endocrinology of the prostate
TRANSCRIPT
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that a wrong diagnosis had been made : "The factswere there but we did not think right." To think logicallyfrom the evidence at hand is the ultimate aim in theeducation of the vast majority of medical practitioners.
THE BUSY MIND
I can hear your impatient exclamation that you haveno time for all this-to keep your patients living andget your own living is the size of your job. It is so fullthat good things have to be pushed out to get goodthings in. As I once cabled to American friends demand-
ing rooms in Gleneagles Hotel in August " Can onlyget more Americans in by turning Americans out." Ido not pretend to know which school of psychology isnow uppermost, but Spearman says " mental competi-tion with the law of constant output rules our actualintellectual lives. The commencement of any mentalactivity causes other activity to cease, and vice versa.The law of constant output is thus stated: Everymind tends to keep its total simultaneous output con-stant in quantity, however varying in quality." Thedifficulty was more attractively and provocativelystated by a medical man who has done more thanmost for human well-being-Conan Doyle, with hischampion therapeutic, Sherlock Holmes, in his veryfirst introduction to the public in " A Study in Scarlet."May I read a few lines ? You will remember thatSherlock always had access to an extraordinary range ofitems of human knowledge in out of the way coroners :
" My surprise reached a climax, however, when Ifound incidentally that he was ignorant of theCopernican Theory and of the composition of theSolar System. That any civilised human being inthis nineteenth century should not be aware thatthe earth travelled round the sun appeared to be tome such an extraordinary fact that I could hardlyrealise it. ’You appear to be astonished,’ he said,smiling at my expression of surprise. ’Now that Ido know it I shall do my best to forget it.’To forget it! ’" You see,’ he explained, I consider that a man’s
brain originally is like a little empty attic, and youhave to stock it with such furniture as you choose.A fool takes in all the lumber of every sort that hecomes across, so that the knowledge which might beuseful to him gets crowded out, or at best is jumbledup with a lot of other things, so that he has a difficultyin laying his hands upon it. Now the skilful workmanis very careful indeed as to what he takes into hisbrain-attic. He will have nothing but the toolswhich may help him in doing his work, but of thesehe has a large assortment, and all in the most perfectorder. It is a mistake to think that that little roomhas elastic walls and can distend two any extent.Depend upon it there comes a time when for everyaddition of knowledge you forget something that youknew before. It is of the highest importance, therefore,not to have useless facts elbowing out the useful ones.’" But the Solar System ! ’ I protested." What the deuce is it to me ? ’ he interrupted
impatiently : ’you say that we go round the sun.It we went round the moon it would not make apennyworth of difference to me or to my work.’ "
Now quite possibly the contemplation of the patientin his position in your scientific problem may detracta little from your bedside manner, and the human touchBut I doubt it. I believe you will so strengthen yourartistic human perceptions by your scientific conceptionsthat you will have a stronger inner sense. After a timethe induction becomes the instinct, the reasoned rulesublimates into the sublimer guesswork. You are not
being asked to carry a new load of facts so much as toacquire and maintain an additional "awareness "-an extra attitude of mind. William James once said:" I have no doubt whatever that most people live,whether physically, intellectually or morally, in a very
restricted circle of their potential being. They make useof a very small portion of their possible consciousness,and of their soul’s resources in general, much like aman who, out of his whole bodily organism, should getinto a habit of using and moving only his little finger."
* * *
Have I been talking high-falutin ? As Kelvin says," We do not know much about anything until we havelearned to measure it." To which you will add: andwhen we have measured it, perhaps its vital spirit haseluded us. Some of you will be cynical and will say inreply to my question, " Is medical practice scienceor art?" what the Oxford don did about logic-it is neither an art nor a science but a dodge.Canon Streeter said : "We shall in no way disparagescience because quality is excluded from its purview;any more than we decry an ordnance map because itcan give us no idea of the view from Richmond Hill."In truth the doctor must have science and art as twoblades of a pair of scissors-singly they are imperfectinstruments, but together the mind uses them to cutinto the fabric of the living unknown.
ENDOCRINOLOGY OF THE PROSTATE
AN annotation on Jan. 21 reviewed several paperson the aetiology of benign enlargement of the prostate.A number of related studies also require consideration.Deming and Neumann (1939), in a report based on
microscopical study of prostates obtained at autopsyfrom subjects aged 45 or more, agree with Cuneoin rejecting the view that the suburethral glands ofAlbarran are involved in the early stages of benignenlargement. In their opinion the hypertrophybegins as a fibromyomatous change in the posteriorwall of the urethra and in the internal sphincter ofthe bladder, and they point out that this musculartissue is partly of mullerian origin, and that thechange therefore corresponds to fibromyomatousgrowths in the uterine wall. They hold that theglandular part of the tumour originates from ductsadjacent to the fibromyomatous nodule, and that theseducts invade the nodule, which in its later stagesthus simulates an encapsulated glandular tumour.Unfortunately, pathological investigations of thekind conducted by Deming and Neumann cannoteither confirm or refute the view (which in a sensedirected their inquiry and is derived from experi-ments) that prostatic adenomata develop as a resultof cestrogenic stimulation of the uterus masculinusand of the fibromuscular tissue within which it lies.
