1239 used. Our trypsin levels were measured spectrophotometrically and theirs by radioimmunoassay, and it would appear that their immunoassay measures trypsin bound to inhibitor as well as free trypsin. In addition, the number of our young cysticfibrosis patients was small. These positive results from New Zealand encourage us to continue our investigations. B. PHILLIPS Medical Department, Booth Hall Children’s Manchester M9 2AA

J. A. DAVIS

Hospital,

M. GOODE

creased risk of endometrial cancer. Therefore we strongly urge the addition of 7-13 days of a progestagen each month so that the benefits of oestrogen may be achieved with no increased risk of endometrial lesions. Department of Obstetrics and Gynxcology, King’s College Hospital,

MARGARET THOM

Department of Obstetrics and Gynaecology, Birmingham and Midland Hospital for Women, Birmingham 11

MICHAEL PATTERSON

ŒSTROGEN THERAPY AND ENDOMETRIAL CARCINOMA

SIR,-Your editorial of May 26 makes

many controversial the that side-effects of points. oestrogen therapy are still under scrutiny but one would have thought that the benefits of oestrogen over placebo are now well accepted by all but the occasional provocative leader writer, having been clarified by the double-blind trial of Campbell and Whitehead’1 and interminable correspondence in the columns of The Lancet over the past year. Hammond2 and his team from Duke have shown the longterm metabolic benefit of oestrogen by significantly lower rates of strokes, heart-attacks, hypertension, osteoporosis, and fractures. They also confirmed an increased incidence of carcinoma of the endometrium with a risk ratio of9.3.3 The great value of this and the Antunes paper cited by you is that details of therapy are given.’ Only 1 of Hammond’s 11 oestrogen-taking patients with cancer was receiving progestagen ("rarely") during her twenty-four years of high-dose cyclical therapy for gonadal dysgenesis. In the Antunes paper none of the 64 patients with cancer of the uterus had taken progestagen: half were on continuous therapy and 9 were receiving stilboestrol (your conclusion was that continuous therapy was as safe as cyclical oestrogen therapy). 7 of Jick’s5 patients had received "progesterone" but no details of type, duration or frequency are given: you conclude that we should refrain from including progestagens in the regimen. We have probably the largest menopause clinic in Europe and have not been able to reproduce these findings and do not support the prediction of Jick et al. that the annual rate of cancer of the uterus in oestrogen users is 20/1000. During the past six years we have had no cases of carcinoma in endometrial biopsies of 1000 non-hysterectomised patients whose treatment we have initiated and supervised. Of the 4 patients who had been referred from elsewhere, 3 had had unopposed continuous oestrogen for in excess of twelve years and the other showed no evidence of carcinoma after four weeks of modifying

It is

true

’

progestagen. Few would doubt that many years of unopposed cestrogens may, in susceptible patients, produce endometrial cancer, but there is good evidence that the addition of progestagen prevents this increased rate of cancer6 and also hyperplasia.7 Our current data strongly support this in that the incidence of cystic hyperplasia with thirteen days of progestagen is 0% whether the oestrogen is given orally or by subcutaneous implant. It is 3% with 7-10 days of progestagen, 7% if low dose cyclical oestrogen is used, and 15% with high-dose cyclical oestrogen. Furthermore, all of 60 patients with cystic hyperplasia had the lesion reversed to normal by two twenty-one-day courses of norethisterone. There is no published evidence that low-dose cyclical oestrogen with progestagen is in any way associated with an in1. Campbell, S., Whitehead, M. Clins Obstet. Gynœc. 1977, 4, 31. 2 Hammond, C. B., and others Am. J. Obstet. Gynec. 1979, 133, 525. 3 Hammond, C. B., and others ibid. p. 537. 4. Antunes, C. M. F., and others New Engl. J. Med. 300, 9. 5 Jick, H., and others ibid. p. 218. 6. Gambrell, R. D. Maturitas, 1978, 1, 107. 7. Sturdee, D., Wade-Evans, T., Paterson, M. E. L., Thom, M., Studd, Br. med. J. 1978, i, 1575.

