THE USE OF ANDROGENS IN THE FEMALE

433 katabolism which goes on to the liberation of potassium and nitrogen. The present observations have the following clinical

THE USE OF ANDROGENS IN THE FEMALE *

applications: specific alteration in renal function after injury to the renal conservation of sodium and the urinary excretion of potassium at a concentration which may exceed that in intracellular fluid. A small output of urine of high specific gravity containing much potassium and little sodium is not only compatible with survival but also appears to be ’he normal sequel to a major surgical operation or to other severe injury and does not call for either intravenous or rectal admistration of fluid to induce diuresis. 2) The large urinary excretion of potassium as part of the normal response to severe injury is readily tolerated by wellnourished patients and does not necessitate the replacement oi potassium salts by intravenous infusion. On the contrary, coring the first forty-eight hours after injury, such infusions are not only dangerous and ill advised but also, because of the tendency to transfer potassium from intracellular to extra,cellular fluid, are unlikely to be of any value. 3) The renal conservation of sodium prevents any large loss of sodium in the urine. Therefore, provided large volumes of gastro-intestinal secretion are not lost by gastric aspiration, diarrhœa, or a fistula, there is seldom any need to administer sodium salts during the first week after operation. (ei) The restriction of drinking for forty-eight hours after gastrectomy reduces the volume of fluid to be removed from the stomach by aspiration. Thirst is as effectively relieved by washing out the mouth with ice-cold water as by drinking, and thus stimulation of secretion in the gastric remnant by swallowed water is avoided.

G. I. M. SWYER M.A., D.M., D.Phil. Oxfd, M.R.C.P.

D The

Summary The effects of stopping the intake of water as well as of food and minerals for forty-eight hours after partial gastrectomy have been observed and are compared with previous observations on patients whose intake was not

restricted.

so

urinarv excretion of sodium was reduced from than 100 m.eq. per twenty-four hours before operation to less than 75 m.eq. during the first twentyfour hours after operation, below 50 m.eq. in the second, and less than 25 m.eq. in the third, fourth, and fifth. Thereafter there was wide variation in the urinary excretion of sodium. The urinary excretion of potassium increased from 25—50 m.eq. per twenty-four hours before operation to 75—125 m.eq. during the first and second twenty-four hours after operation, 25-75 m.eq. in the third and fourth, and 25—50 m.eq. in the fifth and subsequent. After operation there was a large loss of body-weight "hi.’h was greatest during the first forty-eight hours and was 2.1—11.3% of the initial body-weight. Variations from the general pattern and possible "iplanations for the changes observed and their bearing ;- the normal bodily response to injury and postoperative treatment are discussed. The

more

indebted to the

am

patients

who

cooperated

in this

ation, Sister J. A. S. Milne and her staff for assistance in ’ -, wards, and Miss Edna Simpson and Mr. Gordon Shewan for al assistance. REFERENCES

Benedict, F. G. (1915) A Study of Prolonged Fasting. Washington. Blixrenkrone-Moller, N. (1949) Acta chir. scand. 97, 300. Cuthbertson, D. P. (1936) Brit. J. Surg. 23, 505. (1945) Brit. med. Bull. 3, 96. Dudley, H. F., Boling, E. A., Le Quesne, L. P., Moore, F. D. (1954) -

Ann. Surg. 140, 354. L. (1954) Chemical Anatomy, Physiology and Pathology of Extracellular Fluid. 6th ed., Cambridge, Mass. Laragh, J.H., Stoerk, H. C. (1955) J. clin. Invest. 34, 913. Le Quesne, L. P., Lewis. A. A. G. (1953) Lancet, i, 153. Llaurado, J. G. (1955) Ibid, i, 1295. R. A., Widdowson, E. M. (1946) Spec. Rep. Ser. med. Res. Lond. no. 235, 2nd ed. J. W., Pedersen, S., Maddock, W. G. (1941) J. clin. Invest. 20, 91. Wiley, F. H., Newburgh, L. H. (1931) Ibid, 10, 689. A. W., Billing, B. H., Nagy, G., Stewart, C. P. (1949) Lancet, i. 640. (1950a) Ibid, i, 533. (1950b) Ibid, ii, 135. Gamble,J.

