Download Optimizing choice in oral contraception

PANELISTS
Dr Asha Bhatt
Dr Bharat Rangani
Dr Dipti Patel
Dr Tejal Shah
Dr Pooja Nadkarni

A newly married girl comes to you for
information about contraception.

How would you approach this client in terms
of contraception counselling & choice?



Recognize the patient’s goals for control of
fertility
Identify the patient’s health risks that
result in some methods being preferred
over others
WHO CATEGORY 4
Determine the patient’s ability to
consistently and correctly use the preferred
method





Why efficacy depends on correct and
consistent use
Why methods fail, even with proper use
Why long-term methods tend to have
lower failure rates
Why using two methods simultaneously is
more effective than using one alone
Why emergency contraception is a last
chance to prevent pregnancy
What are the usual
barriers to consistent
and correct use of a
contraceptive method?






Experience with the method
Fears and misunderstandings
Ability to remember and use the method
Tolerance of side effects
Cultural, social, or moral concerns
Partner (or parental) objections
How can we help
in overcoming
these barriers?


Listen actively
Assume nothing
 Objective listening offers a common ground
 Your patient may have more ways to solve her
problems than you will
 Believe that your patient knows what she
wants

Respect your patient’s right to privacy
Hatcher R, et al, eds. Contraceptive Technology.
18th rev ed. 2004.
 Patient information handouts Correcting misperceptions
 Non contraceptive health benefits
 Daily alarm on a computer,
personal digital assistant (PDA), or
cell phone
 Encourage her to call if she has
questions or concerns
Myths &
misperceptions??








Cause cancer
Cause blood clots
Are associated with weight gain
Should not be taken by women over the age of 35
Disrupt an existing pregnancy if taken inadverently.
Makes woman infertile
Changes sexual behaviour
Build up in a woman’s body. Women need a “rest”
from taking cocs.
Weight gain (5 lb)
in ~ 25% of women; no
significant difference
between the placebo
group and the users of
oral contraceptive ( 50
g ethinyl estradiol [EE])
Goldzieher et al.,
1971
Reubinoff et al.,
1995
Prospective,
randomized
(N=49)
No statistical difference
in weight gain (0.5 kg)
between users of oral
contraceptives (30 g
EE) and nonusers
Gallo et al.,
2006
Systematic
review of
randomized
controlled trials
No association
between combination
oral contraceptives
and weight gain
Goldzieher JW, et al. Fertil Steril. 1971;22:609-623; Reubinoff BE, et al. Fertil Steril.
1995;63:51 Gallo MF, et al. Cochrane Database Syst Rev. 2006;(1):CD003987.
Mean Change in Body Weight (kg)
1.0
0.5
0
-0.5
-1.0
-1.5
-2.0
3
Month
30 µg EE/3 mg DRSP
20 µg EE/3 mg DRSP
15 µg EE/3 mg DRSP
30 µg EE/0.15 mg LNG
6
7
EE = ethinyl estradiol
DRSP = drospirenone
LNG = levonorgestrel
Oelkers W, et al. J Clin Endocrinol Metab. 1995;80:1816-1821.
Estimated Average Risk/
100,000 Women/Year
100
80
60
40
20
0
Non-Oral
Contraceptive
Users
Oral Contraceptive
Users
Food and Drug Administration. FDA Talk Paper. Nov. 24, 1995.
Pregnant Women
Results of a large epidemiologic study suggest
that oral contraceptives do not cause breast
cancer
 Breast cancer risk in women who have not
taken oral contraceptives for ≥10 years is the
same as those who have never used them
 There is a slightly increased risk of diagnosis in
current users of oral contraceptives and in
those who stopped taking them ≤10 years ago
 Tumors are more likely to be localized in oral
contraceptive users than in nonusers

Collaborative Group on Hormonal Factors in Breast Cancer. Lancet.
1996;347:1713-1727; Collaborative Group on Hormonal Factors in Breast Cancer. Contraception.
1996;54:1S-106S.

Improvement of cyclerelated conditions:
 Acne
 Irregular menstrual
cycles
 Dysmenorrhea
 Menorrhagia
 Anemia
 Functional ovarian
cysts

