COMBINATION ORAL CONTRACEPTIVE PILL Dr.Ashraf Fouda Ob/Gyn. Consultant Damietta General Hospital E....

COMBINATION COMBINATION ORAL ORAL

CONTRACEPTIVE CONTRACEPTIVE PILLPILLDr .Ashraf Fouda

Ob/Gyn. Consultant

Damietta General Hospital

E. mail : [email protected]

The oral contraceptive pill The oral contraceptive pill (combined OC) was (combined OC) was first introduced in 1960first introduced in 1960. .

Since then it has Since then it has undergone many undergone many modificationsmodifications and and has been used by millions has been used by millions of women worldwide. of women worldwide.

INTRODUCTIONINTRODUCTION

Formulations may be :Formulations may be :

1.1. MonophasicMonophasic (each tablet contains a (each tablet contains a fixed amount of estrogen and progestin); fixed amount of estrogen and progestin);

2.2. BiphasicBiphasic (each tablet contains a fixed (each tablet contains a fixed amount of estrogen, while the amount of amount of estrogen, while the amount of progestin increases in the second half of progestin increases in the second half of the cycle); or the cycle); or

3.3. TriphasicTriphasic (the amount of estrogen may (the amount of estrogen may be fixed or variable, while the amount of be fixed or variable, while the amount of progestin increases in 3 equal phases).progestin increases in 3 equal phases).

FormulationsFormulations

Biphasic and triphasicBiphasic and triphasic formulations were formulations were

initially developed with initially developed with the intent of the intent of lowering lowering

the total steroid content the total steroid content of combined OCsof combined OCs..

FormulationsFormulations

Two types of estrogen are used Two types of estrogen are used in combined OCs: in combined OCs: ethinyl estradiol and mestranolethinyl estradiol and mestranol. .

MestranolMestranol is a is a “prodrug”“prodrug” that is that is converted converted in vivo in vivo to ethinyl estradiol.to ethinyl estradiol.

Several different Several different progestins,progestins, of varying degrees of progestational of varying degrees of progestational potency, are used in combined OCs. potency, are used in combined OCs.


Composition of Various

Combination Hormonal

Contraceptives

Composition of Various Combination Hormonal Contraceptives

TheThe progestins progestins may also havemay also have estrogenicestrogenic, , antiestrogenicantiestrogenic, , oror androgenicandrogenic

activity.activity.


Progestins can be classified Progestins can be classified according to their chemical according to their chemical

structure as an: structure as an:

1.1. EstraneEstrane (norethindrone, ethynodiol diacetate)(norethindrone, ethynodiol diacetate) or as a: or as a:

2.2. GonaneGonane (levonorgestrel, desogestrel, (levonorgestrel, desogestrel,

norgestimatenorgestimate).).

ProgestinsProgestins


In general, the In general, the gonane progestinsgonane progestins appear to be appear to be more potentmore potent than the than the estraneestrane derivatives derivatives (smaller doses can be used),(smaller doses can be used), but otherwise differences between but otherwise differences between the estrane and gonane compounds the estrane and gonane compounds

are difficult to characterize.are difficult to characterize.

Progestins have also been classified Progestins have also been classified according to the sequence of their according to the sequence of their

development development (first, second, or third (first, second, or third

generation),generation), but thebut the definitions definitions of of first, second, or third generation first, second, or third generation

progestins are progestins are not universally acceptednot universally accepted. .


Newer progestins Newer progestins (norgestimate and (norgestimate and

desogestrel)desogestrel) have have been shown to have been shown to have little little or no androgenic activity.or no androgenic activity.


When administered in combination with When administered in combination with ethinyl estradiol, produce a net ethinyl estradiol, produce a net estrogen-dominant effectestrogen-dominant effect, , which may explain the effects seen on: which may explain the effects seen on:

1.1. Hepatic proteinsHepatic proteins (increased levels of sex (increased levels of sex hormonebinding globulin), hormonebinding globulin),

2.2. Lipid metabolismLipid metabolism (increased levels of (increased levels of triglycerides and high-density lipoprotein-triglycerides and high-density lipoprotein-cholesterol), and on cholesterol), and on

3.3. Haemostatic variablesHaemostatic variables (increased levels of (increased levels of fibrinogen, plasminogen, and Factor VII).fibrinogen, plasminogen, and Factor VII).


EFFICACYEFFICACY

The combined OC is a highly The combined OC is a highly effective method of effective method of reversible contraceptionreversible contraception. .

With With perfect useperfect use, the combined , the combined OC is OC is 99.9%99.9% effective in effective in preventing pregnancy.preventing pregnancy.

However, However, typical user failure typical user failure ratesrates range from range from 3 - 8%.3 - 8%.

Poor patient compliancePoor patient compliance is a major is a major factor in factor in limiting effectiveness. limiting effectiveness.

EFFICACYEFFICACY

The effect of The effect of body weightbody weight on the efficacy of on the efficacy of the combined OC the combined OC

is is controversial.controversial.

EFFICACYEFFICACY

A retrospective cohort study A retrospective cohort study found that women found that women weighing 70.5 kg weighing 70.5 kg or moreor more had a significantly had a significantly

increased risk of increased risk of combined OC failurecombined OC failure

compared with compared with women of lower women of lower

body weight. body weight.

EFFICACYEFFICACY

The relative risk of The relative risk of failure was 2.6failure was 2.6 among among low dose combined OClow dose combined OC users and users and 4.5 4.5 among among very-low-dose very-low-dose combined OC userscombined OC users..

However, a large cohort study However, a large cohort study failed to findfailed to find evidence of any influence of evidence of any influence of body weight body weight on the risk of accidental pregnancy on the risk of accidental pregnancy in combined OC users. in combined OC users.

Further studiesFurther studies are required before are required before recommendations can be made.recommendations can be made.

EFFICACYEFFICACY

MECHANISM OF ACTIONMECHANISM OF ACTION

The combined OC’s The combined OC’s multiple mechanisms multiple mechanisms of action of action may contribute to its may contribute to its

high efficacy.high efficacy.

