Hormonal Contraceptives: The

Good, The Bad, and The

Controversial
Mark A. Goedecker, MD
York Hospital
Department of Family Medicine
July 5, 2007

Objectives
Describe the pharmacologic differences in
oral contraceptives
Differentiate relative and absolute
contraindications to contraceptives
Review the wide range of contraceptive
choices
Identify patients who need emergency
contraception and describe the methods
of emergency contraception.

Outline
Oral contraceptives
Patch contraceptives
Injectable contraceptives
Ring contraceptives
Implantable contraceptives
Intrauterine devices
Emergency contraception

Disclaimer
I have nothing to disclose and have no
financial relationships with any
pharmaceutical or biotech company
I have used brand names in this
presentation to allow better understanding
and application to practice

SORT Taxonomy
A Consistent, good-quality patientoriented evidence
B Inconsistent or limited-quality patient
oriented evidence
C Consensus, disease-oriented
evidence, usual practice, expert opinion,
or case series for studies of diagnosis,
treatment, prevention, or screening

Important Dates
Egyptian women use a pessary made of crocodile
dung and lubricated with honey to prevent
pregnancy
1700s condoms made of animal intestine used
mainly for prevention of syphilis
1900 The first modern IUD is marketed
1960 FDA approves the first oral contraceptive
containing 150 g of mestranol
1974 Dalkon Shield is withdrawn from the market
2002 Norplant is removed from the U.S. market

Oral Contraceptive
Trends
Lower doses of estrogens
Newer progestins
Chewable tablets
Fewer hormone free days
Longer cycles (or no cycles)

Activity of OCPs
Contraceptive activity (efficacy)
Estrogenic activity
Progestational activity
Androgenic activity
Endometrial activity
Effect on serum lipoproteins
Managing Contraceptive Pill Patients, Twelfth Edition. Dickey R.

Combined vs. Progestin-Only

Most oral contraception prescribed is
combined (estrogen/progesterone)
Progestin-only pills such as Nor-QD,
Micronor, Camila, Errin, Jolivette, and
Ovrette
Effectiveness of the progestin-only pills is
99.5% (ideal use) versus 99.9% for the
combined (actual use 97% for both)

Estrogens in OCPs
Most pills use ethinyl estradiol (EE) as
their estrogen (50 g mestranol = 35 g
EE)
Doses range from 20 g 50 g, but most
are 20 g 35 g
Lower dose estrogens have the benefits of
less bloating and breast tenderness but
may increase the rate of breakthrough
bleeding especially in obese patients

Estrogens in OCPs
2004 Cochrane review
Low-dose estrogen OCPs resulted in
higher rates of bleeding pattern disruptions
Safety or effectiveness at preventing
pregnancy could not be assessed
Differences in progestin types not
accounted for
SORT A
Gallo MF, Nanda K, Grimes DA, Schulz KF. 20 mcg versus > 20 mcg Estrogen
Combined oral contraceptives for contraception. Cochrane Database

Older vs. Newer

Progestins
Newer:
Less androgenic (minimizes side effects such as
acne, hirsutism, nausea, and lipid changes)
Increase progestational effects

Levonorgestrel is the most androgenic available

in US
First, second, third, and fourth generation
progestins
Estranes and gonanes

Newer Progestins
Minimal androgenic effects
Norgestimate

Increases HDL and decreases LDL

Desogestrel (etonogestrel)

Possible increase risk in venous thromboembolism

(VTE)
(Jick S et al. Contraception 2006:73:566-70. SORT B)

Drospirenone

Antimineralocorticoid activity
Theoretically could cause hyperkalemia
Essentially no androgenic activity

Monophasics vs. Biphasics vs.

Triphasics
There is insufficient data that biphasic or
triphasic combined oral contraceptive pills
are better than monophasic pills
(effectiveness, bleeding patterns, or
discontinuation rates)
SORT B

Cochrane Database of Systematic Reviews 2007 Van Vliet HAAM, Grimes DA, Lopez LM, Schulz KF,
Helmerhorst FM. Triphasic versus monophasic oral contraceptives for contraception
Van Vliet HAAM, Grimes DA, Helmerhorst FM, Schulz KF. Biphasic versus monophasic oral contraceptives
for contraception

Choosing the Right Pill

Low androgenic activity is desirable in most if not
all
If patient weighs more than 160 pounds consider
higher estrogen and progestin activity
Low dose estrogen if:
History of nausea, edema or hypertension in
pregnancy
Uterine fibroids
Fibrocystic breasts
Heavy menses
Migraines

Choosing the Right Pill

Low progesterone if:
History of preeclampsia, excessive weight
gain, tiredness, or varicose veins during
pregnancy,
Depression
Excessive premenstrual