This hypothesis assumes that an effective oestro-
genic stimulus may become operative in men ofmiddle age, a possibility which has been discussedby Emmens and Parkes (1938) in view of the knowncestrogenic behaviour of some of the male-hormonecompounds. It appears that several male-hormonesubstances (including testosterone) exhibit a generalgynaecogenic action. One of the androgenic com-pounds, transandrostenediol, shows unmistakableoestrogenic activity, and although it is not knownto occur naturally it may do so, because it belongsto the androsterone-testosterone series. Emmensand Parkes, in an attempt to discover whether itcould be the elusive oestrogen of the testis tried tofind out if testosterone could inhibit the oestrogeniceffect of an extract of pig’s testis in the same wayas it inhibits the effect of cestrone; but, if thecestrogenic activity of the extract of pig’s testishad been due to transandrostenediol, 1 mg. of thesubstance would have had to be present in 7-5 mg.
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of the extract, which would have entailed a corre.sponding androgenic potency far greater (about ninetimes) than that which the extract was subsequentlyshown to possess. Two conclusions regarding thetesticular oestrogen may therefore be drawn fromthis observation : (a) it is not transandrostenediolor any other known member of the androsterone-testosterone series ; and (b) its effect can be inhibitedby testosterone.A further possibility considered by Emmens and
Parkes is that the suprarenal cortex may elaboratean cestrogenic substance in the male. It is knownthat suprarenal disturbance may lead to an increasedexcretion of oestrogens and that cestrogenic substancescan be extracted from the suprarenals. Their possibleparticipation in prostatic enlargement must thereforebe taken into consideration ; but the study of thisaspect of the suprarenals is only beginning, and theavailable evidence is very confusing.
It is well known that the prostate of a newbornhuman baby often exhibits metaplastic changesin its epithelium similar to those that develop inmonkeys and rodents treated with oestrogenicsubstances. This fact is today regarded as indicatingthat oestrogenic substances from the maternal
organism enter the fcetus from the maternal circulation.Hamilton et al. (1937) and Moore and McLellan(1938) have reported on the effects of oestrogenicstimulation on mature men, but their results are
conflicting. According to Hamilton and his co-workerscestrone has no carcinogenic action on the prostateof man, nor does it intensify dysfunction in the
urinary tract. More recently, however, Moore andMcLellan, who injected greater quantities of thehormone, found that cestrone had a profound anddefinite effect on the tissues of the prostate. Themost conspicuous change is in the epithelium of theurethra and prostatic collecting ducts, which showsincreased stratification of the usual transitionalepithelium and foci of true squamous metaplasia.This finding is of particular interest because of thesimilarity of the histological changes to those in theprostate of the newborn infant. The epithelial aciniand stroma of the adenomatous nodules show littleeffect of the oestrogen, but an abundance of lymphoidtissue was noted. All these effects of cestrogenicstimulation in man represent, according to Moore andMcLellan, an intensification of the changes observedin the benignly hypertrophied prostate of a man
not treated with an oestrogen. They are also in partsimilar to the effects, first described by de Jongh andKok (1935), of cestrogenic stimulation on the prostateof the dog. These comprise metaplastic stratificationnot only of the epithelium of the urethra and collectingducts, but also of that of the secretory acini them-selves. Petit and his co-workers (1939) have reinvesti-gated these changes, and they regard them as suffi-ciently similar to those which occur spontaneously inman to entitle their report " realisation expérimentalede Padenome prostatique."
CLINICAL EVIDENCE
If benign prostatic enlargement is due always orsometimes to abnormal cestrogenic stimulation-asit undoubtedly is in the case of the dog (Zuckermanand Groome 1937)-the primary aim of treatmentwould be the restoration of a normal balance betweenmale hormone and cestrogenic hormone. Numerousclinical reports of such treatment have alreadyappeared, and some have been discussed in thesecolumns. The evidence remains conflicting, butit may be worth while to refer to some recent paperson the subject.
