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ndocrinologistTHE
PLUS...
Endocrine disruption -searching for the truth
ProtecT: prostatecancer treatment ontrial
HRT: panacea orPandora’sbox?
HRT: panacea orPandora’sbox?
ED
ITO
RIA
L Promoting the profile ofendocrinology is an important
role of the Society forEndocrinology and this is reflectedin this issue of The Endocrinologist.Recent issues of public concern haveincluded HRT in women, endocrinedisruptive compounds (EDCs) andprostate cancer, and members of thesociety have been actively engagedin these public debates.
The termination of the Women’sHealth Initiative Trial receivedconsiderable publicity. In twoindependent articles, Howard Jacobsand David Purdie, provide differentperspectives on this important HRTtrial. Endocrine disrupters arecommonly discussed in the popularpress with little scientific insight. Thisis corrected in this issue by RichardSharpe who is Chairman of the Societyfor Endocrinology’s EndocrineDisrupting Panel. His article is aninspiration for those who wish tobecome scientific detectives. Finally,prostate cancer is the most commoncancer in men but, despite this, thereis no hard evidence concerning the
effect of screening or aggressive
treatment. Freddy Hamdy and his team
should be congratulated on the trial
that they have established which will
answer important questions
concerning monitoring and therapy.
In his article on page 9, he provides
details of the ProtecT study which has
received a £13 million investment
from the Department of Health and,
essentially, will randomise a quarter of
a million men to monitoring, surgery
or radiotherapy.
If profile means impact then
the endocrinology community
are succeeding and should be
congratulated on the increase in the
impact of their journals as discussed
on page 3. For me, one of the highest
impact sections of The Endocrinologist is
web-spinning and I am always
impressed with Melissa Westwood’s
ability to find us new and interesting
sites. On page 5, you will find out how
to play biological karaoke as well as
discover how to use the molecular
toolbox.
2
ndocrinologistTHE
Editor: Prof Richard RossAssociate Editor: Dr Saffron Whitehead
Co-ordination: Ailsa Bailey and Lara ThompsonSub-editing: Caroline Brewser
Design: Martin Harris
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©2002 Society for Endocrinology
The views expressed by contributors are not necessarily those of the Society
OfficersProf S Franks (Chairman)
Prof SR Bloom (General Secretary)Prof A White (Treasurer)
Prof MG Parker (Programme Secretary)
Council MembersDr R Abayasekara, Prof VKK Chatterjee,
Dr J Hinson, Prof IA Hughes, Prof A Logan, Prof P Lowry,
Prof JP Monson, Prof RJM Ross
StaffExecutive Director: Sue Thorn
Personal Assistant: Brenda ParsonsTel: 01454-642216 for the above
Publications Manager: Steve ByfordProduction Editor: Ailsa Bailey Desk Editor: Lara Thompson
Editorial Assistants: Nathalie Gilmore, Jane Shepleyand Jolene Guy
Peer Review Administrators: Lyn Cole, Kathy Davies and Hélène Dabjat
Tel: 01454-642220 for the aboveSociety Services Manager: Julie Cragg
Secretary: Christine DavisTraining Courses and Grants Administrator: Ann Lloyd
Tel: 01454-642200 for the aboveConference Manager: Helen Gregson
Events Organisers: Liz Brookes and Victoria WithyConference Assistants: Tamara Lloyd and Donna Price
Tel: 01454-642210 for the aboveFinance and Administration Manager: Janet AshtonIT and Administration Assistant: Christopher Wolfe
Accounts Assistant: Jenny ReesIT Officer: Jonathan Seagrave
Tel: 01454-642235 for the aboveExternal Relations Officer/
Business Development Officer: Tom ParkhillPublic Relations Assistant: Becky Torr
Tel: 01454-642205 for the above
2002 Advertising RatesAdvertise your event in The Endocrinologist!
Members: Mono - Half page £100 Full page £150Others: Mono - Half page £300 Full page £450
Colour - Full page £995
Deadline for news items for the Winter 2002 issue: 25 October 2002.
Please send contributions to the above address.
(An Academy of Medical Sciences meeting organised in association with the Society for Endocrinology)
Programme includes:Human male reproductive disorders that may arise duringsexual differentiation Niels SkakkebaekSexual differentiation disorders in wildlife that arise fromenvironmental chemicals John SumpterPathways of endocrine disruption during sexualdifferentiation Richard SharpeLevels of selected endocrine-active compounds in the USpopulation Larry L NeedhamIdentification of endocrine-active chemicals - strengths andweaknesses of available methods Andreas KortenkampA critical look at the evidence for and against humaneffects of endocrine-active chemicals Paul Foster
Are endocrine-active chemicals bad for your health?Thursday 24 January 2003THE MØLLER CENTRE, CHURCHILL COLLEGE, CAMBRIDGE
Please register for this meeting via The Academy of Medical Sciencesweb site (www.acmedsci.ac.uk)The Academy gratefully acknowledges the support of AstraZeneca plc for this meeting.
Journalsincrease impact The recently released impact factors for biomedical
publications show huge increases for the Society’s journals!Both Endocrine-Related Cancer and Journal of Molecular Endocrinology have
reached their highest ever levels, at 3.688 and 3.649 respectively. The value forJournal of Endocrinology reached 2.834, continuing the trend which has seen thejournal’s impact factor increase every year since 1991.
Impact factors are produced annually by the Institute for Scientific Informationand the latest values reflect citations in 2001 of articles published in 1999 and2000. The huge gains illustrate the success of the Society’s initiatives to raise thejournals’ profiles. Work with successive editors and their boards has attractedquality content and maximised the visibility of the electronic versions.
The Society’s official clinical journal, Clinical Endocrinology (published byBlackwell Publishing), fell slightly to 2.465, but other major clinical journalsshowed similar decreases.
Endocrine Nurses NewsTraining CourseOur fifth annual Endocrine Nurse Training Course ‘Endocrine Nasties – theinvestigation and treatment options of endocrine malignancies’ was held at theMøller Centre in Cambridge, an outstanding venue that will be hard to beat. Wewere delighted to welcome 63 nurses from across the UK and as far afield asHolland. The initial feedback has been extremely positive so a big thank you to allthe nurses who accepted the opportunity to either chair a session or to present forthe first time - it was good to see so many people involved.
Following requests for an organised social programme, this year a chauffeuredpunting trip was arranged on the River Cam. The peace and tranquillity of the river wassoon shattered, the wildlife rushed for cover and even those studious souls mindingtheir own business on the riverbank were not safe but, amazingly, no-one fell in!
Nurses Committee nominations soughtThe Nurses Committee is keen to seek a democratic selection of its nursemembers. One committee member is due to retire, and all Society members areinvited to nominate a new committee member. There is a requirement to maintainthe balance of adult and paediatric representation on the Committee and, with thisin mind, we would like to invite nominations primarily for a paediatric nurse tojoin the Committee. The Society would like to make it clear that any endocrinenurse member wishing to stand for election can request a nomination form to becompleted by a suitable sponsor. A nomination form can be found on the Society’sweb site (www.endocrinology.org/sfe/about.htm) – click on Committees, and thenfollow the path to the Nurses Committee and Nomination Form. Forms are alsoavailable from Julie Cragg or Ann Lloyd in the Bristol office.Nominations should be submitted to the Bristol office (c/o Ann Lloyd) not later than 8November 2002. If there are more nominations than vacancies, then a ballot will be heldwithin the committee, and this will be announced in the newsletter.
MAGGIE CARSON, CHAIR, ENDOCRINE NURSE COMMITTEE
November MeetingThe nurse session is on Monday 4 November and is entitled ‘The Impact ofThyroid Eye Disease on Body Image’. We look forward to seeing you there.
Endocrine Nursing NewsDecember’s issue of our new newsletter for nurses will include reports from theSeptember training course and the Nurses session at the November meeting.Endocrine nurses will find this an invaluable way of keeping in touch with oneanother and with activities arranged by the Nurses Committee on their behalf.Contact Ann Lloyd in the Bristol office ([email protected]) if youwould like to submit an article for consideration.
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SOCIETY CALENDAR
4-6 November 2002193rd Meeting of the Society for EndocrinologyRoyal College of Physicians, London, UK (see advert on page 16)
26 February 2003Clinical Cases MeetingLondon, UK
27 February 2003Royal College of Radiologists:Imaging in EndocrinologyLondon, UK
24-26 March 2003BES 2003Glasgow, UK(see advert on page 12)Abstract deadline 15 November 2002!
15-18 July 2003Summer School 2003(Molecular Endocrinology Workshop,Advanced Endocrine Course and ClinicalPractice Day)Manchester, UK
10-12 September 2003Endocrine Nurses Training Course:The Pituitary GlandDurham, UK
Congratulations...to Stephen O’Rahilly of theUniversity of Cambridge, who has beenawarded the 2002 Heinrich WielandPrize. This prize recognisescontributions to the understanding ofthe chemistry, biochemistry, physiologyor clinical science of lipids and fats,and Professor O’Rahilly won the awardfor his work on the genetics of humanobesity and related disorders. He willreceive the prize at a ceremony inNovember at the Institute of Chemistry,University of Munich.