Reduction in cancer of
certain organs:
 Ovary
 Endometrium
 Colon and rectum
Wallach M, et al., eds. Modern Oral Contraception: Updates from The Contraception Report. Emron, 2000.
Hospital-Based
Cohort Community-Based
Study Case-Control Study Case-Control Study
Hildreth
Rosenberg
La Vecchia
Tzonou
Booth
Hartge
et al.,
et al.,
et al.,
et al.,
et al.,
et al.,
WHO,
Wu et al.,
Prazzini et al.,
Newhouse et al.,
Casagrande et al.,
Cramer et al.,
Willet et al.,
Weiss,
Risch et al.,
CASH,
Harlow et al.,
Shu et al.,
Walnut Creek,
Vessey et al.,
Beral et al.,
1981
1982
1984
1984
1989
1989
1989
1988
1991
1977
1979
1982
1981
1981
1983
1987
1988
1989
1981
1987
1988
Summary of relative
risk with ever-use of
an oral contraceptive:
0.64 (95% CI, 0.570.73)
0.0
0.5
1.0
1.5
2.0
Relative Risk
Hankinson SE, et al. Obstet Gynecol. 1991;80:708-714.
2.5
3.0
3.5
Case Control
Cohort
Horwitz
Weiss
Kaufman
Kelsey
Hulka
Henderson
La Vecchia
Pettersson
et al.,
et al.,
et al.,
et al.,
et al.,
et al.,
et al.,
et al.,
CASH,
Koumantaki et al.,
WHO,
Brinton et al.,
Jick et al.,
Ramcharan et al.,
Trapido,
Beral et al.,
1979
1980
1980
1982
1982
1983
1986
1986
1987
1989
1991
1983
1993
1981 0.0
1983
1988
0.5
1.0
1.5
2.0 2.5
Relative Risk
Adapted from Grimes DA, Economy KE. Am J Obstet Gynecol. 1995;172:227-235.
3.0 3.5
Odds Ratio
10
1
0.1
Control
Under 30
30-39
Age (Y) at First Oral Contraceptive Use
Michaelsson K, et al. Lancet. 1999;353:1481-1484.
Over 40
 Which type of pill would you
prefer for this healthy newly
married girl without any
contraindications for OCPs?
 Estrogen dose
Type of progesterone
Mono/triphasic
Low dose
V.low dose
19-Nortestosterone
Estranes
 Norethindrone
 Norethindrone
acetate
 Ethynodiol
diacetate
 Norethynodrel
 Lynestrenol
Gonanes
 Levonorgestrel
 Norgestrel
 Desogestrel
 Norgestimate
 Gestodene
*Not available in the United States.
Adapted from Sulak PJ. OBG Management. 2004;Suppl:3-8.
Spironolactone
 Drospirenone


Triphasic oral contraceptives contain
increasing doses of estrogen or progestin
throughout the menstrual cycle in order to
decrease adverse events
A Cochrane review of triphasic and
monophasic oral contraceptives found:
 Comparable efficacy
 Suggestion of less spotting, breakthrough
bleeding, and amenorrhea with triphasic oral
contraceptives
van Vliet HA, et al. Cochrane Database Syst Rev. 2006;3:CD003553.
A 42 yr old woman on 20 micgm EE pill
for last 2 months comes to you with
breakthrough bleeding.
 Expressing concern about ocpills in
general & at her age in particular
 Overall health good,non smoker,no
CVS risk factors,normotensive, BMI 25

 How would you approach her
breakthrough bleeding?
Breakthrough bleeding…..
DEFINITION?
E ? P ?
21/7 vs 24/4 vs extended cycle

bleeding that is unscheduled, that occurs outside the time of
the hormone-free interval, and also is not within the first 3 to
4 days of active pills within a given OC cycle. Currently, many
people feel that the better term to use is 'unscheduled
bleeding.'between 10% and 30% of women will have some
spotting in the first 2 months of OC use. The high proportion
of the spotting or abnormal bleeding will usually disappear
by the third month.






Any woman beginning a new form of hormonal
contraception
Women who inconsistently use oral contraceptives or miss
doses
Oral contraceptive users who have chlamydial cervicitis
and/or endometritis
 Infection is the likely cause when breakthrough bleeding
appears several months after initiating an oral
contraceptive regimen
Smokers, possibly because of fluctuations in estrogen levels
Vomiting or diarrhea
Taking anticonvulsants or rifampicin
Wallach M, et al., eds. Modern Oral Contraception: Updates from The Contraception Report. 2000.
% Discontinuing
12
10
8
6
4
2
0
Irregular
Bleeding
Nausea
Weight
Gain
Mood
Changes
Rosenberg MJ, et al. Am J Obstet Gynecol. 1998;179:577-582.
Breast
Tenderness
Headaches

A 20-year-old woman would like to begin OC use, but
has an older sister whose severe migraine headaches
began when she started OC use. The patient reports
a personal history of mild headaches occurring 6 to 8
times yearly for the past 4 years. These last 3 to 4
hours and are bilateral, pressing, or tightening in
quality, and not associated with nausea, vomiting,
photophobia, or phonophobia. The headaches
respond well to over-the-counter medications such
as NSAIDs. Her neurologic examination is normal
and there are no other contraindications to OC use.
Safety. There is no evidence that TTH is a risk
factor for the development of ischemic stroke.
 Tolerability. There is no evidence that hormonal
fluctuations play a role in the pathogenesis or
clinical course of TTH. There is modest evidence
that a family history of migraine increases the risk
of developing headache on OCs.
 Guidelines. TTH is not considered a
contraindication to OC use by any professional
guidelines.



