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Case 673: A request for the oral contraceptive pill
Authors and Affiliations
Professor Roger Pepperell
Penang Medical College
Associate Professor Paul Duggan
Discipline of Obstetrics and Gynaecology
University of Adelaide
Dr Cathryn Mills
University of Adelaide
Case Overview
This case discusses a common and important consultation made in general practice - namely the
request made for a prescription for the oral contraceptive pill.
Learning Objectives
The graduating student should be able to appropriately assess a woman who requests a prescription for
the OCP and provide appropriate care for her. This should include knowledge of the:
questions
which should be asked
examination
required
investigations
which should be performed before agreeing to write the prescription
choice
of an appropriate OCP preparation
advice
which should be given concerning the OCP use and possible complications or side effects
Question 1 : MS
Question Information:
Jeanette is a healthy 19-year-old woman attending her local general practice. She is in the second year
of a university Arts program. She has recently become sexually active and she and her partner Tim
have been using condoms except for the 4-5 days immediately after her period. They wish to stop using
condoms. Jeanette has no foreseeable plans for a family and is requesting a prescription for the oral
contraceptive pill (OCP). Jeanette's periods last about 5 days and occur about every 4-5 weeks. They
have always been quite heavy but are no worse recently. She has only been sexually active for the last
3 months and has never had a medical examination. Her last menstrual period commenced about 20
days ago and was normal. The first step for the general practitioner is to take a history.
Question:
Which of the following are key pieces of information to obtain from Jeanette?
Choice 1: Age at menarche Score : -1
Choice Feedback:
Incorrect. The age at the menarche may be important in some presentations (e.g. abnormal secondary
sexual development and/or menstrual abnormalities) but it is most unlikely to be important in Jeanette's
case in determining whether she should be prescribed the OCP.
Choice 2: The characteristics of the menstrual cycle Score : 1
Choice Feedback:
Correct. These data are useful, for example, to exclude dysmenorrhoea, irregular pattern of the cycle,
and intermenstrual bleeding that may pre-exist and be modified by choice of contraception
Choice 3: Current or past liver disease Score : 1
Choice Feedback:
Correct. The OCP should not be prescribed in the presence of liver disease until the cause of the
abnormality has been defined and the liver function tests (LFTs) return to normal. Some genetic causes
of non-hemolytic hyperbilirubinemia are considered benign and do not result in hepatic fibrosis. Gilbert's
syndrome (unconjugated hyperbilirubinemia) is present in 3-10% of Caucasians. The combined OCP or
pregnancy may reveal previously unrecognised Gilbert's syndrome. It is a moot point whether the
combined OCP should be ceased in Gilbert's syndrome as the risk of therapy has to be balanced
against the risk of the alternatives, which includes unwanted pregnancy. It would be reasonable to
obtain an opinion from a gastroenterologist in this situation. Cholestatic jaundice in a previous
pregnancy is a contraindication to the OCP but as Jeanette is nulliparous this is not relevant in her
case.
Choice 4: History of breast cancer Score : 0
Choice Feedback:
Partially correct. Breast cancer is an absolute contraindication to the use of the OCP but is extremely
rare in this age group.
Choice 5: History of venous thromboembolism Score : 1
Choice Feedback:
Correct. A previous deep vein thrombosis or history of venous thromboembolism (VTE) is an absolute
contraindication to the use of a combined oestrogen/progestogen OCP. Some doctors consider
progestogen-only contraception also to be contraindicated with past VTE, but this is not evidence-based
(see Vasilakis et al (1999) and Conard et al (2004) Lidegaard (2009) Vieira et al (2007) and Indqvist et
al (2003)).
Choice 6: Abnormal vaginal bleeding Score : 1
Choice Feedback:
Correct. Women presenting with postcoital bleeding, intermenstrual bleeding and older women
presenting with menorrhagia should first be evaluated before prescribing the combined OCP. This
evaluation includes a full gynaecological examination and Pap smear and may include STI screens, a
pregnancy test and pelvic ultrasound. In teenagers presenting with irregular heavy periods it is
appropriate to trial the OCP without first undertaking a gynaecological examination - but do a pregnancy
test first! Menorrhagia particularly in young teenagers may be a presentation of von Willebrand's
disease. Enquire further in relation to personal and family history of bleeding in such presentations and
considering appropriate laboratory tests (please look this up if you are not already familiar with the
specialised tests required).