...to Vance Trudeau of the Universityof Ottawa who is the recipient of theUniversity’s 2002 Young Researcher ofthe Year Award. The award is given inrecognition of excellence andinnovation by a young researcher, andincludes a $10 000 research grant.Professor Trudeau’s research includesstudies of the effects of sexualhormones on brain development ingoldfish, particularly concentrating ongender differences. He is also interestedin endocrine-disrupting chemicals.
You can read the Society’sjournals online athttp://journals.endocrinology.org(which includes a link to ClinicalEndocrinology).
SOC
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Basic Science Review Lecturer 2002Congratulations to Rob Fowkes from Barts and the Royal London, for winning thisaward with his paper entitled ‘Steroidogenic factor-1: a pivotal regulator ofgonadotroph gene expression’. He will present his lecture during the YoungEndocrinologists session at the Society’s meeting in London in November.
Young Endo GrantsGrants of up to £150 are available to enable young endocrinologist members toattend the Society’s meeting on 4-6 November (in addition to the normal annualoverseas conference grants). The deadline for applications is 21 October. Seewww.endocrinology.org/sfe/grants.htm, or contact Chris Davis in the Bristol office.
Science CommitteeNew members are needed to replace those retiring from the Society’s ScienceCommittee. The Committee’s role is to speak for the basic science community. Itprovides input on scientific sessions at the November and BES meetings, as well asto the UK Life Sciences Committee and other bodies. It meets three times a year,usually in London. Nomination forms are available from Julie Cragg ([email protected]), and shortly at www.endocrinology.org/sfe/commit.htm.
Members on the move...A Allahabadia to Northern General Hospital, Sheffield; F A Antoni to Universityof Edinburgh; S J Assinder to University of Otago; A Dixon to WolverhamptonDiabetes Centre; M A Elrishi to Manor Hospital, Walsall; M Elsheikh to RoyalBerkshire Hospital, Reading; P Goulden to St George’s Hospital, London;S J Gregory to Brigham Women’s Hospital, Boston; B M Harris to Royal UnitedHospital, Bath; C K M Ho to University of Pennsylvania School of Medicine,Philadelphia; S Kanumakala to Royal Alexandra Hospital, Brighton; D Kapoor toBarnsley District General Hospital; J Kisalu to Royal Free Hospital, London;S Kouta to Fairfield Green Hospital, Bury; F Medici to Homerton UniversityHospital, London; J Muburu to Indiana University School of Medicine,Indianapolis; C J Owen to Institute of Human Genetics, Newcastle upon Tyne;B Pan to John Hopkins School of Medicine, Baltimore; E S Quabius to Universityof Aberdeen; R Sheaves to Centre for Endocrinology and Diabetes, London;K A Stokes to University of Bath; S Suliman to Stoke Mandeville Hospital,Aylesbury; D F Wood to Barts and the London, Queen Mary’s School of Medicine& Dentistry, London.
Mary Pickford1902-2002
Lillian Mary Pickford was born inIndia, but educated in England,
and obtained a degree in physiologyfrom Bedford College in 1925.
Because of her gender, herdetermination to pursue a career inresearch met with some resistance.However, she was accepted by E BVerney to work at University CollegeLondon as a part-time researchassistant, and was awarded an MSc in1926. She published her first paper in1927, and was elected a member ofThe Physiological Society in 1928.
She completed her medical trainingat University College Hospital, andpractised for a while in Staffordshire.However, her resolve to pursueresearch remained, and, gaining a BeitFellowship, she moved to Cambridge(still with Verney), subsequentlypublishing a seminal paper on centralactions of acetylcholine on ADHsecretion. She then took a lectureshipin the Department of Physiology in theUniversity of Edinburgh, where sheremained until her retirement, holdinga personal Chair, at the age of 70.
Mary was the first woman to beappointed to a Chair in the Faculty ofMedicine at Edinburgh University. Shewas also the first woman to be electedto the Pharmacological Society. She wasan FRS, and an Honorary Member ofboth The Physiological Society and theSociety for Endocrinology.
Mary had stature, in both meanings.She could be a stern critic of her peers,but was kind and encouraging tojunior colleagues and students, andforgiving of their failings. She will befondly remembered by all those whowere taught by her, or worked withher. Mary died on 14 August 2002, her100th birthday.
JOHN A RUSSELL
This issue’sillustration is by DrD R Bangham, andis entitled ‘Barga,Italy’. Dr Banghamis author of theSociety’s publication‘A History ofBiologicalStandardization’,which looks at thecharacterisation andmeasurement ofcomplex molecules ofimportance inclinical and research
medicine, in the period from 1900 to 1995. Copies of the book (priced £40.00) areavailable from Dr Bangham, 4 Crown Close, Mill Hill, London, NW7 4HN, UK
OBITUARY
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Molecular toolboxwww.mgb.pitt.edu/moleculartoolbox.htm
OK, so some of you will have a‘Favourites’ file that looks a lot like thisweb site. However, I’m sure many willappreciate a one-stop shop for all yourmolecular biology needs. This siteprovides links to searchable databases,numerous programmes for analysis ofDNA (e.g. primer design, restrictionmapping, alignments, gene expression)or proteins (post-translationalmodifications, structure prediction andvisualisation, etc), in addition totutorials, tips and protocols.SERVICES: T, D, L; STRONG POINTS:
Comprehensive, easy to use; WEAK
POINTS: None; RATING: Excellent.
What’s the alternative?ecvam-sis.jrc.it
A web site to keep an eye on. Themission of the ECVAM ScientificInformation Service is to establish,maintain and manage a database onadvanced alternative procedures toanimal experiments. Currently, it’s still
WebspinningHighlighting the best on the web
Thanks to Kevin Ahern and GeneticEngineering News. Don’t forget to visitthe Society for Endocrinology on theweb: www.endocrinology.org; tell usabout your favourite web site:[email protected].
KEY
Services provided at web sites:T Tools - Analytical computing toolsD Data - Searchable or downloadable
database informationG Goods - FTP delivery of useful items
(e.g. full package, bug fix or demosoftware)
L Links - Useful links to other sitesN News - News of interestS Support - Feedback in response to
users’ enquiriesO Others - e.g. Innovative use of web
tools, appearance, editorial point ofview
Ratings: Excellent, Very Good, Good Nothing below good will be reported here.
at the test stage, and so access toinformation is limited, even afterregistration. However, the searchableINVITTOX database does provideinformation on protocols, testcompounds, data analysis, advantagesand disadvantages, state ofdevelopment, validation or regulatoryacceptance, and user and/or referencelaboratories.SERVICES: D, L; STRONG POINTS:
Concept; WEAK POINTS: Need toregister, not particularly easy tonavigate; RATING: Good.
Knock, knockn.webring.com/webring?ring=sciencehumor;list
‘Never replicate a successfulexperiment!’ Useful advice indeed - andmore pearls of wisdom can be foundamongst the collection of jokes, puns,quotes and stories that make up thisweb ring of science ‘humor’ (many areAmerican). Find out how to tell ifyou’re a real scientist, uncover the rulesfor writing a paper, learn the referees’
Grants for BES 2003The Clinical Endocrinology Trust isoffering travel grants to UK-basedyoung endocrinologists (under the ageof 35) to attend the BES meeting inGlasgow in March 2003. Forms areavailable from Chris Davis in theBristol office ([email protected]) and will also beavailable shortly atwww.endocrinology.org/sfe/grants.htm.The deadline for receipt of completedforms is 10 January 2003.
• Plenary sessions - including ‘Quality of life for patients’ byProfessor Ron Akehurst
• 21 workshops on pituitary disorders and lifestyle issues
• Carer issues
• Other endocrine patient support groups
Since 1994, The Pituitary Foundation has provided information andsupport to patients, their families/carers and the medical profession.
For registration details or further information contact: The Pituitary Foundation, PO Box 1944, Bristol BS99 2UB, UK(Tel/Fax: 0870-7743355; Email: [email protected]; Web: www.pituitary.org.uk). Registered Charity No. 1058968
‘Working to support pituitary patients’
creed and find out how to bebiologically PC. Whatever you do, don’tmiss out on biology karaoke. Let’s hearit for that famous ‘70s hit ‘tRNA’. Ofcourse you know it: remember VillagePeople? remember ‘YMCA’? So alltogether now then - t. R. N. A...SERVICES: O; WEAK POINTS: Many pagesaren’t related to biological science;RATING: Good.
4th NationalConference of the PituitaryFoundation
Saturday 23 November 2002
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The outcomes of two trials ofpostmenopausal HRT have been
reported this year. These prospectiverandomised controlled trials haveyielded data of a far higher qualitythan were previously available fromobservational studies, and haveimportant implications for HRT ofpostmenopausal women.
The first of these, the heart andestrogen/progestin replacement study(HERS), aimed to discover whethertreatment with oestrogen andprogestogen prevents further heartattacks in postmenopausal women withcoronary heart disease. It comprised1380 women randomly allocated tocontinuous combined HRT (details ofthe preparation are below), comparedwith 1383 on placebo (average age atentry 67 years). The study’s first reportwas published after an average of 4.1years of treatment, the second (HERSII) after open label extension of thestudy to an average of 6.8 years oftreatment (JAMA 2002, 288 49-57).
