Transcript Document

Contraception Updates
Amr Nadim, MD
Professor of Obstetrics & Gynecology
Ain Shams Faculty of Medicine
Maternity & Women’s Hospital
Definition
• Contraception (birth control) prevents
pregnancy by interfering with the normal
process of ovulation, fertilization, and
implantation.
• There are different kinds of birth control that
act at different points in the process.
• Unfortunately, there is no perfect form of
birth control.
– Only abstinence can protect against unwanted
pregnancy with 100% reliability.
Contraceptive Options
Hormonal Methods
•Progestin Only Injectables / Oral Contraceptives
•Combined Injectable / Oral Contraceptives
•Intrauterine Systems
•Vaginal rings
•Implants
•Patches
Contraceptive Options
Non-Hormonal Methods
IUD
NFP methods
Barriers
Contraceptive Options
Sterilization Methods
Tubal Occlusion
Vas Ligation
Tubal ligation
What are the concerns of any couple about
the method of family planning they need?
• When correctly used, all methods are
more effective than no method.
• Safe methods are those without serious
complications.
• Clients should be given their preferred
(or desired) method if it is not medically
contraindicated.
Risk Misperception & Patients
“…incorrect perceptions of
excess risk of contraceptive
products may lead women to
use them less than effectively
or not at all.”
Gardner J, Miller L. J Womens Health. 2005
Misperceptions Affect Health
Decisions
• 1995 – Warning: possible increased risk of
VTE among users of 3rd generation OCs
• Many women discontinued OC use
• Prescribing patterns changed
• Pregnancy and abortion numbers
increased
• Deemed a “non-epidemic”
Chasen-Taber L. N Engl J Med. 2001.
Drife L. Drug Saf. 2002.
Furedi A. Lancet. 1998.
Spitzer WO. Hum Reprod. 1997.
Definition of Risk
“The possibility of
suffering
harm or loss.”
The American Heritage Dictionary
of the English Language
Risk Calculations
Causality
Weigh
pros and
cons
Hennekens CH. Epidemiology in Medicine. 1987.
Degree to
which
attributable
Associations vs. Causality
• An association does not always mean exposure
caused outcome
• It could be due to random chance or bias
• Making a decision about causality requires that a
number of criteria be met, including (among
others):
– Strength of the association (as measured by relative
risk, for example)
– Consistency of the association over multiple studies
– Temporal sequence (exposure precedes outcome)
• The point is that a weak association found in a
single study should not be taken as concrete
evidence of a cause-and-effect relationship.
Grimes DA. Lancet. 2002.
Commonly Used Risk
Calculations
Absolute
risk
Absolute
risk
reduction
Relative
risk
Absolute Risk
• The percentage of people in a group
who experience a discrete event
Number of People With Event
Total # of People At Risk
NY Academy of Medicine. 2005.
Misselbrook D. Fam Practice. 2002.
Example of Absolute Risk
• Of 100,000 women on 3rd generation OCs,
30 will develop venous thromboembolism
(VTE) per year
Absolute risk
30 per 100,000
woman-years
Mills A. Hum Reprod. 1997.
Absolute Risk Reduction
• The difference in risk of the outcome
between those exposed and those not
exposed
• Risk in exposed – risk in unexposed
• Reflects the reduction in risk
associated with an intervention
NY Academy of Medicine. 2005.
Example of Absolute Risk
Reduction
• Of 100,000 women on 2nd generation OCs,
15 will develop VTE per year
Absolute risk
Absolute risk
reduction
15 per 100,000
woman-years
30 - 15 =
15 per 100,000
woman-years
Mills A. Hum Reprod. 1997.
Attributable Risk
• Similar to absolute risk reduction
• Attributable risk is:
– The difference in risk of the outcome
between those exposed and those not
exposed
– Risk in exposed – rate in unexposed
• Reflects degree of risk associated with
exposure
BMJ Collections. 2006.
Relative Risk
• Used to identify an association between
exposure and outcome
Exposure
Grimes DA. Lancet. 2002.
Hennekens CH. Epidemiology in Medicine. 1987.
Outcome
Odds Ratio
• Used to identify an association between
exposure and outcome in a case-control
study
• Similar to relative risk
Exposure
Hennekens CH. Epidemiology in Medicine. 1987.
Outcome
Relative Risk: Example 1
Absolute risk
Absolute risk
3rd Generation OCs
2nd Generation OCs
30 per 100,000
woman-years
15 per 100,000
woman-years
Relative risk = 30 / 15 = 2
Mills A. Hum Reprod. 1997.
