If sexual and reproductive health are considered to be a right for both women and men, then good practice in contraceptive counselling must involve providing women with informed choice. This means that GPs must be abreast of the range of contraceptive options open to women and men and be able to outline confidently the benefits and risks of each of these for the patient’s particular situation. Practising clinicians can be surprised by the choices women make with regard to contraception, as these choices do not always fit with the stereotypes we may have. What suits one woman may not suit another in similar circumstances.
An approach that is useful is the ‘life-stage approach’, which incorporates the issue of ‘how important is it for you not to get pregnant at this point in time?’. This question recognises the fact that, for younger women who are not in committed relationships, pregnancy may be the last thing they desire, and so very effective forms of contraception that are not user-dependent may be favoured. For women who are in their late 20s or early 30s, however, the issue might be appropriate pregnancy spacing rather than whether or not they get pregnant, and less effective forms of contraception may be more readily accepted.
Whatever type of contraception is chosen, it is important that women feel informed, supported and able to use it effectively. Time needs to be taken to allay fears, dispel myths and provide the necessary knowledge and skills. Back up written information should be provided and opportunities for questions and follow up and review given. Contraceptive counselling is a very challenging part of sexual and reproductive healthcare, especially because you are assessing the risk of unplanned pregnancy and sexually transmitted diseases and dealing with the topic of the patient’s sexuality and sexual practice all at the same time. Nevertheless, providing a woman with the capacity to control her reproductive functions and therefore the direction of her life can be one of the most rewarding aspects of clinical practice.
CASE STUDY: ‘I know we’re going to have sex soon, so I want to start the pill.’
Sarah, 15 years, attended her family’s GP requesting contraception. She had no significant past history or family history and was yet to become sexually active. She had come with a girlfriend from school and asked the GP not to tell her mother about the appointment.
On further questioning, Sarah said she had been with her current boyfriend for 2 months and knew they were going to have sex soon, so she wanted to do the right thing and make sure she was ‘protected’. While she was aware from school sex education classes of the need to use condoms, she also wanted to get ‘the pill’ just to be sure she didn’t fall pregnant. She begged the GP not to tell her parents as they were very religious and she was scared about what they would do if they knew she was going to have sex. After further discussion, the GP felt that Sarah was a responsible girl who was well aware of the potential repercussions of unprotected sex.
The GP spent the rest of the consultation showing Sarah how to use a condom and allowing her to practice the technique on a plastic model. After taking Sarah’s blood pressure, she prescribed her a low-dose combined oral contraceptive and explained how to use it correctly and when she would be safe from a contraceptive point of view. Sarah was given a follow-up appointment for 2 weeks to review the information given at this initial consultation and to follow up with further information. She was also given written information to take away on safe sex, emergency contraception and contraception in young people.
contraception before becoming sexually active. She is also seeking the GP’s confidentiality and is fearful of the consequences of her parents finding out that she has come to see the GP, let alone the fact that she is planning to become sexually active.
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:
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.
|Contraceptive benefits||Other benefits|
• Beneficial for menstruation
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.
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
CASE STUDY: ‘I’ve heard the pill causes cancer.’
Jodie is 17 years old and is completing her final year of high school. She has been sexually active for 2 years and so far she has been using condoms as contraception. In the last 6 months she has needed to use emergency contraception twice. On one occasion the condom broke and more recently she didn’t use a condom at all. Thankfully, both times the emergency contraception has been successful.
This visit was the follow-up consultation 4 weeks after she had taken the emergency contraception. It’s not often that a GP actually gets to see young women at this stage. They are usually reassured by having got their period and don’t bother to turn up for the follow-up visit. Jodie, however, was one of the more conscientious ones, returning for her pregnancy test and STD check.
Now was the perfect time to talk to her about contraception. Her chosen method (condoms) had let her down twice and she may now be more amenable to some information about adding more foolproof forms of contraception. A consultation involving a negative pregnancy test is therefore an ideal time for contraceptive counselling. Before arriving, Jodie was probably nervous and thinking about the possible consequences of an unplanned pregnancy. She would have run through the various scenarios facing her and perhaps made a mental decision to use a different form of contraception. The challenge for the practitioner is to grab this opportunity and use it.