If history of polycystic ovaries, high

progestational and low androgenic

Combined Contraceptives Effect on

Weight
Contraceptive pills and patches do not
lead to major weight gain
SORT A

Gallo MF, Lopez LM, Grimes DA, Schulz KF, Helmerhorst FM. Combination
Contraceptives:effects on weight. Cochrane Database of Systematic Reviews 2007
Issue 2

Newer OCPs on the Market

Femcon Fe
The new name for Ovcon Fe chewable
Chewable spearmint flavored tablet
EE 35 g, norethindrone 0.4 mg (21 days)
Placebo contains 75 mg ferrous fumarate
ADVANTAGE: For those who cannot swallow
pills (and need fresh breath)

Yaz 24/4
Same ingredients as Yasmin but

EE 20 g (instead of 30 g)
3 mg of drospirenone
24 days of active medication and 4 days of placebo
(as compared to the usual 21/7)

ADVANTAGE:
Has an FDA indication for premenstrual dysphoric
disorder (the only hormonal contraceptive with this)
Shorter periods

Loestrin 24 Fe
24 days of hormones (similar to Yaz 24/4)
EE 20 g, Norethindrone 1 mg
Placebo pills contain iron
ADVANTAGE:
Periods last less than 3 days
More pronounced suppression of follicular
development

Extended Cycle Contraceptives

Seasonale, Seasonique, Lybrel
Oral contraceptives taken continuously for
more than 28 days compare favorably to
traditional cyclic oral contraceptives
(bleeding, discontinuation rates, and
reported satisfaction)
SORT A
Edelman AB, Gallo MF, Jense JT, Nichols MD, Schulz KF, Grimes DA. Continuous
Or extended cycle versus cyclic use of combined oral contraceptives for contraception.
The Cochrane Database of Systematic Reviews 2007 Issue 2

Seasonique
Like Seasonale:
EE 30 g, levonorgestrel 0.15 mg for 12 weeks
But
13th week contains EE 10 g (instead of placebo)
ADVANTAGES:
Low dose EE may reduce hormone withdrawal
symptoms (migraines and dysmenorrhea)
May cause less breakthrough bleeding then with
Seasonale (main reason women stop Seasonale)

Lybrel
Taken in a continuous 365-day regimen
EE 20 g and levonorgestrel 0.09 mg
28 pills in a pack
FDA approved and will be released July 2007
ADVANTAGE:

No menstrual bleeding
During the 13 pill pack:
59% of women achieve amenorrhea
20% of women have spotting only
21% of women required sanitary protection due to
breakthrough bleeding

http://www.drugs.com/newdrugs/fda-approves-lybrel-first-low-combination-oralcontraceptive-offering-women-opportunity-period-free-491.html?printable=1

Contraindications to Combined
Oral Contraceptives
Unexplained VTE or VTE associated with
pregnancy or exogenous estrogen use
(unless on anticoagulants)
Women age 35 and older who smoke
Poorly controlled diabetes or diabetes with
complications such retinopathy,
nephropathy, or other vascular
complications
Level A
Use of hormonal contraception in women with coexisting medical conditions. ACOG
Practice Bulletin No. 73. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006: 107:1453-72.

Contraindications to Combined
Oral Contraceptives
OCPs should be stopped one week prior to
surgery or heparin prophylaxis should be
considered
Women with CAD, CHF, or cerebral vascular
disease
Use caution in obese women over the age of 35
Poorly controlled HTN (or complications)
Patients with Factor V Leiden gene mutation or
prothrombin gene mutations
Level B
Use of hormonal contraception in women with coexisting medical conditions. ACOG
Practice Bulletin No. 73. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006: 107:1453-72.

Patients Who it is OK to Use OCPs

Benign breast disease or family history of
breast cancer
Mild lupus with no antiphospholipid
antibodies
Level A

Use of hormonal contraception in women with coexisting medical conditions. ACOG

Practice Bulletin No. 73. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006: 107:1453-72.

Patients Who it is OK to Use OCPs

Healthy, non-smoking women can continue their
OCPs until age 50-55
Well-controlled HTN <35 who do not smoke and
are healthy
Well-controlled DM <35 who do not smoke and
are healthy
Women with migraines who are healthy, do not
smoke, and have no focal neurologic signs
Women with depressive disorders
Level B
Use of hormonal contraception in women with coexisting medical conditions. ACOG
Practice Bulletin No. 73. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006: 107:1453-72.