J. W. W.

J W OHM . S TURD

London SE5

SIR,-When you cite work which questions the effect of on menopausal flushes, it only serves to show that if

cestrogens

searches the literature hard enough one can find papers which prove almost anything. Unfortunately, while maximising the risks and minimising the benefits of oestrogen therapy, you have quoted us as stating that cestrogens only prevent bone loss when administered immediately after the menopause. In fact, we stated clearly in the paper to which you refer’ that, although this effect of oestrogen was most obvious immediately after the menopause, this did not mean that oestrogen therapy at a later stage was ineffective. You also cite the early paper by Aitken et al.,2 in which they made this claim, but failed to quote their subsequent paper which appeared in your own columns,3 in which they withdrew it. Bone resorption can be suppressed and bone loss reduced or prevented by oestrogen therapy at any time after the menopause but the effect is most apparent in the early years because that is the time when loss of bone proceeds most rapidly in untreated subjects.4 one

M.R.C. Mineral Metabolism Leeds General Infirmary, Leeds LS1 3EX

Unit,

B. E. C. NORDIN

PELVIC ACTINOMYCOSIS AND INTRAUTERINE CONTRACEPTIVE DEVICES

SIR,-Five women with severe genital-tract actinomycosis have been detected in two hospitals in the North East Thames region in two years. This is the largest published series of patients in the U.K. with clinical pelvic actinomycosis. Four patients had an intrauterine contraceptive device (LU.D.) at the time of diagnosis, confirming the association between i.u.D. usage and pelvic actinomycosis reported from Europe and North America. 1-12 The clinical features of the patients are summarised in the table. The diagnoses were established only after microscopic examination of surgical specimens. Bacteriological examination of blood, vaginal specimens, and pus in abscesses and peritoneal cavity failed to reveal any evidence of actinomyces. Major surgery was required in all cases, and the immediate

postoperative

recovery

was

complicated by

a

presumed

sep-

ticaemia in one patient and by problems with wound healing in two others. Loss of fertility and ovarian function were usual

sequelx. Actinomycosis 1.

is often very difficult

to

diagnose,

and it may

Horsman, A., Gallagher, J. C., Simpson, M., Mordin, B. E. C. Br. med. J. 1977, ii, 789. 2. Aitken, J. M., Holt, D. M., Lindsay, R. ibid. 1973, iii, 515. 3. Lindsay, R., Holt, D. M., Aitken, J. M., Macdonald, E. B., Anderson, J. B., Clarke, A. C. Lancet, 1976, i, 1038. 4. Horsman, A., Simpson, M., Kirby, P. A., Nordin, B. E. C. Br. J. Radiol. 1977, 50, 504. 5. Henderson, S. R. Obstet. Gynec. 1973, 41, 726. 6. Schiffer, M A , Elguezabal, A., Sultana, M., Allen, A. ibid. 1975, 45, 67. 7. Lomax, C W, Harbert, G. M., Jr., Thornton, W. N. ibid. 1976, 48, 431. 8. Dische, F E, Hurt, J M., Davidson, N J. H., Puntambeker, S. J. Obstet. Gvnœc Br. Commonw 1974, 81, 724. 9. Barnham, M., Burton, A C, Copland, O. Br med. J. 1978, i, 719 10. O’Brien, P. K., Roth-Mayo, L. Can. med. Ass. J. 1975, 112, 596. 11. van Jauer, P-C., Busch, B. Zbl. Gynœk. 197, 97, 228 12. Purdie. P. W., Carty, M. J., McLeod, T. I. F Br. med. J. 1977, ii, 1392.

