharmacy. There sise that it is more important to understand general phar- is a play-off between stocking several individual drugs macological principles, and to appreciate the pharmacology of one category, for each of which there is good evidence of the main classes of drug, than to attempt to memorise of efficacy for distinct indications, and stocking a more details of individual agents. Specific drugs are best learned restricted choice based on indirect evidence that efficacy about when they are encountered in the setting of particu- is likely to be a common feature of different members of lar topics (e.g. noradrenergic transmission), during practi- a class of drugs. Local variations will be encountered (e.g. cal classes or (for therapeutic drugs) near a patient’s as to which angiotensin-converting enzyme inhibitor or bedside. We provide a list (www.studentconsult.com) of non-steroidal anti-inflammatory drugs are stocked in the examples of some of the most important pharmacological hospital pharmacy). If the student or clinician (e.g. doctor, agents. It is not intended as a starting point to learning dentist, veterinarian or nurse) comes to these (e.g. when pharmacology, and we would caution against attempting changing to a job in a new hospital) with a sound appre- to memorise lists of names and properties. The important ciation of the general principles of pharmacology and of agents we list here were selected subjectively; they include the specifics of the various classes of agent involved, he or (but are not limited to) the 100 drugs most likely to be she will be able to look up and understand the details of prescribed by newly qualified doctors in the UK Baker( agents favoured locally and use them sensibly.
    [Show full text]
  • Mifepristone: an Overview for Australian Practice
    Mifepristone: an overview for Australian practice David L Healy, Chairman, Department of Obstetrics and Gynaecology, Monash University, Melbourne Summary day, with at least 500 women dying daily from abortion attempts, 2 Mifepristone was the first antiprogestogen to especially in low income countries. This led the WHO to assess be developed for clinical use. It is not only a the combination of mifepristone and various prostaglandin analogues for medical abortion. progesterone receptor antagonist, but also acts as a glucocorticoid receptor antagonist. The fundamental Several double-blind randomised controlled trials showed importance of progesterone for human conception that mifepristone 200 mg, when combined with misoprostol, a prostaglandin E derivative, was as effective as surgical abortion. and throughout pregnancy has meant that 1 Misoprostol is only about 1% of the cost of other prostaglandins, mifepristone has been used in other countries for is stable at room temperature and is associated with much less emergency contraception and medical abortion in the pain than gemeprost, so it has become widely used.3 first and second trimester of pregnancy. It has also Mifepristone can be used as early as five weeks of pregnancy. By been used to manage fetal death in utero in the third contrast, surgical abortion is generally delayed until seven weeks trimester of pregnancy. There are other potential uses or later. About 1% of women will abort following mifepristone based on its mechanism of action, such as reducing but before the administration of misoprostol. The adverse effects the bleeding associated with uterine fibroids. of mifepristone are minimal, but misoprostol can cause nausea, Key words: Cushing's syndrome, meningioma, pregnancy, vomiting, diarrhoea and headache.
    [Show full text]
  • Emergency Contraceptives Rao 2019
    DRUG PROFILE Emergency Contraceptives CHANDRIKA RAO1 AND NIMRAT SANDHU1 From 1Department of Paediatrics, MS Ramaiah Medical College, Bangalore, Karnataka Correspondence: Dr Chandrika Rao, Professor, Department of Paediatrics, MS Ramaiah Medical College, Bangalore, Karnataka, India. [email protected] Emergency contraceptives are indicated in adolescents as an 'emergency' birth control method after sexual assault or an unprotected intercourse or failure of 'routine' method of contraception. It does not protect against sexually transmitted infections or future pregnancies, when usual birth control methods are not used. It has few side effects and follow up visits are indicated in specific circumstances. Key words: emergency contraceptives, pregnancy Contraception is the deliberate use of artificial methods or other previous pill; techniques to prevent pregnancy as a consequence of sexual intercourse. o Dislodgment, breakage, tearing, or early removal of a diaphragm or The major forms of artificial contraception are the barrier methods, the contraceptive pill and intrauterine devices and sterilisation. cervical cap; o EMERGENCY CONTRACEPTION Failed withdrawal Emergency contraception (EC) refers to methods that can be used to o Failure of a spermicide tablet or film to melt before intercourse; prevent pregnancy after sexual intercourse. These are recommended for o Miscalculation of the abstinence period, or use within 5 days of the intercourse. They are more effective, if they are o Expulsion of an IUD or hormonal contraceptive implant. used soon after intercourse. EC can prevent up to over 95% of pregnancies when taken within 5 days after intercourse. MECHANISM OF ACTION Intra Uterine device (IUD)s are considered the most effective form of Oral emergency contraceptives work primarily by delaying ovulation.