Choice 7: Confirmation that Jeanette is not pregnant Score : 0
Choice Feedback:
Partially correct. Co-existing pregnancy is a contraindication to the use of the OCP. However, it is
already established that Jeanette's LMP was 20 days ago so although it is theoretically possible she
could be pregnant right now there is no way to confirm that. Nothing needs to be done at this time as
Jeanette would not commence the OCP until the start of her next period. If her period was delayed a
pregnancy test would be required before commencing the OCP. Unplanned pregnancy on the OCP is
well documented. Fortunately, there is no evidence that taking the OCP during early pregnancy (as
occurs in "pill failure") is harmful to the embryo.
Choice 8: History of migraines Score : 1
Choice Feedback:
Correct. Migraine sufferers may have worse migraines when on the OCP, although in some the
migraines occur less frequently. If the woman has an aura (visual, olfactory or neurologic), the use of
the OCP is associated with an increased risk of a cerebrovascular accident, and is contraindicated. The
pill may be prescribed in non-aura migraine sufferers with appropriate follow up.
Choice 9: Problems with swelling or fluid retention Score : 1
Choice Feedback:
Correct. If this was the case, an OCP containing the progestogen drospirenone, which has antimineralocorticoid properties, may be considered but is more expensive than other preparations.
Choice 10: Family history of breast cancer Score : 0
Choice Feedback:
A family history of breast cancer is not a contraindication to use the OCP but would need extensive and
sensitive discussion if BRCA1 or BRCA2 mutations were involved.
Choice 11: Previous use of an oral contraceptive pill Score : 1
Choice Feedback:
Correct. In cases of prior OCP use, problems with such use must first be established. For example, if
the use of the OCP was associated with intermenstrual bleeding, a higher dose OCP should be given
on this occasion. If prior use was associated with non-compliance ("forgetfulness") the OCP is not a
good option.
Choice 12: Current medications Score : 0
Choice Feedback:
Partially correct. Current medications may be relevant but it has already been stated Jeanette is healthy
and in this context that clearly implies she is not on any medication. Some medications are especially
important. If the woman is taking an anticonvulsant, an OCP containing an increased estradiol dose;
50ug ethinyl oestradiol should be given because anticonvulsants induce liver enzymes which
metabolise the oestrogen component of the OCP.
Choice 13: Family history of thrombosis or thrombophilia Score : 1
Choice Feedback:
Correct. If there is a clotting disorders within the the family more information will be required to establish
which members of the family have been tested and what the tests showed. Jeanette may require a
thrombophilia screen and the OCP should not be prescribed until these investigations have excluded
any underlying problem.
Choice 14: Any vaccination against human papilloma virus Score : 1
Choice Feedback:
Correct. It is important to know whether or not Jeanette has been vaccinated (with Gardasil) against the
human papilloma virus (HPV).
Question 2 : MS
Question Information:
Jeanette says her menstrual cycles are always regular, occur every 4-5 weeks and are relatively heavy.
They are not associated with any pain or discomfort and have been like this ever since the menarche at
the age of 11 years. She has never used any contraception until the last three months, when her
partner has been using the condom, and had not been sexually active previously. She has never been
on the oral contraceptive pill. She does not have an abnormal vaginal discharge, there is no
dyspareunia or abdominal/pelvic pain. There are no absolute contraindications to the OCP defined from
her history, she had no migraines, and there are no family history of thrombotic problems or breast
cancer. Jeanette does not take any medications.
Question:
Which, if any, of the following examinations is necessary in Jeanette†™s case before making a
decision to prescribe the combined oral contraceptive pill?
Choice 1: Bimanual pelvic and speculum examination Score : -1
Choice Feedback:
Incorrect. One of the key barriers to teenagers seeking adequate contraception is the expectation of
having a pelvic/speculum examination, which is not necessary at this first visit. Thus, although Jeanette
has attended and is, therefore seeking advice appropriately, she may tell her friends about this visit.
Word gets around, and young women are put off attending if they think they will be asked to undergo an
intimate examination. Jeanette is at risk of asymptomatic chlamydia (she and Tim have occasionally
had unprotected sex), which can be investigated by a first morning urinary collection for chlamydia PCR
in preference to a cervical swab. As Jeanette is asymptomatic she is very unlikely to have gonorrhea.
Pap smears are routinely performed every two years in asymptomatic women who are or have been
sexually active. In women who are sexually active, NH&MRC guidelines recommend the first smear
from age 18 years with ongoing smears biannually, or once the patient has been sexually active for two
years (i.e. 21 months from now for Jeanette). Jeanette does not need a Pap smear at her first visit. The
GP would normally discuss this at a later visit once rapport has been well established.
Choice 2: Assessment of her body mass index (BMI) Score : 1
Choice Feedback:
Correct. Many women are concerned that commencing hormone treatment including the OCP will result
in weight gain. A baseline measurement of BMI is appropriate. There is no evidence that the oc pill
causes weight gain.