Its main mechanism Its main mechanism of action is to of action is to

suppress suppress gonadotropin secretiongonadotropin secretion, , thereby thereby

inhibiting inhibiting ovulation.ovulation.


Other mechanisms of action include:Other mechanisms of action include:

1.1.Development of Development of endometrial endometrial atrophyatrophy, making the , making the endometrium endometrium unreceptiveunreceptive to implantation; to implantation;

2.2.Production of Production of viscous cervical mucusviscous cervical mucus that impedes that impedes sperm transportsperm transport;;

3.3.Possible effect on Possible effect on secretion and secretion and peristalsis within the fallopian tubeperistalsis within the fallopian tube, , which interferes with which interferes with ovum and ovum and sperm transportsperm transport..


INDICATIONSINDICATIONS

In the absence In the absence of contraindications, of contraindications, use of the combined OC use of the combined OC may be considered for may be considered for any woman seeking any woman seeking aa reliable, reliable, reversible, coitally-reversible, coitally-independentindependent

method of contraception.method of contraception.

It is particularly suited It is particularly suited for women who wish for women who wish to take advantage of to take advantage of

its its noncontraceptive noncontraceptive

benefitsbenefits..


The use of The use of condomscondoms is still is still recommended in combined recommended in combined

OC users for protection OC users for protection against sexually transmitted against sexually transmitted infections infections (STIs)(STIs) and human and human

immunodeficiency virus immunodeficiency virus (HIV).(HIV).


CONTRAINDICATIONSCONTRAINDICATIONS

The World Health Organization The World Health Organization (WHO)(WHO) has developed a list of has developed a list of

absolute and relative absolute and relative contraindicationscontraindications to the use of combined to the use of combined

OCs, based on the available OCs, based on the available evidence of risks evidence of risks

ABSOLUTE CONTRAINDICATIONSABSOLUTE CONTRAINDICATIONS

1.1. < < 6 weeks postpartum if breastfeeding6 weeks postpartum if breastfeeding2.2. SSmoker over the age of 35 moker over the age of 35 (≥ 15 cigarettes per day)(≥ 15 cigarettes per day)3.3. HHypertension ypertension (systolic ≥ 160mm Hg or diastolic ≥ 100mm Hg)(systolic ≥ 160mm Hg or diastolic ≥ 100mm Hg)4.4. CCurrent or past history of venous thromboembolism urrent or past history of venous thromboembolism (VTE)(VTE)5.5. IIschemic heart diseaseschemic heart disease6.6. HHistory of cerebrovascular accidentistory of cerebrovascular accident7.7. CComplicated valvular heart disease omplicated valvular heart disease 8.8. MMigraine headache with focal neurological symptomsigraine headache with focal neurological symptoms9.9. BBreast cancer reast cancer (current)(current)10.10. DDiabetes with retinopathy/nephropathy/neuropathyiabetes with retinopathy/nephropathy/neuropathy11.11. SSevere cirrhosisevere cirrhosis12.12. LLiver tumour iver tumour (adenoma or hepatoma)(adenoma or hepatoma)

RELATIVE CONTRAINDICATIONSRELATIVE CONTRAINDICATIONS

1.1. SSmoker over the age of 35 moker over the age of 35 (< 15 cigarettes (< 15 cigarettes per dayper day))

2.2. AAdequately controlled hypertensiondequately controlled hypertension

3.3. HHypertension ypertension (systolic 140–159mm Hg, (systolic 140–159mm Hg, diastolic 90–99mm Hg) diastolic 90–99mm Hg)

4.4. MMigraine headache over the age of 35igraine headache over the age of 35

5.5. CCurrently symptomatic gallbladder diseaseurrently symptomatic gallbladder disease

6.6. MMild cirrhosisild cirrhosis

7.7. HHistory of combined OC-related cholestasisistory of combined OC-related cholestasis

8.8. UUsers of medications that may interfere with sers of medications that may interfere with combined OC metabolismcombined OC metabolism

NON-CONTRACEPTIVE BENEFITSNON-CONTRACEPTIVE BENEFITS1.1. CCycle regulation ycle regulation 2.2. DDecreased menstrual flowecreased menstrual flow3.3. IIncreased bone mineral density ncreased bone mineral density 4.4. DDecreased dysmenorrheaecreased dysmenorrhea5.5. DDecreased peri-menopausal symptoms ecreased peri-menopausal symptoms 6.6. DDecreased acneecreased acne7.7. DDecreased hirsutism ecreased hirsutism 8.8. DDecreased endometrial cancerecreased endometrial cancer9.9. DDecreased ovarian cancer ecreased ovarian cancer 10.10. DDecreased risk of fibroidsecreased risk of fibroids11.11. PPossibly fewer ovarian cystsossibly fewer ovarian cysts12.12. PPossibly fewer cases of benign breast diseaseossibly fewer cases of benign breast disease13.13. PPossibly less colorectal carcinomaossibly less colorectal carcinoma14.14. DDecreased incidence of salpingitisecreased incidence of salpingitis15.15. DDecreased incidence or severity of moliminal ecreased incidence or severity of moliminal

symptomssymptoms

SIDE-EFFECTSSIDE-EFFECTS

Some combined OC users Some combined OC users will experience will experience minor side-minor side-

effectseffects, most commonly , most commonly during the during the first 3 first 3

cyclescycles..These side-effects may lead These side-effects may lead

to to discontinuationdiscontinuation of the combined OC. of the combined OC.

Reassurance and adequate Reassurance and adequate counselingcounseling about expected common about expected common

side-effects can help to side-effects can help to prevent unnecessary prevent unnecessary

discontinuation and discontinuation and enhance compliance.enhance compliance.


