Are there any legal issues to consider when prescribing the pill to adolescents?

While exceedingly common, this kind of consultation poses a dilemma for many GPs. Sarah is under age and yet she has acted responsibly in seeking out

Unfortunately, many young women fall pregnant before starting contraception, as they tend to wait several months after commencing sexual activity before presenting to a doctor. Indeed, adolescents have little knowledge of the medical system and are generally apprehensive about seeing GPs whom they have seen with their parents for childhood illnesses for fear of disclosure.

In Sarah’s situation, the ‘mature minor rule’ applies and is based on an English legal precedent called the Gillick case. This case ran in the English courts in 1985. Mrs Gillick was a Roman Catholic mother of 10 children, who was affronted by the prospect of one of her under-age daughters being prescribed the oral contraceptive pill without her mother’s consent.

The final judgment in this case went 3–2 against Mrs Gillick. The conclusion was that there was no provision to hold that a girl under 16 lacked the legal capacity to consent to contraceptive advice, examination and treatment, provided that she had sufficient understanding and intelligence to know what they involved. It was agreed, however, that it would still be most unusual for a doctor to give such advice and treatment without the consent of the parents. In the situation where the girl refused either to tell her parents herself or allow the doctor to do so, the doctor would be justified in proceeding without the parents consent, or even their knowledge, provided that he was satisfied that:

The Gillick case also held that a doctor would not be criminally liable for aiding in the offence of carnal knowledge by prescribing contraceptives or giving contraceptive advice.

What form of contraceptive would you choose?

While this may be the start of sexual activity for Sarah, one should not assume that her partner has yet to become sexually active. Her GP should therefore recommend to her the ‘belt and braces’ approach to contraception, otherwise known as ‘double Dutch’. Sarah requires an effective contraceptive to prevent pregnancy, as well as condoms to prevent her catching a sexually transmitted disease (STD).

Many would argue that Sarah should just use a condom with emergency contraception as a back up (see p 46). However, even in experienced users, condoms can break and/or spillage occur. In the inexperienced hands of teenagers, where lubrication is not always prevalent, condom failure is likely to occur more often. Sarah may also have problems in getting her partner to accept condom use. Sex may also occur after alcohol or drug use. For all of these reasons, Sarah is best off using hormonal contraception as well as condoms. However, GPs should make adolescents aware of the existence of emergency contraception and how to access it, should they need it in the future.

Sarah would therefore benefit from hormonal contraception either in the form of a combined oral contraceptive pill (COCP) or a long-acting reversible contraceptive (LARC) such as Implanon® or Depo Provera®. While the COCP has both contraceptive and non-contraceptive benefits (Table 3.1), LARCs offer higher efficacy because they are not as user-dependent. It is important, however, to offer Sarah a choice of contraceptive methods so that she is informed and able to choose the method that suits her best. For example, if she has a chaotic lifestyle or a poor memory and is fearful of forgetting to take the pill every day (especially if the packet has to be kept out of sight of her parents), then Depo-Provera® or Implanon® is probably the more suitable alternative.

TABLE 3.1 Benefits of the combined oral contraceptive pill

If she wanted to use the COCP, which pill would she start with?

When prescribing hormonal contraception, a general rule of thumb is to use the lowest possible dose of hormones to attain both contraception and cycle control. Possible pills to use in Sarah’s case are a monophasic (either a 20 mg or 30 mg ethinyloestradiol pill) or a triphasic low-dose pill. These pills are low-dose, cheap and easy to use. Monophasic pills have a greater margin for error than their triphasic counterparts. They are also easier to manipulate, should the young woman want to delay her period because she is going swimming, camping or on holiday, and are therefore probably a better option. A monophasic COCP containing levonorgestrel is a good first choice, although pills with different types of progestogen can be used initially, or introduced later if there are side effects.

How commonly are myths about the pill believed?

Wide-ranging misconceptions about the pill exist among women. Many believe that oral contraceptive use is more dangerous than childbirth, that the pill has substantial health risks and that the pill causes cancer.