While the presence of TTH does not
contraindicate OC use in this patient, the
strong family history of migraine does
increase the risk that she will develop newonset migraine with OC use
weighing the potential benefits of OC use and
the strength of other reasons for OC use
against the small but real risk of headache
precipitation

A 23-year-old woman has severe dysmenorrhea that
has been unresponsive to treatment with NSAIDs.
She has migraine without aura and takes sodium
valproate 250 mg twice daily for migraine
prevention. Because she desires contraception, OCs
have been recommended as treatment of
dysmenorrhea. The patient has heard through
friends and the popular press that because she has
migraine she should not use OCs. Her neurologic
examination is normal and she has no other
contraindications to OC use.

Safety. Migraine and OC use are both risk factors
for ischemic stroke. The risk of stroke in
childbearing age women is low, but good quality
evidence suggests that a diagnosis of migraine
without aura increases this risk by a factor of
about 3. The combination of migraine and OC
use increases the risk of stroke by a factor of
about 14. Stroke risk appears to be higher with
OCs containing high doses of estrogen (greater
than 50 µg of ethinyl estradiol).
Interestingly, migraine
appears to be a risk factor
for stroke only in women
under the age of 45.


Tolerability. OCs are widely believed to cause
or aggravate headache, but the evidence that
this is a common or clinically significant
problem is remarkably slim.
Regardless of cause, headache occurring in
association with OC use tended to improve
despite continued OC use.



Migraine in women using traditional COCs is
more likely to occur during the pill-free week,
presumably triggered by estrogen
withdrawal.
OCs containing lower levels of estrogen may
be less likely to provoke headache
There is no evidence that the dose or type of
progestin in an OC has an important influence
on headache


Guidelines.
World Health Organization (WHO) and
American College of Obstetrics and
Gynecology (ACOG) guidelines consider that
for women under the age of 35 who have
migraine without aura, and few or no
cardiovascular risk factors, the benefits of OC
use typically outweigh the risks

The International Headache Society task
force on combined OCs and hormone
replacement therapy in women with migraine
concluded that "there is no contraindication
to the use of COCs in women with migraine in
the absence of migraine aura or other risk
factors.

Recommendations

This patient has migraine without aura, is under
35, has no additional risk factors for stroke, and is
likely to experience important improvement in
another condition from OC use. Avoidance of
unintended pregnancy is especially important in
this patient because she is taking valproate, a
known teratogen.For her, the benefits of OC use
probably outweigh the drawbacks, and this
assessment is supported by professional
guidelines.

It would be wise to obtain a baseline
assessment of the frequency, severity, and
character of this patient's headaches and
then monitor their frequency and severity
while she is using OCs.
 Estrogen-progestin
combinations (8%)
 Progestin-only (8%)
Prevent unintended
pregnancy
Minimize hormonal
fluctuations
Provide additional health
benefits
 Yes
 Yes
 Decreased risk of ovarian/
endometrial cancers
 Bone protection
 Cycle control
*Percentage of women experiencing unintended pregnancy with typical use within first
year of use.
Grimes DA, Wallach M, eds. Modern Contraception: Updates from The
Contraception Report. 1997; Hatcher RA, Nelson AL. In: Contraceptive
Technology. 2004:391-460.




Shortened menstrual cycle
Decreased variability in menses
Less severe bleeding
Reduced incidence and duration of
clotting/flooding
*Minestrin™ = 20 µg of ethinyl estradiol plus 1 mg of norethindrone acetate
Casper RF, et al. Menopause. 1997;4:139-147.
Change from Baseline (%)
Endpoint in Menopause-Specific Quality-of-Life Questionnaire
20
Placebo
20-g EE/1-mg NETA
*P<0.01
NS=not significant
*
15
*
*
10
NS
5
0
-5
Global
Sexual
Physical
Psychosocial
EE = ethinyl estradiol; NETA = norethindrone acetate
Reproduced with permission from Casper RF, et al. Menopause. 1997;4:139-147.
% Bone Mass
105
100
95
90
Reference Standard
Oral Contraceptives
Control
85
80
75
0
6
12
18
Months of Use
Shargil AA. Int J Fertil. 1985;30:15-28.
24
30
36


Determine when an oral contraceptive is no longer needed
 Measure follicle-stimulating hormone and/or estradiol levels after
being off of oral contraceptives for 2 weeks
▪ Serial elevations in follicle-stimulating hormone levels indicate
menopause in most women
 Estimate age of menopause based on onset of perimenopausal
symptoms
 Arbitrarily stop between the ages of 50 and 52
Transition to hormone therapy may be indicated in some women
Premenstrual molimina
 Normal premenstrual discomfort, nonproblematic
 Most common premenstrual disorder
 Premenstrual Syndrome (PMS)
 Bothersome adverse somatic and/or affective symptoms
during the luteal phase
 Premenstrual Dysphoric Disorder (PMDD)
 Significant impairment
 Least common premenstrual disorder