The most common reason patients The most common reason patients discontinue combined OC use is:discontinue combined OC use is:

1.1. AAbnormal menstrual bleeding, bnormal menstrual bleeding, followed byfollowed by : :

2.2. NNausea, ausea, 3.3. WWeight gain, eight gain, 4.4. MMood changes, ood changes, 5.5. BBreast tenderness, reast tenderness, and and 6.6. HHeadache.eadache.


11 . .IRREGULAR BLEEDINGIRREGULAR BLEEDING

Unexpected bleeding occurs Unexpected bleeding occurs in in 10 to 30%10 to 30% of women of women

in the in the first first monthmonth, and is , and is a common reason a common reason

for for discontinuingdiscontinuing use of combined OCs. use of combined OCs.

It does appear that It does appear that breakthrough bleeding breakthrough bleeding or spotting or spotting in women beginning in women beginning combined OC use combined OC use

improves with timeimproves with time..


Amenorrhea occurs Amenorrhea occurs in approximately in approximately 2 to 3%2 to 3% of cycles. of cycles.


22 . .BREAST TENDERNESS AND BREAST TENDERNESS AND NAUSEANAUSEA

Breast tenderness and nauseaBreast tenderness and nausea may occur, but generally may occur, but generally improve with timeimprove with time..

These symptoms may occur These symptoms may occur less often in women who less often in women who use combined OCs containing use combined OCs containing smaller amounts of smaller amounts of estrogenestrogen..

33 . .WEIGHT GAINWEIGHT GAIN

Although weight gain is often thought Although weight gain is often thought to be a side-effect of the to be a side-effect of the combined OC, combined OC, placebo-controlled trialsplacebo-controlled trials have failed to show any have failed to show any association between low-association between low-dose combined OCs and weight gain.dose combined OCs and weight gain.

Studies comparing the combined OC Studies comparing the combined OC to to other contraceptive methodsother contraceptive methods have also have also failedfailed to show a significant to show a significant associated weight gain.associated weight gain.

44 . .MOOD CHANGESMOOD CHANGES

Although women may report Although women may report depression and mood changesdepression and mood changes while taking the combined OC, while taking the combined OC,

placebo-controlled trials have placebo-controlled trials have not demonstrated a not demonstrated a

significantlysignificantly increased risk increased risk of mood changes of mood changes

in combined OC users in combined OC users compared to placebo users.compared to placebo users.

RISKSRISKS

1.VENOUS 1.VENOUS THROMBOEMBOLISMTHROMBOEMBOLISM

The rates of The rates of venous thromboembolismvenous thromboembolism in combined OC users are in combined OC users are 3- to 4-3- to 4-fold higherfold higher than among non-users. than among non-users.

The absolute risk of VTE in combined OC The absolute risk of VTE in combined OC users is users is 1 to 1.5 per 10 000 users per 1 to 1.5 per 10 000 users per yearyear of use. of use.

The risk of VTE The risk of VTE during the first yearduring the first year of use appears to be of use appears to be higherhigher than that than that in subsequent years of use. in subsequent years of use.

22 . .MYOCARDIAL MYOCARDIAL INFARCTIONINFARCTION

In women taking a combined OC In women taking a combined OC containing containing more than 50 µg of ethinyl more than 50 µg of ethinyl estradiolestradiol, , myocardial infarctionmyocardial infarction rates rates increase 3-foldincrease 3-fold..

However, a number of recent studies However, a number of recent studies have found have found no significant increaseno significant increase in in the risk of myocardial infarction the risk of myocardial infarction with preparations containing with preparations containing less than less than 50 µg of ethinyl estradiol,50 µg of ethinyl estradiol, irrespective irrespective of age.of age.

33 . .STROKESTROKE

A significantly A significantly increased risk of increased risk of strokestroke is seen in users of is seen in users of combined OCs that contain combined OCs that contain more more than 50 µg of ethinyl estradiol.than 50 µg of ethinyl estradiol.

Although some studies of low-Although some studies of low-dose combined OCs report dose combined OCs report no no increaseincrease in the risk of in the risk of stroke, others have reported an stroke, others have reported an increased increased risk of up to 2-fold.risk of up to 2-fold.

Smoking and hypertensionSmoking and hypertension are are major risk factors for stroke. major risk factors for stroke.

Combined OC users with Combined OC users with hypertension hypertension are at an are at an increased risk of strokeincreased risk of stroke relative to users without relative to users without hypertension.hypertension.

33 . .STROKESTROKE

44 . .GALLBLADDER GALLBLADDER DISEASEDISEASE

Combined OC use Combined OC use increases the secretion of increases the secretion of

cholic acid in bile, cholic acid in bile, potentially leading to a potentially leading to a

higher incidence of higher incidence of gallstone formationgallstone formation..

55 . .BREAST CANCERBREAST CANCER

The risk of breast cancer in The risk of breast cancer in combined OC users is still combined OC users is still controversial.controversial.

A case-control study published in A case-control study published in 19861986 showed showed no associationno association between between the use of the combined OC and the the use of the combined OC and the risk of breast cancer.risk of breast cancer.

The The best data availablebest data available until recently until recently were the results of a were the results of a large meta-large meta-analysis published in 1996analysis published in 1996..

The results suggested that there was The results suggested that there was a a small but significant increase in risk small but significant increase in risk of breast cancerof breast cancer in women who were in women who were currently takingcurrently taking the combined OC and the combined OC and in the in the first 10 years after first 10 years after discontinuing itdiscontinuing it. .

There There did not appeardid not appear to be a to be a significant excess risksignificant excess risk of having of having breast cancer diagnosed breast cancer diagnosed 10 or more 10 or more years after stoppingyears after stopping the combined OC. the combined OC.


In a In a recent study of over recent study of over 9000 women 9000 women between the between the ages of 35 and 64ages of 35 and 64, ,

there was there was no no significant associationsignificant association between the use of the between the use of the

combined OC and breast combined OC and breast cancer.cancer.