McCance,

Coun.,

Nadal,

CONSULTANT ENDOCRINOLOGIST, DEPARTMENT OF OBSTETRICS UNIVERSITY COLLEGE

-

-

- - - -

-

-

-

-

-

(1951) Ibid, i, 315.

LONDON

No physiological genital role of androgens in the femal has been described and none seems likely. In view of th defeminizing or contrasexual alterations which androge therapy produces in woman, it seems likely that gyneci functions occur despite woman’s androgen moiety rather tha by"virtue of it." (Hamblen 1947.) The androgens are... as important in the economy of th female as are the oestrogens." (Loeser 1951.)

PRESUMABLY the truth lies somewhere between thes extreme views. At all events in the treatment of women androgens may have a potential value, the possibilitie

being

as

follows :

(1) For their contra-oestrogen effects-e.g., in the treatmen of various menstrual disorders and so-called fibrocysti mastopathy and in the palliation of carcinoma of the breast i (2) For their alleged oestrogen synergistic treatment of the climacteric syndrome. (3) For their effect in increasing libido where this is deficient (4) For their nitrogen anabolic effect-e.g., in increasin the weight in anorexia nervosa and other allied states, and the stimulation of linear growth in children of deficien

effects-e.g.,

stature.

The ideal maximal

androgen for these purposes would be one with oestrogen antagonistic or synergistic, and anabolic effect, and minimal virilising effect nitrogen The search for such a substance has led to the introduc tion of various androgen analogues. I report here my expeyiences with methyl testosterone methyl androstanediol, and androstalone (methyl androstane 3-one-17-ol) in 83 patients aged from 4 years

11 months to 55. In all the cases oral treatment was used (the well-known " Greenblatt medical curettage," brought about by intramuscular injections of testosterone

and progesterone [Greenblatt 1947], is very reliable and does not require further consideration).

propionate

Regular Menorrhagia In this group the complaint is that, though the periods

regular, the blood-loss is excessive and the flow often unduly prolonged. The 32 patients were aged 20-50 (average 35-5). 9 patients were treated with methyl testosterone 5 mg b.d. sublingually, starting a week before the expected onset of the period and continuing until the third day of bleeding. The response was good in 2 patients, of whom 1 also experienced amelioration of premenstrual symptoms, but the other later did not respond. 4 patients showed a slight response, but 1 of them complained of are

abdominal discomfort, and 1 other of facial hirsuties after three cycles of treatment. The remaining 3 patients did not respond but later showed some response to treatment with methyl testosterone with ethisterone. This combined treatment consisted of methyl testosterone 5 mg. b.d. and ethisterone 15 mg. b.d.t and was used, in the same way as the methyl-testosterone treatment mentioned above, on 22 patients. Of these, 7 responded well (1had previously failed with methyl testosterone alone) ; 4 showed some, albeit an inadequate, response (1of these later showed spontaneous improve*

Paper read at a joint symposium of the Society for Endocrinology and the section of endocrinology, Royal Society of Medicine, on Selected Aspects of the Practice of

Wilkinson,

-

HOSPITAL,

"

tA

Hormone Administration in Animals and Man on Feb. 22, 1956. tablet combining these substances in the above dosage is available asAndrogeston ’ (British Schering). ’

434 5 showed no response ; and 6, all with strong With the emotional factors, also did not respond. exclusion of these obviously " emotional menorrhagias," the combined treatment had some effect in 12 of 17 patients, compared with 6 of 9 treated with methyl

Dysmenorrhoea

ment) ;

testosterone

alone, and

of 17

patients (7 8 patients

against

a

good

2 of

effect in

relatively

more

9).