Combined continuous HRT wasfound not to prevent further heartattacks. Moreover, in the first years ofthe trial, more heart attacks occurredin the women taking hormones than inthose taking placebo. HRT wasassociated with more venousthromboembolic disease (relativehazard (RH) 2.08, CI 1.28-3.4) andmore biliary tract surgery (RH 1.48, CI1.12-1.95) compared with placebo(JAMA 2002, 288 58-66). There wasno overall reduction in mortality in thewomen on hormone treatment.Compared with women on placebo,those on HRT did have fewer flushingattacks and less vaginal dryness, butthey also had more vaginal dischargeand unscheduled bleeding. Depressivesymptoms were fewer in women onHRT, but this benefit was largelyconfined to those whose flushing hadalso improved (JAMA 2002, 287 591-597). There was no advantage ofhormone treatment with regard tophysical activity and energy.
The second trial was from theWomen’s Health Initiative (WHI)
(JAMA 2002, 288 321-333). Itexamined whether treatment withoestrogen and progestogen reduces therisks of heart disease, breast and coloncancer and fractures. It comprised8506 women randomly allocated tocontinuous combined HRT (the same
preparation as used in HERS)compared with 8106 on placebo(average age at entry 63 years, range50-79). More than 90% of the subjectshad no evidence of coronary heartdisease at entry. The study wasdesigned to run for 8.5 years, but wasterminated after just over 5, becausethe researchers considered that therisks of HRT outweighed the benefits.
Over the course of a year, thefollowing could be attributed tocombination HRT (per 10 000 women):
• 7 more coronary disease events
• 8 more strokes
• 8 more pulmonary emboli
• 8 more invasive breast cancers
• 6 fewer colon cancers
• 6 fewer hip fracturesWhen counting all the adverse
events over the 5 years of the study,the excess in the treated women was100 per 10 000 woman years. Sowhile the risk for any particularwoman was 1 in 100, the resultsshowed that combined HRT neitherpreserved health nor preventeddisease. Adverse effects on the heartbegan to appear in the first 2 years oftreatment in both the HERS and WHIstudies. The increased risk of breastcancer did not appear for 3 years.
In each study, the HRT preparationwas Prempro, which contains Premarin0.625 mg + medroxyprogesteroneacetate (MPA) 2.5 mg. The closest UK
equivalents are Premique (Premarin0.625 mg + MPA 5.0 mg) andPremique Cycle (Premarin 0.625 mg +MPA 10 mg). MPA is also found inIndivina (oestradiol valerate 1-2 mg +MPA 2.5-5 mg) and Tridestra(oestradiol valerate 2mg + MPA 20mg). I think the adverse effects arelikely to result from treatment with acombination of an oestrogen with aprogestogen, and that they are notpreparation-specific. However, sincethis point cannot be considered settled,at the present time it would seem wisefor women to avoid these products.
Both studies were well designedand executed, and produced resultsconsistent with other recent reports.They have shown that there is no rolefor combined continuous HRT inprimary (WHI) or secondary (HERS)prevention of coronary heart disease.There are now several non-oestrogenicpreventive and therapeutic remediesfor osteoporosis that are not associatedwith the risks of treatment withoestrogen. In my opinion, the resultsof the HERS and WHI studies providestrong reasons for using non-oestrogen-based methods to preventheart attacks, osteoporosis and coloncancer in postmenopausal women. Onthe other hand, I do think it isreasonable to continue to prescribeHRT to reverse the symptoms ofoestrogen deficiency. Such treatmentwill usually be short term.
The results of these studies shed nolight on the safety of treatment withoestrogen alone, as used in womenwho have had a hysterectomy.Information from the WHI on thattopic is not scheduled to be publisheduntil 2005.
HOWARD JACOBS
HRT: balancing the benefitsRecent long-term studies in the USA and UK have called the safety of postmenopausalhormone replacement therapy into question. This new work makes it difficult for the non-specialist to make an informed decision on the safety and utility of HRT. We asked for theopinions of two prominent endocrinologists who take differing views on the use of HRT.
‘the results provide
strong reasons for using
non-oestrogen-based
methods to prevent heart
attacks, osteoporosis and
colon cancer’
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The scientific basis for oestrogentherapy in postmenopausal
women centres on the non-reproductive actions of this steroidgroup. Our knowledge in this areahas greatly increased recently, withnew techniques to localise oestrogenreceptors, and clarification of theirphysiological roles, tissue by tissue.Among the many systems thatinclude a role for oestrogens, threeform the basis for contemporaryresearch and, if appropriate,therapeutic use: the trabecularskeleton, vascular tree and CNS.
Functional oocyte exhaustion leadsnot only to infertility but also toelimination of the theca/granulosa cellpartnership as a principal source ofcirculating oestradiol. Ovarianendocrine failure which is obligatory,be it spontaneous or inducedmedically or surgically, withdrawscirculating oestradiol from the nowlargely redundant hypothalamic-pituitary-ovarian axis. It also, however,withdraws oestradiol from othersystems.
The skeleton reacts with a sharplyincreased rate of turnover, togetherwith a tilt in the bone remodellingcycle in favour of resorption. Theultimate consequence for manywomen is loss of integrity within thetrabecular lattice and, ultimately,vertebral crush and low-traumaperipheral fractures. The oestrogen-deprived cardiovascular (CV) systemexhibits an adverse lipid profile and, inin vitro and animal studies, progressiveatherogenesis. The CNS exhibitsoestrogen-sensitive changes inneuronal function, together withalterations in neurotransmitter activityand, in vitro, dendrite projection.
HRT is licensed for the treatment ofoestrogen-sensitive symptoms and forthe prevention and treatment ofosteoporosis. There is a wealth of datafrom randomised controlled trials(RCTs) to support its use for physicalsymptoms like vasomotor instability,insomnia, tiredness and arthralgia, andpsychological symptoms such as lossof short-term memory andconcentration span.
With regard to the CV system, invitro, animal and human observationaldata all suggest that oestrogenreplacement can substantially reduceatherogenesis, myocardial infarction
and, to a much lesser degree, stroke.The human studies, althoughinternally consistent, have all sufferedfrom the bane of observational dataand the possibility of potentialconfounders (such as the lifestyles ofwomen who take HRT being lesslikely to promote CV disease events).
The recent Women’s HealthInitiative (WHI) study (JAMA 2002288 321-333) looked at treatmentwith 0.625 mg equine oestrogens +continuous 2.5 mg MPA. It found anannual excess of 7 per 10 000 patientyears for non-fatal myocardialinfarction and 8 per 10 000 patientyears for stroke in the treated group.The relevance of these US data to UKpractice is severely limited, however,since HRT has never been licensedhere for the primary or secondaryprevention of CV disease. Indeed, the
precise hormone combination used inWHI is not available in the UK. Datafrom further trials, with CV safetyendpoints, that examine oestradiol(natural human oestrogen), andtibolone (synthetic steroid) arerequired.
With the skeletal system we are onsurer ground. Indeed, the 5-year WHIstudy itself showed a significantreduction in all fractures and,specifically, in hip fracture among thetreated women, who were aged 50-79years at entry. These RCT fracture datanow complement the wealth ofsurrogate end-point data which hadindicated that oestrogen restrains boneturnover, rebalances boneresorption/formation and maintainsbone mineral density at the key sitesof spine, hip and distal radius.
The CNS is an area of intensecurrent enquiry. Several case-controlstudies and one meta-analysis indicatethat oestrogen exposure is associatedwith a reduction in the risk ofAlzheimer’s and related dementias(Neurology 2001 57 2210-2216).These observations complement invitro studies where oestradiol atnanomolar concentrations inhibitedthe elaboration of beta-amyloid from
its precursor protein. Its phenolic Aring has also been shown to conferantioxidant activity, believed to becentral to the protection of neuronesand glial cells. However, oestrogenappears to have no role in thetreatment of established dementias,and the encouraging observationaldata have yet to be backed up by RCTswith primary CNS end-points.
The principal adverse eventsassociated with HRT are associatedwith the engagement of the oestrogenreceptor sites in the reproductive tract,and with the vascular tree.Endometrial stimulation, althoughcontrolled by discontinuousprogestogen, results in resumption ofbleeding and a small increase in therisk of endometrial adenocarcinoma.These effects are annulled by the useof continuous combinedoestrogen/progestogen preparations.Although study results are notconsistent, it is generally agreed thatthere is a small but definite increase inthe incidence of breast cancer,compatible with the increased riskassociated with delayed menopause.The excess risk amounts to some 2attributable tumours per 1000 womenreceiving 5 years of HRT between theages of 50 and 70 (Lancet 1997 3501047-1059). Venous thromboembolicphenomena occur more frequently inpatients receiving HRT or raloxifene(Breast Cancer Research and Treatment2001 65 125-143), usually within thefirst 6 months of treatment but, again,the absolute risk is low. Presentresearch is concentrating on thedevelopment of tissue-specificoestrogens such as selective estrogenmodulators and tibolone which willsupply agonism at the required sites,while avoiding the adverse effects ofreproductive tissue engagement.
In summary, individualmanagement is paramount. Givencareful patient selection for thelicensed indications and propersupervision, HRT is generally safe andreliable. Although by no meansabsolutely safe, oestrogen should stillbe considered as a primary treatmentfor menopausal symptoms and for theprevention and treatment ofosteoporosis - with the proviso that inthe individual case, the physician findsthe potential benefits to be greaterthan the risks.