Among Among current combined current combined OC usersOC users, the relative risk , the relative risk was was 1.0 1.0 , , and among and among former usersformer users the the

relative risk wasrelative risk was 0.9 0.9


The risk did not increase with The risk did not increase with ::

1.1. LLonger periods of use, onger periods of use,

2.2. DDifferent dosages of ifferent dosages of estrogen, estrogen,

3.3. DDifferent progestin ifferent progestin components. components.


The risk of breast cancer was not The risk of breast cancer was not increased in women with a increased in women with a family family history of breast cancerhistory of breast cancer who used the who used the combined OC, or in women who combined OC, or in women who started using the combined OC at an started using the combined OC at an earlier age.earlier age.

It is possible that women who carry It is possible that women who carry the the BRCA1 gene or BRCA2 gene BRCA1 gene or BRCA2 gene mutationsmutations may be at a may be at a higher riskhigher risk of of breast cancer than other women when breast cancer than other women when using combined OCs.using combined OCs.


66 . .CERVICAL CANCERCERVICAL CANCER

One study suggests that One study suggests that long-term combined OC uselong-term combined OC use may may increase the risk increase the risk of cervical cancerof cervical cancer in women in women

who are who are HPV HPV positivepositive but not in women but not in women who are who are HPV negativeHPV negative..

A A systematic review of 28 systematic review of 28 studiesstudies of women with of women with

cervical cancer also found cervical cancer also found that that increasing the duration increasing the duration

of combined OC useof combined OC use was was associated with an associated with an increased increased

riskrisk of cervical cancer. of cervical cancer.

6. CERVICAL CANCER6. CERVICAL CANCER

The data, although limited, The data, although limited, suggested that the suggested that the relative risk relative risk of cervical cancer may decrease of cervical cancer may decrease after use of combined OCs ceases. after use of combined OCs ceases.

Infection with HPVInfection with HPV, the major risk , the major risk factor for cervical cancer, is related factor for cervical cancer, is related to to sexual behavioursexual behaviour, and sexual , and sexual behaviour may differ between behaviour may differ between combined OC users and non-users. combined OC users and non-users.


A long-term study published in A long-term study published in 20022002 concluded that, in a well- concluded that, in a well-screened population of HPV-screened population of HPV-positive women followed for 10 positive women followed for 10 years, combined OC use years, combined OC use did not did not increase the risk of cervical cancerincrease the risk of cervical cancer. .

The The specific rolespecific role that combined that combined OCs play in the development of OCs play in the development of cervical cancer cervical cancer remains uncertainremains uncertain..


MYTHS AND MISCONCEPTIONSMYTHS AND MISCONCEPTIONS

1. The combined OC causes cancer.1. The combined OC causes cancer.Fact:Fact:

The combined OC reduces the risks of The combined OC reduces the risks of ovarian and endometrial cancer. ovarian and endometrial cancer.

The risk of The risk of ovarian cancerovarian cancer is reduced by is reduced by at least half in women who use combined at least half in women who use combined OCs.OCs.

A meta-analysis of 20 studies of A meta-analysis of 20 studies of combined OC use indicated that the risk combined OC use indicated that the risk of of ovarian cancerovarian cancer decreased with decreased with increasing duration of OC use.increasing duration of OC use.

Combined OC and ovarian Combined OC and ovarian cancercancer

This reduction in risk of ovarian cancer This reduction in risk of ovarian cancer persists for 10 to 20 years afterpersists for 10 to 20 years after combined OC use has been discontinued. combined OC use has been discontinued.

The reduced risk of ovarian cancer in The reduced risk of ovarian cancer in combined OC users has also been noted combined OC users has also been noted in women who have a pathogenic in women who have a pathogenic mutation in the mutation in the BRCA1 or BRCA2 geneBRCA1 or BRCA2 gene, , a mutation that increases their a mutation that increases their lifetime risk of developing ovarian lifetime risk of developing ovarian cancer.cancer.

The combined OC is associated with a The combined OC is associated with a 50% 50% overall reduction in the risk of endometrial overall reduction in the risk of endometrial cancercancer and the and the protective effect persistsprotective effect persists long after the combined OC is long after the combined OC is discontinued.discontinued.

The combined OC may also have The combined OC may also have a a protective effect against colorectal protective effect against colorectal cancercancer..

There appears to be either There appears to be either no increase or no increase or a very slight increase in the risk of breast a very slight increase in the risk of breast cancercancer in current combined OC users. in current combined OC users.

MYTHS AND MYTHS AND MISCONCEPTIONSMISCONCEPTIONS

2. Women on the combined OC 2. Women on the combined OC should have periodic pill should have periodic pill

breaks.breaks. Fact: Fact:

This is unnecessary. This is unnecessary. Pill breaks place a woman at Pill breaks place a woman at

risk for risk for unintended pregnancy unintended pregnancy and cycle irregularityand cycle irregularity..


3. The combined OC affects 3. The combined OC affects future fertility.future fertility.

Fact: Fact: Fertility is restored within Fertility is restored within

1 to 3 months1 to 3 months after after stopping the combinedstopping the combined

pills.pills.


4. The combined OC causes 4. The combined OC causes birth defects if a woman birth defects if a woman becomes pregnant while taking it.becomes pregnant while taking it.

Fact: Fact: There is There is no evidenceno evidence that the that the

combined OC causes birth defects combined OC causes birth defects if it is taken inadvertently if it is taken inadvertently

during pregnancy. during pregnancy.


5. The combined OC must be 5. The combined OC must be stopped in all women stopped in all women

over 35 years old. over 35 years old. Fact:Fact:

Healthy, non-smokingHealthy, non-smoking women women may may continue to usecontinue to use the the

combined OC until menopause.combined OC until menopause.


6.The combined OC causes 6.The combined OC causes acneacne..

Fact:Fact: Acne improves in women using Acne improves in women using

the combined OC due to a the combined OC due to a decrease in circulating free decrease in circulating free androgenandrogen..

