Download Management of Oral Contraceptives: Updates and Side Effects

Management of Oral Contraceptives:
Updates and Side Effects
MSACOFP
Peter B. Greenspan, DO, FACOG, FACS
Vice Chair, Associate Professor
Department of Obstetrics and Gynecology
UMKC School of Medicine
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Disclosure
I have no conflicts of interest or disclosures
MSACOFP
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Goals and Objectives
Update practitioners on the current state of
contraceptive technology
Discuss Long-Acting Reversible Contraception
Elaborate on the Risks and Benefits of Hormonal
Contraception
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Brief History of OCPs
OCPs have a colorful and complex history involving
intrigue, politics and a “cast of characters” that
includes
Margaret Sanger, Katherine McCormick, John
Rock and many others
The modern feminist movement is closely associated
with the development of contraception and
especially OCP’s
Historians attribute the “Sexual Revolution” to the
availability of reliable and “safe” contraception
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Brief History of OCPs
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Brief History of OCPs
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Brief History of OCPs
Late 1930’s: Ethinyl Estradiol is synthesized
It appears to inhibit ovulation
Is developed as treatment for abnormal uterine
bleeding
Late 1950’s: Enovid is approved by the FDA to treat
AUB
Within 4 years
it is being prescribed to prevent pregnancy
The manufacturer applies to the FDA for a
contraceptive indication
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Brief History of OCPs
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Brief History of OCPs
Despite overwhelming popularity and great
controversy
The new hormonal OCP is producing serious and
dangerous side effects in many women
The greatest concern is
Pulmonary Embolism/Deep Vein Thrombosis
Other Serious Vascular complications
Dr. John Rock and many others embark on vigorous
research and development to make the OCP effective
and SAFE
Fifty years hence, they have succeeded
So, what’s new?
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What’s New?
The latest trend in Contraception Methodology for
primary care physicians is:
Long-Acting Reversible Contraception (LARC)
These methods include:
Implantable Hormones
Intrauterine Devices
Injectable Hormones
Continuous Oral Contraceptives
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LARC
LARCs are the most effective reversible
contraceptive
They do not require ongoing effort on the part of
the user for long-term effective use
They are safe
They are economical when used over as little as a
two-year period, and
Provide prompt return of fertility after removal
Almost all women are eligible for use of one of the
LARCs
including nulliparous women
Adolescents and
women who should avoid exogenous estrogen
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LARC Benefits
Reduction in Dysmenorrhea
Reduction in pelvic pain related to Endometriosis
Reduction of Menorrhagia
with improvement in Iron Deficiency Anemia
related to blood loss
Reduction in risk of Ectopic Pregnancy
Reduction in symptoms associated with
Premenstrual Syndrome and Premenstrual Dysphoric
Disorder
Reduction in risk of Benign Breast Disease
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LARC Benefits
Reduction in development of new ovarian cysts
true for higher dose estrogen pills only
which suppress ovulation
but no effect on existing ovarian cysts
Reduction in ovarian cancer
including some hereditary forms such as
those associated with mutations in the BRCA 1
or BRCA 2 gene
presumably due to inhibition of ovarian
stimulation
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LARC Benefits
More regular menstrual cycles
Reduction in endometrial cancer
Due to the progestin effect
Reduction in colorectal cancer in current users
Reduction in moderate acne
Reduction in hirsutism
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Hormonal Contraception
Side Effects and Complications
Concern about toxicity
such as Thromboembolic events and
Cardiovascular disease
initially limited the long-term use of these
drugs
Decrease in both Estrogen and Progestin content has
led to
a reduction in both side effects and cardiovascular
complications
These preparations are a reasonable contraceptive
option for most women.