Interpreting Relative Risk
Relative risk = 1
No increase in risk
in exposed group
compared with
unexposed group
Relative risk > 1
Increased risk in
exposed group
Hennekens CH. Epidemiology in Medicine. 1987.
Relative risk < 1
Decreased risk in
exposed group
Risk & Health Decisions
“Decisions about risk are not
technical,
but value decisions.”
Baker B. In: Risk Communication and Public Health. 1999.
Relative Risk: Example 2
Risk of cesarean delivery with
elective induction of labor
20%
Risk of cesarean delivery with
spontaneous onset of labor
10%
Relative risk with induction:
20%
10%
Relative risk = 20 / 10 = 2
Grimes DA. Lancet. 2002.
more…
Relative Risk: Example 2
(continued)
• Interpretation:
“The risk of cesarean delivery with
elective induction of labor is 2 times that
associated with spontaneous labor.”
Or, alternatively stated:
“The risk is twice as high.”
more…
Grimes DA. Lancet. 2002.
Relative Risk: Example 2
(continued)
Graph of relative risk of 2
Relative risk
(log scale)
10
Increased risk
1
Decreased risk
0.1
Grimes DA. Lancet. 2002.
Relative Risk: Example 3
Rate with prophylactic
antibiotics
6%
Rate without prophylactic
antibiotics:
12%
= 0.5
Relative risk:
6%
12%
Relative risk = 6 / 12 = 0.5
Grimes DA. Lancet. 2002.
more…
Relative Risk: Example 3
(continued)
Graph of relative risk of 0.5
Relative risk
(log scale)
10
Increased risk
1
0.1
Grimes DA. Lancet. 2002.
Decreased risk
Comparing Relative Risks of 2
and 0.5
Relative Risk (log scale)
10
2
Zone of
increased risk
1
0.5
0.1
Grimes DA. Lancet. 2002.
Zone of
reduced risk
Comparative Risks of VTE
Incidence of VTE per
100,000 woman-years
60
40
20
0
Pregnancy
High-dose
OC
Shulman LP. J Reprod Med. 2003.
Chang J. In: Surveillance Summaries. 2003.
Low-dose
OC
General
Population
Causes of Risk Misperception
about
Hormonal Contraceptives
Weighing the Risks & Benefits
Burkman R. Am J Obstet Gynecol. 2004.
Decision Aid for Risk
Communication
Clarify situation
Provide information
Clarify patient’s values
Screen for implementation problems
O’Connor A, Legare F, Stacey D. BMJ. 2003.
A Final Thought
“Two times a very rare
event is still a very rare
event.”
David Grimes, MD
2006
WHO Eligibility Criteria for Contraceptive Use
Category
Description
When clinical
judgment is
available
1
No restriction for
use
Use the method under
any circumstances
When clinical
judgment is
limited
Use the method
Benefits generally
outweigh risks
Generally use the
method
3
Risks generally
outweigh benefits
Use of method not
usually recommended,
unless other methods
are not
available/acceptable
4
Unacceptable
health risk
Method not to be used
2
Source: WHO, 2004.
Do not use the
method
New Methods
Single-rod Implant
Monthly Injectable
LNG IUS
Vaginal Ring
Patch
Pill Generations
• High court ruling 2002 –failed to show increase of
VTE odds ratio between 3rd and 2nd generation
• Medicines Committee Advice 1999
– The absolute risk of VTE taking third generation
pills is very small & is much less than the risk in
pregnancy.
– There is a small excess risk of 10 cases of VTE
per 100,000 women compared with those taking
second generation pill.
• Provided women are fully informed of the small risks
& do not have medical contraindications, it should
be a matter of clinical judgement and personal
choice which COC is prescribed.
1st, 2nd and 3rd Generation Progestins
• The terms "new', "newer, "second generation" and
"third generation" do not accurately describe OC
progestins.
• Progestins are best classified into
– Gonanes (Levonorgestrel, desogestrel, gestodene and
norgestimate)
– Estranes (Norethindrone, Lynestrenol)
• Estranes and gonanes differ in :
– Bioavailability
• The greater the posthepatic bioavailability , the lower is the dose
needed to be used.
– Only norethindrone, gestodene and levonorgetrel are active as
such. Other progestins are prodrugs and so need to be given in
higher dosages to compensate for hepatic biotransformation.
1st, 2nd and 3rd Generation Progestins
– Serum half-lives
• Long serum half life is associated with more consistent cycle control
and greater contraceptive protection in the event of missed pills.