All combined OCs will result in an All combined OCs will result in an improvement of acne improvement of acne


The combined OC and The combined OC and acneacne

2 combined OCs have received 2 combined OCs have received official labelling for the treatment of official labelling for the treatment of acne; acne; thesethese 2 2 OCs contain ethinyl OCs contain ethinyl estradiol in combination with either estradiol in combination with either levonorgestrel or norgestimatelevonorgestrel or norgestimate. .

The combination pill with The combination pill with cyproterone acetatecyproterone acetate is indicated for is indicated for the treatment of severe acne and the treatment of severe acne and is also a contraceptive. is also a contraceptive.

INITIATIONINITIATION

Before prescribing a combined Before prescribing a combined OC, a OC, a thorough historythorough history should should be taken, including be taken, including potential potential contraindications, smoking contraindications, smoking history, and medications.history, and medications.

The The physical examinationphysical examination should should include a include a blood pressure measurementblood pressure measurement. .

11 . .PATIENT ASSESSMENTPATIENT ASSESSMENT

A A pelvic examinationpelvic examination, although , although an important aspect of well-an important aspect of well-woman care, woman care, is not mandatoryis not mandatory before providing combined OCs. before providing combined OCs.

The pelvic examination may be The pelvic examination may be postponedpostponed until a follow-up visit. until a follow-up visit.


NoNo routine laboratory routine laboratory screeningscreening is required. is required.

Routine screening for Routine screening for thrombophiliasthrombophilias

is is notnot recommended.recommended.


22 . .COUNSELLINGCOUNSELLING

Adequate counseling prior to Adequate counseling prior to initiation of combined OCs initiation of combined OCs may help to improve may help to improve compliance compliance (regular use)(regular use) and and adherence adherence (continuation).(continuation).

Should include the following:Should include the following:

1.1. IInstructions on how to take the combined OCnstructions on how to take the combined OC

2.2. IInformation on potential side-effectsnformation on potential side-effects

3.3. NNon-contraceptive benefits of the combined OCon-contraceptive benefits of the combined OC

4.4. AAddressing common myths and misconceptionsddressing common myths and misconceptions

5.5. DDiscussing risks and warning signs, including iscussing risks and warning signs, including when to seek medical carewhen to seek medical care

6.6. DDiscussing what to do if pills are missediscussing what to do if pills are missed

7.7. EEmphasizing dual protection mphasizing dual protection (the combined OC (the combined OC with condom use to prevent STIs and HIV with condom use to prevent STIs and HIV infection)infection)

8.8. IInformation about emergency contraception in nformation about emergency contraception in the event of missed pillsthe event of missed pills

22 . .COUNSELLINGCOUNSELLING

33 . .PRESCRIPTIONPRESCRIPTION

The choice of a combined OC, The choice of a combined OC, for first-time users, should for first-time users, should take into account the : take into account the : prescriber’s clinical prescriber’s clinical judgment judgment and and the preferences the preferences of the userof the user. .

A A low-dose preparationlow-dose preparation (≤ 35 µg of ethinyl (≤ 35 µg of ethinyl estradiol)estradiol) is preferred. is preferred.

The preparation of choice for The preparation of choice for the combined OC user is the the combined OC user is the

one that provides: one that provides:

1.1. EEffective contraception, ffective contraception,

2.2. AAcceptable cycle control, cceptable cycle control, andand

3.3. TThe least side-effects.he least side-effects.


Various Various start datesstart dates for the for the combined OC are used. combined OC are used.

Conventionally, the Conventionally, the combined OC is started combined OC is started during the first 5 days during the first 5 days of the menstrual cycleof the menstrual cycle. .


If the combined OC is started If the combined OC is started within the first 5 days of the within the first 5 days of the

menstrual cycle, menstrual cycle, a a backup methodbackup method of of

contraception is contraception is not necessarynot necessary for for prevention of pregnancy, prevention of pregnancy,

provided that provided that no pills have been missedno pills have been missed. .


Another alternative is the Another alternative is the Quick Start methodQuick Start method, where a , where a combined OC user takes her first pill in combined OC user takes her first pill in the health-care provider’s office the health-care provider’s office after ruling out after ruling out pregnancy.pregnancy.

A A back-up method of contraceptionback-up method of contraception should be used should be used for the first weekfor the first week after after combined OC initiation if the Quick combined OC initiation if the Quick Start method is used. Start method is used.


The The Quick Start methodQuick Start method method, method, with its simple starting with its simple starting instructions :instructions :

1.1. Improves complianceImproves compliance, particularly , particularly in adolescents, and in adolescents, and

2.2. Is not associated withIs not associated with an increase an increase in the incidence of breakthrough in the incidence of breakthrough bleeding or other side effects.bleeding or other side effects.


Women who use a 21-day Women who use a 21-day preparation should be cautioned preparation should be cautioned never to exceed the 7 day never to exceed the 7 day pill-free intervalpill-free interval between between packs.packs.

The health-care provider may discuss The health-care provider may discuss emergency contraception (EC)emergency contraception (EC) as well as providing an EC as well as providing an EC prescription in advance of need.prescription in advance of need.

Dual protection with condomsDual protection with condoms should be re-emphasized.should be re-emphasized.


A follow-up visitA follow-up visit should be should be scheduled to review the combined scheduled to review the combined OC users’ OC users’ experience, experience, satisfaction, and compliancesatisfaction, and compliance, as , as well as to perform a well as to perform a blood blood pressure checkpressure check. .

If indicated, a If indicated, a pelvic examinationpelvic examination can be performed at the follow-up can be performed at the follow-up visit.visit.


CONTINUOUS USE OF CONTINUOUS USE OF COMBINEDCOMBINED

ORAL CONTRACEPTIVE PILLSORAL CONTRACEPTIVE PILLS

The use of combined oral The use of combined oral contraceptive pill on a contraceptive pill on a

continuous basis was first continuous basis was first studied in 1977, using studied in 1977, using

50 µg ethinyl 50 µg ethinyl estradiolestradiol pills.pills.

