946

INJECTABLE CONTRACEPTION (MEDROXYPROGESTERONE ACETATE) IN

TABLE I-D.M.P.A. CLIENTS COMPARED WITH STERILISATION

CLIENTS

RURAL BANGLADESH LAILA PARVEEN

ABUL QUASEM CHOWDHURY ZAFRULLAH CHOWDHURY

Gonoshasthaya Kendra, P.O. Nayarhat, District Dacca, Bangladesh

Summary

1601

used the

injectable contraceptive agent medroxyprogesterone acewomen

for up to 3 years. The programme was conducted by rural health centre with detailed follow-up. While the continuation-rate, 56% after 1 year, compared favourably with that of other contraceptive methods in Bangladesh, at least half the women experienced troublesome menstrual side-effects and there were indications that milk yield was adversely affected in 147 out of the 1020 women who received the first iniection while lactating.

tate

a

Introduction IN Bangladesh most of the women ready to accept family-planning methods already have four or more

children. Elsewhere, many such women would opt for permanent sterilisation; but in Bangladesh, even if sterilisation were freely available, women would still be deterred by a child-mortality rate which is one of the highest in the world (260 per 1000 liveborn children die in their first 5 years). In this setting, depot medroxyprogesterone acetate (D.M.P.A.) has attractions as a contrait can be injected by health auxiliaries; the effects are reversible (so that the woman can remain potentially fertile until her existing children reach the crucial age of 5 years); there is no drug wastage such as occurs with oral contraceptives; and administration is independent of coitus. Results with this agent have been reported from some 64 countries.1,2 We report here our experience at Gonoshasthaya Kendra, a rural community health and development project.3

From early 1976 to May, 1977, we surveyed 1601 clients in detail. These were women who had had at least one injection OfD.M.P.A. and who lived in villages within 10 miles of the centre. Of these, 227 had their first injection within 3 months before the cut-off date, leaving 1374 for complete analysis; but all 1601 are included in life-table analysis. In the 1374 the age range was 16 to 45 years: 137 were under 20 and 110 were over 36; 135 had eight or more children, 97 had only one (3 of these women lost their single child during the survey); and 904 had between two and five children. Table I compares the general characteristics of D.M.P.A. accepters with those of candidates for tubectomys at the same centre. Of the 454 accepters who had previously practised contraception, 438 had been on oral contraceptives.

ceptive:

Methods Between June, 1974, and May, 1977, over 2000 married with one or more children chose D.M.P.A. contraception, after being informed of the possible side-effects. An obstetric and menstrual history was recorded and subsequently, at the client’s home or at the clinic, a health auxiliary injected 150 mg D.M.P.A. into the deltoid muscle within 5 days after menstruation or in the post-partum period. Thereafter, injections were given every 80-90 days. Initially, all clients were given, with each injection, a tablet or capsule of long-acting oestrogen (quincestradiol 0.4 mg), since McDaniel’s work in Thailand had suggested that this reduced menstrual disturbances. But, like El-Habashy,4 we did not find this useful and we stopped giving oestrogen when the programme was 2 years old. The first 50 clients had general, breast, and pelvic examinations, with routine blood-tests, at the time of each injection, for the first 9 months. All clients had careful follow-up. The village dai (traditional midwife) visited on the day after the injection and was always available. A paramedical worker visited within the month and once a month thereafter. The health centre and subcentres provided additional support. To assure ourselves that clients were sufficiently motivated to attempt the method we charged 2 takas (8p) per injection to uninsured clients and 1 taka to those covered by the health-insurance programme.3 Follow-up and treatment of side-effects was free. women

Results

Pregnancy There was only one pregnancy due to method failure. 3 women had their first injection during the period of lactational amenorrhoea and did not know that they were pregnant at the time. 5 women did know that they were pregnant when they had the first injection; evidently they hoped that D.M.P.A., since it causes increased menstrual bleeding, would result in abortion. 21 women became pregnant after.dropping out. So far, 10 have had normal deliveries and 2 have had spontaneous abortions. No client has reported difficulty in becoming pregnant.

Drop-outs Of the 704 clients who dropped out, 43 proceeded to tubectomy; 27 had earlier been on oral contraceptives. 69 changed to a 6-monthly contraceptive injection and 82 to oral contraception. 553 (79%) of the 704 clients had dropped out by their third injection. Table n gives the clients’ main reason for abandoning the method. Life-table analysis gave continuation-rates of 56% at 12 months, 43% at 18 months, and 33% at 24 months. Menstrual irregularities and amenorrhoea were probably even more important reasons for dropping out than is indicated in table n. For example, of the 47 clients who dropped out because of lower abdominal pain. 38 also had body-ache, general weakness, &c., amenorrhoea. In most instances, menstrual irregularities appeared after the first injection, while only 15 c of women became amenorrhoeic at this time. However, the prevalence of amenorrhoea increased with the number of injections: after 6 months it had risen to 25%, and by