DAVID PURDIE
oestrogen should still be
considered for the
prevention and treatment
of osteoporosis
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Endocrine disruptive compounds (EDCs) and their effects on humans andwildlife have certainly put endocrinology under the spotlight. The
media’s use of alarmist terms like ‘gender-benders’ makes it difficult topresent a balanced scientific view in the public domain. Factors that result inaltered hormone levels and action are an undoubted hazard, and must betaken seriously. But is the level of human exposure to EDCs sufficient tohave a significant effect on our hormone homeostasis?
It is easiest to split this discussion into three: (1) environmentally persistentchemicals such as DDT and PCBs; (2) more recently identified EDCs that are usedubiquitously, for example bisphenolic and alkylphenolic compounds; (3) chemicals that alter endogenous hormone production, action or metabolism.In all cases, fetal/neonatal exposure is likely to have more far-reaching effects thancomparable adult exposure.
It is accepted that the persistent chlorinated environmental chemicals, such asolder pesticides (like DDT and PCBs), exerted pronounced adverse effects on somewildlife (e.g. eggshell thinning, immune-suppressive effects). The evidence for effectsin humans is less convincing, but this is probably associated with the complex taskof ascribing a change to a single chemical exposure. Nevertheless, there is generalagreement that environmentally persistent chemicals are likely to exert adversehealth effects, and that use of such compounds is therefore no longer acceptable.
In tropical countries with endemic insect-dependent disease transmission, wheresuch pesticides may still be used, the issue of risk-benefits is obviously morecomplex. Even though adverse effects of persistent chlorinated chemicalsundoubtedly occur, to what extent these stem from endocrine disruption is not clear.Many of the so-called EDCs possess activities other than their intrinsic hormonalactivity and, in some cases, these may be more important in relation to theirbiological effects.
Whether more recently identified environmental oestrogenic EDCs, such asbisphenolic and alkylphenolic compounds, pose a health risk via endocrine disruptionis more contentious. Integral to this debate are the so-called ‘low-dose’ (≤20 mg/kg)effects of bisphenol A in developing male rodents. These have not been found in allstudies, and their relevance to human male reproductive health is also unclear. If the‘low-dose’ effects are real, they cannot result from the intrinsically weak oestrogenicityof the compounds, though effects may be the result of some other biological activity.
Exposure to a cocktail of EDCs at low (environmental) doses might result inhormonal effects through summation of their intrinsic hormonal activities, apossibility demonstrated in vitro but still to be tested in vivo. It will be a Herculeantask to evaluate ‘real-world’ mixtures in animal models in ways that allowreasoned extrapolation to humans or wildlife, and thus enable proper riskassessment. A continuing obstacle to all such assessments in man is the dearth ofgood human exposure data for the various chemicals.
In the past 3 years, a new and perhaps more worrying dimension has emerged,centred on the ability of some environmental chemicals to alter endogenoushormone production, metabolism, inactivation or excretion. For instance,exposure of rodents in utero to certain phthalate esters can drastically lowerproduction of testosterone by the testes in male fetuses, leading to downstreamsexual differentiation (cryptorchidism, hypospadias) and other disorders (reducedsperm production/fertility). These disorders are a focus for concern in humanmales because of a possible increase in their incidence. Furthermore, humanexposure to the phthalates in question is high, especially in some women ofreproductive age (up to 160 mg/kg per day), though the levels fall short of thoseshown to cause a high prevalence of disorders in rodents (>250 mg/kg per day).
More recently, PCBs and a range of environmental polyhalogenated hydro-carbons have been shown to have inhibitory effects on oestrogen sulphotransferase,the primary enzymatic mechanism for oestradiol inactivation prior to its excretion.PCBs have also been shown to affect thyroid hormone action in several different
ways. Some of these effects have beenshown at nanomolar or lowerconcentrations and, as humanexposure to all of these compounds iswidespread, they raise new possibilitiesfor their relevance to human disease.
Although intriguing, thesepossibilities are still largely theoretical.However, the worldwide induction of‘imposex’ in certain molluscs followingexposure to tributyltin (TBT) provides areal example. TBT acts by suppressingaromatase, thereby interfering withconversion of androgens to oestrogens,which results in a build-up ofandrogens in females (leading toimposex). Its worldwide occurrenceemphasises that when endogenoushormonal systems are disturbed theconsequences can be dramatic. TBT hasno intrinsic hormonal activity, andwould not be detected by most in vitroscreening systems for EDCs. Manyenvironmental chemicals that alterendogenous hormone action do nothave intrinsic hormonal activity (PCBsare an exception), so only in vivo animaltesting at all life stages is likely to detectsuch compounds.
Human male reproductive disordersassociated with altered sex steroid levelsand sexual differentiation are increasingin incidence and may represent asyndrome (so-called ‘testiculardysgenesis syndrome’). Faced with realwildlife changes that result from‘endocrine disruption’ (like the‘coincidence’ of imposex in molluscs andintersex in fish), we must consider apossible connection with the increase inhuman disorders. In doing so, we mustadhere rigidly to a scientific approach.Sexual differentiation is hormone-dependent and so inherently susceptibleto perturbation - but the cause is notnecessarily always the same. We mustalso recognise that most waste productsend up in the aquatic environment.Effects in fish and molluscs maytherefore be ‘worse case’ as they arepermanently immersed, and thesituation may be completely different forhumans. But if there is a link betweenthe wildlife and human changes, thenwe know that it is environmental, andidentification of its cause(s) may allowintervention or prevention, withconsequent health benefits.
So how do we move forward?Concentrating on identifying EDCs andevaluating their effects in vitro is not the
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Endocrine disruption:separating fact from fiction
most efficient approach if our concernis whether such compounds causehealth disturbance in humans orwildlife. We should identify situationswhere health changes consistent withendocrine disruption have occurred,and then seek the cause, recognisingthat this may be related to genetics,lifestyle and/or environment.
An epidemiological approach isneeded, as studies of individuals are oflimited value. This poses otherproblems such as accuracy of thediagnosis. For example, the registrydata for hypospadias andcryptorchidism, which may reflect‘endocrine disruption’ in utero, areunreliable. There are also enormousdifficulties in relating occurrence ofsuch disorders to particularenvironmental exposures duringpregnancy. In reality, only carefullydesigned, prospective studies are likelyto provide definitive information.Several such studies of hypospadias andcryptorchidism are in progress, andtheir results are awaited with interest.
This approach really can work (atleast for wildlife), as exemplified by thecase of intersex fish in UK rivers.Research has indicated that ‘oestrogens’in sewage effluent discharges are thelikely cause. The ‘culprits’ are probablyethinyl oestradiol or endogenousoestradiol, originating from humanurine, rather than weaker EDCs suchas alkylphenols, which were originallysuspected. By focusing on the effect,avoiding the temptation of obviouspossibilities and marrying togetherexposure analyses, laboratory dose-response studies and arduous ‘real-world’ studies (i.e. river-based fish‘epidemiology’), this scientific detectivework nailed the culprit, not the primesuspect. I cannot think of a betterguide for all of us working in this area.
RICHARD SHARPE
Richard Sharpe is Chairman of the Society forEndocrinology’s Expert Group on EndocrineDisruptors, which aims to provide a source ofreferral and expert advice. While hoping not tohave misrepresented the views of othermembers of the group in this article, Dr Sharpetakes responsibility for the emphasis given tocertain aspects.
A 1-day meeting on ‘Endocrine disruption andhuman male reproductive disorders’, organisedby the Academy of Medical Sciences inconjunction with the Society for Endocrinology,will take place in Cambridge on 24 January2003 (see page 2 andwww.acmedsci.ac.uk/f_contac.htm).
Management of prostate cancer remains a popular topic of discussion,presentation, publication and controversy in urology. There is no hard
evidence that screening for the disease is beneficial, nor do randomisedcontrolled trials show that aggressive treatment of clinically localised cancersimproves survival or quality of life.
Previous attempts to mount randomised trials of treatment have failed, largelydue to methodological problems. Randomised trials of screening are taking placein Europe and the USA. Whilst the results are awaited eagerly, the studies aresuffering from increasing contamination issues, related to increasing publicawareness of the disease, and the wide availability of testing for prostate specificantigen.
Following failure by the MRC to recruit patients to its treatment study in theearly 1990s, a trial of treatment including a ‘watchful waiting’ arm was deemedimpossible. However, the controversy regarding the appropriateness of treatmentin early disease persisted. In 1991, approximately 36 radical prostatectomies wereperformed in the UK. This escalated to some 700 procedures performed by Britishsurgeons in 1999. No recent conclusive evidence has influenced these numbers.Surgeons simply learn how to perform the operation, radiotherapists advocate anddeliver radiotherapy (and more recently brachytherapy), and both treatments areoffered with confidence to men who are uncertain about the fate of their cancer.
In view of these controversies, and despite the conclusion of the MRC study, ateam of researchers from Sheffield, Bristol and Newcastle responded to a call forprimary research by the Health Technology Assessment (HTA) panel of the NHSR&D programme in 1997, and submitted a 2-phase proposal known as ProtecT:prostate testing for cancer and treatment.