MSACOFP
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Hormonal Contraception
Side Effects and Complications
While the US FDA had previously set upper age limits
for HC use as 35 years for smokers and 40 years for
nonsmokers
the age limit was removed in 1989 for healthy,
nonsmoking women
OCs can be given until menopause in such women
Caution is still needed in prescribing OCs for
women who smoke
and an effort to induce smoking cessation
should be made first
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Early side effects of HCs include:
Bloating
Nausea and
Breast Tenderness
Although they may be bothersome enough to lead to
discontinuation of the HC
these side effects usually subside in several
months
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Hormonal Contraception
Side Effects and Complications
Abnormal Bleeding is a common problem that
often resolves without intervention
Numerous strategies have been developed to
address Abnormal Bleeding that doesn’t
resolve spontaneously
Weight Gain is not a consistent finding with lowdose pills
Despite patient perception to the contrary
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Hormonal Contraception
Side Effects and Complications
Breakthrough Bleeding
Breakthrough Bleeding is the most common side
effect of HCs
Does not indicate a decrease in efficacy
but reflects tissue breakdown
as the endometrium adjusts to a new thin state
in which it is fragile and atrophic
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Hormonal Contraception
Side Effects and Complications
More of a problem with lower doses of estrogen
because estrogen stabilizes the endometrium
Bleeding is more common with extended and
continuous regimens
although most women eventually develop
amenorrhea
The most common cause of breakthrough
bleeding is still thought to be missed pills
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Approach to treatment of bleeding starts with
patient reassurance and
encouragement to take the OC for at least
three cycles before making any changes
If the bleeding does not stop
Perform a cervical examination and pelvic
ultrasound to rule out structural causes of
bleeding such as
uterine fibroids or polyps
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Hormonal Contraception
Side Effects and Complications
Amenorrhea
Amenorrhea is the GOAL with the continuous and
extended estrogen-progestin regimens
Amenorrhea may also occur with the standard
preparations
containing 21 days of hormone and seven days
of placebo
most commonly with the lower dose pills
containing 20 mcg
MSACOFP
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Hormonal Contraception
Side Effects and Complications
If the woman is taking a low dose (20 mcg) OC
and desires evidence of menstrual bleeding
switching to a 30 to 35 mcg preparation often
restores menses
simple reassurance of the patient helpful
Amenorrhea does not mean that the patient
isn’t getting reliable contraception
Women who do not menstruate 3 months after
discontinuing an OC
should undergo the same evaluation for
amenorrhea as any amenorrheic woman
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Hormonal Contraception
Side Effects and Complications
Drug Interactions-Anticonvulsants
OC metabolism is accelerated by any drug that
increases liver microsomal enzyme activity:
Phenobarbital
Phenytoin
Griseofulvin and
Rifampin
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Hormonal Contraception
Side Effects and Complications
WHO suggests that women taking
anticonvulsants including
Phenytoin, Carbamazepine, Barbiturates,
Primidone, Topiramate or Oxcarbazepines
should not use HC
with the exception of DepoMedroxyprogesterone Acetate
Anticonvulsants that do not appear to reduce
contraceptive efficacy include:
Gabapentin, Lamotrigine, Levetiracetam and
Tiagabine
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Hormonal Contraception
Side Effects and Complications
Drug Interactions-Antibiotic
Rifampin in the only antibiotic proven to
decrease serum Ethinyl Estradiol and progestin
levels in women using HCs
A nonhormonal method is recommended in
these patients
Rifampin may also decrease the effectiveness
of transdermal and vaginal ring preparations
MSACOFP
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Hormonal Contraception
Side Effects and Complications
In spite of anecdotal reports of OC failure
other antibiotics have not been proven to
affect the pharmacokinetics of EE
For women taking antibiotics with HCs (other
than Rifampin)
back-up contraception is not required
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Hormonal Contraception
Side Effects and Complications
St. John's Wort induces cytochrome P450
which may increase OC metabolism and reduce
therapeutic efficacy
Two small clinical trials of women on OCs
reported an increase in breakthrough bleeding
with the addition of St. John's Wort
Although serum progesterone concentrations
were unchanged
concerns remain that contraceptive efficacy
could be reduced with this combination
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Hormonal Contraception
Side Effects and Complications
Cardiovascular Disease:
The greatest concern surrounding the use of
Estrogen-Progestin contraceptives has been
the increase in Cardiovascular morbidity and
mortality
that occurred with the early high-dose pills
The reduction in Estrogen content has increased
safety substantially
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Hormonal Contraception
Side Effects and Complications
Because Myocardial Infarction is an extremely