• The shortest half life is that of norethindrone (7 hours) and the
longest is that of levonorgestrel (15 hours).
– Relative binding affinity to the progesterone receptors.
• Greater relative binding affinity means that a smaller dose is needed
for a consistent clinical effect to be achieved. Among OC progestin,
levonorgestrel has the highest relative binding affinity followed by the
active metabolite of the desogestrel.
• Strong Evidence suggests that all progestins effectively reduce free
testosterone levels by 40-50% in average women.
1st, 2nd and 3rd Generation Progestins
– All OCs inhibit the 5 -reductase in the skin
resulting in lower levels of active
dihydrotestosterone with subsequent better
control of acne and hirsutism.
There is no evidence to support that one class
of progestin is superior to another with
regard to androgen related conditions.
Anti-androgenic Progestogens
Cyproterone Acetate-(in Diane/ Brenda)
• Anti-androgen with
progestogenic qualities
• Binds strongly to androgen
receptors and prevents action
of testosterone
• Major indication is in those with
significant hirsutism or acne
• Takes 3 months for effect on
acne and 6 months for effect on
hirsuitism
• Can accelerate effect by adding
in extra Androcur initially
Anti-androgenic Progestogens
Drosperinone-(in Yasmin)
• Yasmin-Ethinyloestradiol
30 µg and drospirenone
3mg
• Drosperinone related to
Spironolactone
– Has mild diuretic effectsless fluid retention
– Antiandrogenic effects
• Weight Loss ?- mainly due
to fluid loss-0.5 kg over 12
months
New Oral Contraceptives
• Yasmin
– 30mcg ethinylestradiol +3mg drosperinone
• Cerazette
– 75 mcg desogestrel
• ovulation inhibition
• efficacy same as for COCs
• ?12 hours leeway but current licence 3 hours as other
POPs
• safe if migraine with aura or risk of VTE
• trend towards more amenorrhoea and less bleeding
with time
• no effect on lactation
Cerazette
• A 75 mg POP containing desogestrel
• Assumed to inhibit ovulation
Emergency Contraception
• WHO Study in 1996-7
compared the older Yuzpe
method using high dose
Combined Pills (Nordiol 2 X 2)
with high dose progestogenonly regime(0.75 mgs LNG X2)
• The POP regime was found to
be more effective with less side
effects.
• Yuzpe and the WHO trial both
used divided doses (12 hours),
up to 72 hours after USI
Emergency Contraception Effectiveness
LNG
Pregnancy rate 1.1%
YUZPE
3.2%
Efficacy rate 85%
(pregs.prevent
-ed vrs pregs.
expected)
76%
Emergency Contraception
• Both methods are
more effective the
earlier they are
commenced after
USI
• Less nausea on
progestogen only
method- 2% vrs
22%
• No need for routine
anti-emetics
Emergency Contraception
• Microlut +25 pills
where cost or
confidentiality an issue
• 2 pill progestogen-only
ECP: Postinor 2
Hot off the Presses!
• Lancet article published December 2002
showed
– POP emergency contraception retained some
effectiveness up to 120 hours (5 days) after
unprotected sex
– A single stat dose of 1.5 mgs seemed to be
slightly more effective than the divided dose
Von Hertzen H et al. Lancet 2002; 360:1803-10
• FPA Health has now changed its Clinical
Protocols on ECP to reflect this study
• TGA recently approved ECP as a
pharmacist-supplied item
Absorption of oral preparations
• hormones are absorbed from the upper small
intestine.
• peak plasma levels reached within 2 hours
• vomiting within 2 hours of ingestion reduces the
amount of hormones absorbed, & missed pill
instructions should be followed during the attack and
for the next 7 days.
• in the case of combined oral contraception, the pill
free interval should be omitted if less than 7 pills
remain in the packet.
• diarrhoea (unless severe) is unlikely to affect drug
levels; there are no studies showing any
pharmacological basis for failure.
Metabolism in the liver
• Drugs which increase metabolism of EE and
progestogens, during and up to one month after
stopping treatment.
– anticonvulsants (with the exception of sodium
valproate, clobazam, vigabactrin, gabapentin and
lamotrigine),
– griseofulvin,
– barbiturates,
– ritonovir (and possibly other protease inhibitors
amprenavir, indinavir, lopinavir, nelfinavir, and
saquinavir)
Use of COC and liver enzyme
inducing drugs
• COC users need at least 50mcg of EE to
ensure contraceptive action
• efficacy may be further increased by
tricycling, and/or decreasing the pill free
interval
• common practice (for which there is no
evidence) to consider the absence of break
through bleeding as a marker of sufficient
contraceptive cover in this situation.