Ginsburg KA, Dinsay R. In: Ransom SB, ed. Practical Strategies in Obstetrics
and Gynecology. Philadelphia: W.B. Saunders Company; 2000:684-694;
Kessel B. Obstet Gynecol Clin North Am. 2000;27:625-639.
• Other disorders must be excluded
• Must include dysfunction in social or economic performance
• Symptoms must be present in the absence of pharmacologic
therapy, hormone ingestion, or drug or alcohol use
Affective Symptoms
Irritability†
Depression
Angry outbursts
Anxiety
Confusion
Social withdrawal
Somatic Symptoms
Breast tenderness
Abdominal bloating
Headache
Swelling of extremities
ACOG=American College of Obstetricians and Gynecologists
*Limited core of symptoms; †Hallmark affective symptom
Adapted from ACOG Practice Bulletin No. 15. Obstet Gynecol.
2000;95(4): supplemental material at end of issue.
• Must have ≥ 5 symptoms, including at least 1 core symptom
• Symptoms must occur during the last week of the luteal phase
• Symptoms are relieved within a few days of starting menses
Core Symptoms
• Depressed mood
• Moodiness
• Anxiety, edginess, nervousness
• Anger or irritability
Other Symptoms
• Physical symptoms (headache, breast tenderness
and/or swelling, bloating, joint/muscle pain, etc.)
• Fatigue, lethargy
• Decreased interest in
• Insomnia/hypersomnia
usual activities
• Difficulty concentrating
• Feeling overwhelmed/
• Appetite changes/cravings
out of control
American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric
Association, 2000.
Calendar of Premenstrual Experiences (COPE)
 Symptom calendar
 4-point Likert scale
 10 physical and 12 behavioral symptoms
Premenstrual Symptoms Screening Tool (PSST)
 19-item questionnaire
 Rating scale with degrees of severity for DSM-IV symptoms
Visual Analogue Scale (VAS)
 100-mm vertical line (“no symptoms” to “severe” symptoms)
 Irritability, tension, depression and mood swings
Daily Record of Severity of Problems (DRSP)
 24-item questionnaire
 Symptoms and functional impairment
 6-point scale
PMS=premenstrual syndrome; PMDD=premenstrual dysphoric disorder
Feuerstein M, Shaw WS. J Reprod Med. 2002;76:279-289; Steiner M, et al. Arch Women Ment
Health. 2003;6:203-209; Steiner M, et al. J Affect Disord. 1999;53:269-273; Endicott J, et al.
Arch Womens Ment Health. 2006;9:41-49.



Lifestyle changes
 Aerobic exercise
 Dietary modification
Cognitive-behavioral therapy
Pharmacologic agents
 Selective serotonin reuptake inhibitors (SSRIs)
 The SSRIs that have an FDA-approved indication for treating
premenstrual dysphoric disorder are:
▪ Fluoxetine hydrochloride
▪ Sertraline hydrochloride
▪ Paroxetine hydrochloride
 Spironolactone
 Anxiolytics
 Gonadotropin-releasing hormone (GnRH) agonists
 Hormonal contraceptives
ACOG Practice Bulletin No. 15. Obstet Gynecol. 2000;95(4):
supplemental material at end of issue.
Exercise
 Regular aerobic exercise
reduces premenstrual
syndrome, possibly due
to release of endorphins
 Recommendation: 20–30
minutes/day of aerobic
exercise at least 3 days
per week
Dietary supplements
 Calcium supplements
have modest effects
on symptoms
 Limited data indicate
a possible benefit of a
beverage containing
complex and simple
carbohydrates
Ginsburg KA, Dinsay R. Premenstrual syndrome. In: Ransom SB, ed. Practical Strategies in
Obstetrics and Gynecology. Philadelphia: W.B. Saunders Company, 2000:684-694; ThysJacobs S, et al. Am J Obstet Gynecol. 1998;179:444-452; Sayegh R, et al. Obstet Gynecol.
1995; 86:520-528; Freeman EW, et al. Int J Gynaecol Obstet. 2002;77:253-254.
Agent
Results
CBT vs. no
treatment1
4 weeks of group CBT superior to no treatment (placebo) for
reducing PMS severity; gains maintained up to 18 months
CBT vs. IFT2
CBT and IFT equally effective for reducing premenstrual
levels of negative mood and physical changes; effects
maintained at 12 months
CBT vs. fluoxetine
vs both3
All treatments equally effective at 6 months. Fluoxetine
therapy had more rapid effect. No added benefit for
combining treatments
CBT vs. no
treatment4
CBT more effective than no treatment for reducing PMS
symptoms, associated impairments and depression
PMS=premenstrual syndrome; CBT=cognitive-behavioral therapy; IFT=information-focused
therapy (training in relaxation, assertion, and child management, nutritional/vitamin
guidelines, dietary/lifestyle changes)
1.
2.
3.
4.
Taylor D. Res Nurs Health. 1999;22:496-511.
Christensen AP, Oei TP. J Affect Disord. 1995;33:57-63.
Hunter MS, et al. J Psychosom Res. 2002;53:811-817.
Blake F, et al. J Psychosom Res. 1998;45:307-318.
Visual Analogue Scale
25
*P<0.01 vs. baseline
†P<0.01 vs. placebo
*
*
20
15
Baseline
Spironolactone
Placebo
*†
10
*†
5
0
Anxiety, Tension,
Irritability, Fatigue,
Depression
Cheerfulness, Wellbeing, Friendliness,
Energetic Feeling
Wang M, et al. Acta Obstet Gynecol Scand. 1995;74:803-808.
Headache, Feeling of
Swelling, Craving of
Sweets, Breast
Tenderness