A useful opening line to someone like Jodie, with the pregnancy test sitting squarely on the desk facing both GP and patient, is: ‘What are you thinking about contraception for the future?’ It is usually at this stage that GPs hear a barrage of misinformation about the pill. As it turns out, a lot of it comes from schoolyard talk with girlfriends, but a lot also originates from the mouths of mothers. Perhaps mothers say these things in order to dissuade their daughters from becoming sexually active and thereby unwittingly encourage unprotected sex.
Another common objection is from young women who have been experimenting with speed, ecstasy and cocaine who say that they don’t want to go on the pill because they don’t want to put chemicals in their body.
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
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.
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
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
|COCP use for 5 years up to age:||Excess cases of breast cancer in 10,000 women|
(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
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:
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.
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
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.
Explaining the beneficial effects of COCP use is only one aspect of contraceptive counselling. It is important to take the time to explain the mechanism of action of the pill and to ensure that the woman knows how to take it correctly and understands the importance of not missing pills. What to do when a pill is missed should be explained, together with the fact that the most dangerous ones to miss are the hormone pills taken immediately before and after the sugar pills. This information should be accompanied by written instructions that the woman can refer to in a time of need.
Given that many women discontinue the pill during the first year of use (stopping and starting as they go in and out of relationships), advice about the non-contraceptive benefits of the pill and the lack of long-term morbidity should reassure women that they can continue to take the pill even when they are not sexually active. This will then bring to an end another commonly held myth about the pill ‘that you need to take a break from it every now and then’ and perhaps succeed in preventing what is often a consequence of pill cessation – an unplanned pregnancy.
CASE STUDY: ‘I want to go on the pill.’
Tina is 18 years old and is asking to start on the pill. Having checked her past and family history, ascertained that she is a non-smoker and checked her blood pressure, you now commence counselling her about how to take the pill. How do you go about this and what points need to be stressed?
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).
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
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.
Traditionally women have been told to wait until their next period to begin the COCP in order to ensure that they are not pregnant when they start. Waiting makes women vulnerable to pregnancy, however, and may discourage women from starting contraception because of the need to wait.
To overcome this problem the ‘quick-start’ method has been devised.13 It involves starting the COCP on the day of the consultation, regardless of the patient’s menstrual cycle day, and means that no counselling about when to begin is necessary. The woman swallows her first pill in the clinic immediately after prescription, and continues to take a pill each day. All patients who receive the first pill during the clinic visit first undergo a urine pregnancy test and emergency contraception if needed and receive at least one pack of the COCP so that they do not have to go to a pharmacy to fill a prescription before beginning. The quick-start method is outlined in Box 3.2.
BOX 3.2 The quick start method
(From Westhoff et al13)
Most young women do not understand how the pill works. They believe that since they are getting a ‘period’ every month they must be having a normal cycle and so they talk about having premenstrual symptoms even when they are taking the pill, despite the fact that they are not cycling. Ask them to show you the most dangerous time to miss a pill. They will often point to midway through the packet, showing their lack of understanding of the mode of action of the pill. It is therefore important to explain to a young woman that the COCP in essence puts the ovaries to sleep and that if taken correctly, no eggs are released and that is why she will not fall pregnant. Explain that when first starting the pill it takes 7 days to put the ovaries to sleep and that therefore she is not safe from a contraceptive point of view until she has taken seven active pills. Subsequent pills taken keep the ovaries asleep (quiescent).
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.
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
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).
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.
Should a woman vomit within 2 hours of taking a pill, the absorption of the hormones is questionable and another active pill should be taken (from the end of the pack). If the replacement pill and a second one taken 25–26 hours later fails to stay down then the missed pill rules should be followed. Diarrhoea without vomiting is not a problem unless it is ‘cholera-like’.9
No study has reliably investigated if the efficacy of the COCP is reduced with concurrent antibiotic use. Short-term antibiotic use alters gut flora and reduces the enterohepatic circulation of oestrogen. Gut flora recovers after 3 weeks of antibiotic use.15
If a woman starting the COCP has been using a non-liver-enzyme-inducing antibiotic for ≥3 weeks, no additional contraceptive behaviour is required unless the antibiotic is changed, when it should be managed as for short courses (<3 weeks) of antibiotic use. Women using the COCP who are given a short course (<3 weeks) of non-liver-enzyme-inducing antibiotics should be advised to use additional contraceptive protection while taking the antibiotic and for 7 days after stopping the antibiotic.16
One of the most common reasons women avoid using the pill is fear of weight gain. This is especially true of adolescents, who can sometimes be obsessed with their weight and dieting. While progestogens such as levonorgestrel may stimulate the appetite, young women starting contraception are often at the end of their pubertal growth spurt and may be putting on weight anyway. In a study of women who used the COCP for 12 cycles, approximately equal numbers of women gained or lost more than 2 kg in weight, with the majority (74%) being unchanged or within ± 2 kg of their baseline weight before starting the COCP.17 Other side effects, such as nausea and break-through bleeding, usually lessen with time, and young women starting the pill should be advised to continue for at least 3 months in order to see whether commonly experienced side effects dissipate. Many young women chop and change their pills too quickly. Such moves result in added problems that make them declare that they are unable to use the pill. This is a shame, as they have 30 or so potentially reproductive years ahead of them and may well need to use the pill in the future.