Decreased incidence of: Decreased incidence of: 1.1. Pelvic pain, Pelvic pain, 2.2. Headaches, Headaches, 3.3. Bloating/swelling, and Bloating/swelling, and 4.4. Breast tendernessBreast tenderness for women who for women who

experience these symptoms during the pill-experience these symptoms during the pill-free interval; free interval;

Improved control over symptoms of Improved control over symptoms of endometriosis and polycystic ovary endometriosis and polycystic ovary syndromesyndrome; and ; and

Greater convenienceGreater convenience due to fewer withdrawal bleeds per due to fewer withdrawal bleeds per year. year.

ADVANTAGESADVANTAGES OF CONTINUOUS USE OF OF CONTINUOUS USE OF COMBINED ORAL CONTRACEPTIVE COMBINED ORAL CONTRACEPTIVE

PILLS PILLS

Include little information on :Include little information on :1.1. Long-term safety Long-term safety (although there (although there

are long-term data for comparable are long-term data for comparable total estrogen- progestin doses total estrogen- progestin doses per month)per month) and a and a

2.2. Slightly higher cost for Slightly higher cost for medications medications (an extra 3 pill (an extra 3 pill packages per year for a 91-day packages per year for a 91-day cycle).cycle).

DISADVANTAGESDISADVANTAGES OF CONTINUOUS OF CONTINUOUS USE OF COMBINED ORAL USE OF COMBINED ORAL

CONTRACEPTIVE PILLSCONTRACEPTIVE PILLS

These potential disadvantages must be These potential disadvantages must be weighed against the likely reduction in weighed against the likely reduction in

the: the:

1.1. Cost of sanitary suppliesCost of sanitary supplies, ,

2.2. Pain medicationPain medication, and , and

3.3. Time off work or schoolTime off work or school; ;

4.4. More breakthrough bleeding initiallyMore breakthrough bleeding initially; ; and and

5.5. Possible delay in the recognition Possible delay in the recognition of pregnancy of pregnancy..

DISADVANTAGESDISADVANTAGES OF CONTINUOUS USE OF CONTINUOUS USE OF COMBINED ORAL CONTRACEPTIVE OF COMBINED ORAL CONTRACEPTIVE

PILLSPILLS

A retrospective study of 267 women A retrospective study of 267 women who initiated a continuous who initiated a continuous

OC regimen found OC regimen found that:that:

1.1. 64%64% of the women continued with of the women continued with this regimen; this regimen;

2.2. 86%86% reported an improvement in reported an improvement in their original problem such as their original problem such as headache and dysmenorrhea and headache and dysmenorrhea and

3.3. 76%76% reported a high degree of reported a high degree of satisfaction.satisfaction.

CONTINUOUS USE OF COMBINEDCONTINUOUS USE OF COMBINEDORAL CONTRACEPTIVE PILLSORAL CONTRACEPTIVE PILLS

The women were counseled to take the The women were counseled to take the combined OC until :combined OC until :

1.1. They They experienced breakthrough bleedingexperienced breakthrough bleeding, , or or

2.2. CompletedCompleted 2 pill packages (42 days), 2 pill packages (42 days), 3 pill packages (63 days), or 3 pill packages (63 days), or 4 pill packages (84 days). 4 pill packages (84 days).

The The mean cycle lengthmean cycle length was was 84 days84 days, , with most women choosing a hormone- with most women choosing a hormone-free interval of 4 to 5 days. free interval of 4 to 5 days.


Breakthrough bleeding and Breakthrough bleeding and spottingspotting was a common reason was a common reason for returning to a 21-day for returning to a 21-day combined OC regimen. combined OC regimen.

It is therefore essential to It is therefore essential to counselcounsel that that breakthrough breakthrough bleeding will decrease over bleeding will decrease over timetime..


The use of The use of a monophasic pill regimen or a monophasic pill regimen or a 21-day OC regimen a 21-day OC regimen prior to extending the prior to extending the cyclecycle has been shown to has been shown to

decrease the incidence of decrease the incidence of breakthrough bleedingbreakthrough bleeding

when using the extended when using the extended combined OC regimens. combined OC regimens.


VAGINAL ADMINISTRATION OF COMBINEDVAGINAL ADMINISTRATION OF COMBINEDORAL CONTRACEPTIVESORAL CONTRACEPTIVES

Six clinical trialsSix clinical trials have evaluated the have evaluated the administration of combined OCs administration of combined OCs given vaginally.given vaginally.

Theoretical advantagesTheoretical advantages in in administering the combined OC administering the combined OC vaginally include avoiding the vaginally include avoiding the “first pass”“first pass” metabolism by the liver, metabolism by the liver, which may help to which may help to decrease decrease side effects and improve side effects and improve tolerancetolerance. .

The largest study of this method of The largest study of this method of administration involved administration involved 1055 women1055 women and and

resulted in resulted in Pregnancy rates of Pregnancy rates of :: 3% at one year3% at one year with use of a preparation with use of a preparation

containing containing 50 µg ethinyl estradiol with 250 50 µg ethinyl estradiol with 250 µg levonorgestrelµg levonorgestrel (1 Ovral tablet daily), and (1 Ovral tablet daily), and

4.5%4.5% at one year with use of a preparation at one year with use of a preparation containing containing 30 µg ethinyl estradiol with 150 30 µg ethinyl estradiol with 150 µg desogestrelµg desogestrel (1 Marvelon tablet daily). (1 Marvelon tablet daily).

VAGINAL ADMINISTRATION OF COMBINED VAGINAL ADMINISTRATION OF COMBINED ORAL CONTRACEPTIVESORAL CONTRACEPTIVES

TROUBLESHOOTINGTROUBLESHOOTING

11 . .BREAKTHROUGH BLEEDINGBREAKTHROUGH BLEEDING

The The rates of irregular bleedingrates of irregular bleeding reported reported by women in clinical trials of by women in clinical trials of combined OCs combined OCs vary widelyvary widely. .