Phase 1 was to deal with the feasibility of mounting a full-scale randomisedtrial of treatment effectiveness in clinically localised prostate cancer in the UK. Themain aim was to decide whether it would be possible to recruit men to a 3-arm(monitoring, surgery or radiotherapy) or to a 2-arm (surgery versus radiotherapy)trial, following an intensive programme of case-finding and delivery ofinformation. This was accompanied by comprehensive qualitative research, takinginto account patients’ perspectives. Phase 2 was to mount the main treatmentstudy, based on the findings from the feasibility trial.
Phase 1 was completed in June 2001, showing not only that such a trial iseminently feasible in the UK, but that the majority of men recruited agreed to berandomised to the 3-arm study. Qualitative research, teamwork and scrutinisingthe attitudes of men and recruiters allowed the previous misconceptions to berejected.
The Department of Health, through its HTA programme, has agreed to fundthe main treatment trial (£13m) involving nine clinical centres in the UK, inviting230 000 men to be recruited to the trial over the next 5 years. The primary end-point will be survival to 10 years, with many secondary end-points includingdisease progression, sensitivity/specificity of diagnostic tests, and associated basicscience research.
Compared to the £98 000 spent by our Government in 1998 on prostatecancer research, this is a major achievement for the urological community in theUK, and for patients with prostate cancer worldwide. At last, a feasible trial oftreatment effectiveness in early prostate cancer is on the horizon.
FREDDIE C HAMDYON BEHALF OF THE ProtecT RESEARCH TEAM
Principal Investigators in the ProtecT study are Freddie Hamdy (Sheffield), Jenny Donovan (Bristol)and David Neal (Newcastle).
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ProtecT: prostate treatment on trial
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MolecularEndocrinologyWorkshopReading, UK, 9 July 2002
About 30 delegates attended thisworkshop, some travelling a greatdistance to hear the excellent talks.Attendees could be equally dividedamong those already undertakinglaboratory research, those looking to doso in the near future, and others whowere undecided and wanted to learnmore about such a career decision.
The day started with informativesessions on steroid receptors andchromatin, and human breastepithelium stem cell biology. The firstof these was an excellent introductionto the mechanisms by which thenuclear receptor superfamilyinfluences gene transcription. Asubsequent talk entitled ‘Imaging ofcell signalling and gene expression’described techniques whereby thefirefly luciferase gene can be used toyield important genetic information bylabelling proteins.
My current area of investigation ischildhood obesity and insulinresistance, so I found the discussionon the role of genetics in thedevelopment of obesity veryinteresting. Particular reference wasmade to the clinical syndromes thatresult from leptin or melanocortin-4receptor deficiency. Further talkscovered the functional analysis ofgenetic polymorphisms, andconditional and specific gene targeting,though this latter discussion may havebeen pitched a little too high for theattendees present.
I would have liked some moregeneral talks on the use of researchmethods to explain molecularendocrinology, and less of a biastowards genetics. However, theworkshop was definitely informativeand educational, and I am very pleasedthat I attended.
M SABIN
ENDO 2002: 84th Annual Meeting of the Endocrine SocietySan Francisco, CA, USA, 19-22 June 2002
The focus of the meeting was ‘The impact of the human genome onendocrinology’. The importance and potential of genomics was certainly broughthome, as was the promise of other exciting areas, like proteomics and stem cellresearch. The conference enabled me to bring the literature review for my PhDright up to date, and included posters on the cloning of a second marsupial GnRHreceptor, a study using lamprey GnRH, and another on the importance ofextracellular loops in binding non-peptide antagonists to the GnRH receptor.
KEVIN PFLEGER
I particularly enjoyed the plenary lectures on ‘Genomics, medicine and society’and ‘What genomic medicine will mean for you’. They reviewed the latestadvances, and also looked at the social implications of genomic screening. Thesymposium on ‘Nutrition and bone’ was highly relevant to my work, and includedan outstanding presentation on vitamin D by M Holick.
LUCIA MANCINI
The greatest benefit for me was the opportunity to gather feedback on myfindings, from both scientists and clinicians. My PhD examines the effects ofdietary polyunsaturated fatty acids on reproductive processes in the sheep. Asidefrom technical queries, I was posed many questions about the clinical relevance ofmy results in terms of solving everyday fertility problems. This gave me anexcellent insight into a clinician’s perspective of the sorts of questions we shouldbe trying to answer. It will also help me focus the discussions when writing up mythesis, both in terms of basic science and clinical relevance.
SUSAN KIRKUP
Numerous symposia helped me plan future experiments for my PhD, whichaddresses neural regulation of the adrenal cortex. I especially enjoyed ‘Molecularrecognition of the HPA axis’, ‘Nuclear receptor co-activators’, ‘Steroid hormonereceptors’ and ‘Orphan nuclear receptors and metabolic signalling’. As well aslearning about areas of direct relevance to my project, the conference alsoincreased my general knowledge of endocrinology.
OURANIA KOSTI
This was the perfect opportunity to attend sessions relevant to my interests,including the cross-talk between steroid receptors and cell signalling pathways, andsymposia on diabetes and thyroid research. The ‘New technology lectures’ are alwaysa great favourite of mine, and help to increase my knowledge of cutting-edgeresearch methodology.
PING YE
I attended the 28th International Aldosterone Conference before ENDO 2002.This was an excellent opportunity to meet with specialists in the field. Highlightsincluded Melyssa Bratton’s impressive work, showing that the mineralocorticoidreceptor can interact directly with cardiac myosin binding protein-c. This meansthat it may be able to exert effects more rapidly than if it acted through a genomicmechanism, and so may have important implications in cardiac fibrosis.
SCOTT MACKENZIE
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The Society is pleased to be able to support its members’ attendance at meetings throughthe provision of travel grants. Here are some reports from recent events.
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Albumin,evolution andsteroid actionThe evolution of albumin, steroidhormone action and the origin ofvertebrates are inter-related in thisfascinating review, which forms part ofa special issue entitled ‘Beyond carrierproteins’. Here, Baker suggests that anancestral albumin was present inprotochordates and primitivevertebrates. During its evolution intothe major human serum protein, itmay have played an essential role insteroid hormone signalling.
Albumin’s modulation of steroidaction would depend on its abundanceand differences in affinity for steroidhormones, their metabolites,analogues and receptors. Similarly, itcould prevent disruption of endocrineresponses by exogenous chemicals.The author also analyses the phylo-genetic origins of adrenal and sexsteroid receptors, which are believedto originate from genome duplicationsbefore or during the Cambrianexplosion, over 500 million years ago.
Twelve exciting reviews make upthis special issue of Journal ofEndocrinology, and take a cross-cuttinglook at the multifunctional andregulatory roles of hormone-bindingproteins. They originate from asymposium held at the 2002 AnnualMeeting of the Society for Integrativeand Comparative Biology.(See the full article in Journal ofEndocrinology 175(1), October 2002 orread it, free of charge, athttp://journals.endocrinology.org)
Corticosteroidactions onosteoclastsAlthough often prescribed for theiranti-inflammatory and immuno-suppressive properties, chronictreatment with corticosteroidscommonly causes bone loss andosteoporosis. The precise mechanisms
are unclear, but are thought to involvethe bone-remodelling unit of osteo-blasts and osteoclasts. This study byHirayama et al. analyses the effect ofdexamethasone, a synthetic cortico-steroid, on the formation and bone-resorbing activity of humanosteoclasts in vitro.
Dexamethasone had a biphasiceffect. It promoted differentiation andproliferation of multi-nucleate cellswith osteoclastic markers when addedto monocytes in early stages of culture.This agrees with observations ofincreased osteoclast numbers in bonebiopsies from patients with steroid-associated osteoporosis. Delayedtreatment with dexamethasone had aless dramatic effect, inhibiting bone-resorption by mature osteoclasts. Thismay be attributed to increased osteo-clast apoptosis.
The authors conclude that theinhibition of osteoclast formation maybe an effective basis for therapy ofcorticosteroid-induced osteoporosis,with the aim of stabilising the bone-remodelling unit. (See the full article in Journal ofEndocrinology 175(1), October 2002)(Subsequent work (Journal of Pathology, In
Press) has indicated that steroids
specifically inhibit receptor activator of NF-
kappaB ligand-induced, but promote
cytokine-induced, osteoclast formation.)
Model for adipose
a2-ARsCatecholamines regulate white adiposetissue function and development viaadrenergic receptors (ARs). Inhumans, this tissue mainly expressesa2-ARs, with few or no b3-ARs.Rodents show a predominance of b3-ARs, which has limited theirusefulness in studies of a2-ARs inadipose development.
In this paper, Boucher andcolleagues report the use of transgenicmice for studies of human hyperplasticobesity. Lines were established thatcarried the human b3-AR and a2-ARtransgenes (including the human generegulatory elements) on a murine b3-AR gene knockout background.Analysis showed a ‘human-like’pattern of adipocyte a2-ARexpression. When the mice were fed ahigh fat diet (unlike controls) they
became obese due to hyperplasiarather than hypertrophy. Interestingly,they did not have elevated glucose andinsulin levels and did not suffer frominsulin resistance or high bloodpressure (as is usually the case forobese mice).