Choice 3: Blood pressure measurement Score : 1
Choice Feedback:
Correct. If the blood pressure is elevated, the cause should be sought and the OCP not prescribed
initially. It is also important to have a baseline measurement as occasionally the OCP will cause
hypertension.
Choice 4: Look for evidence of androgen excess Score : 1
Choice Feedback:
Correct. If Jeanette has evidence of androgen excess (e.g. hirsutism, acne, a deep voice) she may
need to be first investigated and not simply put on an OCP.
Choice 5: Breast examination Score : -1
Choice Feedback:
Incorrect. There is no benefit apparent from breast examination in asymptomatic women in this age
group. Conversely, there may be indirect harm because the expectation of a routine breast examination
(or other intimate examination) acts as a barrier to teenagers seeking appropriate contraception. It is
appropriate to have a discussion about the expected effects on the breast following commencement of
the oc pill (initial breast discomfort, slight breast enlargement) and to discuss breast self examination
and ask the woman to report if she notices a breast lump or has any other concerns.
Question 3 : MS
Question Information:
The clinical examination is normal. Jeanette's blood pressure is 110/70 mmHg. It is now necessary to
consider if Jeanette requires any investigations before a decision is made on prescribing the oral
contraceptive pill.
Question:
Which of the following investigations should be performed?
Choice 1: Cervical cytology Score : -1
Choice Feedback:
Incorrect. This is not an essential investigation prior to prescribing the OCP to Jeanette. Australian
NH&MRC guidelines promote routine screening with Pap smears every two years for women between
the ages of 18 (or two years after first sexual intercourse, whichever is later) and 69 years and this can
be discussed at a subsequent visit.
Choice 2: Urine pregnancy test Score : -1
Choice Feedback:
Incorrect. It is not usually done unless the period is late, or the last menstrual period was abnormal
which is not the case for Jeanette.
Choice 3: Urine polymerase-chain-reaction (PCR) for chlamydia Score : 1
Choice Feedback:
Correct. This is very appropriate in someone such as Jeanette who is sexually active and has not been
using condoms all the time. This is because chlamydia is endemic in teenagers and young adults in our
community and is often asymptomatic. If other risk factors apart from the age-related risk of chlamydia
were present further testing for STI may be required. If you discovered that Tim was an IV drug user,
you might want think what other tests should be considered. This is essential knowledge but beyond the
scope of this case.
Choice 4: Endocervical swab culture for gonorrhoea Score : 0
Choice Feedback:
Incorrect. Jeanette is asymptomatic and the incidence of gonorrhoea is very low in her context. It would
be preferable to enquire of Jeanette whether Tim has any penile discharge (or other symptoms of
urethritis or prostatis) and to forgo this invasive examination if he is asymptomatic, too. A positive
urinary chlamydia PCR is an indication for taking a cervical swab for gonorrhoea as both ST's may coexist.
Choice 5: Coagulation profile Score : -1
Choice Feedback:
Incorrect. Whilst a coagulation profile may come to mind in women presenting with abnormal bleeding,
for young women like Jeanette the commonest abnormality is von Willebrand†™s disease, which is
not detected by a routine APTT and PT. The test for von Willebrand†™s disease has to be specially
requested.
Choice 6: Bilateral breast mammography Score : -1
Choice Feedback:
Incorrect. This is unnecessary in a woman of her age, when no mass is felt in the breasts, and is more
difficult to assess when performed in someone of her age. If some abnormality had been felt in either
breast, a more useful investigation would be ultrasound examination - the increased breast density in
young women can make interpretation of the mammogram difficult.
Choice 7: Pelvic ultrasound examination Score : -1
Choice Feedback:
Incorrect. Pelvic ultrasound examination would be an unnecessary investigation. The probability of
finding on ultrasound an explanation for heavy periods in a 19-year-old with regular periods and a
normal clinical examination is too small to justify the expense and inconvenience of the procedure.
Choice 8: Serum androgens Score : -1
Choice Feedback:
Incorrect. Such an assessment is unnecessary in the absence of clinical features of androgenisation.
Choice 9: Liver function tests Score : -1
Choice Feedback:
Incorrect. Such an assessment is not done unless there is evidence of previous or current liver disease.
Choice 10: Complete blood picture Score : 0
Choice Feedback:
Partially correct. Jeanette has quite heavy periods and anaemia needs to be considered. However, she
is otherwise asymptomatic and not clinically anaemic, and as the OCP will reduce her menstrual loss
this investigation is superfluous.
Choice 11: Thrombophilia screen Score : -1
Choice Feedback:
Incorrect. Thrombophilia screening is only indicated if there is a suspicion of a familial risk of VTE or
past history of VTE.