rare event in otherwise healthy women of
reproductive age
even a doubling of the risk would result in an
extremely low attributable risk
Risk in older women who smoke outweighs the
risk of an unwanted pregnancy
But prescribing to this subset is very
controversial
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Hormonal Contraception
Side Effects and Complications
Coronary Heart Disease
Epidemiologic studies have reported an increase
in MI
thought to be related to a thrombotic
mechanism
rather than the development of atherosclerotic
plaques and
an increase in CV mortality in E-P
contraceptive users over age 35 years who
smoke
MSACOFP
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Hormonal Contraception
Side Effects and Complications
A consensus panel reviewing the issue of OCs in
women over 35 years who smoke suggested that
OCs should not be given to those who smoke
more than 15 cigarettes per day
but OCs can be considered in women who
smoke fewer than 15 cigarettes per day
since the risks of pregnancy in this age group
are greater than the risks associated with
OC use
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Hormonal Contraception
Side Effects and Complications
American College of Obstetricians and
Gynecologists states that the risk of OC use is
unacceptable for women over 35 years who
smoke at all
However, the benefits of OCs appear to
outweigh the risks
even among heavy smokers
as long as there is no family history of
thromboembolic disease
Women who have taken an OC in the past are not
at increased risk for CHD later in life
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Hormonal Contraception
Side Effects and Complications
Hypertension
OCs frequently cause a mild elevation in blood
pressure within the normal range
However, overt Hypertension can occur
Although OC-induced hypertension is not
common
its recognition is important
as hypertensive OC users appear to be at
increased risk of MI and stroke relative to
nonusers
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Hormonal Contraception
Side Effects and Complications
Stroke
OC use has been associated with a small but
significant increase in Ischemic Stroke risk in
many but not all studies
This was a particular concern with early OC
preparations that contained high doses of
estrogen
OC preparations containing less than 50 mcg of EE
are associated with a lower risk of stroke than
high-dose preparations
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Hormonal Contraception
Side Effects and Complications
In otherwise healthy young women (non-smokers
without hypertension)
the attributable risk is extremely low because
baseline risk of ischemic stroke is so low in
this population
In all of these studies
the absolute risk of stroke was very low in
young women
11.3 per 100,000 patients per year
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Venous Thromboembolic Disease
Increased risk of Venous Thromboembolic disease
is seen with both high and low dose estrogen OC
preparations
Although the reduction in steroid content of OCs
has improved the safety and side effect profile of
the pill
the increased risk of venous thrombosis has
not been eliminated
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Hormonal Contraception
Side Effects and Complications
The absolute risk of Thromboembolism is very
low in healthy women
and the potential risk of VTE with the use of
OCs is far less than the risks associated with
unintended pregnancy
Obesity further increases risk of VTE
Among OC users in two case-control studies
obese women had a two to 24 fold higher
risk of VTE as non-obese women
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Increasing age is also associated with increased
risk of VTE
The risk of VTE rises sharply after age 39
years among women taking estrogenprogestin OCs
The third generation progestins
Desogestrel and Gestodene
may be associated with a higher risk of
VTE when compared with levonorgestrel
Use of OCs significantly increases the risk of
thrombosis in women with hereditary
thrombophilia
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Risk of Cancer
OC use has been associated with an increased risk
of certain types of cancer and a decrease in others
However, it appears that the pill
is not associated with an overall increased risk
of cancer
MSACOFP
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Hormonal Contraception
Side Effects and Complications
In pill users compared with nonusers
risks were significantly lower for
colorectal, uterine, and ovarian cancer
The incidence of breast cancer was similar in pill
users and never users
But there were significant trends of increasing risk of
cervical and central nervous system cancer in pill
users
MSACOFP
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Hormonal Contraception
Side Effects and Complications
MSACOFP
Cervical Cancer
There appears to be an increased risk for
developing cervical cancer among women who
have taken OCs
The increased risk of cervical cancer was
demonstrated after
adjusting for the number of sexual partners
previous cervical smears
Smoking
histology (adenocarcinoma or squamous cell)
Human Papillomavirus (HPV) status*
and use of barrier methods
HPV-negative OC users do not have an increased
risk of cervical cancer
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Hormonal Contraception
Side Effects and Complications
Ovarian cancer
Epidemiologic studies have consistently shown
that prolonged use of OCs reduces the risk of
ovarian cancer
compared with women who had never used