Use of progestogens and liver
enzyme inducing drugs
• POP users should switch to injectables or another
form of contraception
• IUS no evidence of interaction
– most of its progestogenic effect is directly on the
endometrium with little absorption
• EHC experts suggest that the dose is increased by
50%
– levonorgestrel 0.75 mg 2 + 1 tablets or 3 tablets stat
• injectable progestogen methods are often given 2
weeks early
– data sheet for Depo-Provera states that no
adjustment is needed
Powerful enzyme inducing
drugs
• Rifampicin and rifabutin are such powerful enzyme
inducers that even short courses of 2 days of the
former
– (used as prophylaxis in close contacts of cases of
Neisseria meningitis) reduce contraceptive
efficacy for a month.
• Longer courses may have an interactive effect for
up to 2 months after stopping.
• Oral contraceptive methods should not be relied on
during this time.
• The same principles should apply to injectables,
implants and IUS
Broad spectrum antibiotics
• EE is excreted into the bile; and reabsorbed into the
circulation from the colon
• broad-spectrum antibiotics (mainly ampicillin and
tetracycline)affect these bacteria
• accepted UK practice that COC used alone is
unreliable while taking short courses of penicillins
and tetracyclines and for 7 days after stopping; the
pill free interval should be omitted if less than 7 pills
remain in the pack
– when the drug is continued beyond 2 weeks, the gut flora
appear to become resistant, allowing a return to
reabsorption of EE.
• effectiveness of the POP, progestogen-only
emergency contraception, injectables, implants and
The only drugs known to have a clinically
significant impact on contraceptive efficacy
• rifampicin and rifamycin,
• griseofulvin,
• some anticonvulsants
– topiramate,
– barbiturates,
– carbamazepine,
– primidone
• ritonovir,
• and in some women short courses of tetracyclines
and ampicillin.
Why Another Contraceptive
Method?
CHOICE
Varney SJ. Pharmacoeconomics. 2004
Why Implantable
Contraception?
•
•
•
•
Long duration of action
Not patient dependent
Continuous steady state steroid levels
Avoidance of first-pass effect from GI
absorption and hepatic metabolism
• High bioavailability
Why is it among the most
effective?
“Implants constitute one of the
safest and most effective forms
of contraception that exist.”
WHO, 2003
World Health Organization. 2003
Unmet Need for Contraceptive
Method
Highly
effective
Safe
No daily
motivation
Rapidly
reversible
Implant Systems
6-Rod
Norplant
2-Rod
Jadelle
1-Rod
Implanon
Contraceptive Implant Track
Record
1966
Implant R&D
1985
WHO acceptance
1968
Ongoing
clinical
trails
Population Council. www.popcouncil.org
Organon Data on File
1993
Norplant
launch UK
1990
Norplant
launch US
more…
Contraceptive Implant Track
Record (continued)
1998
Implanon enters
international market
2002
Norplant removed
from US
2002
Jadelle approved but
not marketed in US
Population Council. www.popcouncil.org
Organon Data on File
2006
FDA
approves
Implanon
Subdermal Implant
• Single-rod system with disposable
inserter
• Releases etonogestrel
(3-ketodesogestrel) for three years
• As of July 2002 not approved by the
FDA
Features of Contraceptive
Implants
• Highly effective
• Not motivation dependent
• Can be used during
lactation
• Discreet, virtually invisible
• Rapidly reversible
more…
Reinprayoon D, et al. Contraception. 2000.
Diaz S. Contraception. 2000.
Features of Contraceptive
Implants (continued)
•
•
•
•
Stable hormone levels
Extended protection
Contain no estrogen
Safe
Reinprayoon D, et al. Contraception. 2000.
Diaz S. Contraception. 2000.