1240 CLINICAL FEATURES OF FIVE PATIENTS WITH PELVIC ACTINOMYCOSIS

*Specimens from vagina, pus of abscesses and from peritoneal cavity, and blood. tDetermined by histological examination of surgical specimens. No actinomycosis was found in the appendix specimens. tchemotherapy included various regimens of ampicillin, metronidazole, penicillin, clindamycin, and lincomycin. be missed unless great care is taken in sample collection, bacteriological culture, and microscopic examination of surgical

specimens. The cytological detection of actinomyces colonies on cervical smears

has been described elsewhere and may be of value

as

screening procedure for women using the I.U.D!3-16 The frequency with which actinomyces is found on routine smear exa

amination suggests that minor infection with this bacterium is not uncommon.l5 One fatal case of pelvic actinomycosis has been described.16 The possibility of this diagnosis should be borne in mind with any case of pelvic inflammatory disease associated with use of an I.U.D., especially since the disease is probably more common than is usually realised. Departments of Obstetrics and Gynæcology, Reproductive Physiology, and Pathology, St. Bartholomew’s Hospital,

M. CHARNOCK T. J. CHAMBERS

London EC1

LAPAROSCOPY IN DIAGNOSIS OF PELVIC TUBERCULOSIS

of the continuing decline in the patient’s general health and the absence of any localising signs. Laparoscopy was not difficult and bulky uterine curettings were obtained. Pelvic tubercles were clearly identified. But when the laparoscopic cannula was removed from the abdomen, inoffensive green material was noted. An immediate laparotomy revealed perforated small intestine and confirmed the diagnosis of abdominal tuberculosis with dense adhesions. Biopsy specimens of the peritoneum were taken and. the damaged bowel resected with end to end anastomosis. The patient made an uninterrupted recovery on appropriate antituberculous therapy. Histological examination of uterine curettings and peritoneum confirmed the diagnosis of tuberculosis. We feel that laparoscopy in the diagnosis of pelvic tuberculosis or any condition in which there may be extensive bowel adhesions is fraught with danger. It is also a contraindication according to Steptoe.’ Matted tuberculous adhesions do not always give rise to a "doughy" abdomen and in fact they can be remarkably silent. We would therefore advise that curettage be done first and if the histology of the uterine curettings is negative, a "mini-laparotomy" may well be wiser than laparoscopy.

p.

SIR,-The paper by Mr Wolfe and his colleagues (April 21, 852) prompts us to report our salutary experience in using

the

tuberculosis.

laparoscope diagnose pelvic Perhaps warning to others. A 28-year-old Indian patient was referred from medical outpatients for gynaecological opinion because of a 6-month history of malaise, secondary menorrhagia, and secondary dysmenorrhoea. Although her husband had had pulmonary tuberculosis, full general medical evaluation, including chest X-ray, to

it may

serve as a

had shown no evidence of active disease apart from a mild anxmia and a raised erythrocyte sedimentation-rate. An endometrial biopsy was planned but laparoscopy was done because P. K., Hollander, D. H., Frost, J. K. Acta cytol., Baltimore, 1976, 20, 295. 14. Spence, M. R., Gupta, P. K., Frost, J. K., King, T. M. Am. J. Obstet. Gynec. 1978, 131, 295. 15. Bhagavan, B. S., Gupta, P. K. Hum. Path. 1978, 9, 567.

13.

16.

Gupta,

Hager, W. D., Majmudar, B. Am. J. Obstet. Gynec. 1979, 133, 60.

General

K. L. MENDIS H. WAGMAN J. S. KENEFICK K. GRAY

Hospital,

Barnet, Herts EN5

3DJ

PREGNANCY, BREAST-CANCER RISK, AND MATERNAL-FETAL GENETICS

SIR,-Professor Doll (March 10, of one aspect of the

559) has challenged the epidemiological data that supports 327) that immune suppression durp.

validity my hypothesis (Feb. 10, p. ing pregnancy increases the

risk of breast cancer in the short and decreases it in the long run. He suggests that the cross-over of breast-cancer rates among single and married

run

1.

Steptoe,

P. C. Laparoscopy in

Gynæcology. Edinburgh,

1967.