Patients Who it is OK to Use OCPs

Women with well-controlled dyslipidemia
Remember progestin only contraceptives
can be safely used in most women
Level C

Use of hormonal contraception in women with coexisting medical conditions. ACOG

Practice Bulletin No. 73. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006: 107:1453-72.

Other Subgroups
BRCA1 and BRCA2 mutation carriers
No increased breast cancer risk before age
50 with at least one year of use
Possible increased risk in BRCA2 carriers
who have been on OCP's for at least 5 years

Lower risk of ovarian cancer is well

documented (fewer ovulatory cycles)
Possible lower risk of colon cancer

Ortho Evra Transdermal

Contraceptive Patch
EE 20 g/d and norelgestromin 0.15 mg/d
One patch weekly for three consecutive
weeks followed by one patch-free week
Mean serum concentrations are not
affected by heat, humidity, exercise or
cold-water immersion
Contraceptive failure is higher in women
with body weight >90 kg

Ortho Evra Transdermal

Contraceptive Patch
Possible increased risk of venous
thromboembolism (VTE)
This is due to the increased serum
concentration
Peak serum estrogen concentration is 25%
less than the peak level with the pill (30 g)
But women with the patch are exposed to
60% more estrogen than taking the pill
NuvaRing 3.4 times less estrogen exposure
than patch and 2.1 less than the pill
Thacker H, Falcone T, Atreja A, Jain A, Harris CM. How should we advise patients
about the contraceptive patch given the FDA warning?
Cleveland Clinic Journal of Medicine 2006: 73(1): 45-47.

The Patch and VTE

Two-fold increase in the risk of VTE
versus norgestimate-containing oral
contraceptives with 35 g of EE
Overall, the number needed to harm
(NNH) was 4,444 (AMI, VTE, stroke)
There is a five-fold increase in risk of VTE
in pregnancy
There is no increased risk for acute
myocardial infarction or stroke
Cole J, Norman H, Doherty M, Walker A. Venous thromboembolism, myocardial
infarction, and stroke among transdermal contraceptive system users.
Obstet Gynecol 2007: 109(2):339-46.

Injectable Contraceptives
Only one currently available is DepoProvera
Lunelle was withdrawn from the US due to
lack of demand and a recall (half-filled
syringes)

Depo-Provera
Medroxyprogesterone 150 mg given IM every 1113 weeks
New Depo-subQ Provera 104
Given every 12-14 weeks
Can be administered by the patient in the thigh or
abdomen

Side effects are similar

Slow return to fertility (14 weeks to 9 months)

Irregular bleeding
Short-term loss of bone mineral density

Depo-Provera and Osteoporosis

FDA has required a black-box warning since
2004
only use as long-term birth control method(>2
years) if other methods inadequate
It has not been associated with
postmenopausal osteoporosis or fractures
Society for Adolescent Medicine, ACOG and
WHO have recommended continuing Depo after
appropriately counseling

Depo-Provera and Osteoporosis

Short- or long-term use of DMPA in
healthy women should not be considered
an indication for DXA or other tests that
assess bone mineral density.
Level C

Use of hormonal contraception in women with coexisting medical conditions. ACOG

Practice Bulletin No. 73. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006: 107:1453-72.

NuvaRing
EE 15 g/day and etonogestrel 0.12mg/day
Inserted into vagina and left in for three weeks
Removed for one week
Can be re-inserted if it has been out for less than
three hours (rinse with cold or warm water, not
hot)
8/10 partners do not feel the ring during
intercourse (can removed prior to intercourse)

http://www.nuvaring.com/HCP/PrescribingNuvaRing/StartingYourPatients/index.asp

Implantable Contraceptives
Norplant was on the US market from
1991-2002
Six rods containing levonorgestrel
Several class action law suits over:
Failure to disclose side effects (irregular
bleeding)
Difficulty removing rods

Implantable Contraceptives
IMPLANON released August 2006
One rod containing etonogestrel
Can be left in for up to three years
Only providers who have completed a
comprehensive practical training session
can insert IMPLANON (sponsored by
Organon)
www.implanon-usa.com

IMPLANON
Mean insertion time 1.3 minutes (range 115 minutes)
Mean removal time 3.8 minutes (range 160 minutes)
4 cm long and 2 mm in diameter

IUDs
Fell out of favor in the 70s and 80s
There are two on the market today
Paragard
Lasts 10 years
Copper (non-hormonal)
Increase bleeding with menses

Mirena
Lasts 5 years
Contains levonorgestrel
Bleeding will decrease or even become absent!