OCs
Any use of OCs
was associated with a significant reduction
in risk of developing ovarian cancer
The protective effect persisted for 30 years
after cessation of OCs
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Hormonal Contraception
Side Effects and Complications
Endometrial cancer
OC pills decrease the risk of endometrial cancer
The protective effect of OCs persists for at least
15 years after cessation of use
This benefit is likely related to the progestin
effect of OCs
which suppress endometrial proliferation
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Hormonal Contraception
Side Effects and Complications
Melanoma
The impact of OCs on the risk of melanoma has
been unclear
One study demonstrated a twofold increased
risk in current OC users
Numerous studies show no evidence for an
increased risk of melanoma with OC users
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Hormonal Contraception
Side Effects and Complications
Breast Cancer
Neither long-term past OC use nor current
use is associated with an increased breast
cancer risk
Breast cancer risk is not associated with
estrogen dose
duration of use
initiation at a young age (<age 20 years)
or race
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Hormonal Contraception
Side Effects and Complications
Overall Mortality
OC use in women over age 35 years who smoke is
associated with an increased risk of death from
cardiovascular events
However, overall mortality rates are not increased
and may actually be decreased
among ever users of OCs compared with
never users
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Hormonal Contraception
Side Effects and Complications
Carbohydrate and Lipid Metabolism
Years ago, Abnormal Glucose Tolerance tests were
fairly common in women taking high-dose OCs
but few women developed diabetes
Women taking low-dose OCs have normal glucose
tolerance
But mild insulin resistance has been reported
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Hormonal Contraception
Side Effects and Complications
The effect of OCs on serum lipid values depends
upon
the estrogen dose and
the androgenicity of the progestin
Serum Triglyceride concentrations rise slightly
But there are no consistent changes in serum
HDL or LDL cholesterol concentrations
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Hormonal Contraception
Side Effects and Complications
Pregnancy and Fertility
“Inadvertent” OC administration during early
pregnancy has not been associated with an
increase in risk of congenital anomalies
A possible exception is congenital urinary tract
abnormalities
the frequency of which was increased in one
study
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Hormonal Contraception
Side Effects and Complications
When OCs are discontinued
several months may elapse before ovulatory
cycles return
but there is no increased risk of infertility
To the contrary
the risk of primary infertility may be reduced in
women who have taken an OC
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Hormonal Contraception
Side Effects and Complications
Estrogen-progestin contraceptives in Lactating
Women
Theoretically, estrogen-progestin contraceptives
(pills, patch, ring) could suppress milk production
in the early postpartum period
Two studies have reported data supporting this
hypothesis
But there is no strong evidence of a significant
difference in infant outcomes due to use of
hormonal contraception during lactation
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Sexual function
Data on the impact of estrogen-progestin
contraceptives on female sexuality are conflicting
Although OCs suppress serum testosterone
concentrations
there are no definitive data that they have a
negative impact on libido
Uterine Fibroids
Use of low dose OCs does not cause fibroids to
grow
administration of these drugs is not
contraindicated in women with fibroids
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Liver disorders
A number of liver disorders have been thought to
be associated with OC use
Evidence for an association with hepatic adenoma
is good
while evidence for an association with focal
nodular hyperplasia and hepatocellular
carcinoma is inconclusive
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Estrogen-progestin contraceptives containing ≤35
mcg of ethinyl estradiol have not been shown to
have an adverse effect on liver function tests
this includes pills containing early generation
progestins, third generation progestins, and
drospirenone
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Pancreatitis
Oral exogenous estrogen raises serum triglyceride
concentrations
and has been associated with
hypertriglyceridemia-induced acute pancreatitis
it is recommended to avoid OCs in women whose
serum triglyceride levels are >500 mg/dL
due to a heightened risk of this complication
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Weight
Many women and their clinicians believe that OCs
cause weight gain
However, available data suggest that this is not
the case
Headaches
Headache is among the most common side effects
that are reported with OC use
and is a frequently cited reason for
discontinuation
There does not appear to be a strong relationship
between OC use and headache for most women
MSACOFP
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Hormonal Contraception
Side Effects and Complications
It appears that concerns about headache should
not be a major factor in the decision about
whether to use OCs
OCs should not be used in women with
