Contraception—The next 25 years

Contraception—The next 25 years

526 CONTRACEPTION-THE NEXT 25 YEARS John A. Loraine The importance of birth control in an overcrowded planet needs no emphasis. Yet often research ...

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526

CONTRACEPTION-THE NEXT 25 YEARS John

A. Loraine

The importance of birth control in an overcrowded planet needs no emphasis. Yet often research in this field has not been characterized by success. This article describes three of the more modern approaches to contraception and also discusses the value of breast feeding at the global level. Keywords: social sciences;

contraception;

breast feedins

of

THE 2&H CENTURY has witnessed a great expansion human numbers-from 1500 million in 1900 to nearly 5000 million in 1985.’ Global population growth is believed to have peaked at 2.1% in the late 1960s. Since then a slight fall to 1.7 % has taken place largely due to fertility declines in industrialized countries, in China and to a lesser extent in South America and the Caribbean. Nevertheless, because of the age structure in developing countries and in particular the high proportion of young people, the momentum of population growth remains very considerable.’ In 1984, the 83 million added to the planet was the highest figure in human history; by the 1990s the increment is likely to exceed 90 million. ESarring a major global catastrophe, especially a nuclear war, the century will close with about 6000 million people and by 2010 (the period covered by this article), numbers could well be in excess of 7 500 million.” The paramountcy of adequate contraception in an overcrowded world is generally accepted. Birth control is a tried and well recognized component of any population policy and unless it is properly addressed no country is likely to succeed in retarding its growth of numbers. Birth control also has a major role to play in raising the quality of life of individuaIs, enabling them to make free, informed and rational choices in respect of famify size and child spacing. Given the nature of the population problem it might have been anticipated that flair and ingenuity would have dominated contraceptive research and that the tempo of new discovery would have been rapid. However, this has not been the case.4 Instead, recent work on reproductive biology has been uneven, erratic and often sluggish. This is not to say that major advances have not been made, the oral contraceptive pill being the outstanding example here. But elsewhere, Dr John A. Caraine is a senior lecturer at the Department of Community Medicine, formerly Director, CIinical Endocrinology Unit and Centre for Human Ecok~gy, University of Edinburgh, UK.

MRC

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new ideas have not flourished and this together with exiguous funding at the global level has led to apathy and even to disillusionment and frustration among research workers. J. M. Keynes once wrote that we live by our ideas and by precious little else. What ideas do we have about birth control? How is the future of contraception likely to develop and in particular what will the situation be like 25 years from now? This article considers three possible approaches-hormonal contraception, pregnancy vaccination and the male pill. It also discusses the importance and practice of breast feeding now and in the future. Hormonal

contraception--the

Steroid hormones

continuing

quest

and the future

There has been more research on the pill and more written about it probably than any other drug in history. 5 Since it was first introduced into clinical practice more than 150 million women around the world are believed to have taken it. After 20 years of use it was estimated that 50 million women in developed and developing countries were taking it, that more than 25% of women of reproductive age were regular users in developed countries such as Australia, Canada, FR Germany and the Netherlands and that in China about 15 million women were receiving the medication. The popularity of the pill continued to increase and probably reached its high watermark at the end of the 1970s when between 80 and 100 million women were believed to be taking it and it was available on or off prescription in some 150 countries. In the early days of pill usage only minor side effects were encountered and these were acceptable to most women in return for the high effectiveness of the method. Soon, however, it became clear that the pill carried with it a significant health risk.6 In 1969 cardiovascular problems related to hormonal steroids contained in the pill came to light. These included heart attacks, stroke and blood clots in the lung. They were encountered more frequently in older women and particularly in cigarette smokers. With time the unease grew and also there was the greatly feared and much debated possibility of the carcinogenicity of the pill with special reference to the breast and cervix uteri. What is the likelihood that during the next 25 years major developments in the field of oral contraception will take place? Carl Djerassi, one of the research chemists responsible for the synthesis of the original pill, is not optimistic. In his classical treatise The Politics of Contraception, 7 Djerassi emphasizes the difficulties of work in this area. Costs would be high; the lead time intervening between animal experimentation and clinical application would be prolonged. Also any new pill could well suffer from the fundamental disadvantage of its predecessor, namely from its propensity to disturb the woman’s hormonal balance. Given this somewhat sombre outlook it is scarcely surprising that much of the research in steroid contraception in recent years has been devoted to devising alternative delivery systems to the pill. Foremost among such approaches have been injectables, steroid implants and vaginal rings.