947 TABLE II—REASON FOR DROP-OUT BY DOSES OF D.M.P.A.

the end of 3 years to 50% (see figure). Village women in Bangladesh believe that amenorrhcea, except during pregnancy, means a collection of "bad blood"; and some of their symptoms may have been caused or aggravated by the psychological effects of amenorrhoea. "Husband’s objections" were entirely due to frequent or continuous spotting. According to Islamic precepts, intercourse is prohibited during menstruation, and spotting is interpreted as a prolonged menstrual period. This form of menstrual disturbance also disrupts the religious observances of both Muslim and Hindu women, who are banned from daily prayers and visits to their temples during menstruation. Many women who gave "social and religious" reasons as their motive for discontinuing had experienced this problem. "Lack of service" indicates that clients were unable to visit the clinic or were not available at home when the medical worker called. But the survey established later that 12 of these 23 women had also had some menstrual problem. Also, some of the women who reported discontinuing to have more children had experienced menstrual disturbances and their decision may have been strongly influenced by these side-effects. Similarly, some women became pregnant while avoiding subsequent injections because of menstrual problems. Among the 253 women who gave menstrual irregularities as the reason for dropping out, 10 experienced excessive bleeding and 6 had to be admitted to hospital. All 10 were treated with depot-cestradiol injection fol-

Menstrual patterns of 670 continuers

lowed by oral ’Norinyl’ (norethisterone 1 mg, mestranol 50 jjLg) twice daily for ten days. 2 were admitted to hospital twice, each having dilatation and curettage during the second admission. 1 year after the last injection, none had returned to a normal menstrual pattern. Lactation 1020 accepters were breast-feeding at the time of their first injection. 147 of them reported a decrease in lactation, 37 an increase; the rest reported no change. In some mothers, lactation may have been drawing to a natural close, but in all cases the age of the youngest child was less than 18 months, and 11 babies were under 6 months. In 20 cases, milk production declined sharply soon after the first dose of D.M.P.A. One healthy mother had her milk production completely cease within 20 days of injection, when her child was only 40 days old, and another with a 5-month-old child reported a substantial decrease during the first week after D.M.P.A. Discussion In most of the accepters, acetate caused disturbances

depot medroxyprogesterone justifiably been termed menstrual chaos.6 Nevertheless, the population aspect of D.M.P.A. is good; the continuation-rate after 1 year was 56%, and if we include those who changed to 6-monthly injectables it was 60%. This compares favourably with the continuation-rate for oral contraceptives in Bangladesh--40% after 6 months.The success of our D.M.P.A. programme is no doubt partly due to the convenience of the injection method, but another important factor is the careful follow-up by paramedical workers from the centre. In an injectables series from Dacca,8 the continuation-rate was only 40% which have

after 9 months. We did not design the investigation to assess effects on lactation. Nevertheless our observations are disturbing. One possible influence was the oestrogen supplement, but there was no difference in the frequency of decreased lactation between those who received the supplement and those who did not. Indeed among the 147 women who reported decreased lactation only 38 received the supplement, while 14 of the 37 women who reported increased lactation also had the oestrogen supplement. When we began the study the general view seemed to

948

be that D.M.P.A., if anything, increases milk production. And, lately, the I.P.P.F. Medical Bulletiny stated: "Depoprovera [D.M.P.A.] uniquely among progestational drugs, appears to elevate prolactin levels. This finding is the probable basis of the very strong suspicion that exists that Depoprovera injections increase the quantity of milk when given to lactating women." Since prolactin levels were not measured in any of the studies cited, the statement that they were elevated must have been an inference from the reported increases in milk yield. But there are reports both of increases 10, 11 and of decreases (Egypt,12 Sri Lanka,13 Bangladesh14); and since in all D.M.P.A. studies the most commonly reported menstrual side-effect is increased bleeding and spotting, while rising prolactin levels are associated with post-partum amenorrhoea, the I.P.P.F. statement implies a certainty which the evidence does not justify. This matter must be resolved before D.M.P.A. can be considered as the basis for a nationwide family-planning programme. In Bangladesh lactation is the only way to ensure adequate infant nutrition, and lactating mothers commonly come for family-planning advice. In the United States, the Food and Drug Administration has withheld approval of D.M.P.A. as a contraception because the drug has produced malignant breast nodules in beagles. In addition, there have been suggestions that long-term use of D.M.P.A. may predispose to cervical carcinoma. Our survey can offer nothing on these matters. As in previous surveys of D.M.P.A., the clients’ main complaint was of menstrual irregularities. Yet we judge that, with careful follow-up, many women can tolerate these. Unfortunately there exists a strong possibility that the drug will be misused. If governments, perhaps under pressure from international agencies, adopt a "speed and numbers" approach to family planning, the result is likely to be havoc. For such reasons, the intrauterine contraceptive device has become unacceptable to the population. If women are not well motivated to use D.M.P.A., educated in its drawbacks, and carefully followed-up, they are likely to drop out; and they, in turn, will tell their neighbours to avoid the "injectable". We gratefully acknowledge the assistance of Mr. A. Y. Chowdhury, of Johns Hopkins University Fertility Research Project, Dacca, and of Susanne Chowdhury, Mary Clare, Kanan Dey, Sandhaya Roy, B. Rahman, and other paramedics of Gonoshasthaya Kendra.

