784

COPIES OF APPLICATIONS

SiR,-May I ask that the regional boards be moremodest in their demands for copies of applications forappointments. I am convinced that no " short-listing

"

subcommittee could possibly require more than threecopies of an application in the first instance, and thatno candidate would begrudge the balance of ten or fifteenshould he be selected to appear for interview. I am

engaged at present with twenty-six copies of applicationsfor three appointments.

CANDIDATE.

ŒSTROGEN THERAPY IN MENSTRUAL ANDPREGNANCY DISORDERS

SiR,-Your leading article of April 1, adopts a welcometone of scepticism. It is, however, a pity that this

scepticism has so closely approached obsession as -tohave led to misrepresentation and misquotation of mypaper 1 to which you refer in some detail.

There are two main reasons why the daily dose ofstilbcestrol advised for the control of prolonged uterinebleeding is given as 2-5 mg. In the first place, thishas proved sufficient’ in most of my patients, and

experience since the above-mentioned report was writtenhas not changed my view ; in the second place, by usingthe minimal effective dose the incidence of toxic reactionsto stilboestrol is kept to a low figure. Parenthetically,I have not found that ethinyl oestradiol, in effectivedoses, is much less liable than stilboestrol to producetoxic effects. Moreover-and this you omitted-thefurther advice is given that the dosage should be doubledif (and here I quote verbatim from my paper)

" after48 hours there is no sign of improvement." This

expedient has seldom proved necessary, and when usedhas seldom failed.

It is stated that I have claimed 100% success for thetreatment advocated in cases of prolonged and excessiveirregular uterine bleeding. Such a claim would clearlybe ridiculous and the statement, as well as the sentencepreceding it, is a gross misrepresentation. In point offact, no claims of any sort were made, and in thisparticular group of patients evidence for the occurrenceof ovulation following treatment was reported in 8 outof 19 patients, not 8 out of 8 as is suggested.

I did not find " secretory endometrium in all of ...8 cases in which initial biopsy showed a proliferativeendometrium or cystic glandular hyperplasia." Incase 1, for example, which is reported in detail, an initialproliferative biopsy was found in the 13-year-old subjectof puberal menorrhagia, but no post-treatment biopsywas taken and it was quite obvious that ovulation wasnot occurring after treatment. In case 9, aged 27, alsoreported in detail, a proliferative endometrium wasobtained after treatment which had followed the originalHamblen technique and relapse soon occurred ; a secondcourse following the modification I have described was,howevei, succeeded by a secretory endometrial biopsyand the patient remains well.

It is also deprecated that the ages of the patients andthe interval between pre-treatment and post-treatmentbiopsies were not given. Actually, the ages and certainsummarised details of all the cases mentioned in the

report are given in tables, which, as was explained in afootnote to the paper, could not be published on accountof restriction of space but which are available on applica-tion to anyone interested. The interests of accuracymight have prompted you to inquire for a copy of thesetables.

Finally, it is suggested that puberty bleeding and the" metropathic " type of maturity bleeding are likely toundergo spontaneous remission, the inference being thatsuch an occurrence could explain the apparently success-

1. Swyer, G. I. M. Brit. med. J. 1950, i, 626.

ful results of treatment. Certainly spontaneous remis-sions occur ; an example is described in my paper. Butin my experience this has been exceptional possiblybecause the majority of the patients referred to me havealready had symptoms extending over many months oryears (4 months to 15 years in the group of cases reported)and have already failed to respond to treatment at thehands of other doctors. In cases such as these it seemsat least as reasonable to suggest that a course of treat-’ment (which, incidentally, relieves the patient of hersymptoms at once) followed by apparent cure has playedsome part in producing the cure as to claim that the" cure " is no more than a spontaneous remission.

University College Hospital,Obstetric Hospital,London, W.C.1.

G. I. M. SWYER.

* * * We were confining our comment to the 8 casesin which (we believed) biopsy was performed both before.and after treatment. That there were 8 cases of thiskind was suggested by the following passage in Dr.Swyer’s paper :

" Endometrial biopsies were taken before treatmentin nine cases ; they showed a proliferative type of endo.metrium in seven cases and cystic glandular hyperplasiain two. In no case, therefore, was evidence of ovulationobtained. Biopsies were taken after treatment in eightinstances (excluding a case of spontaneous cure) andshowed secretory changes in seven of them. The singleinstance of a post-treatment proliferative biopsy ...followed a ’ C.D.’ (constant dosage) course of treat.ment, and relapse occurred three months afterwards;a ’D.S.-I.E.’ (diminishing stilbcestrol and increasingethisterone dosages) course of treatment was then used,and three months after the end of this second course theendometrium was found to be secretory."

It is now clear, however, that the before-treatment andafter-treatment biopsies were not all performed on thesame patients, and our suggestion of 100% success

in this series therefore falls to the ground. Our mis-

interpretation of the passage in question was, we think,excusable ; but we regret the wrong impressiongiven.-ED. L.

RESEARCH ON ARTHRITIS TREATMENT

SIR,—The successful treatment of rheumatoid arthritiswith deoxycortone plus ascorbic acid, introduced byLewin and Wass6n,l raises at once the question as to themechanism by which ascorbic acid is able to modify thephysiological response to deoxycortone so profoundly.Although there is little doubt that ascorbic acid plays animportant part in steroid metabolism, it appeared to meunlikely-especially in view of the high dose required toproduce clinical improvement-that this effect could beentirely specific to ascorbic acid.The paper by Hallberg 2 has confirmed my opinion.

Objections may be raised, however, against the role ofa biological oxidising agent assigned to ascorbic acid inthis article, unless it is assumed that oxidation of ascorbicacid preceded that of deoxycortone. In this case therapywith deoxycortone plus dehydroascorbic acid shouldgive equally good results. Moreover, a much smallerdose of dehydroascorbic acid would probably be required,since it can hardly be postulated that all the ascorbicacid used in the Lewin and Wassen therapy is oxidised.An alternative hypothesis would be that ascorbic acidacts by suppressing heavy metal inhibition of an oxidaseinvolved in steroid metabolism.The fact that identical clinical results have been

obtained with a reducing agent (ascorbic acid) and anoxidising agent (methylene-blue) seems to indicate thatthe biological reactions involved in the modification ofthe physiological response to deoxycortone are complex.

1. Lewin, E., Wassén, E. Lancet, 1949, ii, 993.2. Hallberg, L. Ibid, Feb. 25, p. 351.