FUTURES August 1966

Experience with injectable contraceptives dates back to the early 1960~.~ The favoured compound has been Depo-Provera (DMPA) which so far has been used as a contraceptive by over 10 million women around the world; next in importance is norethisterone oenanthate (NET OEN). Both prevent ovulation by acting at the hypothalamic level of the brain; there are also direct contraceptive effects on the uterus, fallopian tubes and cervix.g DMPA has been endorsed by the World Health Organisation and by the International Planned Parenthood Federation and is currently available for long-term administration in more than 80 countries, Its use is particularly high in the Third World. Among industrialized countries the situation vis ci vis injectables varies greatly. Sweden, Denmark, FR Germany, the Netherlands and New Zealand permit its long-term application but the Food and Drug Administration in the USA has vetoed its use and in the UK a long-term licence for its administration was not obtained until as late as 1984. NET OEN has recently been marketed in the UK and is freely available in FR Germany; in the Third World, Mexico, Peru and Zimbabwe favour it as a contraceptive method. Third World countries usually have experience of antibiotic administration and vaccination and here injectables are readily acceptable as a method of birth control. Other advantages of injectables include their independence of coitus, the fact that they can be safely used during lactation and that unlike other forms of contraception such as the condom, cap and intra-uterine device, they do not Their major disadvantage stems from their necessitate genital handling. propensity to cause weight gain and to disrupt the menstrual cycle producing heavy and irregular bleeding. In recent years, injectables, particularly DMPA, have been the focus of acute and bitter controversy in the media. ” Their safety has been questioned as has their effect on future fertility. Racist issues and the women’s rights movement have also been involved in the dispute and the accusation has been levelled that in Third World countries DMPA has been given without the free and informed consent of the woman. The increasing politicization of the issue is to be greatly deplored. No valid scientific reasons can be adduced for the controversy and injectables although so far evaluated much less thoroughly than pills, would appear to be reliable and It can only be hoped that well before 2010, the effective contraceptives. acrimony will have subsided and that injectables wiil have attained their rightful place in the global contraceptive armamentarium. Research on hormonal implants is proceeding actively in a number of centres around the world.” A major advantage, of course, is their prolonged effect and much ingenuity has been shown in devising suitable vehicles for delivery of the hormones. Implants are designed to permit controlled and continuous release particularly of derivatives of the female hormone progesterone, and they are capable of maintaining adequate blood contraceptive levels for several years. Implants also constitute a highly adaptable form of birth control and can readily be removed prior to their natural exhaustion should the woman wish to become pregnant. An advanced system of steroid implant, effective for at least four years, is FUTURES August 1996

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termed Norplant and contains the substance laevonorgestrel. Norplant has recently been approved for use in Finland where it is becoming increasingly popular. Another delivery system involving the release of hormones from vaginal rings has been under study for more than a decade. ‘* The work is quite promising and research activity in the area is growing. Absorption of hormones from vaginal rings is claimed to be satisfactory and new designs are being produced which may enable the ring to remain in situ for long periods of time and still permit adequate menstrual control. Claims have been made that minor side effects such as headache, nausea and breast tenderness are less frequent with vaginal rings than with the pill but the incidence of major hazards, particularly cardiovascular disease, remains to be established. Given adequate funding at the world level the outlook for vaginal rings is not unpromising. Further toxicological studies will obviously be required with special reference to their effect on blood fats and other biochemical parameters; better control of bleeding patterns will have to be achieved if acceptability is to be improved. It is to be hoped that by 2010 these and other problems will have been resolved and that vaginal rings will have established themselves as an important if not a pivotal method in the general area of steroid contraception. Contraception

and releasing factors

An alternative form of hormonal contraception exists. It involves so-called releasing factors which travel from the hypothalamic area of the brain to the pituitary gland. There they promote the production of the gonadotrophic hormones, the main regulators of the human menstrual cycle. Th e gonadotrophin releasing hormone (luteinising hormone releasing hormone, LHRH) was first isolated in the 1970s.13 Soon after LHRH analogues, both agonists and antagonists, were prepared in which one or more of the ten amino acids constituting the molecule was replaced. The major aim of this work was to develop a contraceptive method with a central action which might be effective, relatively free of side effects, acceptable and easily applicable. ‘* Until now, very limited clinical studies have been made with LH-RH antagonists largely because the preparation of sufficiently potent compounds has proved unexpectedly difficult. It has, however, been shown that when such materials are given to normally menstruating women by the intramuscular route, they can inhibit ovulation and reduce the response of plasma gonadotrophins to LH-RH. However, during the medication some of the subjects complained of heavy and irregular menstrual bleeding which if prolonged could cause anaemia. l5 In oophorectomized and postmenopausal women with high blood gonadotrophin readings LH-RH antagonists lowered such levels and also diminished the pulsatile secretion of the hormones. Clinical work with these compounds is obviously at a very early stage and much research will have to be done before any conclusion regarding the efficacy of the method can be drawn. Paradoxically LH-RH agonists, originally introduced into clinical practice to treat infertility, have proved rather more promising as contraceptive agents. l6 The best known of this group is probably the compound buserelin which has