Women are often surprised to hear that the pill actually has benefits in addition to being a contraceptive. One hopes that this information, once given, will spread through the schoolyard and back to mothers, so that siblings will not grow up learning

the same falsehoods. GPs should make it a practice to discuss the non-contraceptive benefits of the pill routinely with women presenting for a discussion about their contraceptive options.

The first issue to highlight is that whenever they think of the side effects of contraception they should be comparing these to the side effects of pregnancy. In 90% of cases women who are sexually active without contraception will fall pregnant within a year. Yet doctors rarely speak about the mortality and morbidity associated with pregnancy and the fact that these are much higher than the morbidity and mortality associated with the use of oral contraception.

It is important also to explain to young women why it is that all these myths have arisen about the pill. The pills that women take today are not the same as the ones taken by their mothers. The dosage has come down from 100 mg of oestrogen, which used to make women vomit and was related to strokes and heart disease, to 30 mg or less. The COCP is one of the most researched pharmaceutical products in the world. Provided women are healthy, have normal blood pressure and do not smoke, these events are no more likely to occur than if they were not on the pill.¹

How safe is the pill?

An British study of 46,000 women (which began in 1968) tracked users of oral contraceptive pills containing 50 mg of oestrogen for 25 years.² This study showed that over the entire follow-up period the risk of death from all causes was similar in never-users of the pill to ever-users. For women who had stopped using the pill more than 10 years previously, there were no significant increases or decreases either overall or for any specific cause of death.

Does the pill cause cancer?

The pill acts in a preventive fashion against ovarian and endometrial cancer. Use of combined oral contraception decreases the risk of a woman developing ovarian cancer by 40%. The longer a woman uses the pill, the greater the effects. Ovarian cancer is associated with many factors, such as family history, decreased parity, late age of menopause and early menarche. It is thought that women who do not bear children have a 2–2.5-fold increased risk of developing ovarian cancer, and this is perhaps because of the increased opportunities for monthly follicular development. The pill suppresses follicular activity and is therefore associated with a relative risk of 0.6 in ever-users and 0.4 in women who use the pill for >5 years.³ The increasing protection with increased duration of use has been confirmed in other studies.⁴

Endometrial cancer occurs in 0.1 per 100,000 women aged 20–24 and in 12 or more women per 100,000 in those aged 40–44. The risk factors for this cancer are similar to those of ovarian cancer and include obesity, nulliparity, early menarche and late menopause, and the administration of unopposed oestrogen. The effect on endometrial cancer of taking the pill is similar to that of ovarian cancer, with use of the pill decreasing risk of endometrial cancer by 50%. This effect is maintained for at least 20 years after discontinuation of the pill.⁴

While the explanation is unclear, several studies have found that ever-users of the COCP have a 60% reduction in bowel cancer.⁵

Unfortunately, use of the pill may increase the risk of a woman developing breast cancer. The relationship between breast cancer and the pill has now been the subject of numerous studies. Collectively they suggest the following:⁶

It is important to assist women to gain some perspective about this increased risk, given the degree of awareness of breast cancer in the community. This can be done using the information given in Table 3.2 (p 42). Given that the incidence of breast cancer increases with age naturally (1 in 500 women have breast cancer by age 35 compared with 1 in 100 by age 45 and 1 in 12 by age 75), the risk attributable to COCP use by women increases in older women.⁷

TABLE 3.2 Excess number of breast cancer cases/10,000 women who had used the COCP for 5 years and were followed up for 10 years after stopping, compared with never-users

(From Collaborative Group on Hormonal Factors in Breast Cancer⁹⁸)

The COCP appears also to increase the risk of cervical cancer (five extra cases per 100,000 women per year), but it is unclear whether this is a causal relationship.⁸ Long-duration follow-up studies certainly show a clear effect of duration of pill use, with the odds ratio of developing cervical cancer being 2.9 after 4 years of COCP use and 6.1 after 8 years.⁴ Despite this, it is important to remember that HPV is the primary carcinogen and that smoking is probably a more important co-factor than the COCP.⁹

Regarding other cancers, liver cancer might be increased by the pill (but it is a rare cancer anyway), and the role of the COCP in the development of malignant melanoma remains controversial.⁷

Are women who take the pill at increased risk of adverse cardiovascular events?