This model will be invaluable instudying factors that affect theregulation of a2-AR, such as nutritionand hormones. It will also aidunderstanding of the interactionbetween a high fat diet and a2-AR inthe development of white adiposetissue, and could be used to assess theefficacy of drugs in obesity.(See the full article in Journal ofMolecular Endocrinology 29(2),October 2002)
Monitoring breast cancerComparison of neoadjuvant (pre-surgical) with adjuvant chemotherapyin breast cancer has principallyconcluded that the neoadjuvantapproach leads to a slight reduction inmastectomy, but with a marginallyhigher risk of local recurrence.
However, neoadjuvant therapy alsoprovides a unique opportunity tostudy tumour response. In this review,Cleator and co-workers discuss the useof serial biopsies in the course ofneoadjuvant chemotherapy. In theabsence of a means of predictingresponse to chemotherapy, thesebiopsies may yield predictive markersthat show a correlation with patientoutcome. This could increaseunderstanding of the molecularmechanisms of tumour growth anddrug resistance, and help determineoptimum modes of treatment.
The authors describe how tumourprogression is measured, the mostcommon anti-cancer drugs, and thebiological basis of drug resistance inbreast cancers. As new data emerges,we may be able to use newtechnologies such as comparativegenomic hybridisation, real-time PCR,expression microarray and proteomicsto improve the outcome for breastcancer sufferers.(See the full article in Endocrine-RelatedCancer 9(3), September 2002)
Hot TopicsHighlights from articles in the Society’sjournals, brought to you by NathalieGilmore and Jane Shepley.
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ReferenceManager 10ISI ResearchSoft 2002
(www.adeptstore.com)
Anyone with experience in
research, writing papers or
theses, will appreciate the amount
of work involved in tracking down
references, creating databases and
generating a bibliography in the
appropriate format. Reference
Manager aims to ease this task.
The package comprises an online
research tool, reference database and a
bibliography maker. It provides a simple
way of searching online bibliographic
databases and can import and store the
files in reference databases. When you
use Reference Manager to insert citations
into your documents, it will generate a
bibliography in any format that you need.
Reference Manager 10 has severaladditional features. These include newfields in each reference page to addlinks to documents, PDF files, imagesand articles, and an auto-updatefeature to download updates to theprogram and content files via theinternet. The ‘cite while you write’feature, which allows you to insertreferences as you write yourdocument, has been upgraded to havean instant formatting function. Thisgenerates a formatted bibliographyinstantly.
The ‘travelling library’ is one of thebest new features. It is createdautomatically as you cite references inMicrosoft Word. Information about thecitation is stored in the appropriatefield code, which allows yourcollaborators to insert citations intothe document and create abibliography without having to sharedatabases (i.e. they can use their own).
Symposia• Androgens and prostate cancer
• Prolactin: novel aspects
• Apoptosis/survival signalling
• Trophic control of size
• The adipocyte as an endocrine organ
• Emerging hot topics
• Dominant endocrine cancer syndromes
• Radio-iodine biology in the 21st century
plus Plenary Lectures, Clinical Management and Molecular EndocrinologyWorkshops, ‘The Expert View’, Focussed Science Session, Oral Communications, andYoung Endocrinologists and Nurses Sessions
Abstract deadline: Friday 15 November 2002
Further details and preliminary programmes from: Liz Brookes, BES, 17/18 The Courtyard, Woodlands, Bradley Stoke, Bristol BS32 4NQ (Tel: 01454-642210; Fax: 01454-642222; Email: [email protected]; Web:www.endocrinology.org/sfe/confs.htm)
BES 200322ND JOINT MEETING OF THE
British Endocrine Societies24-26 March 2003Glasgow, UK
However, if your collaborators havethe same reference in one of theirdatabases as you have in yours, butthe record number is different, thenthe reference will not be recognised asthe same citation and will thereforeappear twice in the bibliography!
The only inconvenience I foundwas associated with upgrading from anolder version. I had to install the newversion and then copy all my old filesto it. I found a slight ambiguity in theinstructions and had to repeat theprocess several times. If you have anyproblems, the technical support viaemail is excellent.
I think investing in ReferenceManager 10 is very worthwhile. Anyinitial time spent learning how to usethe package is more than compensatedfor by the immense amount of timeand effort it saves.
PEAK MANN MH
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It was back in 1949 that Hench,Kendall, Slocumb and Polley’s seminalobservations on the use of compoundE in rheumatoid arthritis appeared.Perhaps the after effects of the 2002World Cup have brought out the JohnMotson in me, but I couldn’t helpnoticing that the editors of thisvaluable work have assembled animpressive team of 49 contributorsfrom a large range of specialities. Isuspect, however, that this symmetryis entirely fortuitous!
This is a comprehensive exposé ofthe use of corticosteroids in 21st
century medicalpractice. Asexpected, thebook is bang upto date, andcovers thetherapeuticpotential, as wellas the side effect‘dark side’, ofsteroid use. For
those seeking the cosy warmth ofMotson-esque statistics, it is dividedinto 5 sections: 2 introductorychapters, 2 on basic science, 10addressing systemic effects, 13 onclinical usage, and 6 on specialmanagement issues, including medicallegal aspects (for readers in the USA).
There is relatively little repetitionand I thoroughly enjoyed this book,and certainly revised a lot of generalmedicine. It is in this aspect that Ithink that it scores highly - as a quick
and authoritative text on the use ofcorticosteroids to manage the manyand varied inflammatory conditionsthat we all encounter in the acutemedical setting. When ‘playing athome’, in the chapters on investigationand management of hypo- orhyperadrenalism, I found myself inbroad agreement, though,unsurprisingly, could not agree witheverything. I am sure that othersreading from the perspective of theirown specialities will have a similarexperience. Overall, however, I wasimpressed with the clarity of writingand general layout.
This book should certainly be anessential part of any library and, forthose involved in general medicine, apersonal copy on the office shelf wouldbe highly relevant and most comforting.It is not, nor does it attempt to be, aspecialised endocrine text.
JOHN NEWELL-PRICE
‘Nothing is simple about thispathway ... all aspects are fascinating’conclude Rozman and Waterman intheir chapter on sterol biosynthesis.That statement for steroid aficionadosapplies to the whole book.
The current knowledge ofcholesterol dynamics is covered veryeffectively, and a number of functionaland developmental disordersattributable to abnormalities ofcholesterol and steroid synthesis aredescribed. Mutations have providedvaluable information concerning thestructure-function relationships of anumber of the enzymes, and willinfluence the design of new therapeuticagents. There are now few parts of themetabolic pathway yet to be geneticallydefined. The search for proteinsinvolved in cholesterol trafficking willprobably remain a difficult task.Molecular biology has clarified a
number ofissues insteroidendocrinology.Lipoid adrenalhyperplasia iscaused bydefects insteroidogenicacute regulatory(StAR) protein
and not side chain cleavage, asenvisaged by biochemical studies. Thediscovery of StAR may represent one ofthe most significant advances in steroidresearch in recent years. Consideringthe immense interest of Britishendocrinologists in 11b-hydroxysteroiddehydrogenase, the enzymes and genesare given limited coverage in a shortchapter on peripheral steroidmetabolism. Animal and humanmodels of oestrogen deficiency haverevealed unsuspected roles foroestrogens in males and females.
In terms of function, the nuclearreceptor family is responsible for theactions of steroids, and is presentedprimarily in one general chapter onregulation of gene expression. Thischapter lacks the clinical scenarios thatare featured in most other contributions,
so that some misconceptions are notcovered. Hence, pseudohypoaldo-steronism is rarely due to disorders ofthe mineralocorticoid receptor but isusually the consequence of profoundrenal sodium loss through a defectiveamiloride-sensitive, epithelial sodiumchannel. The non-genomic actions ofsteroids through membrane receptorsare sadly only discussed in relation toactions of steroids in the brain. Theregulation of the pathways and theenzymes themselves are now underintense investigation for the relevantrepressors, co-repressors, co-activatorsand co-integrators. An outstandingchallenge is a full explanation for theindependent regulation of the multiplefunctions of CYP17, although thechapter went some way to clarifyingthis. New directions of exploration areto be anticipated in relation to steroidsin the brain.
The references are in the main fromthe 15 years up to 2001, usefullyreflecting the period of intense activityto define genes and locate the basis ofgenetic disorders. The book highlightsmany new and exciting opportunitiesfor future research.
JOHN W HONOUR
Principles ofCorticosteroidTherapyA N Lin & S A Paget (Eds), Arnold,2002, 465 pp, £85.00, ISBN 0 340 75934 8
Genetics of SteroidBiosynthesis andFunctionEd J I Mason, Taylor & Francis, 2002,479 pp, £75.00, ISBN 0 415 27878 3
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9th European Federation of EndocrineSocieties Postgraduate Course in ClinicalEndocrinologyComo, Italy, 17-19 October 2002.Contact: Organising Secretary, Centro Culturale AVolta, Villa Olmo, Via Cantoni 1, 22100 Como,Italy (Tel: +39-03-1579812; Fax: +39-03-1573395; Email: [email protected]).
Peptides and Non-peptides ofNeuroendocrine and Oncologic RelevanceComo, Italy, 17-19 October 2002.Contact: Eugenio E Müller, Department ofPharmacology, University of Milan, Via Vanvitelli32, 20129 Milan, Italy (Tel: +39-02-58357010/7012; Fax: +39-02-58357011; Email: [email protected]).
