3 Artificial contraception
3.1 Chemical contraceptives
These methods rely to a large extent on an understanding of the physiology of the reproductive process. They are targeted at preventing the production or release of gametes, i.e. the sex cells – sperm and eggs – which need to fuse to produce a new individual. To date, most effort in this area has been directed towards preventing a woman from ovulating, i.e. releasing an egg, although more recently trials have begun on ‘male pills’ which block sperm production.
Ovulation in women generally occurs once every 28 days or so. During part of this time, the lining of the womb thickens, ready to receive a fertilized egg. If fertilization does not take place, the lining is shed as menstrual blood. This gives the 28-day cycle its common name of the menstrual cycle. The menstrual cycle is under the infuence of two main hormones, oestrogen and progestogen, produced by the body at varying levels during the menstrual cycle as shown in Figure 3. The important thing to remember is that it is the relative levels of the two hormones that determine whether, and when, an egg is released. Chemical contraceptives interfere with this delicate balance and prevent ovulation.
Figure 3, Levels of the hormones oestrogen (black line) and progestogen (continuous red line) during the menstrual cycle. M=menstruation. The downward-pointing arrow shows the time of ovulation. (The dashed red line shows what the progestogen level would be if fertilization occurred during the cycle.)
You can see from Figure 3 that there are several ways of interfering with the balance between oestrogen and progestogen.
Q List three ways of doing this.
A Altering the oestrogen level, altering the progestogen level, or altering the levels of both hormones, but to differing extents.
In practice, the last two methods have been most effective. There are combined pills, containing various levels of oestrogen and progestogen, and progestogen-only pills. Combined pills give a cocktail of oestrogen and progestogen designed to vary throughout the cycle, complementing natural levels, so that the critical balance required for ovulation is never reached. Progestogen-only pills consistently increase the level of progestogen, mimicking the pregnant state (Figure 3), so that ovulation and implantation cannot occur. The failure rate (i.e. the number of pregnancies per year per hundred women using a particular method, expressed as a percentage) associated with these pills varies between less than 1% and 4% (that is, between one and four women will become pregnant for every 100 taking the pills for a year), depending on how regularly – at the same time each day – the pills are taken.
Q From general knowledge, can you suggest why it is important to take the pills regularly?
A Not only do hormone levels vary throughout a month, but they also vary over each 24-hour period, showing a diurnal or circadian rhythm. (If you did not know this, don't worry – you will learn more about the rhythms of hormones elsewhere in this course.)
Thus in order to make sure that the hormone levels do not accidentally reach the critical point for ovulation to occur, it is necessary to take the pills at the same time each day. With the progestogen-only pill, a delay of as little as three hours can result in ovulation and hence pregnancy, although the combined pill is a little more fexible in this respect.
As women go about their daily business, it is not always possible for them to be as regular in their pill taking as is necessary. But there is another option available. It consists of an implanted source of progestogen, which releases the hormone slowly and continuously for a long period. This can be two or three months, from a single injection, to as much as five years from one or more matchstick-sized plastic tubes containing the hormone inserted into the upper arm. As you might expect, the failure rates from this form of contraception are lower than those associated with pill taking.
Q What would you predict the failure rate to be?
A You would probably say zero, since pregnancy cannot occur without ovulation.
Progestogen implants have been used extensively in some developing countries, where it can sometimes be very difficult for a woman to keep to a regular timetable, so a lot of information is available about their efficacy. The failure rate is actually as much as 2% over a five-year period. This is because although in some women the administration of this dose of progestogen does indeed prevent ovulation, in some others it does not. In these women, progestogen can still act as a contraceptive, but for other reasons (see below). This variation illustrates an important point: we are all individuals, and although our bodies and physiologies are broadly similar, many differences exist between us, which must be accommodated in any discussion of health and well-being.
The other effects of progestogen are to thicken the cervical mucus (that is, the wet, sticky substance produced by the neck of the womb), making it difficult for sperm to penetrate, and also to alter the lining of the womb, making it difficult for a conceptus (newly-formed embryo) to attach there; attachment, or implantation, as you will see below, is essential for a successful pregnancy. A look back to Figure 3 will remind you that progestogen is indeed normally present at high levels during the third week of the cycle, but drops during the fourth week, when implantation of a conceptus would occur. It is believed that these auxiliary effects of progestogen actually contribute more to its contraceptive effect than does its variable ability to prevent ovulation.
Q Can you suggest any advantage offered by one of these other effects of progestogen?
A Thick cervical mucus will hinder the passage not only of sperm, but also of any pathogenic (disease-causing) organisms. Thus, in women, cervical mucus is one of the body's defence barriers.
Of course, no drug is without its side-effects, and contraceptive pill use has been associated with a number of adverse conditions. Perhaps the most serious is the increased risk of cardiovascular disease among women – particularly those who smoke – who have taken the combined pill for a number of years and whose blood pressure is raised. Another potentially serious effect is the apparent increase in some forms of cancer, particularly of the cervix and breast, although the evidence for this is not clear-cut. More commonly, women may experience headaches or nausea. On the positive side, there is some evidence that the pill provides some protection against developing cancers of the ovary and endometrium (the lining of the uterus, or womb). Menstrual bleeding is usually lighter and more regular. Users of the progestogen-only pill report different side-effects: their menstrual bleeding tends to be irregular, they have an increased frequency of cysts on their ovaries. They also have an increased risk of ectopic pregnancy, i.e. one where implantation occurs in the wrong place, such as in the Fallopian tube, the tube leading from the ovary, where the egg is produced, to the uterus. This is an extremely serious condition which can result in infertility or even death.
Q Why do you think this increase in ectopic pregnancies occurs?
A Because of the reduced receptiveness of the uterus to implantation.
A lot of research has been carried out into the feasibility of a chemical contraceptive for men. The most popular approach has been to use a cocktail of hormones that interfere with sperm production. The main drawback is that because of the length of time required to produce sperm (more than nine weeks; see below), there is a significant delay before any effect of the hormones is apparent, and furthermore, there is a similar delay when contraception is no longer required, before sperm production is resumed. Moreover, getting the dose right is a problem: even on high doses, some men still produce sperm, and the sperm may be abnormal, which could in theory lead to abnormal pregnancies. Finally, there seems to be some resistance among men to using chemical contraceptives: the term ‘chemical castration’ demonstrates how scared some men are of losing their ability to produce sperm, with all the psychological implications which this might have.