Anxiolytic agent
0.25 mg once or twice daily in luteal phase;
dose should be tapered at menses
Studies have given inconsistent results
Contraindicated in women with a history
of drug abuse or dependence
Sedation bothersome for some women
ACOG Practice Bulletin No. 15. Obstet Gynecol.
2000;95(4): supplemental material at end of issue.
Mean Change from Baseline in Daily
Record of Severity of Symptoms
0
*
-5
-10
-15
-20
-25
-30
-35
† †
*P<0.01; †P<0.05
* *
Fluoxetine 10 mg
Fluoxetine 20 mg
Placebo
Mood
Physical
Symptoms
Symptoms
DRSP=Daily Record of Severity of Problems
*
Social
Functioning
Cohen LS, et al. Obstet Gynecol. 2002;100:435-444.
Total DRSP
Score


Standard estrogen and progestin combination
contraceptives in a 21/7 regimen show no or minimal
improvement to symptoms
Decline in endogenous estradiol levels during the last
week of hormonal contraception may be responsible for
the estrogen-withdrawal symptoms beginning to appear
during the last week, thus exacerbating premenstrualtype symptoms during the subsequent 7-day hormonefree interval
Agent
 Monophasic ethinyl estradiol/
Study
Type
RCT1
desogestrel
 Monophasic ethinyl estradiol/
levonorgestrel
 Triphasic ethinyl estradiol/
levonorgestrel
 Ethinyl estradiol/norethindrone
Results
 Mood scores improved
from baseline for all 3 OCs
 Benefit no different than
that seen with placebo in
other studies
RCT2
 Decreased premenstrual
breast pain and bloating
compared with placebo
 No beneficial effect on
mood
 Various OCs
NCCS3

No effect on mood
21/7=21 days of an active hormone followed by a 7-day hormone-free interval; OC=oral
contraceptive; RCT=randomized, controlled trial; NCCS=nested case-control study
1. Backstrom T, et al. Contraception. 1992;46:253-268
2. Graham CA, Sherwin BB. J Psychosom Res.1992;36:257-266
3. Joffe H, et al. Am J Obstet Gynecol. 2003;189:1523-1530.
N=262
21 Active
Days
7 HormoneFree Days
P Value
Pelvic pain
21%
70%
<0.001
Headache
53%
70%
<0.001
Breast tenderness
19%
58%
<0.001
Bloating/swelling
16%
38%
<0.001
Needing pain meds
43%
69%
<0.001
Cycle-Related
Symptom
21/7=21 days of an active hormone followed by a 7-day hormone-free interval
Sulak PJ, et al. Obstet Gynecol. 2000;95:261-266.
Average Score on DSR17* Item
28-day cycle
0.5
168-day cycle
0.4
0.3
†
†
†
†
0.2
†
§
0.1
0
Headache
Swelling,
Bloating,
Weight Gain
Anxiety
Irritability Mood Swings Depression
*DSR17=Penn State Daily Symptom Report; †P<0.0001; §P=0.0001.
Coffee AL, et al. Am J Obstet Gynecol. 2006;195:1311-1319.
Change from Baseline
0
-4
-8
-12
†
§
†
-16
-24
§
1
2
3
†
†P=0.01 vs. placebo
§P=0.001 vs. placebo
†
-20
†
1
†
2
Drospirenone-EE
Placebo
†
3
1
2
Mood
Physical
Behavioral
*Factor scores comprised of individual items from the Daily Record
of Severity of Problems (DRSP). PMDD=premenstrual dysphoric
disorder; EE=ethinyl estradiol.
Yonkers KA, et al. Obstet Gynecol. 2005;106:492-501.
3
Contraceptive Progestins
in Current Use
Levonorgestrel
Family
(Gonanes)





Levonorgestrel
Norgestrel
Desogestrel
Norgestimate
Gestodene*
Norethindrone
Family
(Estranes)
 Norethindrone
 Norethindrone
acetate
 Ethynodiol
diacetate
 Lynestrenol*
*Not available in the United States.
SpironolactoneDerived
 Drospirenone

Women with contraindications for
combination hormonal contraceptives,
including a history of:
 Venous thrombosis
 Vascular disease
 Hypertension
 Heavy smoking (>35 years)

Lactating women
Heinemann LA, et al. Eur J Contracept Reprod Health Care. 1999;4:67-73;
Tankeyoon M, et al. Contraception. 1984;30:505-522.