Limitations of Contraceptive
Implants
• Can cause irregular
bleeding
• Requires clinician visits
for insertion and removal
• Does not protect from
STDs
Single-Rod Implant
One rod 4 cm x 2 mm
• Core
• 40% ethylene vinyl acetate
(EVA)
• 60% etonogestrel (68 mg)
• Rate-controlling
membrane
• 100% EVA
Pharmacology
Class
Progestin-only
Route
Subdermal
Formulation
Implantable rod; 68 mg
etonogestrel
Bioavailability ~100%
Metabolism
Hepatic via CYP3A4
Half-life
~ 25 h
Excretion
Primary urine; some fecal
ANON. Obstet Gynecol. 2007
Mechanism of Action
• Suppresses ovulation
• Increases cervical mucus viscosity
• Alters endometrium
IMPLANONTM Physician insert, 2006
Components of the Single-Rod
Implant Insertion System
Funk S. Contraception. 2005
Preparation Tips
• Supine position
• Nondominant arm, flexed
and externally rotated
• Subdermal groove
• Hold applicator up
(vertical) before insertion
Insertion Steps Overview
Mark site and sterilize
Inject local anesthetic just under skin
Remove applicator, maintain sterility
Verify implant is within needle of applicator
Remove needle cover
more…
Insertion Steps Overview
(continued)
Stretch skin at insertion site
(a)
Lift or tent skin with needle tip
while inserting and insert
needle to full length (b)
Press the obturator support
to break seal of applicator
more…
Insertion Steps Overview
(continued)
Turn obturator 90 degrees
and fix with one hand (c)
With other hand, pull
needle out (d)
Palpate to verify correct
insertion
Removal Tips
• Inject local anesthetic
under rod
• Incision over distal end
• Use sharp or blunt
dissection if encapsulated
• Insert new implant
through same incision or
opposite arm
Removal Steps Overview
Locate rod and mark site
(a)
Sterilize site
Inject local anesthetic under
distal end of rod (b)
Press down on proximal end of rod
more…
Removal Steps Overview
(continued)
Use scalpel to make 2–3 mm
incision over distal end (c)
Gently push rod toward incision, then
grasp with mosquito forceps (d)
Close with steri-strip closure
Trouble Shooting: Removals
•
•
•
•
Unrecognized non-insertion
Deep placement
Significant weight gain
Migration
James P. Aust N Z J Obstet Gynecol. 2006.
Piessens SG. Aust N Z J Obstet Gynecol. 2005.
Vaginal Ring
• Steroid release
– Progestin: Etonogestrel: 120 mcg/day
(~1500 pg/ml)
– Estrogen: Ethinyl estradiol: 15 mcg/day
(~20 pg/ml)
• Worn for three weeks out of four
• Approved by the FDA in October 2001
Vaginal Ring: Characteristics
•
•
•
•
•
Self administered
Insertion every four weeks
Foreign body in vagina
Expulsions
Limited published data on efficacy
Vaginal Ring: Efficacy
Number of women
16
Woman-cycles of use
16 cycles
Cumulative pregnancy Limited
rate
published
data
Timmer and Mulders. Clin Pharmacokinet 2000;39:233
Contraceptive Patch
• Steroid release
– Progestin: norelgestromin 150 mcg/day
– Estrogen: ethinyl estradiol 20 mcg/day
• Worn for three weeks out of four
• Approved by the FDA in November 2001
Contraceptive Patch:
Characteristics
•
•
•
•
Self administered
Once-a-week administration
Hormonal side effects
Efficacy similar to combined oral
contraceptives
Audet et al. Jama 2001;258:2347
Patch: Efficacy
Number of women
1,417
Woman-cycles of use
2,440
Cumulative pregnancy rate 1%
Shangold et al. Obstet Gynecol 2000;95:S36
History of Intrauterine
Contraception
1909:
Grafenberg develops
ring-shaped IUD device
1967:
"T" shaped device
developed
1962:
1st international conference on
IUDs; designs for plastic spiral
and plastic loop presented
more…
Richter R. Deutsche Med Wochenschr. 1909.; Grafenberg E. 1929.; Ishihama A.
Yokohama Med Bull. 1959.; Oppenheimer W. Am J Obstet Gynecol. 1959.; Berelson B.
1964; Marguiles LC. 1962.; Lippes J. 1962.; Hubacher D, Cheng D. Contraception. 2004.
History of Intrauterine
Contraception (continued)
1968:
Contraceptive action of
intrauterine copper reported
1980:
LNG IUD tested in
randomized clinical trials
1976:
Copper T 200 becomes
first copper IUD
Lee NC. Obstet Gynecol. 1983.
History of Intrauterine
Contraception (continued)
1988:
Copper T 380 IUD
available in the U.S.
Today:
Only 2% of US
women use IUDs
2001:
LNG IUD available
in the U.S.
Mosher WD, et al. 2004.
Comparison of Copper IUDs
1st Year Failure
per 100 women
Recommended
Lifespan
TCu 380A
0.3
12 years
Multiload Cu 250
1.2
3 years
Multiload Cu 375
1.4
5 years
TCu 200
2.3
3 years
Nova T
3.3
5 years
Source: FHI clinical trials, 1985-1989.