REFERENCES

Department of Medical and Public Affairs, George Washington University Medical Center. Population Reports, 1975, series K, p. K1. 2. Rosenfield, A. G. Am. J. Obstet. Gynec. 1974, 120, 537. 3. Lancet, 1976, i, 26. 4. El-Habashy, M. A., Mishell, D. R., Jr., Moyer, D. L. Obstet. Gynec. 1970, 35, 51. 5. Chowdhury, S., Chowdhury, Z. Lancet, 1975, ii, 567. 6. Br. med. J. 1976, iii, 131. 7. Khan, A. R., Huber, S. C., Chowdhury, A. Y., Khatoon, S. Johns Hopkins University Fertility Research Project, Dacca, report no. 8, November, 1.

1976. 8.

Khan, A. R., Mosley, W. H., Jahan, F. A. Johns Hopkins University Fertility Research Project, Dacca, report no. 7, September, 1976. 9. I.P.P.F. med. Bull. 1977, 11, 2 10. Koetsawang, S., Chiemprasert, T., Kochananda, P. Clinical Proceedings of I.P.P.F. South-east Asia and Oceania

Regional Medical and Scientific Congress, Sydney, August, 1972, p. 84. 11. Karim, M., Ammar, R., el Mahgoub, S., el Ganzoury, B., Fikri, F., Abdou, I. Br. med. J. 1971, i, 200. 12. Kader, A. M. M., et al. Am. J. Obstet. Gynec. 1969, 105, 978. 13. Chinnatamby, S. Aust. N.Z. Jl Obstet Gynaec. 1971, 11, 233 14. Khatoon, S., Johns Hopkins University Fertility Research Project, Dacca, report no.4, February, 1976.

HÆMOSTATIC, LIPID, AND BLOOD-PRESSURE PROFILES OF WOMEN ON ORAL CONTRACEPTIVES CONTAINING 50 µg OR 30 µg ŒSTROGEN R. CHAKRABARTI D. J. HOWARTH YVONNE STIRLING

T. W. MEADE A. P. HAINES W. R. S. NORTH

M.R.C./D.H.S.S. Epidemiology and Medical Care Unit, Watford Road, Harrow, Middlesex,

Northwick Park Hospital,

HA1

Summary

In 15

3UJ

oral contraceptives con30 µg œstrogen, mean values for

women on

taining

factors II, VII, and x, fibrinogen, fibrinolytic activity, antithrombin III, cholesterol, and fasting triglycerides were intermediate between values for 63 women on preparations containing 50 µg œstrogen and those for 243 premenopausal women not on oral contraceptives. Mean blood-pressure levels, however, were higher in women on 30 µg than in those on 50 µg preparations. In 28 women on 50 µg preparations containing 3 mg or 4 mg norethisterone, mean values of factor VII, fibrinogen,

fibrinolytic activity, cholesterol, fasting triglycerides, and systolic blood-pressure were higher than in 15 women whose preparations contained only 1 mg of norethisterone. A less consistent picture was found in women on 30 µg œstrogen preparations containing either 250 µg (10 women) or 150 µg (5 women) d-norgestrel. It is concluded that 30 µg œstrogen preparations probably result in smaller hæmostatic and lipid changes than 50 µg preparations but that they may have a bloodpressure-raising effect attributable to the particular progestagen, d-norgestrel, used in 30 µg preparations. The safety of these 30 µg œstrogen preparations may thus depend partly on the balance between these two sets of effects. It is also concluded that norethisterone may have effects similar to those attributed to œstrogens.

Introduction FOLLOWING a recommendation by the Committee on Safety of Medicines in 1969, oral contraceptives containing 75-100 µg of oestrogen were largely replaced by those containing 50 µg. The Royal College of General Practitioners’ studyl suggested that this change resulted in a drop of about 25% in the incidence of deep-vein thrombosis in women on oral contraceptives. In 1970, Inman et al.,2 using data collected between 1965 and 1969, reported a positive correlation between oestrogen dosage and thromboembolic episodes. On the other hand, BeraP found a strong association between cardiovascular mortality in women and oral-contraceptive usage in 21 countries at a time (1971-72) when preparations containing more than 50 µg were no longer in use in many of the countries, and she pointed out that there is still doubt whether the vascular complications of oral contraceptives are related to oestrogen dose. She did not make a direct comparison of the effects of different doses but regarded the cardiovascular mortality associated with the newer lower dose preparations as "dis-

turbing". Since 1973, preparations containing 30 ug oestrogen have been increasingly prescribed, and in April, 1977, these were designated as "approved and preferred" by