IUDs - Contraindications
ACTIVE pelvic inflammatory disease
Pregnancy
Current sexual behavior suggesting a high risk
for PID
Post-pregnancy or post-abortion uterine infection
in the past three months
Cancer of the uterus or cervix
Infection of the cervix
Vaginal bleeding of unknown cause
http://www.paragard.com/hcp/custom_images/ParaGard_HCP_Safety_Info.pdf

IUDs - Complications
PID/endometritis
Very rare use of prophylactic antibiotics
confer little benefit prior to insertion
(Grimes DA, Schulz FK. The Cochrane
Database of Systematic Reviews SORT A)

Uterine perforation
Expulsion of IUD

Emergency Contraception

Emergency Contraception
Levonorgestrel (LNG) emergency
contraception (EC):
Has little or no effect on post-ovulation events
(i.e. fertilization, implantation)
In rare circumstances EC may prevent
implantation but by a similar mechanism as
OCP's
Does not increase risk to an established
pregnancy or developing embryo
Novikova N et al. Effectiveness of levonorgestrel emergency contraception given
before or after ovulation a pilot study. Contraception 2007:75:112-18.

Emergency Contraception
Treatment with EC should be initiated as
soon as possible after unprotected
intercourse
EC should be made available to patients
who request it up to 120 hours after
intercourse
No clinician examination or pregnancy
testing is necessary before EC is given

Emergency Contraception
FDA approved over the counter sales of
LNG-EC (Plan B) August 2006
Patient must be 18 or older and present
an ID to the pharmacist
Insurance may not pay without a
prescription
Average cost is $42 per pack

Emergency Contraception
LNG-EC is more effective and is
associated with less nausea and vomiting
than estrogen-progestin regimens (1.1%
vs 3.2%)
LNG-EC can be taken as a single dose
The two doses of LNG-EC are equally
effective if taken 12-24 hours apart
Level A
Emergency contraception. ACOG Practice Bulletin No. 69. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2005: 106:1443-52.

Emergency Contraception
Preven (combined EC) no longer available
in the US
OCP's can be used
Regimens can be complicated
Combined OCPs associated with nausea and
vomiting

Insertion of an IUD within 120 hours of

intercourse can be used

Summary
Newer progestins and lower dose estrogens
have greatly improved combined oral
contraceptive choices
Venous thromboembolism remains the greatest
risk to all combined oral contraceptive users
(especially those who smoke and are over age
35)
Extended cycle contraceptives are excellent
choices but have increased risk of breakthrough
bleeding

Summary
Ortho Evra and Depo-Provera remain
good options in the right patients
Dont forget about IUDs and NuvaRing for
those patients who cannot remember to
take pills
Emergency contraception is contraception

A Must-Have Book for the Office

Managing Contraceptive Pill Patients, 12 th
edition. Dickey R.

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References
Gallo MF, Nanda K, Grimes DA, Schulz KF. 20 mcg versus >
20 mcg Estrogen combined oral contraceptives for
contraception. Cochrane Database of Systematic Reviews
2007 Issue 2
Van Vilet HAAM, Grimes DA, Helmerhorst FM, Schulz KF.
Biphasic versus monophasic oral contraceptives for
contraception. Cochrane Database of Systematic Reviews
2007 Issue 2.
Van Vliet HAAM, Grimes DA, Lopez LM, Schulz KF,
Helmerhorst FM. Triphasic versus monophasic oral
contraceptives for contraception. Cochrane Database for
Systematic Reviews 2007 Issue 2.
Gallo MF, Lopez LM, Grimes DA, Schulz KF, Helmerhorst
FM. Combination Contraceptives: effects on weight.
Cochrane Database of Systematic Reviews 2007 Issue 2.

References
Edelman AB, Gallo MF, Jense JT, Nichols MD, Schulz
KF, Grimes DA. Continuous or extended cycle versus
cyclic use of combined oral contraceptives for
contraception. The Cochrane Database of Systematic
Reviews 2007 Issue 2.
FDA approves Lybrel, first low dose combination oral
contraceptive offering women the opportunity to be
period-free over time.
http://www.drugs.com/newdrugs/fda-approves-lybrel-first
-low-combination-oral-contraceptive-offering-women-oppo
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Use of hormonal contraception in women with coexisting
medical conditions. ACOG Practice Bulletin No. 73.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006: 107:1453-72.
Cole J, Norman H, Doherty M, Walker A. Venous
thromboembolism, myocardial infarction, and stroke
among transdermal contraceptive system users. Obstet
Gynecol 2007: 109(2):339-46.
Thacker H, Falcone T, Atreja A, Jain A, Harris CM. How
should we advise patients about the contraceptive patch
given the FDA warning? Cleveland Clinic Journal of
Medicine 2006: 73(1): 45-47.
Courtney K. The contraceptive patch: latest
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