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been claimed to inhibit the mid-cycle surge of gonadotrophins and to prevent ovulation. Buserelin also depresses follicular development as judged by oestrogen secretion and reduces gonadotrophin production by a direct action on the pituitary gland. LH-RH agonists can be given under the skin, into the muscles or preferably in the form of a nasal spray. They could well be associated with fewer hazards than the pill; they would also seem to be especially indicated in women aged 30 and over who have achieved their desired family size and yet face two decades of potential fertility. But the method is bound to be very expensive at least in its early stages and its use would have to be limited to developed countries. Also optimum dosage schedules require to be worked out and there well might be unacceptable side effects particularly heavy bleeding and symptoms of hormonal deprivation as evidenced by hot flushes and weight gain. LH-RH analogues, both agonists and antagonists, offer hope of a new approach to contraception which might be generally available by 2010. But like all other methods which change the woman’s hormonal balance they carry with them risks as well as benefits and the likely overall efficiency of the technique will require careful appraisal. Outlook for pregnancy vaccination The concept of vaccination dates back to the 1780s when Edward Jenner developed protection against smallpox by injecting a very similar but relatively Work in reproductive harmless virus vaccina, into one of his patients. immunology leading to the development of an antifertility vaccine is an intriguing prospect for many people. l7 It has the potential to provide long standing protection against pregnancy; it would not necessarily come within the purlieu of doctors and could be readily administered by paramedical staff; it would be especially valuable in Third World countries where for many years, techniques involving vaccination have been used to treat a variety of diseases. During the 1970s antihormone vaccines came under scrutiny especially those involving gonadotrophins and subunits of their molecules. la Human chorionic gonadotrophin (HCG) is the hormone produced by the placenta in large amounts during early pregnancy and is thought to be responsible for the maintenance of ovarian function at this time. Vaccination against a subunit of HCG was shown to be successful in preventing pregnancy in baboons and there was considerable optimism that the technique might be applicable to humans. But when the method was eventually tested by clinicians in India a series of problems arose. These included variation in individual response, a variety of unexpected side effects and inadequate protection from pregnancy. Obviously the clinical trials were premature and they have not been repeated. The development of a vaccine based on male sperm represents another promising angle in this field. lg Intervention could take place at several sitesduring the formation and production of sperm in the testes, during sperm maturation in the organ known as the epididymus, and during the interaction between sperm and egg in the woman’s reproductive tract. So far the number of sperm antigens prepared is limited. But work in the area is gaining momentum and, in particular, methods involving monoclonal anti-