Bleeding rates Bleeding rates at 3 monthsat 3 months do not appear do not appear to differ significantly from those to differ significantly from those at 1 at 1 monthmonth; ;

Therefore, new users of a combined OC Therefore, new users of a combined OC should be should be encouraged to continueencouraged to continue with the with the expectation that any irregular bleeding expectation that any irregular bleeding will will subside,subside, rather than rather than switching to another combined OC. switching to another combined OC.

1.1. A Pap smear, A Pap smear, 2.2. STI testing, or STI testing, or 3.3. A pregnancy testA pregnancy test

may be performed if indicated. may be performed if indicated. If the: If the: 1.1. Bleeding persists after the third cycle Bleeding persists after the third cycle

of useof use, or , or 2.2. Has a Has a new onsetnew onset, ,

other causes of bleeding other causes of bleeding must be ruled out. must be ruled out.


Possible reasons for irregular bleeding while Possible reasons for irregular bleeding while taking the combined OC include:taking the combined OC include:

1.1. Irregular pill taking, Irregular pill taking, 2.2. Smoking, Smoking, 3.3. Uterine or cervical pathology, Uterine or cervical pathology, 4.4. Malabsorption, Malabsorption, 5.5. Pregnancy, Pregnancy, 6.6. Use of concomitant medications Use of concomitant medications

(e.g. anticonvulsants, rifampicin, herbal (e.g. anticonvulsants, rifampicin, herbal medicines),medicines), and and

7.7. Infection.Infection. Health-care providers should rule out these Health-care providers should rule out these

potential causes of irregular bleeding.potential causes of irregular bleeding.


The patient should be asked about the:The patient should be asked about the:1.1. DDuration of pill use, uration of pill use, DDosage ,osage ,TTiming, iming, 2.2. MMissed pills, issed pills, 3.3. SSymptoms of pregnancy, ymptoms of pregnancy, 4.4. DDiarrhea or vomiting in the last cycle, iarrhea or vomiting in the last cycle, 5.5. DDyspareunia, yspareunia, 6.6. VVaginal bleeding after intercourse, aginal bleeding after intercourse, 7.7. SSmoking, moking, andand8.8. UUse of other medication.se of other medication.


New onset of irregular bleeding New onset of irregular bleeding in a long-term combined OC user in a long-term combined OC user may be a may be a marker for chlamydia infectionmarker for chlamydia infection

(up to 29% of these (up to 29% of these women may have a positive women may have a positive

chlamydia test),chlamydia test), so so that these women should be that these women should be

screened for Chlamydia infectionscreened for Chlamydia infection..


Several empirical regimensSeveral empirical regimens have been used to have been used to

manage breakthrough manage breakthrough bleeding bleeding once other causes once other causes

have been eliminatedhave been eliminated, , although there although there

is no reliable evidence to is no reliable evidence to support them.support them.


In the case of persistent or new In the case of persistent or new onset bleedingonset bleeding, a , a short course short course of oral estrogen may be of oral estrogen may be helpfulhelpful, , such as such as 1.25 1.25 mg of conjugated estrogen or 2 mg of mg of conjugated estrogen or 2 mg of estradiol-17β estradiol-17β daily for 7 daysdaily for 7 days. .

If no improvement is seen, If no improvement is seen, a a therapeutic trialtherapeutic trial of another of another combined OC may be indicated. combined OC may be indicated.


It may be useful to offer a It may be useful to offer a combined OC containing combined OC containing a a different type of progestindifferent type of progestin, , such as switching from such as switching from

a preparation that a preparation that contains a contains a gonane gonane progestinprogestin to one that to one that

contains an contains an estrane progestinestrane progestin (or (or vice versa). vice versa).


There is There is no combined OC no combined OC preparation that is less likely preparation that is less likely than others than others to cause to cause breakthrough bleeding.breakthrough bleeding.

These should be emphasizedThese should be emphasized 1.1. Consistent pill use, Consistent pill use, 2.2. Dual protection, and Dual protection, and

3.3. Smoking cessation.Smoking cessation.


22 . .MISSED PILLSMISSED PILLS

Missing pills at the beginning Missing pills at the beginning or end of the 21-day cycle or end of the 21-day cycle has the effect of has the effect of lengthening the lengthening the hormone-free intervalhormone-free interval. .

If the hormone free interval If the hormone free interval exceeds 7 daysexceeds 7 days, the risk of , the risk of ovulationovulation and possible and possible conceptionconception is is increasedincreased. .

Forgetting tablets in Forgetting tablets in the second or third weekthe second or third week of the 21-day cycle of the 21-day cycle

is is unlikely to unlikely to increase the risk increase the risk of ovulationof ovulation if if

the hormone-free interval the hormone-free interval does not exceed 7 daysdoes not exceed 7 days..

22 . .MISSED PILLSMISSED PILLS

33 . .AMENORRHEAAMENORRHEAAmenorrhea occurs in Amenorrhea occurs in 2 to 3%2 to 3%

of combined OC users. of combined OC users. Pregnancy should first be ruled outPregnancy should first be ruled out

in any OC user who develops in any OC user who develops amenorrhea. amenorrhea.

Amenorrhea in women taking Amenorrhea in women taking combined OCs combined OCs is not dangerousis not dangerous, and , and many women readily many women readily accept accept the absence of withdrawal the absence of withdrawal bleeding. bleeding.

If amenorrhea is unacceptableIf amenorrhea is unacceptable, , adding exogenous estrogenadding exogenous estrogen (e.g., 0.625–1.25 mg conjugated (e.g., 0.625–1.25 mg conjugated estrogens)estrogens) for 10 days per cycle will for 10 days per cycle will often result in resumption of often result in resumption of bleeding.bleeding.

Switching to another preparationSwitching to another preparation may be effective. may be effective.

There is usually no indication There is usually no indication to switch to a pill containing to switch to a pill containing

50 µg ethinyl 50 µg ethinyl estradiol.estradiol.