The efficacy rate of progestin-only pills is
comparable to combination oral
contraceptives, but consistently timed
ingestion is required
 Plasma levels fall to baseline after 24 hours
 If ingestion occurs more than 3 hours after a
required dose, back-up contraception should be
used for 48 hours
21 Active
Days
7 Hormonefree Days
P value
Pelvic pain
21%
70%
<0.001
Headaches
53%
70%
<0.001
Breast tenderness
19%
58%
<0.001
Bloating/swelling
16%
38%
<0.001
Use of pain meds
43%
69%
<0.001
N=262
Sulak PJ, et al. Obstet Gynecol. 2000;95:261-266.
Brand Name
Estrogen
Dose
Seasonale®
30 µg EE
TM
Progestin Dose
150 µg levonorgestrel
Regimen
84/7
84/7*
Seasonique
30 µg EE
150 µg levonorgestrel
Yaz
20 µg EE
3 mg drospirenone
24/4
Loestrin 24
Fe
20 µg EE
1 mg norethindrone
acetate
24/4*
Lybrel
20 µg EE
90 µg levonorgestrel
EE= ethinyl estradiol
*7 days 10 µg EE
*4 days of iron
365 days (noncyclic daily dosing)
Discontinuations Due
to Adverse Event(s)
Pregnancy
15
Percentage of Women
Percentage of Women
2
1.5
1
0.5
0
10
5
0
Conventional Extendedcycle
Conventional Extendedcycle
*30 µg ethinyl estradiol/150 µg levonorgestrel
Anderson FD, Hait H. Contraception. 2003;68:89-96.
Median Number of Breakthrough
Bleeding/Spotting Days/Cycle
12
10
8
6
4
2
0
Cycle
Day
1
2
3
4
1-84
92-175
183-266
274-357
*30 µg ethinyl estradiol/150 µg levonorgestrel.
Anderson FD, Hait H. Contraception. 2003;68:89-96.
Premenstrual
symptomatology
 Menstrual migraine
headaches
 Menorrhagia, irregular
bleeding
 Anemia
 Endometriosis
 Pain
 Infertility
 Dysmenorrhea




Ovarian cysts
Perimenopausal
symptomatology
 Shorter cycles
 Cycles further apart
and lighter
Adolescent
symptomatology
 Facial acne
 Menorrhagia
Hematologic conditions
 Anemia
 Bleeding disorders
 Clotting defects
 Developmental disabilities
 Professional/social obligations
 Military service
 Professional athletics
 Performing arts (e.g., ballerinas)
 Vacation/honeymoon

1
Red = Typical pattern during
spontaneous menstrual cycle
Estradiol Levels
Intitiation of Hormone
withdrawal symptoms on OCP
Initiation of hormone withdrawal
symptoms during spontaneous cycle
Black = theorized pattern during
OCP cycle with 7 day HFI
0
-7
0
7
14
Cycle day
Slide courtesy of Thomas J. Kuehl, PhD
21
28



36 women used triphasic, 30-µg monophasic, or 20-µg
monophasic oral contraceptives for three consecutive cycles
Transvaginal ultrasound was performed every three days to
monitor ovarian follicular development
 If a follicle reached ≥14 mm, each subject had a daily
sonogram and a serum estradiol measurement
Results: Follicles develop to an ovulatory diameter during the
hormone-free interval
Baerwald AR, et al. Contraception. 2004;70:371-377.


Randomized double-blind study (N=60)
 20 µg ethinyl estradiol (EE)/75 µg gestodene
 21/7 regimen vs. 23/5 regimen
 5 cycles (1 pretreatment, 3 treatment, 1 posttreatment)
 Ovarian suppression, assessed by follicular development and EE
levels, was more pronounced with the 23/5 regimen
Randomized investigator-blinded controlled trial (N=54) compared 3
cycles of 3 combination oral contraceptives:
▪ 21/7 regimen of 20 µg EE/100 µg levonorgestrel
▪ 21/2/5 regimen of 20 µg EE/placebo/10 µg EE
▪ Continuous 20 µg EE/150 µg desogestrel
 The difference among the three groups was statistically significant
(P=0.005)
Spona J, et al. Contraception. 1996;54:71-77.
Schlaff WD, et al. Am J Obstet Gynecol. 2004;190:943-951.
Brand Name
Seasonale®
Estrogen
Dose
30 µg ethinyl
estradiol
Progestin
Dose
150 µg
levonorgestrel
SeasoniqueTM
30 µg ethinyl
estradiol
150 µg
levonorgestrel
Yaz
20 µg ethinyl
estradiol
3 mg
drospirenone
Loestrin 24 Fe
20 µg ethinyl
estradiol
1 mg
norethindrone
acetate
Regimen
84/7
84/7*
*7 days 10 µg
ethinyl estradiol
24/4
24/4*
*4 days of iron