treated with androstalone in combination with ethisterone given as described above. In 1 of them the dose of androstalone was 10 mg. daily and the response was less good than that with methyl testosterone and ethisterone. 5 patients received androstalone 50 mg. daily with ethisterone : in 2 of them the effect was good (1of these also gave a good response to methyl testosterone and ethisterone but was unaffected by androstalone 50 mg. daily alone) ; in 2 there was a partial response (in 1 of these treatment increased acne on the back) ; and the other 1 did not respond. 2 patients received androstalone 25 mg. daily with ethisterone, as described above : 1 of them responded well, and the other partially, doing no better with double the daily dose of androstalone. Thus, of the 7 patients receiving combined treatment with androstalone 25 or 50 mg. daily 6 showed some response and 3 a good one. were

Other Menstrual Disorders

This group comprised 12 patients aged 23-42 (average 308), who complained of the following menstrual disorders : irregular uterine bleeding (6 patients) ; "premenstrual dribbling " (2 patients), in which a bloody discharge precedes the period by two to fourteen days and continues until the onset of the period proper ; other intermenstrual bleeding (2 patients) ; and climacteric menorrhagia (2 patients). Organic causes had, of course, been excluded in all the cases. Irregular Uterine Bleeding.—I patient, with strong emotional accompaniments, received methyl testosterone 10 mg. daily for two months with no benefit. 2 similar patients received androstalone 50 mg. daily for two months with equal lack of benefit ; 1 of these had also 1 other patient, not responded to methyl testosterone. who also complained of intermenstrual pain, derived no benefit from methyl testosterone 30 mg. daily for two 2 others were treated with androgen and months. ethisterone in combination : 1 received androstalone 25 mg. and ethisterone 30 mg. with good effect, and the other methyl testosterone 10 mg. with ethisterone with slight effect. Treatment of this 2nd patient produced depression and abdominal distension. "Premenstrual dribbling" usually reponds well to ethisterone alone. 2 patients were tried on androstalone 25 mg. daily : in 1 the duration of bleeding was reduced from ten to fourteen days to seven days, with an accompanying decrease in the amount of loss ; she relapsed on stopping treatment and later responded to methyl testosterone and ethisterone. The other patient showed no response to androstalone 25 mg. daily but responded well to ethisterone 40 mg. daily given from the fifteenth day of the cycle for ten days. Intermenstrual Bleeding.—2 patients with this complaint received methyl testosterone 15 mg. daily ; 1 showed no response, and the other, who also complained of abdominal pain, responded well as regards the bleeding but less well as regards the pain. Climacteric Menorrhagia .—Androstalone 25 mg. daily 1 other responded well was without effect in 1 patient. to methyl testosterone and ethisterone but relapsed when the treatment was stopped. Resumption of treatment gave satisfactory results for fourteen months, when it was changed to androstalone 50 mg. daily This gave even better results and with ethisterone. was continued for six months, after which there was no relapse in the subsequent six months without treatment.

tried in 5

patients, aged 19-29 Androgens complaint. 2 patients were treated with methyl testosterone daily from the seventh to the thirteenth day cycle by the method for which good results were c by Filler (1950). 1 was unaffected by the treatmen the other received minimal benefit. Methyl testos 10 mg. daily given for a week before the onset menstrual period was without effect on another p Androstalone 25 mg. daily, given to a patien fibrocystic mastopathy, considerably decrease dysmenorrhoea. Another patient, in whom &oel treatment had caused nausea and vomiting, was with androstalone 50 mg. daily, starting a few days the onset of each menstrual period, with moderatel results. After ten months of this therapy she no complained of symptoms sufficiently serious to were

this

treatment.