Question 4 : SC
Question Information:
Nothing abnormal is found on the tests performed. The general practitioner can now counsel Jeanette
on the most appropriate oral contraceptive pill to use.
Question:
Which one of the following choices of preparation would be most appropriate?
Choice 1: A combined OCP containing 20 ug of ethinyl oestradiol and 100 mcg levonorgestrel (e.g. Microgynon
20/Logynon) Score : -1
Choice Feedback:
Incorrect. Such preparations are much more expensive than the 30ug ethinyl oestradiol containing
preparations, are more likely to result in breakthrough bleeding, have slightly lower efficacy, and may be
associated with osteoporosis with long term use. 20 mcg preparations may be considered as second
line options if estrogenic side effects on the 30 mcg preparation did not abate and provided cycle
control was satisfactory on the 30 mcg preparation.
Choice 2: A combined OCP containing 30 ug of ethinyl oestradiol and 150 mcg levonorgestrel (e.g. Levlen ED)
Score : 1
Choice Feedback:
Correct. This would be the most appropriate choice of OCP. It would provide adequate contraception
and would almost certainly reduce the menstrual loss.
Choice 3: An OCP containing 35 ug of ethinyl oestradiol and cyproterone acetate (2 mg) (e.g. Diane 35) Score :
-1
Choice Feedback:
Incorrect. Jeanette does not have an indication for this preparation, which is primarily for women with
hyperandrogenism. For women with acne and hirsutism, newer regimens containing the progestagen
drosperinone are likely to be better tolerated than a preparation containing cyproterone acetate and
have a lower risk of thromboembolism (possibly related to estrogen doses). An OCP containing
cyproterone acetate is appropriate for managing severe acne or hirsutism if there has been no
response to preferred alternatives. There is no evidence that women with polycystic ovarian syndrome
should be prescribed these preparations in preference to cheaper alternatives.
Choice 4: An OCP containing 30 ug of ethinyl oestradiol and drospirenone (e.g. Yasmin) Score : -1
Choice Feedback:
Incorrect. This is expensive but may be more appropriate if there is fluid retention, acne or hirsutism,
which is not relevant to Jeanette. Not only are these forms of oral contraception more expensive
(compared with agents such as Levlen), but reports suggest that drospirenone-containing preparations
have a greater risk of venous thromboembolism compared with those based on levonorgestrol.
Choice 5: A combined OCP containing 50 ug of ethinyl oestradiol (e.g. Microgynon 50) Score : -1
Choice Feedback:
Incorrect. This would only be used if there had been problems such as breakthrough bleeding with the
use of a 30 ug pill, or if Jeanette was on a pharmacologic agent (e.g. an anticonvulsant or rifampicin)
which increased liver enzyme activity.
Question 5 : MS
Question Information:
Jeanette is prescribed the OCP Levlen ED (containing 21 tablets of ethinyl oestradiol 30ug and
levonorgestrel 150 ug, and 7 inactive tablets) although this is not the lowest dose preparation available.
The reason for her doctor's choice is that this particular OCP is cheaper than the other preparations, is
safe, has high efficacy and a relatively low side effect profile. Some further discussions with Jeanette
are advisable. She will be counselled about common minor side effects (nausea, breast discomfort,
headache) and what she should do if she misses a pill or develops diarrhoea whilst she is taking the
active preparation. In addition she will be counselled on some of the rarer but potentially serious
complications need to be discussed.
Question:
Which of the following aspects of counselling are necessary?
Choice 1: Discuss contraception required in the current cycle Score : 1
Choice Feedback:
Correct. This advice is essential, because she is now well outside the best time in the cycle to
commence the OCP, and the most appropriate contraception for her to use now would be for her
partner to use condoms. Alternately, she could start the active tablets now, use condoms for 7 days,
skip inactive tablets and go on to next pack starting with active tablets.
Choice 2: Commence the active tablets during the next period Score : 1
Choice Feedback:
Correct. This would result in adequate contraception after 7 days of hormone tablets, and the first cycle
would be about 26 days, but 28 days thereafter. During the first 7-10 days on the OCP she should
continue to get her partner to use condoms to provide contraceptive protection.
Choice 3: Discuss the use of condoms in addition to the OCP Score : 1
Choice Feedback:
Correct. It is Jeanette†™s decision whether to stop using condoms as requested by her partner but it
is not necessarily good medical advice. Jeanette is in the highest risk age group for chlamydia and its
sequalae and is also at risk of other STI. This aspect of counselling is vital. As a university student
Jeanette may well be aware of these risks, but this should not be taken for granted. It is important that
by the end of the consultation Jeanette understands the potential risks and their long-term
complications such as infertility.