In a prospective analysis, patients who experienced >7 consecutive days
of breakthrough bleeding/spotting were counseled to:
 Take a 3-day hormone-free interval and resume the extended regimen
OR
 Continue the extended regimen
 If bleeding/spotting was unresolved after seven days, take a 3-day
hormone-free interval and then resume the extended regimen
All patients whose breakthrough bleeding/spotting continued despite
either intervention were counseled to:
 Institute a 3-day hormone-free interval after another seven days of
bleeding/spotting but not before 14 days had passed since the previous
3-day hormone-free interval
Sulak PJ, et al. Am J Obstet Gynecol. 2006;195:935-941.
Prospective analysis of bleeding among women (N=111) taking a
21/7 pre-extension regimen followed by a 168-day extended
regimen of an oral contraceptive containing 30 µg ethinyl
estradiol/3 mg drospirenone
 During the extended cycle:
 Continuation of active pills usually resulted in continued flow
with a greater tendency to require a 3-day hormone-free
interval
 Taking a 3-day hormone-free interval resulted in an initial
increase in flow usually followed by a cessation of flow after a
few days

Sulak PJ, et al. Am J Obstet Gynecol. 2006;195:935-941.
Patients do not have to adhere to a fixed cycle (e.g., 49 days, 91
days)
 Patients should expect breakthrough bleeding and spotting. If
either occurs, patients should chose one of the following options:
 Option A:
▪ Keep taking active pills as spotting/bleeding will decrease over
time
 Option B:
▪ Take a 3- to 4-day hormone-free interval, relabel the pill pack
to the correct day of the week, and restart active pills
 The option chosen should be based on the significance of the
bleeding/spotting and the severity of the hormone withdrawal
symptoms a patient experiences

Adolescents may benefit from a regimented extended cycle
because they may have difficulty determining when to take a
hormone-free interval (i.e., to allow withdrawal bleeding) if on
a flexible oral contraceptive schedule
 Consideration of their preferences may promote initiation
and continuation
 Cost may be an issue, unless the adolescent purchases both
pills and personal hygiene products
 Adolescents must understand that although there is a
reduction in bleeding days, unscheduled bleeding occurs more
often, but it decreases with continued use

Schwartz JL, et al. Contraception. 1999;60:263-267;
den Tonkelaar I, Odden BJ. Contraception. 1999;59:357-362;
Omar H, et al. J Pediatr Adolesc Gynecol. 2005;18:285-288.
Study population
 Women who underwent endometriosis
surgery within one year
 Recurrent dysmenorrhea despite cyclic
use of oral contraceptives
Intervention
 Continuous ethinyl estradiol (0.02 mg)
Outcomes
 Reduction in frequency/severity of
and desogestrel (0.15 mg) for two
years
dysmenorrhea
 80% of women satisfied
 12% reported relief of menstrual
migraines
Vercellini P, et al. Fert Steril. 2003;80:560-563.
Percentage of Respondents
60
Ages 18–24 years (n=101)
Ages 25–29 years (n=45)
Ages 30–39 years (n=150)
45
Ages 40–49 years (n=195)
30
15
0
Once/
month
Every
other
month
Once/
Once/
3 months 6 months
Association of Reproductive Health Professionals.
Harris Poll, June 14-17, 2002.
Once/
year
Never
Extended Oral Contraceptive Regimens:
Attitudes of Health-Care Professionals
Toward Associated Risks
Choices*
Increase risk of breast cancer
Increase risk of deep vein
thrombosis/pulmonary embolism
Create future fertility problems
Affect none of the above
*Respondents could check multiple responses.
Sulak PJ, et al. Contraception. 2006;73:41-45.
N=551
7%
13%
3%
83%
Extended Oral Contraceptive Regimens:
Attitudes of Health-Care Professionals
Toward Monthly Bleeding
Choices*
N=551
Has health benefits and is
necessary
12%
Only serves to reassure a woman
that she is not pregnant
49%
Is unnecessary and has no health
benefits
52%
*Respondents could check multiple responses.
Sulak PJ, et al. Contraception. 2006;73:41-45.
Extended Oral Contraceptive Regimens:
Prescribing Patterns of Health-Care Professionals
Choices
N=551
No
19%
Yes, but rarely
19%
Yes, occasionally
36%
Yes, frequently
24%
Yes…
Sulak PJ et al. Contraception. 2006;73:41-45.
2%
Current and future extended-cycle contraceptive methods will favorably
affect menstruation, associated hormone-withdrawal symptoms, and
pregnancy risk
 Decreased incidence of hormone-withdrawal symptoms
 Reduced bleeding
 No development of functional ovarian cysts
 Decreased number of unintended pregnancies
Counseling patients regarding alterations in menstruation and safety is
critical to initiation and continuation of these contraceptive methods
 Breakthrough bleeding and spotting should be expected and can be
managed
 Long-term risks of such regimens are not known