Dispelling Common Myths
About IUDs
• In fact, IUDs:
– Are not abortifacients
– Do not cause ectopic pregnancies
– Do not cause pelvic infection
– Do not decrease the likelihood of future
pregnancies
– Are not large in size
more…
Hubacher D, et al. N Engl J Med. 2001.; Stanwood NL, et al. Obstet Gynecol. 2002.
Forrest JD. Obstet Gynecol Surv. 1996.; Lippes J. Am J Obstet Gynecol. 1999.
Dispelling Common Myths
About IUDs (continued)
• In fact, IUDs:
– Can be used by nulliparous women
– Can be used by women who have had an
ectopic pregnancy
– Do not need to be removed for PID treatment
– Do not have to be removed if actinomyceslike organisms (ALO) are noted on a Pap test
Duenas JL. Contraception. 1996.; Stanwood NL. Obstet Gynecol. 2002. Forrest JD.
Obstet Gynecol Surv. 1996; Lippes J. Am J Obstet Gynecol. 1999. Otero-Flores JB.
Contraception. 2003.; WHO. 2004.; Penney G. J Fam Plann Reprod Health Care. 2004.
Safety: IUDs Do Not Cause PID
• PID incidence for IUD users is similar to
that of the general population
• Risk is increased only during the first
month after insertion
• Preexisting STI at time of insertion, not
the IUD itself, increases risk
Svensson L, et al. JAMA. 1984.
Sivin I, et al. Contraception. 1991.
Farley T, et al. Lancet. 1992.
Rate of PID by Duration of IUD
Use
Rate per 1,000 woman years
N = 20,000 women
9.25
1.6
<21 days of use
Adapted from Farley T, et al. Lancet. 1992.
21 days - 8 years of use
Risk of Fetal Abnormality
• IUD is extra-amniotic
• No increase in birth
defects for copper IUD
Atrash HK, et al. 1994.
Layde PM, et al. Fertil Steril. 1979.
Simpson JL. Res Front Fertil Regul. 1985.
Safety: IUD Does Not Cause
Infertility
• IUD is not related to infertility
• Chlamydia is related to infertility
Odds Ratio
10
1
0,1
Hubacher D, et al. NEJM. 2001.
Tubal infertility by previous
copper T IUD use and
presence of chlamydia
antibodies, nulligravid women
Fertility Rates in Parous Women
After Discontinuation of
Contraceptive
100
Pregnancies (%)
80
IUC
60
OC
Diaphragm
40
Other methods
20
0
0
12
18
24
30
Months After Discontinuation
Vessey MP, et al. Br Med J. 1983.
Andersson K, et al. Contraception. 1992.
Belhadj H, et al. Contraception. 1986.
36
42
Safety: IUDs May Be
Used by HIV- Positive
Women
• No increased risk of
complications
compared with HIVnegative women
• No increased cervical
viral shedding
• WHO Category 2
rating
WHO. Medical Eligibility Criteria for Contraceptive Use. 2004.
Morrison CS, et al. Brit J Obstet Gynaecol. 2001.
Richardson B, et al. AIDS. 1999.
Safety: LNG IUD Does Not
Increase Breast Cancer Risk
Average Finnish
population:
LNG users:
Incidence rate Incidence rate per
Age Group per 100,000
100,000 woman(y)
woman-years
years
30–34
27.2
25.5
35–39
74.0
49.2
40–44
120.3
122.4
45–49
203.6
Backman T, et al. Obstet Gynecol. 2005.
50–54
258.5
232.5
272.6
Safety: IUDs May Be Used in
Nulligravid Women
• No evidence of increased
infertility
• Risk of PID and
subsequent infertility
dependent on non-IUD
factors
WHO. 2004.; Hubacher D, et al. NEJM. 2001.; Delbarge W, et al. Eur J Contracept
Reprod Health Care. 2002.; Hov GG, et al. Contraception. 2007.
Penney G, et al. J Fam Plann Reprod Health Care. 2004.
Screening: Appropriate
Candidates for Intrauterine
Contraception (continued)
Copper T IUD
Women who don’t
want hormonal
contraception or want
contraception for
more than 5 years
LNG IUD
Women who request
less menstrual flow
and/or who
experience
dysmenorrhea or
dysfunctional uterine
bleeding
Screening: Poor Candidates for
Intrauterine Contraception
•
•
•
•
•
Known or suspected pregnancy
Puerperal sepsis
Immediate post septic abortion
Unexplained vaginal bleeding
Cervical or endometrial cancer
more…
WHO. Medical Eligibility Criteria for Contraceptive Use. 2004.