Fibrocystic Mastopathy

patients, aged 20-44 (average 33-3), complai breast pain, either continuous or intermittent, and the typical palpatory findings of so-called fibr mastopathy. A further patient, who complain intermittent pain in the left breast but had no abn physical sig 7

ceived

no

from treat with androst 25 mg. dail was conside h a ve inter

myalgia, not cystic mastop

Androsta

given patients wi typical phy findings. daily gave

was

lent results patients, fo of whom on alternate proved less tive. One of

patients (age received

2

daily for Fig. ’-Body-weight in case 2. months although th tion of her menstrual periods decreased from days to just over a day, she nevertheless conceived under treatment. The remaining patient ob complete relief from 10 mg. daily for a month follo 5 mg. daily for a further two months ;the sympto not return when the treatment was 5 patients all benefited from treatment with methy osterone either 5 or 10 mg. daily. In 1 of these pa 5 mg. proved definitely less effective than and dros 25 mg. daily. In 1 other patient relief lasted six m or more after treatment for a month or so at a ti further patient complained of discharge from one in addition to the pain ;; after treatment for a during which time the pain disappeared thoug discharge persisted, she remained free from pain further three months.

stopped.

Deficiency

of Libido

There were 5 patients, aged 22-37, with defici libido. 1 of them was treated with androstalone daily and with methyl testosterone 10 mg. da menstrual irregularities ; neither substance increas

43

3 patients receivedMixogen ’ t : 1, for whom oestrog alone had been unsatisfactory, was well controlled on tablet daily and less ; another obtained much less bene from one or two tablets daily than from stilboestrol 0-2 m daily ; and the 3rd, who had had little benefit from stilboest 0-2 mg. daily with phenobarbitone, was very well control with mixogen two tablets daily (omitted for fourteen days the end of every four weeks), but after eight months complained of increased growth of facial hair. A combined tablet, containing ethinyl oestradiol 0-02 mg ethisterone 20 mg., and methyl testosterone 8 mg.§ was us for 4 patients, who took one tablet on alternate days. 1 these was the last of the above-mentioned patients ; s obtained no benefit. Another was the 2nd of those natie who had not benefited from

deficient libido. The remainms4 patients all experienced an merewl-e in libido on treatment with

methyl

testo-

either5 or 10 mg. d.uly. 1 of these patients further notice : Case 1, aged 37, complained

aerone

M

complete

of

loss

libido

following hysterectomy and oophoreetomy. The position Tas complicated by the existence of a strong conflict between her and her husband. In spite of this methyl testosterone 10 mg. daily increased her libido within a few days, but after a

case

3.

month her libido decreased aram although treatment was being continued. Resumption of treatment with 15 mg. daily after its omission for a month led to a prompt return of libido, but, after four months’ treatment, for three weeks out of every four she developed acne, and further treatment was abandoned.

Climacteric Symptoms Only a proportion of patients with climacteric symptoms require hormonal treatment, and for most of these (Mtrogens in small dosage and in interrupted courses of the " diffimuallv provide satisfactory relief. Most cult " patients are those who have had

prolonged aestrogen therapy in excessive dosage and therefore experience oestrogendeprivation symp-

oestrogen mixtures

but was less effective in preventing hot flushes, after a

prove

very

mixseldom

opinion such Fig. 3-Bodyweight

4.

tures

are

superior to cestrogen alone in .n-nup of

uncomplicated cases. The results on a small patients aged 37-55 treated with various

hormone mixtures

are as

endome-

triosis ; although the e triplee combination abolished her

useful, but in my case

oophorectomy for

toms whenever treatment is stopped. For these androgen-

may

in

for her the triple combination proved very effective. It was successful for a 3rd patient, the dose being reduced to one tablet every fourth day after months six and stopped altogether three months later, with no return of symptoms. The 4th patient, aged 37, had had bilateral salpingo-

mixogen;

Fig. 2-Body-weight in

follows :

depression

year’s

treatment

she remained essentially free from symptoms.

Fig. 5-Body-weight

and

height

in

case

10

co

pared with averages.