Topical Agents
Comedolytics
- Retinoids
- Salicylic acid (in many
OTC agents)
Antimicrobials
- Benzoyl peroxide
- Clindamycin
- Erythromycin/
combination
Systemic Agents
 Oral antibiotics
-
Tetracycline
Minocycline
Doxycycline
Clindamycin
 Vitamin A derivatives
- Oral isotretinoin
 Hormonal therapies
- Oral contraceptives
- Spironolactone
OTC = over the counter
Zaenglein AL, Thiboutot DM. Pediatrics. 2006;118:1188-1199.
Mild Acne
Comedonal
First-line
Therapy
Alternatives
Topical
retinoid
Papular/
Pustular
Topical
retinoid +
BPO or
BPO/AB
Moderate Acne
Papular/
Pustular
Nodular
Topical retinoid ± oral
antibiotic + BPO or BPO/AB
Oral
isotretinoin
Salicylic acid
Severe
Nodular Acne
Oral isotretinoin
Topical retinoid ± oral
antibiotic + BPO or
BPO/AB
Alternatives
for Female
Patients
Hormonal therapy + topical
retinoid ± BPO or BPO/AB
Hormonal therapy + topical
retinoid ± BPO or BPO/AB
Hormonal therapy + oral
antibiotic + topical
retinoid ± BPO or
BPO/AB
Maintenance
Therapy
Topical retinoid ± BPO or
BPO/AB
Topical retinoid ± BPO or
BPO/AB
Topical retinoid ± BPO
or BPO/AB
AB = topical antibiotic; BPO = benzoyl peroxide
Zaenglein AL, Thiboutot DM. Pediatrics. 2006;118:1188-1199.

 Androgen secretion in the ovaries and
adrenal glands through their estrogenic
effects
  Production of testosterone
  Levels of free testosterone
  Production of dihydrotestosterone


 Sex hormone-binding globulin to bind
androgens
 5-reductase activity
van der Vange N, et al. Contraception. 1990;41:345-352; Cassidenti DL, et al.
Obstet Gynecol. 1991;78:103-107.
Inflammatory
Lesion Counts
Total Lesion
Counts
Mean Change
0
-20
-40
EE/DRSP
EE/NGM
-60
-80
Cycle 6
EE/DRSP = ethinyl estradiol 30 µg/drospirenone 3 mg; EE/NGM=ethinyl estradiol
35 µg/norgestimate 180-215-250 µg
Thorneycroft IH, et al. Cutis. 2004;74:123-130.



May be more effective for inflammatory
lesions (papules, pustules, nodules) than
noninflammatory ones (comedones)
May be used concurrently with topical
agents
May be used as ongoing maintenance
therapy
Thiboutot D. Arch Fam Med. 2000:9:179-187; Usatine RP, et al. Prim Care.
2000;27:289-308; Wallach M, Grimes DA. In: Modern Oral Contraception:
Updates from The Contraception Report. 2000:155-168.

Before, during, and after isotretinoin
(Accutane)
 ...[E]ffective contraception must be
used for at least 1 month before
beginning Accutane therapy, during
therapy, and for 1 month following
discontinuation of therapy….
 ...[I]t is critically important that women
of childbearing potential use two
effective forms of contraception
simultaneously…..
Accutane [package insert], 2000 (Revised. May 2000).
Treat mild to moderate acne
 Topical/systemic agents as appropriate
 Prescribe oral contraceptives for women with acne who also need
contraception
 Counsel women that most oral contraceptives improve acne for most
women
 Counsel women not to discontinue previously prescribed topical or oral
agents when oral contraceptives are initiated
 Refer patients with severe acne to a dermatologist
 If the dermatologist prescribes isotretinoin (Accutane), a potential
teratogen, counsel women on contraception before, during, and after the
drug’s use
 Oral contraceptives provide additional benefits

Accutane [package insert], 2000 (Revised. May 2000); Thiboutot D. Arch Fam
Med. 2000:9:179-187; Usatine RP, et al. Prim Care. 2000;27:289-308; Wallach
M, et al. In: Modern Oral Contraception: Updates from The Contraception
Report. 2000.

There have been 3 OCs that have gained FDA
approval for an indication for the treatment
of mild-to-moderate acne. As I mentioned
before, it is the triphasic norgestimate pill,
the estraphasic norethindrone acetate pill,
and most recently, the 24-4 20-mcg
[estrogen]/DRSP pill.
A 37-year-old mother of 2 comes to your office
because she is interested in starting an OC.
 Her medical history –
 a benign fibroadenoma in her left breast 10 years
ago
 postpartum depression after having her first child.
Her younger sister was diagnosed with breast
cancer at the age of 26, but otherwise her family
history is unremarkable. Her physical examination
shows BP 129/76 mm Hg, pulse 79 beats per minute,
BMI 31 kg/m2


Given this patient's age, which of the
following characteristics would be a reason
for not recommending a combined OC on the
basis of current recommendations?