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bodies should prove useful in identifying the antigens and in elucidating Present research suggests that a vaccine appropriate sites of intervention. stimulating the production of several antibodies is likely to be the most effective and there are reasons to believe that this technique would be applicable to males as well as females. The ovum itself and the membranes investing it are also susceptible to pregnancy vaccination techniques. Here the most promising leads depend on antigens derived from the zona pellicudu, the protein shell which proliferates around the egg during fertilization and which binds sperm in the early stages of maturation. So far animal experiments involving rats, mice and pigs have given promising results but clinical trials in humans are unlikely to be undertaken in the foreseeable future. Although formidable difficulties still exist, the prospect of being able to vaccinate women against pregnancy remains alluring. Success in the venture may not be possible by 2010 but given reasonable luck, research efforts in the area may be crowned with success well before the middle of the 21st century. Slow progress with the male pill To state that fertility control in men is just as important as in women, is of course, a truism. Yet research in male contraception has not prospered in recent decades. There has been little enthusiasm for the project; no great leap forward has taken place; there have been few research grants and overall funding has been characterized by extreme parsimony. There have, however, been a few promising leads.” Various combinations of steroid hormones (usually a progestogen along with the male hormone androgen) have successfully diminished spermatogenesis mainly through a central action on the pituitary gland. But associated side effects have remained the major problem and in particular the partial loss of libido has been greatly resented. In the 1970s a compound cyproterone acetate seemed a likely candidate for the ‘male pill’. It acted as a potent antagonist for the male hormone androgen, its effect was central and it rapidly reduced sperm counts. But side effects were difficult to control and there was also doubt about the overall contraceptive efficacy of the medication. A testicular product known as inhibin also seemed to offer some possibilities. Here, however, synthetic analogues would have to be prepared and so far this has not proved feasible. There was considerable excitement in the early 197Os, when an anti-fertility compound, gossypol, was tested in China.‘l Gossypol, a polyphenolic yellow pigment and an ingredient of cotton seed oil, is certainly not in short supply, there being an estimated 25 kg available for every inhabitant on earth! Early reports about gossypol were optimistic and even to some experienced family planners it seemed that a relatively simple answer to the world’s population problem was at hand. By 1979, over 4000 healthy male volunteers had been treated in China; by 1981 the total had risen by a further 6000. Definite evidence had now accumulated that gossypol had a strong antispermatogenic action, capable of causing severe oligospermia or azoospermia in over 90% of cases. Its mode of action had been intensively studied and the

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Contraception-the next 25 years

consensus of opinion was that its effect was direct on the testes and was not medicated through the endocrine system. But the optimism for gossypol was shortlived and soon it became obvious that its disadvantages were so great that they would virtually preclude its widespread use in clinical practice. The main problem was that in a relatively high proportion of cases azoospermia persisted many weeks after treatment with gossypol had been withdrawn. Also symptoms such as lack of appetite, excessive fatigue, dizziness and decreased libido were reported; even more serious a type of paralysis due to potassium deficiency was observed.” In spite of this setback the work on gossypol did not represent time wasted, for undoubtedly the compound was the most important non-steroidal male contraceptive discovered in recent decades. Future work in this area must obviously concentrate on the preparation of analogues which possess gossypol’s antispermogenic activity, but lack its side effects. It is too much to hope that such a breakthrough will take place before 2010? Breast

feeding-

nature’s

method

of birth control

It has been recognized from ancient times that when a woman is nursing her baby she is unlikely to conceive. So called lactational amenorrhoea-inhibition by breast feeding of ovulation and hence of the menstrual flow-has traditionally played an important role in child spacing. Now, however, the practice of breast feeding has declined throughout the world and the latter is practised as a major fertility-regulating mechanism, only by a few traditional hunter-gatherer societies such as the !Kung in the Kalaharia Desert and isolated tribal communities in Australia, Papua-New Guinea and South America.23 It should be emphasized that when utilized in this way breast feeding can be highly effective as a contraceptive measure. Thus the !Kung have an average completed family size of only 4.7 children; their mean birth interval is approximately four years; given their relatively high infantile mortality rate it would take 300 years for the !Kung population to double. The inexorable decline of breast feeding together with the sharp rise in supplementary feeding has had two major global effects neither of them benelicial.24 The first concerns health. Infantile mortality rates, especially in developing countries, have soared and in addition there has been a steep rise in respiratory and diarrhoeal diseases in neonates. As of now in the Third World more than 10 million babies a year die before their first birthday (more than the total death rate from Hiroshima and Nagasaki each week) and the drift away from breast feeding must take major responsibility for this. Growth rates which in recent years The second relates to population. have risen markedly in Africa and have been associated with the stampede from breast feeding have adversely affected the continent’s carrying capacity as regards both resources and environment. It must, however, be stressed that in spite of the increasing preference worldwide for bottle feeding, breast feeding still remains an important check on maternal fertility. 25 Indeed, even in the 1980s more pregnancies are probably prevented through lactational amenorrhoea than by all other family planning