Anorexia Nervosa and Other States of Emaciation There were 6 patients, aged 19-36, in this group

All

placed on a 3000-calorie diet (which none followed properly) and received androgens f their nitrogen anabolic effects in addition. 1 patient o androstalone 50 mg. daily gained no weight ; another on androstalone 25 mg. daily, gained 23/4 lb. in tw months, her weight remaining stationary on stopping th androgen ; and a 3rd gained 3/4 lb. in three months whil taking methyl testosterone 30 mg. and dried thyroi gland gr. 11/2 daily, but no further weight in the nex four months on androstalone 25 mg. and dried thyroi gland gr. 2 daily. The results in the 3 other patients a shown in figs. 1-3. Case 2 (fig. 1), aged 36 and 5 ft. 5 in. tall, whose initi weight was 981/2 lb., was put on cod-liver oil and malt were

course

addition to the 3000-calorie diet. She gained 71/? lb. in t first three months, only to lose 3 lb. in the next three months She was then given methyl testosterone 10 mg. daily an gained 7 lb. in the next two months. On methyl andro stanediol 20 mg. daily she lost 2 lb. in the next three month but gained 1/2 lb. in the following three months on the increas dose of 50 mg. daily. She lost 1 Ib. in the following six month while taking no hormones. tablet

of mixogen (Organon) contains ethinyl cestradi methyl testosterone 3-6 mg. § Kindly supplied by Dr. A. Gremeaux, of Roussel Labora

Each

Fig, 4-Height in

0-004 mg. and

case 8 compared with average height.

tories Ltd.

436 Case 3, aged 19, 5 ft. 43,/4 in. tall, and weighing 106 lb., complained of hypomastia, which was merely part of a general state of emaciation. On a 3000 - calorie diet with androstalone 50 mg. daily she gained 81/2 lb. in seven months

grew 1 in. in four months on methyl testosterone 5 mg thyroid gland gr. 1 dany. In the next three months, on m androstanediol 20 mg. and thyroid gland gr. 1 daily ther no further growth ; nor was there any during a further p of treatment with methyl testosterone 5 mg. and th gland gr. 2 dailYj even though her radiological bon remained normal. Case 8, her sister, aged 9 years 7 months, was also short (3 ft. 73/4 iii., about 81/4 in. below the average f age). Over a period of intermittent treatment with thy methyl testosterone and androstalone lasting twentymonths (fig. 4) she grew 6 in. in height (expected incr 41/2 in.), and her menarche came on at the age of Ill,, in spite of the androgen therapy. During the next e months without treatment she grew only 3/4 in. (exp increment 23/4 in.). She developed rather severe acne o face after tredtment with methyl testosterone 5 mg. dai three months, followed by 10 mg. daily for three months, a gap of fout months without androgen, followed by 1 daily for six months. The acne persisted in spite o

(fig. 2). Case 4 (fig. 3), 5 ft. 71/2

aged 25,

in. tall, and

weighing 951/2 lb., was given androstalone 50 mg. daily for two months, during

which time she gained 9 lb. In the next three months without hormone she lost 21/2 lb., and a further 1/2 lb. in the next three months while taking androstalone 10 ma. daily. When the dose was increased to 25 mg. daily, she gained 21/2 lb. in three months, only to lose 31/2 lb. in the following three months when not taking the hormone. Promotion of Growth in Children

withdrawal of androgen therapy. Case 9, aged 14 years 8 months, 4 ft. 101/4 in. tall, of n bone age, had not grown at all in nine months without ment. During three months while taking androstalone 5 daily she grew 3/4 in., but she did not grow any more i next three months while continuing treatment and developed amenorrhoea for six months. Case 10, aged 14/s, weighed 116 lb. (9’ /Z lb. abov average for her age) in spite of being only 4 ft. 61/2 in (73/4 in. below the average). Dietary measures had little

value of androgens in combination with thyroid hormone for promoting growth in children was described by Escamilla and Bennett (1951), who showed this combination to be far superior to purified growthhormone in causing growth in a case of pituitary infantilism. I have now accumulated a considerable experience of this treatment for undersized children of either sex, but the following observations will be confined to female from patients. The data are available from 9 girls, aged Z!> 4 years 11 months to 161/2 years when first seen. Case 5, aged 16, 4 ft. 91/2 in. tall, of normal radiological The

potential

bone age grew with methyl

1/2 in. in five months while under treatment testosterone 10 mg. and thyroid gland gr. P/9 Her had this time, and she did not grow any more. Case 6, aged 161/2’ 4 ft. 6 in. tall, also of normal bone age, showed no growth in two months on

daily.