Another common side effect is the change in appearance of menstrual flow that younger women, especially, are not prepared for and may think is abnormal. Menstrual flow is usually reduced and may become quite dark in appearance. If women are not prepared for this, they may take it as a sign of illness or infection.
Tell your doctor if you are taking any other medicines including medicines you buy without prescription from a pharmacy, supermarket or health food shop. There may be interference between —— and some other medicines including:
These medicines may affect how well —— works. You may need to use an additional form of contraception (such as condoms or a diaphragm) while you are taking the other medicine and for 7 days following. Your doctor may also advise you to skip the 7 pill-free days (the pill-free days are when you would normally be taking the green pills). If you take —— you may need to use additional contraception for 4 weeks after finishing the course of ——.
CASE STUDY: ‘That must be how I got pregnant!’
When counselling a young woman and her relatively young mother about the pill, the GP mentioned to them that antibiotics might decrease pill absorption and lead to pill failure. At that point the mother said, ‘Is that so? No one ever told me that. That must have been how I got pregnant with her!’
The issue of what advice to give women about the interaction between broad-spectrum antibiotics and the COCP is important for two reasons: firstly because the COCP is one of the most popular forms of contraception and is used by millions of women around the world, and secondly because of the very serious consequences of having an unwanted pregnancy.
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.
CASE STUDY: ‘I’m not taking any medication but I’m on the pill.’
Melanie was 27 years old and had a history of sinusitis. This particular day she came in requesting a script for some antibiotics. She had a fever and was complaining of maxillary and frontal pain. Not having met her before, the GP asked her if she was allergic to anything, to which she answered ‘No’. The GP then asked if she was taking any medication, to which she again answered ‘No’. The GP turned to the computer and started using the script-writing software. As the GP double-clicked on ‘cefaclor’, a warning sign flashed up on the screen: ‘Warning: potential drug interaction between antibiotics and the combined oral contraceptive pill! Do you wish to proceed?’ The GP turned back to Melanie and said, ‘The computer is telling me you are taking the pill’. ‘Oh yeh, sorry’, she answered. ‘I’ve been on it for ages. I don’t really think of it as medication …’
The GP continued with the prescription and, on handing it to Melanie, thought about the options—should she be allowed to walk out without further advice, or should the possibility of decreased efficacy of the pill when using antibiotics be mentioned? The decision is made even more difficult knowing that the latter option entails giving a mini-lecture that goes something like this: ‘Now, you know that the pill may not be as effective when you are taking antibiotics. If you want to be 100% safe, you need to use condoms or abstain from having sex while you’re taking the antibiotics and for 7 days afterwards. You should still continue taking your pills as normal, but if you get to the sugar pills during that time just skip them and go straight onto the next lot of hormone tablets. That’ll mean that you won’t have a period this month, but that doesn’t matter. Any questions?’
Not only is this a mouthful, but it is quite complicated. It takes a good deal of time to demonstrate with a sample pack of pills and all the while the woman is looking at the GP astounded because she has probably not been given this advice on the numerous occasions when she has taken antibiotics in the past. This will either be because the GP wasn’t aware that she was on the pill or was hedging his/her bets and didn’t give the warning.
Would that have been such a bad thing to do? Especially when the rather complicated set of instructions that have to be given may well lead to patient confusion, poor compliance and a higher ‘user failure rate’ of the pill?
and progestins. Anticonvulsants most likely to have this effect are:
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.