In general women are at low risk of adverse cardiovascular (CVS) events before the menopause. This is even truer for young women, who are the usual COCP users. The risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke and venous thromboembolism in COCP users are related to:

The COCP magnifies all of these underlying risks and usage of the pill should be carefully considered in women who have any of these risk factors.⁶

What long-term health benefits result from using the pill?

Some long-term health benefits of the pill proved by research include a decrease in menstruation-related disorders, pelvic inflammatory disease and benign breast disease. Possible effects attributed to pill use include protection against the development of benign ovarian cysts, fibroids and osteoporosis.

The COCP results in improvements in acne, menstrual disorders and benign breast disease and decreased rates of pelvic inflammatory disease (PID).

However, GPs should note that most of the findings described above were associated with use of the 50 mg oestrogen pills, while most women these days are on lower dose pills.

Is the pill associated with weight gain?

Another major misconception held by young women concerns weight. Every patient can recount stories of friends who put on ‘massive’ amounts of weight when on the pill. A recent systematic review, however, has found no evidence supporting a causal association between combination oral contraceptives, or a combination contraceptive skin patch, and weight gain.¹⁰

What about acne?

Doctors should explain to teenagers that most COCPs will actually improve acne. If, in rare cases, acne is worsened on a levonorgestrel-containing pill, it is worth trying the norethisterone-containing pills or a third-generation pill containing one of the newer progestogens. COCPs containing cyproterone acetate actually target acne more specifically because of their anti-androgenic action, as do COCPs containing drospirenone (Yasmin and Yaz). The benefits may take up to 6 months to take effect, however, and the woman should be warned that on stopping the pill her acne might recur.

What are the contraindications to the pill?

Before starting a woman on the pill, a GP must rule out any contraindications to its use. These contraindications have been classified by the World Health Organization¹¹ into four categories (Box 3.1, p 44).

What examination needs to be carried out before a woman starts the pill?

The only examination routinely required prior to first prescription of the COCP is blood pressure. In asymptomatic women, breast and pelvic examinations are unnecessary. Blood tests are also unnecessary unless there is a specific clinical indication.¹²

What messages need to be conveyed to women starting the COCP for the first time?

Many young women are familiar with the pill before they even get to the consulting room. Information has already been obtained from girlfriends who may be using it, from sex education at school or from reading magazines.

It is important to do a couple of things in addition to counselling the patient. The first is to tell them not to be scared about what they read in the product information, which is based on medicolegal necessities and is not altogether representative of what they will experience. The second important thing is to give the patient an objective source of information that has in writing what you are about to tell them.

The following points are a summary of important issues to cover (and assume you are starting the woman on a 28-pill packet).

Missed pills

After asking the young woman to show you the most dangerous times to miss a pill, explain that this is in fact immediately before and after the sugar pills. This fits in nicely with the analogy of putting the ovaries to sleep. If the pills before or after the sugar pills are missed, the ‘pill-free interval’ is lengthened, thereby allowing the ovaries to wake up and release an egg. (The pill-free interval has been set arbitrarily at 7 days by manufacturers in order to replicate a normal 28-day cycle, except for Yaz, which has a 4-day pill-free interval—see Box 3.3.) If more than 7 days go by (i.e. if more than seven pills are missed), there is a chance that ovulation, and therefore pregnancy, could occur.

BOX 3.3 Benefit of a 4-day pill-free interval

Yaz is the first COCP to be manufactured with a 4-day pill-free interval rather than seven. Shortening the pill-free interval gives the user a greater margin of error should she forget to recommence her next pill packet on time (i.e. if she misses the first pill of her next pack).

There has recently been some controversy over whether advice to women regarding missed pills should differ according to the oestrogen dose in the pill.^9,14 The simplest advice (erring on the side of caution) for pills that have the traditional 21 active pills and 7 sugar pills is outlined in Box 3.4 and Figure 3.1 (p 46). Where a pill like Yaz (24 active pills and 4 sugar pills) is used, the advice for missed pills is dependent on whether more than 7 pills have been missed.