epiphyses fused by

thyroid gland 11/2 and methyl testogr.

sterone

5 mg.

daily, grew 1/-1 in. in the next three months on the same of dosage

thyroid gland methyl

with

testosterone 10 mg. daily, and grew no more in the following without year treatment.

Fig.

7-Body-weight and

Case 7, aged and 4 ft. 3’-’.in. tall, 14

height

in case 12.

Fig. 8-Height

in

case

13.

her

weight beyond preventing it from rising although growing slowly, and she actually lost 3 lb. in six mo during which she was taking androstalone 25 mg. and thy gland gr. P/2 daily and in which she grew 1/2 in. (fig. 5). Case 1 l.-Fig. 6 shows the somewhat surprising cours girl aged 15 years 3 months at the start of treatment. height was then 4 ft. 9 in. (6 in. below the average for on

was

age). Over the preceding seventeen months she had growing at no more than the expected rate (3 in. during time). She was given androstalone 50 mg. and thyroid g gr. ]1/2 daily for three months, in which she grew 2B4 in. increased rate of growth was maintained over the next

months without further treatment, and at the end of time her height (5 ft. 3 in.) was only 3/4 in. below the ave for her age (161/2 years). Her menarche came on at 16 y 2 months. Case 12, aged 4 years 11 months, was 3 ft. 21’2 in. (33/4 in. below the average for her age) (fig. 7). There wa growth in six months without treatment ; she was then g androstalone 25 mg. and thyroid gland gr. 1 daily for se months, during which time she grew 21/2 in. (11,4 in. expec and gained 7 lb. (21,’2 lb. expected). Treatment was stop because slight, though definite, enlargement of the ch had developed ; there was no hirsutism or other evidenc virilisation. In the next ten months she grew 21/4 in. (13 expected) and gained 33, lb. (3lí lb. expected). This su

437 that, as in case 11, the course of treatment had had a trigger effect on growth, which continued at an enhanced rate even after the cessation of therapy. Case 13, aged 5 years 5 months, was 3 ft. 1 in. tall (6 in. below the average for her age) (fig. 8). During eleven months’ treatment with

methyl

testosterone 5 mg.

daily

and

thyroid

gland gr.12daily for the first three months (thyroid therapy was

stopped at this point because it appeared to cause undue

restlessness), she grew 2 in. (13/4 in. expected). Treatment

was

interrupted for three months (during which time she grew 1 in.) and then resumed with androstalone 25 mg. daily for nine months and 5 mg. daily for three further months. During these twelve months she grew 21/2 in. (21/4 in. expected). In the next thirteen months without treatment she grew only j1 jin. (2¼ in. expected). Conclusions