33 . .AMENORRHEAAMENORRHEA

44 . .CHLOASMACHLOASMAChloasma, Chloasma,

a darkening of facial skin a darkening of facial skin pigmentationpigmentation, may occur during OC , may occur during OC use. use.

Changing to another pillChanging to another pill will will not helpnot help..The hyperpigmentation may The hyperpigmentation may

never completely disappearnever completely disappear. . The use of The use of sunscreen sunscreen may help may help

to prevent further pigmentation. to prevent further pigmentation.

5. BREAST TENDERNESS 5. BREAST TENDERNESS (MASTALGIA) AND GALACTORRHEA(MASTALGIA) AND GALACTORRHEA

Mastalgia often Mastalgia often resolves resolves after after several cyclesseveral cycles of of combined OC use.combined OC use.

Decreasing caffeine intakeDecreasing caffeine intake may be helpful in may be helpful in reducing mastalgia. reducing mastalgia.

Decreasing the estrogen contentDecreasing the estrogen content may also be helpful.may also be helpful.

The presence of The presence of galactorrhea galactorrhea during combined OC use is during combined OC use is rare and is an indication rare and is an indication for performing for performing a a serum prolactin serum prolactin assayassay..

5. BREAST TENDERNESS 5. BREAST TENDERNESS (MASTALGIA) AND (MASTALGIA) AND GALACTORRHEAGALACTORRHEA

66 . .NAUSEANAUSEA

Nausea is a common side effect Nausea is a common side effect during the during the first cyclesfirst cycles of combined of combined OC use, and usually OC use, and usually decreases with decreases with timetime..

Nausea or vomiting may occur when Nausea or vomiting may occur when a woman a woman takes 2 pills at the takes 2 pills at the same timesame time. .

Taking the pills a Taking the pills a few hours apartfew hours apart may be helpful in this case. may be helpful in this case.

Taking the pill Taking the pill with food or with food or at bedtime at bedtime will often will often control the nausea. control the nausea.

A A lower estrogen doselower estrogen dose may may improve the nausea. improve the nausea.

If nausea occurs in a long-time If nausea occurs in a long-time pill user, pill user, pregnancy must be pregnancy must be ruled outruled out..

66 . .NAUSEANAUSEA

77 . .PREGNANCYPREGNANCY

If pregnancy occurs in a woman If pregnancy occurs in a woman taking a combined OC, taking a combined OC, she should stop taking the she should stop taking the pill immediatelypill immediately. .

She should be informed that She should be informed that there is there is no increased risk of no increased risk of birth defectsbirth defects as a result of as a result of inadvertent combined OC inadvertent combined OC use during pregnancy.use during pregnancy.

DRUG INTERACTIONSDRUG INTERACTIONS

Ethinyl estradiolEthinyl estradiol is metabolized is metabolized at several different sites. at several different sites.

1.1. First, it is First, it is sulphatedsulphated in the intestinal in the intestinal wall, wall,

2.2. then it is then it is hydroxylatedhydroxylated in the in the cytochrome P450-3∆4 pathway of the cytochrome P450-3∆4 pathway of the liver, liver,

3.3. after which it isafter which it is conjugated conjugated with with glucuronidesglucuronides and passes into the and passes into the enterohepatic circulation.enterohepatic circulation.

These processes may These processes may vary between womenvary between women and may and may be be affected by affected by other medications. other medications.

Drug interactions may occur Drug interactions may occur via alterations in : via alterations in :

1.1. AbsorptionAbsorption, ,

2.2. Serum protein bindingSerum protein binding, ,

3.3. Receptor bindingReceptor binding or in or in

4.4. Hepatic metabolism.Hepatic metabolism.


It has been suggested that It has been suggested that less than 5%less than 5% of drug interactions of drug interactions with combined OCs with combined OCs result in result in pregnancypregnancy..

Due to the widespread use of combined Due to the widespread use of combined OCs, health-care professionals must OCs, health-care professionals must be aware of be aware of concurrent medication concurrent medication useuse and the and the potential for drug potential for drug interactionsinteractions..


Evidence from a single Evidence from a single pharmacokinetic interaction study pharmacokinetic interaction study suggests that a suggests that a woman taking the anticonvulsant woman taking the anticonvulsant

phenytoin or phenytoin or carbamazepinecarbamazepine should should use a combined OC preparation use a combined OC preparation

containing 50 µg ethinyl estradiolcontaining 50 µg ethinyl estradiol, , rather than a lower-dose rather than a lower-dose

preparation.preparation.


Monitoring of Monitoring of phenytoin concentrations phenytoin concentrations is important is important

because because combined OCs combined OCs

may inhibit their may inhibit their metabolism.metabolism.


Whether or not Whether or not antibiotic useantibiotic use has an effect on the efficacy has an effect on the efficacy of combined OCs has been of combined OCs has been a matter of a matter of controversy.controversy.

A significant pharmacokinetic A significant pharmacokinetic interaction between combined OCs interaction between combined OCs and antibiotics, apart from and antibiotics, apart from rifampicin and griseofulvinrifampicin and griseofulvin, , has not been proven. has not been proven.


Some medications may result in Some medications may result in contraceptive failurecontraceptive failure if used if used concomitantly with combined concomitantly with combined OCs. OCs.

Some medications Some medications may increase may increase the activity of the combined the activity of the combined OCOC, resulting in increased , resulting in increased estrogenic side-effects. estrogenic side-effects.


Oral contraceptives may also Oral contraceptives may also decrease the clearance decrease the clearance of other medications of other medications, , thereby thereby

increasing their increasing their activityactivity..


COMBINATION ORAL CONTRACEPTIVE PILL Dr.Ashraf Fouda Ob/Gyn. Consultant Damietta General Hospital E....

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Transcript of COMBINATION ORAL CONTRACEPTIVE PILL Dr.Ashraf Fouda Ob/Gyn. Consultant Damietta General Hospital E....