Choice 4: Arrange review next in 12 months Score : -1
Choice Feedback:
Incorrect. Review at a much earlier time is usually recommended (at 1-2 months after the OCP has
been commenced) to check her blood pressure has not become elevated and to evaluate whether she
is having problems with break-through-bleeding and other common side effects.
Choice 5: Advise a month off treatment each year to prevent †œpost-pill infertility†• Score : -1
Choice Feedback:
Incorrect. The pill should generally only be ceased when the woman wishes to conceive, is no longer
sexually active or has reached age 50-52 years (non-smoker) or 35-40 years (smoker). Ovulation in
fertile women usually returns quickly following cessation of the OCP and true post-pill infertility (as
opposed to infertility due to an incidental, unrelated cause such as PCOS) is rare. Such inappropriate
advice could result in an unwanted pregnancy.
Choice 6: Discuss risks of venous thromboembolism Score : 1
Choice Feedback:
Correct. Whilst rare, these risks must be discussed with all women who consider starting the OCP. For
something life-threatening such as a VTE women must be informed not just of the very small risk, but
how to recognise the symptoms and what to do about it.
Choice 7: Discuss potential adverse effects on liver function Score : 1
Choice Feedback:
Correct. Liver-related complications of the OCP are rare but important. Any symptoms of possible liver
disease may require cessation of the OCP. Jaundice on the OCP should be reported to the doctor, who
should investigate it and arrange alternative contraception.
Choice 8: Advise that chloasma is likely to occur Score : 0
Choice Feedback:
Incorrect. The darkening and increased skin pigmentation that can occur in pregnancy (melasma or
chloasma gravidarum) may also occur when taking the OCP. The follow up visits allow for detection of
melasma and will provide an opportunity to offer non-estrogen based contraception if melasma is of
concern.
Synopsis
This is a common presentation of a request for reliable, reversible contraception. The case has been
structured as a request for the OCP, but often the doctor will need to discuss contraceptive options. In
Jeanette's case, the etonogestrel implant (Implanon) could be considered a suitable alternative if she
preferred not to have to remember to take a pill every day. The case introduces two important health
prevention issues related to STI and cervical dysplasia. Jeanette may not have participated in a schoolbased immunisation program against HPV. The tetravalent vaccine Gardasil is now widely used in
Australia and is expected to substantially lower the incidence of both genital warts and cervical
dysplasia. It is projected that there will be a 70% reduction in the incidence of squamous cell carcinoma
of the cervix attributable to this exciting new initiative. In Jeanette's case, her HPV vaccination history is
important and if she has not already been vaccinated she should be given this opportunity. The authors
of the case expect there may be an element of controversy in our stance that breast and gynaecological
examination should not be undertaken at Jeanette's first visit, as traditional teaching has been to do so.
It is our opinion that the traditional teaching is not evidence based whereas there is clear evidence that
intimate medical examinations in healthy young women are not only unnecessary but are counterproductive for the reasons discussed in the case. The following detailed information is provided to assist
students to understand some of the social, pharmacological and medical issues surrounding the
complex topic of OCP prescribing.
Background
The oral contraceptive pill was originally a high dose progestagen only product. Side effects including
irregular bleeding resulted in a change to a combined preparation containing an estrogen and
progestagen, leading to the marketing in the USA in 1960 of a monophasic, combined oral
contraceptive pill. Withdrawal bleeding in the seven day pill free period mimicked menstruation in an
attempt to make †œthe pill†• more acceptable to women and some religious authorities. Availability
of †œthe pill†• is arguably one of the most important recent sociological events affecting women in
advanced countries globally.
Metabolism
The metabolism of the oc pill is complex and not fully understood. Absorption occurs as far down the
gastrointestinal tract as the terminal ileum. Function of the gut may significantly affect hormone
absorption and metabolism. It has been postulated that some broad spectrum antibiotics reduce the
effectiveness of the combined oc pill by interfering with gut absorption and metabolism, but this is
overstated as a potential cause of contraceptive failure. Metabolites excreted in the urine are mostly
inactive so renal clearance seems unimportant in this context.
Modes of Action
The combined oral contraceptive pill has several modes of action. Oestrogens and progestagens bind
to steroid receptors found throughout the body. In the brain, hypothalamus and pituitary such action
down regulates FSH and LH production and thus suppresses the natural ovarian cycle usually
preventing ovulation. This also results in a substantial suppression of ovarian production of estradiol
and testosterone. Ovulation occurs in about 2% of women who are correctly taking the combined oc pill
(higher on 20mcg and triphasic preparations). The low failure rate of the combined oc pill (research the
Pearl Index) may in part be explained by other contraceptive mechanisms including alterations to
cervical mucus that hinder sperm migration, altered fallopian tube transportation of fertilised ova, and
endometrial changes that inhibit implantation of a blastocyst.