Screening: Poor Candidates for
Intrauterine Contraception
(continued)
• Uterine fibroids that interfere with
placement
• Uterine distortion (congenital or acquired)
• Current PID
• Current purulent cervicitis, chlamydia, or
gonorrhea
• Known pelvic tuberculosis
WHO. Medical Eligibility Criteria for Contraceptive Use. 2004.
IUD Insertion After
Spontaneous or Induced
Abortion
• May be safely inserted immediately after
spontaneous or induced abortions
• Not recommended after septic abortion
Grimes D, et al. Cochrane Library. 2000.
ParaGard label. 2006.
WHO. 1983.
IUD for Postpartum Use
May be safely inserted in postpartum
women
LNG IUD
Copper T IUD
Within 48 hours
postpartum
6 weeks postpartum
OR
After 4 weeks once
uterus is involuted
Treiman K, et al. Population Reports. 1995; Mishell DR, et al. Am J Obstet Gynecol. 1982;
Kennedy KI, et al. In Hatcher RA, et al. Contraceptive Technology. 18th revised ed. 2004.
IUD Use During Lactation
•
•
•
•
•
Effectiveness not decreased
Uterine perforation risk unchanged
Expulsion rates unchanged
Decreased insertional pain
Reduced rate of removal for bleeding and
pain
• LNG comparable to copper T in
breastfeeding parameters
Chi I-C, et al. Contraception. 1989;
Mirena label. 2006.
Shaamash AH, et al. Contraception. 2005.
Checklist for STI Risk
Assessment
Circle appropriate answer
Is the client < 25 years old?
Is she currently living apart from
her husband or partner?
During the last year, has she had
bleeding between periods or
bleeding or spotting within 24
hours after sex?
Is her school education <
Morrison CS, et al. Contraception. 2007.
secondary level?
Yes
No
1
0
1
0
1
0
more…
1
0
Checklist for STI Risk
Assessment (continued)
How many different sexual None
partners has she had during
One
0
the last 3 months?
If she has had one or more
partners, how often has she
used a condom in the last 3
months?
>
One
Never used condoms
0
1
Sometimes used condoms
1
1
0
0
Morrison CS, et al. Contraception. 2007.
Always used condoms
Scoring STI Risk Assessment
Recommended
action
Counsel/refer for IUD
insertion without any
reservations
Consider
presumptive
treatment for
chlamydia/ gonorrhea
Morrison CS, et al. Contraception. 2006.
(if available) or
counsel/refer to use
Low cervical
infection
population
(<10%)
High cervical
infection
population
(=10%)
If score is
0–2
If score is 0
If score is 3+
If score is 1+
Levonorgestrel Intrauterine
System (LNG IUS)
Steroid reservoir
levonorgestrel 20
mcg/day
Approved December 2000
LNG IUS: Characteristics
•
•
•
•
•
•
•
•
High efficacy
Long-term reversible method
Reduction in menstrual blood loss
Low systemic levels of LNG
Early spotting common
Foreign body in the uterus
Expulsions
Requires professional insertion
LNG IUS: Mechanism of Action
• Fertilization inhibition:
– Cervical mucus thickened
– Sperm motility and function
inhibited
– Endometrium suppressed
– Weak foreign body reaction
induced
– Ovulation inhibited (in some
cycles)
Jonsson et al. Contraception 1991;43:447
Videla-Rivero et al. Contraception 1987;36:217
LNG IUS: Efficacy
• Overall failure rate 0.14 per 100
woman-years
• Gross cumulative five-year rate is
0.71 per 100 women
Andersson et al. Contraception 1994;49:56
Luukkainen et al. Contraception
1987;36:169
LNG IUS: Efficacy
Five-Year Cumulative Pregnancy
Rates per 100 Women by Age and
IUD Type
2,9
3
2,5
LNG IUS
Nova T
2
1,5
1
0,5
0
1,5
0,8
0
0,1
0,1
<=25
26 - 30
31 - 35
0,6
0,2
36+
Age (Years)
Luukkainen and Toivonen. Contraception 1995;52:269
LNG IUS: Comparison to
Sterilization
5-year gross cumulative failure rate per 100
women
LNG IUS
2
Nova T
1,4
1,3
All Sterilization
Post Partum
Salpingectomy
1
0,5
0,6
0
Andersson et al. Contraception 1994;49:56