BOX 3.4 Missed pills

One pill missed (late by up to 24 hours)

1. Take the pill as soon as you remember.

2. Take the next pill at the usual time.

3. Keep taking active pills as usual.

More than one pill missed (>24 hours)

As well as 1–3 (above), avoid sex or use condoms for 7 days.

If pills are missed in week 1 (days 1–7) (because the pill-free interval has been extended), emergency contraception should be considered if unprotected sex occurred in the pill-free interval (sugar pills) or in week 1, restarting the COCP with the next active pill within 24 hours of taking emergency contraception.

If pills are missed in week 3 (days 15–21) (to avoid extending the pill-free interval) finish the pills in current pack and start a new pack the next day, thus omitting the pillfree interval (sugar pills).

FIGURE 3.1 Flow chart for management of missed pills (when using a 28-day pack)

It is also important to stress that a ‘period’ on the pill is only in fact a withdrawal bleed (and not related to having a normal cycle). Draw diagrams of the endometrium being nurtured and sustained by hormones, only to shed away when the hormones are not present.

When starting a woman on the pill, a GP should explain that the pill ‘puts the ovaries to sleep’ and that when starting the pill it takes 7 days for this to happen.

What is the background efficacy of the pill?

When considering drug interaction, it is important to know what the efficacy of the pill really is. The failure rates in clinical trials have been shown to be as low as 0.1/100 woman years. Typically, however, these very low rates of pregnancy are not achieved because of ‘user failure’. Time and again studies have shown the difficulty in remembering to take a pill every day and so, with typical usage, up to 5% of women will have an unintended pregnancy during their first year of COCP use. The possibility of interactions with broad-spectrum antibiotics should therefore be looked at with this figure in mind.

What is the mechanism of drug interaction with the pill?

There are several ways that drugs can potentially interact with the COCP, including inducing liver enzymes and reducing the enterohepatic recirculation of oestrogen.

Some anticonvulsants are well known to induce liver enzymes that cause the breakdown of oestrogens

Sodium valproate, clonazepam, clobazam and the newer anti-epileptics (including vigabatrin and lamotrigine) do not have this effect. In cases where women are taking anticonvulsants that interact with the pill, the contraceptive efficacy of the pill is reduced, especially with ‘low-dose’ pills. The solution is therefore to use a pill that contains 50 mg of oestrogen.

Rifampicin and griseofulvin have similar enzyme-inducing effects, particularly rifampicin, which is very potent in this regard. Even if it is given only as a short-term dose (as is the case for prophylaxis against meningitis), increased elimination of the pill components must be assumed for 4 weeks afterwards. This necessitates the use of alternative forms of contraception for all of this time.

When the pill is taken, the progestogen component is 80–100% bioavailable from the upper part of the small bowel. Ethinyloestradiol, however, is subject to the ‘first-pass’ phenomenon. This means that the oestrogen is conjugated with sulfate in the gut wall and carried in the hepatic portal vein to the liver. The liver metabolises the steroid-forming glucoronides. The metabolites are then excreted via the bile back into the gut, where bowel flora remove the sulfate and glucoronide groups and the oestrogen is reabsorbed.

Theoretically, broad-spectrum antibiotics can eradicate the gut flora responsible for the deconjugation of the ethinyloestradiol metabolites and therefore reduce the amount of reabsorption that occurs during short-term antibiotic use or during the initial days of long-term antibiotic use before resistant gut flora emerge. In practice, however, the evidence backing this theory remains unclear, with one study showing increased faecal excretion of conjugated metabolites but no demonstrable reduction in plasma unconjugated oestrogen concentrations.

The argument becomes interesting because the bioavailability of orally administered ethinyloestradiol is usually 40%, but varies markedly from 20% to 65% in different individuals. This variation in initial bioavailability may account for the sporadic cases of pregnancy that occur with concurrent antibiotic use. For example, if the woman had a low background availability of ethinyloestradiol, coupled with a large enterohepatic circulation and gut flora sensitive to the antibiotic being prescribed, she might be more likely to fall pregnant. The problem is that the very small subgroup of women who may have all these factors concurrently cannot be identified by any routine diagnostic tests.