†œLow dose†• combined oral contraceptive preparations
The first †œlow dose†• pills contained 30 mcg ethinyl estradiol and it is only recently that pills
containing 20 mcg ethinyl estradiol have been marketed. This follows the principle of using the lowest
possible efficacious dose and is also a ploy to increase market share. Current 20mcg preparations
(which typically also contain lower doses of a progestagen e.g. levonorgestrel 100 mcg) are more likely
to be associated with breakthrough bleeding, failure with missed pills, and risk of osteoporosis with long
term use and it seems that 20mcg preparations are close to the limit of what will be acceptable and
efficacious. Currently, pills with 20, 30, 35 and 50 mcg ethinyl estradiol are available in Australia.
Progestagens in combined oral contraceptive preparations
The progestagens used in oral contraceptive preparations are related to either testosterone or
progesterone. The older progestagens levonorgestrel (LN) and norethisterone acetate (NETA) are
testosterone derivatives. Several newer progestagens have been synthesised in an attempt to retain
the potent effects on hypothalamic and pituitary down regulation of FSH seen with older preparations
and to produce desired (progestagenic and antiestrogenic) effects on the endometrium for improved
cycle control, and to avoid side effects related to androgen, estrogen and glucocorticoid receptor
interaction. The extent to which improved laboratory parameters of newer progestagens have translated
to improvements in the clinical setting is not yet established. LN and NETA have been the dominant
progestagens since the 1970†™s. Current preparations contain 100, 150 or 250 mcg LN or 500mg or
1000mg of NETA. The higher doses are typically available with higher doses of ethinyl estradiol and are
indicated when breakthrough bleeding has occurred on standard dose preparations or when enhanced
hepatic metabolism of the combined pill is expected (e.g. coexisting use of hepatic enzyme inducers
such as anti epileptics). Newer progestogens e.g. drosperinone, have antiandrogenic properties, giving
therapeutic advantages to specific preparations including these, although this must be balanced with an
increased side effect risk profile.
Metabolic effects of combined oc preparations
Ethinyl estradiol has enhanced receptor affinity compared with natural estradiol and is thus substantially
more potent. Ethinyl estradiol is cheap to manufacture, is stable in vitro and in vivo, and has proven to
be effective in maintaining good cycle control and contraceptive efficacy in combination with the various
progestagens. The major metabolic effects of ethinyl estradiol include enhanced hepatic synthesis of
globulins (some causing hypercoagualability) and increased blood pressure in susceptible women.
Conversely, ethinyl estradiol has a beneficial effect on lipids by enhancing HDL synthesis. Fluid
retention, mastalgia and depression have been attributed to ethinyl estradiol. Androgenic effects
attributed to LN and NETA include peripheral insulin resistance, a lowering of HDL cholesterol, nitrogen
retention, and nervousness. Depression is also seen in women taking progestagens. Metabolic effects
are dose related and the currently available low dose preparations have minimal adverse metabolic and
clinical effects. In current clinical practice androgenic side effects of LN and NETA are seldom a
problem. This partly reflects the suppression of natural ovarian androgens via down regulation of
pituitary FHS and LH and also the marked elevation in Sex Hormone Binding Globulin (SHBG) caused
by ethinyl estradiol. SHBG is the major carrier protein for testosterone (albumin has much less affinity).
The combined oc pill substantially reduces available free testosterone to tissue receptors thus limiting
potential androgenic effects of the progestagen in the preparation.
Antiandrogens and combined oral contraceptive preparations
The anti†•androgen cyproterone acetate (CA) became available in the 1980†™s as an alternative to
a progestagen in the combined pill and is currently marketed as a preparation containing 35mcg ethinyl
estradiol and 2mg CA. This preparation is more expensive, may cause mastalgia, and has been
associated with up to a 7 fold increase in incidence of venous thromboembolism relative to standard
preparations. Many of these adverse effects are likely to be related to the higher dose of ethinyl
estradiol in this preparation. Preparations containing CA should be reserved for women with significant
acne and/or hirsutism. However, the recent availability of preparations containing drosperinone, which
also has antiandrogenic properties and in addition to being suitable for women with acne has
antimineralocorticoid properties, may well render the CA containing preparations redundant.