The observations reported here were made with the deliberate intention of attempting to assess various oral androgen preparations in a rather wide group of disorders in the female. Consequently the number of patients with any one disorder who have been treated is relatively small, and it would therefore be unwise to draw other than tentative conclusions. However, there seems to be little doubt that androgens may be of value in quite a number of disorders, though equally doubtless is the fact that a favourable response cannot be anticipated in every case. Of the menenorrhagias those clearly due to emotional causes (which may well be the majority) are very unlikely to respond to hormonal treatment of any kind. Where the emotional element can be ruled out, or is relatively unimportant, androgens alone have proved to be of little value, though the combination of methyl testosterone or androstalone and ethisterone has helped numerous patients. The results in the treatment of irregular uterine hleeding are unimpressive. Some patients with dysmenorrhœa may respond favourably to androgens ; in the small .series reported androstalone seemed to be the most promising. The discomfort of fibrocystic mastopathy may rather confidently be expected to respond to androgens, good results having been obtained with methyl testosterone and androstalone. Increase in libido may follow treatment with methyl testosterone, but such a response cannot confidently be predicted in women complaining of frigidity. In the dosage of 50 mg. daily androstalone has not affected libido, The superiority of androgen-oestrogen preparations over oestrogens alone in the treatment of the climacteric syndrome is not invariable, the reverse being true for )ome patients. Nevertheless these combinations do prove particularly helpful in some cases. For increasing the weight of much-underweight patients androgens prove helpful in some cases. In the patients studied the benefits of treatment may have been due to ,tli effect on appetite, possibly a consequence of increased itrogen anabolism ; it is unlikely that they were merely the consequence of retention of fluid. The limited observations suggest that methyl androstanediol, even H,a dosage of 50 mg. daily, is of little value ; that methyl testosterone 10 mg. daily may produce positive results ; and that androstalone 25 or 50 mg. daily may also be

effective. The value of androgens, either alone or in combination with thyroid hormone, for the promotion of growth in dren is unpredictable, but evidence has been adduced that it may be considerable in some cases. Sometimes it that a limited course of androgen therapy may a trigger action, not only increasing the rate of growth at the time but also being followed by a sustained rease in growth-rate. It can be argued that, by

earlier epiphyseal closure, androgen therapy,

though increasing the growth-rate, may lead to earlier tion of growth ; hence the end-results are no better might be worse) than if no treatment had been given.

My limited observations do not support such a view, bu the possibility cannot be disregarded, and some nice of judgment in giving and withholding the treatmen must be exercised. The obvious drawback to androgen therapy in th female is its potentially defeminising and virilising effect In sufficient dosage it may cause amenorrhoea, hirsutism acne, and deepening of the voice due to irreversib growth of the laryngeal cartilages. Some of these effec may be unavoidable in some patients, even with wha might be regarded as therapeutic doses of any of th available androgens. It is therefore most important t be on the look-out for such undesirable effects of androgen used for the purposes considered here, even though the may be relatively unimportant when androgens are use to palliate carcinoma. Though evidence of the suscepti bility of some people to methyl testosterone and t androstalone is presented (and susceptibility to methy androstanediol is known to exist), it is also reassuring t know that conception and the menarche may take plac while patients are undergoing effective androgen therapy

My sincere thanks are due to Dr. A. Gremeaux, of Rousse Laboratories Ltd., for supplies of androstalone and of oth hormone preparations ; and to Mr. G. H. Wilkinson, of Briti Schering Ltd., for supplies of androgeston. REFERENCES

Escamilla, R. F., Bennett, L. L. (1951) J. clin. Endocrin. 11, 221. Filler, W. (1950) J. Amer. med. Ass. 143, 1235. Greenblatt, R. B. (1947) Office Endocrinology. 3rd ed., Sprin field, Ill. Hamblen, E. C. (1947) Endocrinology of Women. Springfield, Ill. Loeser, A. A. (1951) Gynécologie practique. Paris ; vol. 2, p. 213.

INTRASPINAL EPIDERMOID TUMOURS (CHOLESTEATOMAS) IN PATIENTS TREATED FOR TUBERCULOUS MENINGITIS C. CHOREMIS M.D. Athens PROFESSOR OF PÆDIATRICS IN THE UNIVERSITY OF ATHENS

D. ECONOMOS M.D. Athens CHIEF NEUROSURGEON, ATHENS POLYCLINIC

C. PAPADATOS M.D. Athens ASSOCIATE, PÆDIATRIC CLINIC,

UNIVERSITY OF ATHENS

A. GARGOULAS M.D. Athens INTERN,

PÆDIATRIC

CLINIC, UNIVERSITY

OF

ATHENS