Prader-Willi Syndrome as a Model forObesity: Symposium in Memory ofAndra PraderZürich, Switzerland, 18-19 October 2002.Contact: Dr Urs Eiholzer, for Growth PubertyAdolescence Foundation, Möhrlistrasse 69, 8006Zürich, Switzerland (Tel: +41-1-3643700; Fax:+41-1-3643701; Email: [email protected];Web: www.childgrowth.org).
2nd International Conference on Obesity: Obesity - a Woman’s Health ProblemCorfu, Greece, 26 October 2002.Contact: Dr A Michalopoulos (Tel: +30-661-037540; Fax: +30-661-034206; Email:[email protected]; Web: www.corfuxenos.gr).
193rd Meeting of the Society forEndocrinology, including a jointEndocrinology and Diabetes Day inassociation with Diabetes UKLondon, UK, 4-6 November 2002.Contact: Society for Endocrinology, 17/18 TheCourtyard, Woodlands, Bradley Stoke, BristolBS32 4NQ, UK (Tel: +44-1454-642210; Fax: +44-1454-642222; Email: [email protected]; Web: www.endocrinology.org/sfe/confs.htm).
30th Meeting of the British Society for Paediatric Endocrinology andDiabetes 2002Plymouth, UK, 13-15 November 2002.Contact: BioScientifica Ltd, 16 The Courtyard,Woodlands, Bradley Stoke, Bristol BS32 4NQ, UK(Tel: +44-1454-642210; Fax: +44-1454-642222;Email: [email protected]; Web: www.bspe.shef.ac.uk).
Hormones, Body Composition andPhysical PerformanceTurin, Italy, 15 November 2002.Contact: Organising Secretariat, Centro CongressiInternazionale srl, Via Cervino 60, 10155 Torino,Italy (Tel: +39-01-12446911; Fax: +39-01-12446900; Email: [email protected]; Web: www.congressiefiere.com).
University of Exeter Advanced Diabetes CourseExeter, UK, 20-22 November 2002.Contact: Ruth Hooper, Department of Diabetesand Vascular Medicine, Barrack Road, Exeter EX25AX, UK (Tel: +44-1392-403089; Fax: +44-1392-403027; Email: [email protected]).
2nd International Symposium onProgestins, Progesterone ReceptorModulators and ProgesteroneAntagonistsSiena, Italy, 20-23 November 2002.Contact: Tzina Lindenberg (Tel: +972-2-6555188; Fax: +972-2-6522018;Email: [email protected]; Web: www.unisi.it/eventi/progestins).
Parathyroid Localisation: Utility of Diagnostic ImagingLondon, UK, 22 November 2002.Contact: Daksha Thakrar, BMS Medical Imaging(Fax: +44-20-83617982; Email: [email protected]).
Brain-Immune Interactions in Stress:The Impact of Hormones on DiseaseBristol, UK, 30 November 2002.Contact: David Jessop, University ResearchCentre for Neuroendocrinology, University ofBristol, Bristol Royal Infirmary, MarlboroughStreet, Bristol BS2 8HW, UK (Tel: +44-117-9283402; Fax: +44-117-9283315; Email: [email protected]; Web: www.bris.ac.uk/depts/bing/main.htm).
Are endocrine active chemicals bad for your health?Cambridge, UK, 24 January 2003.Contact: Susan Wicks, The Academy of MedicalSciences, 10 Carlton House Terrace, LondonSW1Y 5AH, UK (Tel: +44-20-7969-5289; Fax: +44-20-7969-5298; Email: [email protected]; Web: www.acmedsci.ac.uk).
7th International Symposium on Graves’ Ophthalmopathy,Pisa, Italy, 6-8 February 2003.Contact: Tre Emme Congressi srl, ViaRisorgimento 4, 56126 Pisa, Italy (Tel: +39-05-044154; Fax: +39-05-0500725; Email: [email protected]; Web: www.treemmecongressi.it).
2nd International Workshop on the Genetics of Bone Metabolism and DiseaseDavos, Switzerland, 15-18 February 2003.Contact: European Calcified Tissue Society, POBox 4, Dursley GL11 6YL, UK (Tel: +44-1453-549929; Fax: +-44-1453-548919; Email: [email protected]; Web: www.ectsoc.org).
Society for Endocrinology Clinical Cases MeetingLondon, UK, 26 February 2003.Contact: Society for Endocrinology, 17/18 TheCourtyard, Woodlands, Bradley Stoke, BristolBS32 4NQ, UK (Tel: +44-1454-642200; Fax: +44-1454-642222; Email: [email protected]; Web: www.endocrinology.org/sfe/train.htm).
Imaging in EndocrinologyLondon, UK, 27 February 2003.Contact: Caroline Eason, Royal College ofRadiologists, 38 Portland Place, London W1N4JQ, UK (Tel: +44-207-6364432 ext 124; Email: [email protected]).
BES 2003: 22nd Joint Meeting of the British Endocrine SocietiesGlasgow, UK, 24-26 March 2003.Contact: British Endocrine Societies, 17/18 TheCourtyard, Woodlands, Bradley Stoke, BristolBS32 4NQ, UK (Tel: +44-1454-642210; Fax: +44-1454-642222; Email: [email protected]; Web: www.endocrinology.org/sfe/confs.htm).
NOMINATIONS FOR THE
ELI LILLY HYPOCCS 2003 AWARD
The award consists of a certificate and a financial reward of US $20,000 and will be presented on the occasion of the next
annual HypoCCS Symposium in Prague, Czech Republic, 12-15 March 2003. The recipient will be invited to give a lecture
and submit a manuscript that will be published in theproceedings of the HypoCCS Symposium
Please contact Pierre Sizonenko (Email: [email protected]) for further information
Nominations must be received by 15th October 2002
Serono Foundation for the Advancementof Medical Science: Workshop onMolecular SteroidogenesisBath, UK, 24-27 April 2003.Contact: Helen Gregson or Liz Brookes,BioScientifica Ltd, 16 The Courtyard, Woodlands,Bradley Stoke, Bristol BS32 4NQ, UK (Tel: +44-1454-642212; Fax: +44-1454-642222; Email: [email protected]; Web: www.eurosterone.org/serono/index.html).
6th European Congress of EndocrinologyLyon, France, 26-30 April 2003.Contact: Congress Agency Scientific Secretariat,Transit Communications, 18 Place Tolozan, F-69001 Lyon, France (Tel: +33-4-72985858; Fax: +33-4-72985898; Email: [email protected]; Web: www.endocrinology2003.com).
ALDO‘03: International Symposium onAldosteroneLondon, UK, 28-30 April 2003.Contact: Helen Gregson or Liz Brookes,BioScientifica Ltd, 16 The Courtyard, Woodlands,Bradley Stoke, Bristol BS32 4NQ, UK (Tel: +44-1454-642212; Fax: +44-1454-642222; Email: [email protected]; Web: www.bioscientifica.com/aldo03).
30th European Symposium on Calcified TissuesRome, Italy, 8-12 May 2003.Contact: Janet Crompton, The Old White Hart,North Nibley, Dursley GL11 6DS, UK (Tel: +44-1453-549929; Fax: +44-1453-548919; Email: [email protected]; Web: www.ectsoc.org).
ENDO 2003: 85th Annual MeetingPhiladelphia, PA, USA, 19-22 June 2003.Contact: Beverly Glover, Administrative Assistant,Meetings, The Endocrine Society, 4350 East WestHighway, Suite 500, Bethesda, MD 20814-4410,USA (Tel: +1-301-9410220; Fax: +1-301-9410259; Email: [email protected]; Web: www.endo-society.org).
4th International Symposium onHormonal CarcinogenesisValencia, Spain, 21-25 June 2003.Contact: Tandria Price/Dr Jonathan J Li,Department of Pharmacology, Toxicology andTherapeutics, Mail Stop 1018, University ofKansas Medical Center, 3901 Rainbow Blvd,Kansas City, KS 66160-7417, USA (Tel: +1-913-5884744; Fax: +1-913-5884740; Email: [email protected]; Web: www.kumc.edu/hormonecancers).
National Osteoporosis Society: 9th Bath Conference on OsteoporosisBath, UK, 22-26 June 2003.Contact: Jackie Brown, National OsteoporosisSociety, Camerton, Bath BA2 0PJ, UK (Tel: +44-1761-471771; Fax: +44-1761-471104; Email:[email protected]; Web: www.nos.org.uk).
FOR
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A workshop covering the following topics:
Proteins and receptors
Impact on reproduction anddevelopment
Cell differentiation and cancer
Inflammation
Inhibins, Activinsand Follistatins
Siena, Italy
3-4 July 2003
Contact: P Florio/D D’Antona/S Luisi, Obstetrics and Gynecology, University of Siena, Viale Bracci, 53100 Siena, Italy (Fax +39-0577-233454;
Email: [email protected]; Web: www.unisi.it/eventi/inhibin2003)
SCIENTIFIC COMMITTEE:
N P Groome (UK)
D de Kretser (Australia)
F Petraglia (Italy)
Alan Schneyder (USA)
Wylie Vale (USA) Abstract deadline: 31 January 2003
75th Annual Meeting of the AmericanThyroid AssociationPalm Beach, FL, USA, 16-21 September 2003.Contact: ATA, 6066 Leesburg Pike, Suite 650,Falls Church, VA 22041, USA (Email:[email protected]; Web: www.thyroid.org).