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methods put together. The precise mechanism whereby breast feeding delays renewed conception remains to be elucidated.26 Hormonal factors are undoubtedly important and here the pituitary gland and the hypothalamic area of the brain are probably involved. The suckling stimulus is also of major significance and at the time of delivery the sensitivity of the nipples increases markedly. Suckling may also have a more direct effect on hormonal secretion. Thus it can stimulate the production of the oxytocic hormone from the posterior pituitary gland and of prolactin from the anterior pituitary. The former causes contraction of cells in the mammary gland and is responsible for milk ejection, while the latter probably plays a key role in long-term milk secretion. breast feeding remains something of a Within the practice of medicine, ‘Cinderella’. No speciality is immediately responsible for it. The obstetrician ceases to be involved when the child has been delivered and the mother discharged from hospital. The paediatrician is more interested in the treatment of the sick child than in the encouragement of breast feeding in a normal home environment. For the family planning doctor breast feeding is not regarded as a significant part of the contraceptive armamentarium and courses in this speciality make little mention of it. In modern industrialized societies bottle feeding remains in the ascendant although in recent years there has been some return to breast feeding mostly by privileged and better educated women. 27 A survey in the USA in 1966 indicated that only 18% of babies were breast fed at the time of discharge from a maternity hospital. In England and Wales in 1975 only 51% of mothers started to breast feed their babies and as of 1985 continuance rates remain very poor. Numerous factors have contributed to this state of affairs in developed countries.‘s They include the steady progress of urbanization, the everincreasing proportion of working mothers, the ready availability of suitable breast milk substitutes and the pervasive effects of advertising and the mass media. Also, among Western women the idea of having to breast feed in public is embarrassing and is thought to detract from their femininity. Research on breast feeding is at a low ebb in developed countries. The subject arouses little general interest or excitement and this situation seems likely to persist into the next century and well beyond 2010. The rate of contraceptive usage by women in the Third World has been estimated at 20%. Accordingly 80% of the community must be dependent on a natural method of fertility control and among these, breast feeding is undoubtedly the most significant. Even so, the incidence of breast feeding is still declining in developing countries and this is happening particularly among the urban, educated and reasonably affluent women who are usually the trendsetters within the community. Thus in Taiwan between 1966 and 1980, the number of women who breast fed fell from 90% to 50% and the average duration of lactation declined from 14.6 to 8.8 months; in Thailand between 1969 and 1979 the drop was from 22 to 17 months. If women in Third World countries continue to abandon breast feeding and if modern contraceptive methods are adopted too slowly, future demographic effects are likely to be serious if not catastrophic. For example, in Bangladesh, where only 9 % of women use contraceptives and where the average duration of FUTURES August 1988

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Contraception-the next 25years

lactational amenorrhoea is 18.5 months, in order to decrease the period of six months, the use of contraceptives would have to rise fivefold, truly a Herculean task in such a type of society. Kenya currently has a population growth rate of over 4% per annum: numbers present average level of fertility

could well double in less than 20 years and the stands at eight births per woman. It is currently

estimated that only 7% of Kenyan women use any form of birth were the contraceptive effect of breast feeding to be further population situation would become even more menacing. The falling incidence of breast feeding can only be regarded

control eroded

and the

as a global

tragedy. It is yet another factor increasing our predicament and pushing the planet ever nearer the rim of catastrophe. The prognosis for breast feeding is not good and there

is little hope that present

trends

will be reversed

before

2010.