Thromboembolism and combined oc preparations In a recently published study from the Denmark
national registry involving over 3 million women years of exposure to oc pills and over 4000 incident
cases of venous thromboembolism in pill users, it was concluded that †œthe risk of venous
thrombosis in current users of combined oral contraceptives decreases with duration of use and
decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral
contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher
risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestagen only pills and
hormone releasing intrauterine devices were not associated with any increased risk of venous
thrombosis.†• Selection of the †œright†• preparation With such a wide availability of choice
selecting †œthe best†• preparation is challenging. Choice is confounded by marketing including the
widespread use in pharmaceutical trials of surrogate end points (e.g. coagulation and lipid profiles) to
estimate risk of a significant event (e.g. thromboembolism and stroke). Surrogate end points are used
because they are relatively readily available and easy to measure, whereas changes in incidence of
serious rare events such as thromboembolism and stroke may take years to become evident. Making
logical prescribing decisions is made more difficult by the common approach of studying in the
laboratory the effects of the individual components of the combined pill rather than the effect in
combination of its ingredients. Fortunately, for the prescriber there are some simple rules: confirm the
indication(s) exclude contraindications undertake detailed counselling select the cheapest available
monophasic preparation undertake appropriate follow-up.
Confirming the indications:
In addition to the obvious indication of reversible contraception consider other relevant matters:
dysmenorrhoea, sexual history and risk of STI, prior contraceptive experience, family planning
intentions, presence of acne and/or hirsutes, relevant medical conditions such as diabetes, epilepsy.
Exclude contraindications
Contraindications to the oral contraceptive pill include:
A
previous venous thrombosis or pulmonary embolus
Previous
oestrogen dependent malignancy such as breast cancer
Previous
cholestatic jaundice
Unexplained
vaginal bleeding
Pregnancy
Current
active liver disease. The OCP should not be given until the process is no longer active and
the LFTs have returned to normal. Migraine, especially if the headache is preceded by an olfactory,
visual or neurologic aura, when a cerebrovascular accident is more likely if the OCP is given
Evidence
of an acquired or inherited thrombophilia, when venous thromboembolism is much more
likely if the patient is prescribed the OCP.
Undertake detailed counselling:
For a first time user this will need to be very detailed. The desired endpoints are:
Reliable,
reversible contraception
Protection
from STI
Discussion
of side effects
For the oral contraceptive pill to be reliable it must be taken properly. The most risky time to miss a pill
is at either end of the †œpill free†• or †œinactive†• section. WHO recommendations for
managing missed pills are shown below and should be discussed in context of the selected preparation.
A similar approach is necessary if there are concerns about pill absorption (e.g. vomiting) or metabolism
(e.g. prophylaxis with Rifampicin against meningitis). To get in to the habit, the pill should be taken at a
similar time each day, usually in relation to something that is done daily at a regular time (getting up or
going to bed, brushing teeth). It is most helpful to have a pill packet available and to go through the
different coloured sections with the woman. Protection from STI is an important consideration for all
women and most essential in high risk groups: all younger women, sex workers. The peak incidence of
chlamydia genital tract infection in women is at age 19 years in the UK (and likely to be the same in
Australia). In an Australian survey published in 2003, 41% of males and 33% of females in the 16 to19
years age group reported multiple sex partners in the past year. The oc pill is not adequate protection
against chlamydia, gonorrhoea and important sexually acquired viral infections including hepatitis
viruses, HIV and HPV. Male condoms appear to greatly increase protection for most STI†™s but are
not protective against HPV, which if present is readily transmitted by scrotal perineal contact. If a
woman is high risk from HPV (e.g. immunosuppression, high risk partner) the female condom may offer
best protection.
First time users are likely to initially experience a number of short term side effects including headache,
nausea, breast discomfort and spotting. Most of the time these effects resolve in 2 to 3 months. Period
like breakthrough bleeding is uncommon and an indication for reviewing the regimen. Skin changes on
the oc pill are common. Acne is common in teenagers, is usually but not always improved by standard
preparations, and may be an indication for switching to a preparation containing drosperinone or
cyproterone acetate. Chloasma is irreversible facial pigmentation secondary to the estrogen and is most
noticeable over the zygoma. Fibrocystic disease of the breast is an uncommon side effect of the oc pill
and can be detected by breast self examination. First time users should be informed of the potential for
rare, serious side effects. Thromboembolism risk increases significantly in the first year after starting the
oc pill (possibly reflecting unrecognised thrombophilia) and although very rare in young women should
be discussed. The woman should be informed what the signs of thromboembolism are and what to do if
she suspects this (urgent Doppler scan, if delay for scan stop pill, use other protection). Jaundice is
rarely seen and must be reported and investigated, though may be related to minor congenital
derangements in conjugation of bilirubin (e.g. Gilbert†™s syndrome).