Cuneo (1938) and Jomain (1938), who accept thetheory, primarily derived from experiments on
monkeys, that prostatic adenomata originate fromthe epithelial and fibromuscular tissue of the uterusmasculinus, report on the treatment of patients withtesticular extract. They prefer extracts to syntheticsubstances, such as testosterone, for they are notconvinced that one isolated chemical substancepossesses the powers of the whole testicular secretion.The initial dose given is equivalent to 1-2 g. of thegland daily, the effect includes rapid improvement offunctional disorders, and rectal and urethroscopicexamination suggests that the prostate becomessmaller. Cuneo does not claim that his treatmentcan reduce prostatic hypertrophy, but he believesthat prolonged treatment can prevent furtherenlargement.Laroche (1937) favours the use of the acetate and
propionate of testosterone. He apparently securedlasting relief from the distressing symptoms of pros.tatic hypertrophy, and there were no relapses eveneight months after cessation of the treatment. He
gave large doses (40-60 mg. daily of the acetate and10-20 mg. of the propionate). He too is uncertainabout the precise effect of the treatment on theprostate, but his further findings (Laroche and’Bompard 1938) have been confirmed by Laporte(1938) and Marcel (1938). All these workers agreethat the results of treatment with the esters oftestosterone differ according to the stage of thedisease. In simple prostatitis a favourable resultcan almost always be expected. In chronic but
incomplete retention improvements are frequentand great enough to justify this therapy. Distensionof the bladder presents an almost constant obstacleto hormonal action. The evolution of complete andpermanent retention, however, is often modifiedby the treatment, which in these cases must usuallybe prolonged and intensive. The French writers
definitely advise the treatment in inoperable casesand suggest it as a useful postoperative measureto prevent further enlargement. General agreementwith these views has been expressed by Nestmann(1939) as well as by Bolend (1939), who, apart fromreporting considerable symptomatic relief from andro-genic therapy, makes observations on the effects ofsuch therapy on the prostate itself. He too wasunable to demonstrate any decrease in the size ofthe organ, but biopsy specimens nevertheless showedthat while there was an increase in the glandularactivity of the prostatic acini, there was either nochange or a decrease in the amount of stroma and areduction in the inflammatory reaction. Cary, intwo reports on 44 patients (1938, 1939), also recordsconsiderable success in the symptomatic treatment ofthe disease, and he refers to three other Americanclinical studies, which have not been dealt with inthis review, and which yielded results similar to hisown.
The importance attached to the question of theeffect of male hormone on the tissues of an enlargedprostate perhaps lends undue significance to thenegative observation of Moore and McLellan thattestosterone propionate (in doses comparable withthose used by Laroche) had no significant effect onthe prostatic epithelium or stroma. This observa-tion, based on only five cases in which treatmentwas not continued very long, does not invite beliefthat the generally admitted symptomatic relief, whichandrogenic treatment provides in prostatic enlarge-ment, is due to any immediate change in the prostate.A possible explanation of this immediate relief isoffered by Champy and his co-workers (1937), who
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point out that retention of urine does not alwaysappear to be related to the size of the prostate, andthat one of the most obvious results of treatment withmale hormone is the rapid appearance of perivascularoedema near the verumontanum. They suggestthat retention is due to an irregular contraction of thevesical sphincter, causing the lobes of the prostateto be pressed into such a position as to block thepassage of urine. Relief can be obtained by operatingon the posterior part of the contracted sphincter,and they claim that relaxation of the muscle wouldhave the same result. If such relaxation accom-
panies perivascular oedema in this region, an explana-tion is offered of the rapid action of male hormonein urinary dysfunction.Laroche, Simmonet, et al. (1938) also report on the
general effects of male hormone on elderly men.
Quantitative tests were made of the effects producedby the administration of esters of testosterone on
subjects suffering merely from senility, and consider-able improvement, such as an increase in weightand muscular power, was observed, though fatigueset in much earlier. There was also some psycho-logical improvement in their patients. These resultswere apparently permanent; but since an oldorganism is prone to many frailties that cannotbe remedied by sex hormones, Laroche points outthat it is doubtful whether the improvement was forthe ultimate good of the patient, and for that reasonhe advises caution in rejuvenating treatments.Weiss (1939) reports on the beneficial effect of testo-sterone propionate on men and women sufferingfrom severe and depressing results of endocrine
derangements, and Joltrain (1938) remarks that theacetate of testosterone seems to have a less excitingeffect on the vegetative nervous system than does thepropionate. He notes, too, that apart from its reliefof functional troubles in prostatic hypertrophy,testosterone also seems to augment renal permeability.He suggests that testosterone associated with strongdoses of strychnine and, in some cases, of the anteriorlobe of the pituitary, favourably influences arteria,l
spasm.COMMENTS
If the papers reviewed here indicate the presentposition, it is clear that in general the problem of thetreatment of prostatic hypertrophy has not yet beensolved Perhaps testosterone is not the only testicularhormoLe but only a part of a necessary chemicalcomplex, or perhaps the injected testosterone under-goes metabolic changes-a possibility consideredin our issue of April 22 (p. 948). The variable resultsof the hormone treatment of prostatic hypertrophymay be due to these and other factors, but the factsobserved strongly support the view that prostatichypertrophy is of endocrine origin.
