LONDON, SATURDAY 20 OCTOBER 1979

MEDICAL
JOURNAL
Tomorrow's contraceptives-yesterday's problem?
In 1970 research into contraception seemed full of promise.
New areas were being explored, and with the perils of over-
population becoming widely recognised funds for this
research were readily available. At the end of the decade the
picture has changed. In many developed countries population
growth has slowed. In the developing world, though there
has been some decline in fertility, the main problem with
population control is now seen to be making the contraceptives
we have both available and culturally accept'able-not
developing new methods. Furthermore, in most industrialised
nations the amount of government spending on contraceptive
research has levelled out or declined since 1974, and of today's
budget the proportion contributed by institutions and
pharmaceutical companies is about half of what it was 10
years ago. Finally, worthwhile results from this research have
proved elusive: for example, the development of a vaccine
against pregnancy has run into many problems, and the
"male pill" seems as far away as ever.

Referring to some of these difficulties in his introduction to
the British Medical Bulletin's issue on reproduction,1 Professor
R V Short reminds us that our current preoccupation with
recession and the energy crisis should not obscure the pressing
problem of world overpopulation. The decline in the British
birth rate now seems to have halted, and women are becoming
disenchanted with the limitations of oral contraceptives2 and
intrauterine devices. As more side effects are discovered public
confidence in existing methods of contraception will be
eroded further. A World Health Organisation research
programme, applying existing knowledge, has failed to produce
new contraceptives of widespread applicability. We need more
basic research, and the British Medical Bulletin's wide-ranging
series of reviews suggests several approaches.3
Immunology provides promising possibilities: vaccination

against pregnancy can be carried out by immunising women
against pregnancy-specific proteins. Primates4 and indeed
human beings5 have been immunised against the s-subunit of
chorionic gonadotrophin with the aim of making pregnancy
fail as soon as the gonadotrophin is produced. Unfortunately
a form of tolerance develops, so that miscarriages occur later
and later in pregnancy. Perhaps this problem could be
avoided by immunisation against spermatozoa, or against the
complex proteins of the zona pellucida of the ovum-or by
immunological attack against other transmitters15 which the
conceptus produces before implantation to signal its existence

BRITISH MEDICAL JOURNAL 1979. All reproduction rights reserved.

to the mother. Implantation is made possible by the persistence
of the corpus luteum, which is itself vulnerable to luteolytic
agents (such as prostaglandins or diethylstilboestrol): luteolysis
could also be achieved by inhibition of luteotrophic hormones,
using analogues of chorionic gonadotrophin or agents which
interfere with binding at luteinising-hormone receptors.

Developing a male pill requires suppression of spermato-
genesis without loss of libido. This can be produced by
gestogens in combination with testosterone implants, or by
cyproterone acetate-which, although it causes oligospermia
and decreased sperm motility, seems a poor contraceptive.
Oligospermia might be achieved with normal plasma testo-
sterone concentrations by developing a synthetic analogue of
"inhibin," a testicular hormone which acts on the pituitary
(independently of testosterone) to decrease the production of
follicle-stimulating hormone. Nevertheless, inhibin has proved
extremely difficult to isolate and would probably be equally
difficult to synthesise and administer.

Other possibilities include antiprogestins to prevent the
action of progesterone on the endometrium, or analogues of
gonadotrophin-releasing hormone to exhaust the pituitary
supply of gonadotrophins. But perhaps the most attractive
idea is the mimicking of "nature's contraceptive"-the
infertility associated with lactation.7 Anovulation during
lactation appears to be caused by high concentrations of
prolactin acting on the hypothalamus to inhibit the production
of gonadotrophin-releasing hormone. Clarification of this
mechanism might lead to a more physiological method of
contraception.

In all these possibilities the gap between theory and
application is still wide, and inevitably some possibilities will
be ruled out by unwanted side effects. Even so, as Professor
Short points out, not all side effects are unwanted, and our
goal should be "healthy infertility"-contraception which
promotes good health rather than compromising it.

Short, R V, British Medical Bulletin, 1979, 35, 97. Obtainable from the
British Council, 65 Davies Street, London WiY 2AA, price £5.

2 Nuttall, I D, et al, British Medical3Journal, 1979, 2, 641.
3 Aitken, R J, British Medical Bulletin, 1979, 35, 199.
Hearn, J P, in Maternal Recognition of Pregnancy: CIBA Foundation

Symposium No 64. Amsterdam, Excerpta Medica, 1979.
5 Talwar, G P, et al, Proceedings of the National Academy of Sciences, 1976,

73, 218.
6 Heap, R B, Flint, A P, and Gadsby, J E, British Medical Bulletin, 1979,

35, 129.
McNeilly, A S, British Medical Bulletin, 1979, 35, 151.

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