If the woman is a smoker, this is a good opportunity to reinforce the need to quit. Select the cheapest
available monophasic preparation Currently in Australia this is a generic preparation containing ethinyl
estradiol 30mcg and levonorgestrel 150mcg (Levlen ED). The so called ED form contains 21 active
tablets and 7 inactive tablets in a foil based blister pack. Normally 4 blister packs are dispensed with
two repeats allowed per script. The cost to the PBS eligible patient is about $17 per 4 pack script or
about $7 for health care card holders. If continuous use of active tablets is planned (to skip menses, to
help manage severe dysmenorrhoea or for convenience) the woman can safely discard the inactive
tablets that remain in the ED blister pack. A monophasic preparation is preferred to the similarly priced
triphasic preparation (Logynon ED) as it is simpler to manage and has a slightly lower failure rate.
Triphasic preparations were marketed on the dual basis that the variation in hormone dose more closely
mimics what occurs in a natural cycle and that there is overall a lower exposure to hormones with
potentially less effect on glucose homeostasis. Triphasic preparations may be considered as an
alternative if minor side effects related to the monophasic preparation do not settle. Undertake
appropriate follow up Follow up for a first time user would normally occur 6 to 12 weeks after
commencing the oc pill. The purpose of the follow up visit is to confirm that minor side effects have
(hopefully) settled, to exclude serious complications, and to answer questions as required. Attention to
the minor and major issues mentioned above is necessary as is a BP check. If BP is elevated or other
contraindications to continuing the oc pill emerge, search for an underlying cause and arrange
alternative non estrogen based contraception.
Management of continuing minor side effects is case by case. Six weeks may be too early for nausea
and breast discomfort to have resolved and perseverance for a few more weeks is indicated. If side
effects, other than breakthrough bleeding, are more troublesome, switching to a lower dose preparation
may be indicated. Alternatively, consider the vaginal ring (estradiol and etonogestrel marketed as Nuva
Ring), as avoiding the oral route may solve the problem. Breakthrough bleeding is usually managed by
changing to a higher dose oral preparation, but the Nuva Ring may be an effective alternative.
Summary of 2004 WHO guidelines for missed pills (applicable to current combined oc preparations
containing ethinyl estradiol only)
1.
A woman who has missed any inactive pills should discard missed inactive pills and continue
active pills
2.
For women taking 30 mcg (or higher dose) pills:
a. if one or two active pills missed or pack started one or two days late, take missed active pill ASAP
plus that days active pill then continue taking active pills daily. No additional contraception required.

b. if three or more active pills missed or starting three or more days late, take missed active pill
ASAP plus that days active pill then continue taking active pills daily. Additional precautions or
abstinence required for 7 days.

c. If missed pills occur in week three do not take inactive tablets in week four but move straight to
active tablets in next pack d. If missed pills occur in week 1 this represents greatest likelihood of failure
and emergency postcoital contraception should be considered.

3.
For women taking 20 mcg (or lower) dose pills:
a. if one active pill missed or pack started one day late, take missed active pill ASAP plus that
day†™s active pill then continue taking active pills daily. No additional contraception required.

b. if two or more active pills missed or starting two or more days late, take missed active pill ASAP
plus that days active pill then continue taking active pills daily. Additional precautions or abstinence
required for 7 days.

c. If missed pills occur in week three do not take inactive tablets in week four but move straight to
active tablets in next pack. Additional precautions or abstinence required for 7 days. d. If missed pills
occur in week 1 this represents greatest likelihood of failure and emergency postcoital contraception
should be considered.

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Jeanâ€
“ Jacques A, Tripathi V. Contraception for women: an evidence based overview. BMJ
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Pharmac. (1982), 14, 31†“ 42
de
Visser RO, Smith MA, Rissel CE, Richters J, Grulich AE. Heterosexual experience and recent
heterosexual encounters among a representative sample of adults. Aust N Z J Public Health 2003; 27:
146†•54
Jick
SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral
contraceptives containing drospirenone compared with women using oral contraceptives containing
levonorgestrel: case-control study using United States claims data. BMJ 2011; 342:2151.
Lesnewski
R and Prine L. Initiating Hormonal Contraception. Am Fam Phys July 1, 2006 Volume 74,
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Lidegaard
L, Likkegaard E, Svendsen A, Carsten, Agger C. Hormonal contraception and risk of
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American Society for Reproductive Medicine Hormonal contraception: recent advances and
Controversies. Fertil Steril 2008;90:S103†“ 13.
Parkin
L, Sharples K, Hernandez RK. Risk of venous thromboembolism in users of oral
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Sitrukâ€
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Soares
G. M., Vieira C. S., de Paula Martins W., dos Reis R. M., de SaÃ…L M. F. S., Ferriani R. A..
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Reviewed and updated by Dr Amy Hercus, University of Adelaide. June 2016