    [Show full text]
  • Quality of Information on Emergency Contraception on the Internet. Br J Fam Plann 2000
    331 Quality of information on emergency contraception on the Internet. Br J Fam Plann 2000 Jan;26(1):39-43 Latthe M, Latthe PM, Charlton R OBJECTIVE: To evaluate the quality of patient information about emergency contraception on the Internet. DESIGN: We performed an on-line search of the Internet and found relevant World Wide Web sites by combining the key phrases 'emergency contraception' and 'patient information' in two Web subject guides and two search engines. We defined quality as the extent to which the characteristics of a Web site satisfied its stated and implied objectives. Our assessment focused on credibility and content of each Web site. Credibility was assessed by source, currency and editorial review process and content of Web site was assessed by hierarchy and accuracy of evidence. RESULTS: Our search revealed 32 relevant Web sites, none of which complied with all of the criteria for quality of credibility and content. Twenty- eight Web sites displayed the source clearly, 17 Web sites showed currency, and none of the Web sites had an editorial review process. Only six of the 32 sites mentioned hierarchy of evidence. None of the Web sites depicted all the criteria for accuracy of contents. CONCLUSION: None of the Web sites provided complete information to patients about emergency contraception according to the quality criteria used in this study. As previous studies have shown, people need to be wary about the quality of information on the Internet. 332 Provider knowledge about emergency contraception in Ghana. J Biosoc Sci 2000 Jan;32(1):99-106 Steiner MJ, Raymond E, Attafuah JD, Hays M Family Health International, Research Triangle Park, NC 27709, USA.
    [Show full text]
  • Synthesis of Potential Antiprogestogens
    123 SYNTHESIS OF POTENTIAL ANTIPROGESTOGENS Bernard0 Beyer*, Lars Terenius, Robert W. Brueggemeier, Vasant V. Ranade, and Raymond E. Counsell** Laboratory of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48104, U.S.A., and Department of Medical Pharmacology, University of Uppsala, Uppsala, Sweden, Received: l.l/6/75 ABSTRACT Aoylated derivatives of 17cr-hydroxyprogesteronewere prepared in order to test the hypothesis that dialkylamino alkyl moieties have the effect of transforming progestogens into antiprogestogens. This approach has been successful with certain estrogens. Compounds with other functional groups were synthesized to determine whether these might exert binding influence outside the area occupied by progesterone itself. The compounds were tested for competitive affinity against tritiated progesterone and receptor from rabbit uterus cytosol. The low affinity of all derivatives makes it unlikely that they would be active as antiprogestationalagents. As an approach to fertility control, there is considerable inter- est in an agent that will antagonize the hormonal actions of urogest.er- one. Progesterone is essential for the induction of implantation and for the maintenance of pregnancy. Conversely, interruption of this action would cause pregnancy to terminate, To date, a true antiprogestogenhas not been discovered. Such an agent might compete with progesterone for the binding sites on progesto- gen-receptor proteins in target organs such as the uterus and the ovi- duct. The progestogen-receptorprotein has a key function in progester- one action and receptor blockade would prevent this action. * Taken in part from thesis research performed in partial fulfill- ment of the requirements for the Doctor of Philosophy degree, University of Michigan.
    [Show full text]
  • Drug/Substance Trade Name(S)
    A B C D E F G H I J K 1 Drug/Substance Trade Name(s) Drug Class Existing Penalty Class Special Notation T1:Doping/Endangerment Level T2: Mismanagement Level Comments Methylenedioxypyrovalerone is a stimulant of the cathinone class which acts as a 3,4-methylenedioxypyprovaleroneMDPV, “bath salts” norepinephrine-dopamine reuptake inhibitor. It was first developed in the 1960s by a team at 1 A Yes A A 2 Boehringer Ingelheim. No 3 Alfentanil Alfenta Narcotic used to control pain and keep patients asleep during surgery. 1 A Yes A No A Aminoxafen, Aminorex is a weight loss stimulant drug. It was withdrawn from the market after it was found Aminorex Aminoxaphen, Apiquel, to cause pulmonary hypertension. 1 A Yes A A 4 McN-742, Menocil No Amphetamine is a potent central nervous system stimulant that is used in the treatment of Amphetamine Speed, Upper 1 A Yes A A 5 attention deficit hyperactivity disorder, narcolepsy, and obesity. No Anileridine is a synthetic analgesic drug and is a member of the piperidine class of analgesic Anileridine Leritine 1 A Yes A A 6 agents developed by Merck & Co. in the 1950s. No Dopamine promoter used to treat loss of muscle movement control caused by Parkinson's Apomorphine Apokyn, Ixense 1 A Yes A A 7 disease. No Recreational drug with euphoriant and stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. It is often claimed that BZP was originally Benzylpiperazine BZP 1 A Yes A A synthesized as a potential antihelminthic (anti-parasitic) agent for use in farm animals.
    [Show full text]