REFERENCES
Bolend, R. (1939) South. med. J. Birmingham, Ala. 32, 154;Abstr. J. Amer. med. Ass. April 8.
Cary, F. S. (1938) Illinois med. J. 73, 486.- (1939) Med. Pr. April 19, p. 393.
Champy, C., Heitz-Boyer, M., and Coujard, R. (1937) Bull.Acad. Méd. Paris, 118, 93.
Cuneo, B. (1938) Bull. Soc. Méd. Paris, 142, 723.- and Jomain, J. (1938) Pr. méd. 47, 913.
de Jongh, S. E., and Kok, D. J. (1935) Acta. brev. neerl. Physiol.5, 177.
Deming, C. L., and Neumann, C. (1939) Surg. Gynec. Obstet.68, 155.
Emmens, C. W., and Parkes, A. S. (1938) J. Path. Bact. 47, 279.Hamilton, J. B., Heslin, J. E., and Gilbert, J. (1937) J. Urol.
37, 725.Joltrain, E. (1938) Bull. Soc. Méd. Paris, 142, 741. Laporte, G. (1938) Ibid, p. 735.Laroche, G. (1937) Les regulations hormonales, Paris, p. 389.- and Bompard, E. (1938) Bull. Soc. Méd. Paris, 142, 728.— Simmonet, H., Bompard, E., and Huet, J. A. (1938) Bull.Acad. Med. Paris, 119, 639.
Marcel, J. E. (1938) Bull. Soc. Méd. Paris, 142, 739.Moore, R. A., and McLellan, A. M. (1938) J. Urol. 40, 641.Nestmann (1939) Med. Klin. 35, 178.Petit, G., Gley, P., and Béraut, E. (1939) Bull. Acad. Méd.
Paris, March 28, p. 430.Weiss, O. L. (1939) Dtsch. med. Wschr. 65, 261.Zuckerman, S., and Groome, J. R. (1937) J. Path. Bact. 44, 113.
MEDICINE AND THE LAW
Maintenance of a Violent Patient
THE county-court judge at Barnet last month hadto adjudicate upon the claim of a nursing-home fora fee for a private mental patient whose violence hadcaused the termination of the contract for her main-tenance. Dr. H. R. S. Walford, the proprietor of thenursing-home, claimed 24 19s. 6d. from Mr.Arthur Levy, the patient’s son. This sum repre-sented an agreed fee of £ 12 12s. for a week’s main-tenance, ;E2 2s. for the issue of a temporary certificatein connexion with the patient’s removal to anotherhome, and the cost of repairing damage done by thepatient. The plaintiff gave evidence of his havingagreed (after conversation with her medical attendant)to take Mrs. Levy at a fee of £ 12 12s. a week. The. patient was drowsy for the first two days, as thoughunder the influence of a sedative. She then becameviolent. She threw a clock through a window, brokethe bedroom furniture against the wall and tore upblankets. She was removed to another room andcaused similar damage there. Dr. Walford thentelephoned to the patient’s son and said she must bemoved. Mrs. Levy was taken away after 32 days’residence. She entered another mental home as avoluntary patient and was now recovering.
It was contended for the defendant that he wasnot liable for his mother’s maintenance, that in anycase he should not be charged for a full week, andthat the plaintiff, knowing that mental patients maybecome violent, might have taken more efficientaction to prevent the damage. If this last contentionmeans that the patient should have been placed underphysical restraint or deprived of furniture andblankets, it is easy to imagine the complaints whichthe suggested action would have evoked.Although the defendant insisted that he had never
admitted liability for his mother’s maintenance inDr. Walford’s nursing-home, the judge said there wasno doubt that the son was liable, although he hopedthat whatever sum was recoverable would come outof the mother’s property. The judge held that theproper amount payable for maintenance was ;E6 6s.-namely, half the weekly charge. It was at Dr.Walford’s request that Mrs. Levy left the home.With regard to the fee for the issue of a certificate,the judge apparently disallowed the claim for j62 2s.,remarking that Dr. Walford had done no more thansign his name on a piece of paper. He gave judgmentfor a total of E15 15s. with costs.No disrespect is intended to the justice administered
in our county courts if two observations of a generalnature are added. First, had this been the case of anordinary contract for taking in a lodger at a boarding-house, the landlady would presumably have beenentitled to pay for a week, notwithstanding that,owing to the unexpected violence of her visitor, shehad to ask the visitor to leave half-way through theweek. Secondly, the law allows, and indeed in manycases requires, members of the medical profession tosign certificates. All they do, it is true, is to signtheir name on a piece of paper; but it would be