Pseudotumor Cerebri (Idiopathic Intracranial
Hypertension)
or Migraines with focal symptoms
MSACOFP
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Hormonal Contraception
Side Effects and Complications
The association of Pseudotumor Cerebri with
prothrombotic abnormalities (antithrombin III
deficiency and antiphospholipid antibodies)
and an increased risk of Cerebral Vein
Thrombosis
represents an unacceptable risk for using
combined estrogen-progestin contraceptives
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Migraine Headaches
Migraine headaches have been reported to
worsen, improve, or not change in women taking
an OC
If Migraines occur during OC therapy
it is typically during the hormone-free interval
Use of extended cycle OC regimens or OCs with
a shortened pill-free interval (four days) appear
to result in fewer and less severe migraines
when compared with standard OCs with a
seven-day pill-free interval
MSACOFP
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Hormonal Contraception
Side Effects and Complications
WHO and ACOG have concluded from the
literature that
women with a history of migraine headaches
who take OCs are at increased risk for cerebral
thromboembolism
and that the risks of OC use usually outweigh
the benefits in women over age 35 years with
migraines
In addition
they suggest that for women of any age with
migraines associated with aura or focal
symptoms
the risk of OC use is s unacceptable
MSACOFP
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Hormonal Contraception
Side Effects and Complications
Inflammatory bowel disease
The literature is conflicting with regard to a
possible role of OCs in predisposing to the
development of inflammatory bowel disease
it is reasonable to continue the OC in women with
inflammatory bowel disease who are doing well
Systemic Lupus Erythematosus
Studies in women with mild and stable SLE did not
find evidence of an association between oral
contraceptive use and SLE flares
OCs containing lower concentrations of estrogen
are probably safe in patients with mild, wellcontrolled SLE.
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Summary and Conclusions
Early side effects of oral contraceptives (OCs) include
bloating
nausea
and breast tenderness
Although they may be bothersome enough to lead to
discontinuation of the OC
these side effects usually subside in several
months
MSACOFP
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Summary and Conclusions
Breakthrough bleeding is the most common side
effect of OCs
The most common cause of breakthrough bleeding is
thought to be missed pills
but it is common in women who do not miss pills
Its occurrence does not indicate a decrease in
efficacy
but reflects tissue breakdown as the
endometrium adjusts to a new thin state in which
it is fragile and atrophic
MSACOFP
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Summary and Conclusions
OC use does not cause subsequent menstrual cycle
disorders
including amenorrhea
Women who do not menstruate three months
after discontinuing an OC should undergo the
same evaluation for amenorrhea as any woman
with amenorrhea
Most data suggest that weight gain is not a
consistent finding with OCs
MSACOFP
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Summary and Conclusions
OCs may be associated with an increased risk of
myocardial infarction (MI)
However, because MI is an extremely rare event in
otherwise healthy women of reproductive age
even a doubling of the risk would result in an
extremely low attributable risk
Risk in older women who smoke outweighs the
risk of an unwanted pregnancy
MSACOFP
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Summary and Conclusions
Low-dose OCs may be associated with a small
increase in stroke risk
If present, the absolute increase in risk is
extremely low
particularly in healthy women under age 35 years
(non-smokers without hypertension)
MSACOFP
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Summary and Conclusions
An increase in the risk of venous thromboembolic
disease (VTE) is seen with both high and low dose
estrogen OC preparations
Although the reduction in steroid content of OCs has
improved the safety and side effect profile of the pill,
the increased risk of venous thrombosis has not
been eliminated
Risk is affected by
patient age
weight and
thrombophilia status
MSACOFP
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Summary and Conclusions
The absolute risk of thromboembolism is very low in
healthy women, and the potential risk of VTE with
the use of OCs is far less than the risks associated
with unintended pregnancy.
MSACOFP
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Summary and Conclusions
The risk of ovarian and endometrial cancer are both
reduced with OC use
The risk of cervical cancer appears to be increased
while data on breast cancer are conflicting
MSACOFP
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Summary and Conclusions
The World Health Organization (WHO) and American
College of Obstetricians and Gynecologists (ACOG)
conclude from the literature that women with a
history of migraine headaches who take OCs are at
increased risk for cerebral thromboembolism
and that the risks of OC use usually outweigh the
benefits in women over age 35 years with
migraines
It is suggested that for women of any age with
migraines associated with aura or focal symptoms
the risk of OC use is unacceptable
MSACOFP
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Thank You!
Questions?
MSACOFP
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