Notes and references 1. J. A. Loraine, “The future practice of medicine: the challenge of global factors”, Futures, 14, (3), 1982,pages 171-179; J.A. Loraine, “World population, the present and the future”, Global Signposts &othe 21st Century Family Practice, 1, 1984, pages 122-132; J. A. Loraine, “World population perspectives”, (London, UK, Peter Owen, 1979); J. A. Loraine, Medicine and War, 1, (3), 1985; L. R. Brown, U. Chandler, 0. Flavin et al, State ofthe World (Worldwatch Institute Publication, New York, USA, Norton, 1985); and A. Ehlrich, “The American Zoolog, 2.5, 1985, pages 395-406. human population: size and dynamics”, 2. Loraine; and Ehlrich, op tit, reference 1. DC, Population Reference Bureau, 1985). 3. World Population Data Sheet (Washington, 4. Loraine, op tit, reference 1. Textbook of Contraceptive Practice, 2nd edition (Cambridge, UK, 5. M. Potts, P. Diggory, The Pill, 3rd edition (Oxford, UK, Cambridge University Press, 1983); J. Guillebaud, Handbook of Family Planning (Edinburgh, Oxford University Press, 1984); N. Loudon, Scotland, Churchill Livingstone, 1985); D. F. Hawkins, M. G. Elder, Human Fertility Control. 1979); and M. J. K. Harper, Birth Control Theory and Practice (London, UK, Butterworths, Technologies: Prospects by the Year 2000 (London, UK, Heinemann Medical Books, 1983). 6. E. Grant, The Bitter Pill. How Safe is the Perfect Contraceptive? (London, UK, Elm Tree Books, 1985); and Guillebaud, London, Hawkins, op tit, reference 5. The Politics of Contraception (New York, USA, Norton, 1979). 7. C. Djerassi, Scotland, a. J. A. Loraine, E. T. Bell, Futility and Contraception in the Human Female(Edinburgh, Churchill Livingstone, 1968). 9. Loudon, op tit, reference 5. 10. B. R. Gold, “Depo Provem: the jury still out”, Family Planning Perspectives, 15, 1983, pages review of injectable contraception 17-81; and I. S. Fraser, E. Weihberg, “A comprehensive with special emphasis on depot medroxy progesterone acetate”, Medical Journal of Australia, 1, 1981, pages 3-19. 11. Harper, op tit, reference 5; and Djerassi, op tit, reference 7. “Initial clinical studies of intravaginal rings 12. D. R. J. Mishell, M. Lumkin, T. Jackaninz, containing norethindrone and norgestrel”, Contraception, 12, 1975, pages 253-260; and D. R. J, Mishell, D. R. Moore, S. Poy, P. F. Brenner, M. A. Page, “Clinical performance and endocrine profiles with contraceptive vaginal rings containing a combination of ostradiol Ammican Journal Obstetrics and Gynecology, 130, 1978, pages 55-62. and D-norgestrel”, structure of the ovine hypothalmic M. Amoss et al, “Primary 13. R. Burgus, M. Butcher, Proceedings National Academy Science, USA, 2, 1983, luteinising hormone releasing factor”, pages 1-15; and H. Matsud, Y. Baba, R. M. C. Nair, A. Arimura, A. V. Schally, “Structure of the procie LH- and FSH-releasing hormone. 1. The proposed amino acid sequence”, Biochemistry Biophysics Research Communication, 43, 1971, pages 1334-1339. status of Antagonistic Analogues of LH-RH as a contraceptive 14. A. V. Schally, “Current method in the female”, Research Frontiers in F&lily Regulation, 2, 1983, pages 1 - 14.

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15. E. S. Canales, H. Montivelinsky, H. Zarate, A. J. Hastin, D. H. Coy, A. V. Schally, “Suppressive effect of an inhibitory LH-RH in normal woman”, International Journal of Fertility 25, 1980, pages 190-192. 16. H. M. Fraser, “New prospects of luteinising hormone releasing hormone as a contraceptive and therapeutic agent”, British Medical Journal, 285, 1982, pages 990-991; and R. J. Aitken, Developments in Human Reproduction and Their Eugenic and Ethical Implications (London, UK, Academic Press, 1983). against pregnancy”, Royal Society discussion, Contraceptives 17. J. P. Hearn, “Immunisation ojthe Future, London, UK, 1976; “Immunological methods of fertility regulation: report of a Research Frontiers in Fertility Regulation, 3, 1985, pages l-l 1; and Aitken, op tit, workshop”, reference 16. 18. Aitken, op tit, reference 16; and ibid. 19. Ibid. “Towards a pill for man”, Royal Society discussion, Contrweptives of the 20. P. M. de Kerster, Future, London, UK, 1976; and Aitken, op tit, reference 16. a possible male antifertility agent: report on a 21. D. G. I. Zatuchni, C. K. Osborn, “Gossypol: workshop’ ’ , Research Frontiersin Fertility Regulation, 1, (4), 1981, pages 1-15; Z. Q. Liu, G. Z. Liu, L. S. Hei, R. A. Zhang, C. T. Yu, “Clinical trials of Gossypol as a male antifertility agent”, Recent Advances in FertiliQ Regulation (Geneva, Switzerland, Atar SA, 1981); and S. P. Yue, “Studies on the antifertility effect of gossypol, a new contraceptive for males”, Recent Advances in Fertility Regulation (Geneva, Switzerland, Atar SA, 1981). 22. Aitken, op tit, reference 16. Royal Society discussion, London, UK, 23. R. V. Short, “Evolution of human reproduction”, 1976; and R. V. Short, “Breast feeding”, Scientijic American, 250, (4), 1984, pages 23-29. 24. Short, op tit, reference 33. 25. Guillebaud, op tit, reference 5. 26. Short, op tit, reference 23; and W. M. Cutting, M. Ludlam, “Making of breast feeding”, Family Practice, 1, 1984, pages 69-77. 27. Cutting, op tit, reference 26. “Maternal and child health and breast feeding”, Modern Problems 28. A. Petros-Barvazian, Paediatrics, 12, 1975, pages 155-168.

FUTURES August 1986