42nd Annual Meeting of the EuropeanSociety of Paediatric EndocrinologyLjubljana, Slovenia, 18-21 September 2003.Contact: Dr Ciril Krzisnik, Department ofPaediatric Endocrinology, Diabetes and MetabolicDiseases, University Children’s Hospital,University Medical Center Ljubljana, Vrazov trg 1,1000 Ljubljana, Slovenia (Tel: +38-6-12320887;Fax: +38-6-12310246; Email: [email protected]; Web: www.eurospe.org/meetings.jsp).
25th Annual Meeting of the AmericanSociety for Bone and Mineral ResearchMinneapolis, MN, USA, 19-23 September 2003.Contact: ASBMR, 2025 M Street, NW Suite 800,Washington, DC 20036-3309, USA (Tel: +1-202-3671161; Email: [email protected]; Web: www.asbmr.org).
10th European Federation of EndocrineSocieties Postgraduate Course inClinical EndocrinologyOxford, UK, 26-28 September 2003.Contact: Helen Gregson, BioScientifica Ltd, 16The Courtyard, Woodlands, Bradley Stoke, BristolBS32 4NQ, UK (Tel: +44-1454-642212; Fax: +44-1454-642222; Email: [email protected]; Web: www.euro-endo.org).
59th Annual Meeting of the AmericanSociety for Reproductive Medicine(ASRM 2003)San Antonio, TX, USA, 11-16 October 2003.Contact: ASRM, 1209 Montgomery Highway,Birmingham, AL 35216-2809, USA(Tel: +1-205-9785000; Fax: +1-205-9785018;Email: [email protected]).
194th Meeting of the Society for EndocrinologyLondon, UK, 3-5 November 2003Contact: Society for Endocrinology, 17/18 TheCourtyard, Woodlands, Bradley Stoke, BristolBS32 4NQ, UK (Tel: +44-1454-642210; Fax: +44-1454-642222; Email: [email protected]; Web: www.endocrinology.org/sfe/confs.htm).
BES 2004: 23rd Joint Meeting of theBritish Endocrine Societies in association with EFESBrighton, UK, 22-24 March 2004.Contact: British Endocrine Societies, 17/18 TheCourtyard, Woodlands, Bradley Stoke, BristolBS32 4NQ, UK (Tel: +44-1454-642210; Fax: +44-1454-642222; Email: [email protected];Web: www.endocrinology.org/sfe/confs.htm).
31st European Symposium on Calcified TissuesNice, France, 5-9 June 2004.Contact: European Calcified Tissue Society, POBox 4, Dursley GL11 6YL, UK (Tel: +44-1453-549929; Fax: +44-1453-548919; Email: [email protected]; Web: www.ectsoc.org).
ENDO 2004: 86th Annual MeetingNew Orleans, LA, USA, 16-19 June 2004.Contact: Beverly Glover, Administrative Assistant,Meetings, The Endocrine Society, 4350 East WestHighway, Suite 500, Bethesda, MD 20814-4410,USA (Tel: +1-301-9410220; Fax: +1-301-9410259; Email: [email protected]; Web: www.endo-society.org).
International Society of EndocrinologyCongress 2004Lisbon, Portugal, 1-4 September 2004.Contact: ISE, Department of ChemicalEndocrinology, 51-53 Bartholomew Close, LondonEC1A 7BE, UK (Tel: +44-20-76064012; Fax: +44-20-77964676).
43rd Annual Meeting of the EuropeanSociety of Paediatric EndocrinologyHaifa, Israel or Basel, Switzerland, 10-13September 2004.Contact: Professor Ze’ev Hochberg, Department ofPediatrics, Rambam Medical Center, PO Box 9602,Haifa 31096, Israel (Tel/Fax: +972-4-8542157;Email: [email protected]; Web: www.eurospe.org/meetings.jsp).
30th Annual Meeting of the European Thyroid AssociationIstanbul, Turkey, 18-22 September 2004.Contact: Prof. Gurbuz Erdogan (Email:[email protected]).
76th Annual Meeting of the American Thyroid AssociationVancouver, Canada, 29 September-3 October 2004.Contact: ATA, 6066 Leesburg Pike, Suite 650,Falls Church, VA 22041, USA (Email:[email protected]; Web: www.thyroid.org).
Serono Foundation for the Advancementof Medical Science: Workshop onInhibins, Activins and FollistatinsSiena, Italy, 3-4 July 2003.Contact: Pasquale Florio, Obstetrics andGynecology, University of Siena, Viale Bracci,53100 Siena, Italy (Tel/Fax: +39-05-77233454;Email: [email protected]; Web: www.unisi.it/eventi/inhibin2003).
FEBS 2003 Meeting on SignalTransduction: Signal Transduction - from Membrane to Gene Expression,from Structure to DiseaseBrussels, Belgium, 4-8 July 2003.Contact: V Wouters (Tel: +32-2-7795959; Fax: +32-2-7795960; Email: [email protected]; Web: www.febs-signal.be).
12th Vitamin D WorkshopMaastricht, The Netherlands, 6-10 July 2003.Contact: Dr R Bouillon, LEGENDO, Onderwijs enNavorsing (9e Verd), Gasthuisberg, B-3000,Leuven, Belgium (Tel: +32-16-345971; Fax: +32-16-345934; Email: [email protected]).
Bone and Tooth Society Annual MeetingSheffield, UK, 9-11 July 2003.Contact: Janet Crompton, The Old White Hart,North Nibley, Dursley GL11 6DS, UK (Tel: +44-1453-549929; Fax: +44-1453-548919;Email: [email protected];Web: www.batsoc.org.uk).
University of Exeter Advanced Diabetes CourseExeter, UK, 9-11 July 2003.Contact: Ruth Hooper, Department of Diabetesand Vascular Medicine, Barrack Road, Exeter EX25AX, UK (Tel: +44-1392-403089; Fax: +44-1392-403027; Email: [email protected]).
Fertility 2003: Joint Meeting of theSociety for Reproduction and Fertility,British Fertility Society and BritishAndrogen SocietyAberdeen, UK, 13-17 July 2003.Contact: Victoria Withy, BioScientifica Ltd, 16The Courtyard, Woodlands, Bradley Stoke, BristolBS32 4NQ, UK (Tel: +44-1454-642210; Fax: +44-1454-642222; Email: [email protected]; Web: www.fertility2003.com).
Advances in the Molecular Pharmacologyand Therapeutics of Bone DiseaseOxford, UK, 15-16 July 2003.Contact: Janet Crompton, The Old White Hart,North Nibley, Dursley GL11 6DS, UK (Tel: +44-1453-549929; Fax: +44-1453-548919;Email: [email protected]; Web: www.paget.org.uk).
Society for Endocrinology SummerSchool 2003 (Molecular EndocrinologyWorkshop, Advanced Endocrine Courseand Clinical Practice Day)Manchester, UK, 15-18 July 2003.Contact: Ann Lloyd, Society for Endocrinology,17/18 The Courtyard, Woodlands, Bradley Stoke,Bristol BS32 4NQ, UK (Tel: +44-1454-642200;Fax: +44-1454-642222; Email: [email protected]).
International Symposium on Paget's DiseaseOxford, UK, 16-19 July 2003.Contact: Janet Crompton, The Old White Hart,North Nibley, Dursley GL11 6DS, UK (Tel: +44-1453-549929; Fax: +44-1453-548919;Email: [email protected]; Web: www.paget.org.uk).
Society for Endocrinology Endocrine Nurses Training Course: The Pituitary GlandDurham, UK, 10-12 September 2003.Contact: Ann Lloyd, Society for Endocrinology,17/18 The Courtyard, Woodlands, Bradley Stoke,Bristol BS32 4NQ, UK (Tel: +44-1454-642200; Fax: +44-1454-642222; Email: [email protected]; Web: www.endocrinology.org/sfe/train.htm).
4-6 November 2002Royal College of Physicians, London
European Medal Lecture I HuhtaniemiAsia & Oceania Medal Lecture E SimpsonSociety for Endocrinology Medal Lecture ICAF Robinson
SymposiaMaintenance of pregnancyTranscriptional control of endocrine development and functionAgeing and cellular senescenceNovel aspects of thyroid disease
plus Debate, Oral Communications, Poster Presentations,Young Endocrinologists and Nurses Sessions
New for 2002!
Additional day in association withLecturesPPARg - M GurnellPolycystic ovary disease - S FranksPKC inhibitors and glucose toxicity - P DodsonObesity symposiumAppetite control - S BloomHuman mutations causing obesity - S O’RahillyCurrent therapeutics of obesity - N Finer
plus SpR posters, Expert Sessions (Impotence, Lumps in the Thyroid) and Workshop
Further information from:Liz Brookes, Society for Endocrinology,17/18 The Courtyard, Woodlands, Bradley Stoke, Bristol BS32 4NQ, UK (Tel: 01454-642210; Fax: 01454-642222; Email: [email protected]; Web: www.endocrinology.org)
193rd Meeting of the Society for Endocrinology