Peterson et al. Am J Obstet Gynecol
Cumulative pregnancy rate (%)
LNG IUS: Return to Fertility
LNG IUS
100
Copper IUD
80
60
40
20
0
3
6
Months
9
12
Andersson et al. Contraception 1992;46:575
Belhadj et al. Contraception 1986;34:261
Plasma concentrations (pg/mL)
Plasma Concentrations of
Levonorgestrel
7000
6000
5000
4000
3000
2000
1000
0
LNG IUS
Implant
Mini-pill
Combined OCs
Nilsson et al. Acta Endocrinol 1980;93:380
Diaz et al. Contraception 1987;35:551
LNG IUS: Endometrial Effect
Months
Ovulation
Days of cycle
Changes in the endometrium during normal menstrual c
LNG IUS: Endometrial Effect
Months
Ovulation
Days of cycle
Endometrium in “resting state” with LNG IU
Pakarinen et al. Fertil Steril 1997;68:5
LNG IUS: Early Spotting
• Endometrial suppression effect is not
immediate
• Takes three months for full effect on
the endometrium
• Spotting is common during this time
Silverberg et al. Int J Gynecol Pathol 1986;5:
LNG IUS: Number of Bleeding
Days
Days
6
Copper IUD
4
2
LNG IUS
0
0
4
8
12
16
20
24
Months
Luukkainen and Toivonen. 1992;90
LNG IUS: Bleeding Patterns
• 20 % of women will
have no bleeding
at all after 12
months
Pekonen et al. J Clin Endocrinol Metab 1992;75:660
Luukkainen et al. Contraception 1987;36:169
LNG IUS: Non-contraceptive
Therapeutic Uses
• Alternative to hysterectomy
– Cancelled hysterectomy: 80 % LNG IUS
vs. 9 % normal care
• Treatment of menorraghia
– 97 % decrease in menstrual blood loss
(MBL)
Hurskainen et al. Lancet. 2001 Jan 27;357:273
Andersson and Rybo. Br J Obstet Gynaecol. 1990 Aug;97:690
LNG IUS: Non-contraceptive
Therapeutic Uses (cont)
• Hormone replacement therapy (HRT)
– Days of bleeding/spotting at 12 months:
2 LNG IUS vs. 6 oral LNG
• Adjuvant therapy for tamoxifen users
– Decidual change in endometrium of all
women with LNG IUS
Barrington and Bowen-Simpkins. Br J Obstet Gynaecol. 1997
May;104:614
Gardner et al. Lancet. 2000 Nov 18;356:1711
US Preventive Services Task
Force Ratings
LNG IUS Finding
Strength of
conclusion
Increases concentration of
hemoglobin
A
Effective treatment for
menorraghia
A
Well-accepted alternative to
hysterectomy
B
Hubacher and Grimes. Obstet Gynecol Surv 2002 Feb;57:120
US Preventive Services Task
Force Ratings (cont)
LNG IUS Finding
Strength of
conclusion
Prevents anemia
A
Can be used as a vehicle for
hormone replacement therapy
(HRT)
A
Mitigates tamoxifen-induced
endometrial effects
B
Hubacher and Grimes. Obstet Gynecol Surv 2002 Feb;57:120
LNG IUS: Possible
Complications
Symptoms
Consider
Return of menstruation Expulsion
Fever/chills
Infection
Continuous bleeding
and/or pain after first
month post-insertion
Perforation, infection,
or partial expulsion
LNG IUS: Possible Complications
(cont)
Symptoms
Consider
Irregular bleeding and/or Dislocation or
pain in every cycle
perforation
Missing string
Dislocation or
perforation
LNG IUS: Potential
Contraindications
• Pregnancy or suspicion of pregnancy
• Active cervical or endometrial
infections
• Uterine anomaly
• Complete list included in the package
labeling
LNG IUS: Potential
Complications
• Expulsions
– Most occur during the first six months
after insertion
– The five-year cumulative expulsion rate
is 4.9 per 100 women
• Perforations
– Occur at the time of insertion
– Rare events, fewer than one per
Andersson et al. Contraception 1994;49:56
thousand
LNG IUS: The Inserter
LNG IUS: Insertion
• Different insertion technique than
other intrauterine contraception
–New, one-handed insertion
–Requires hands-on training
• Efficacy and user continuation
dependent on skillful insertion
LNG IUS: Counseling
•
•
•
•
•
•
•
Efficacy
Return to fertility
Side effects
Changes in bleeding patterns
Non-contraceptive health benefits
Safety
Insertion and follow-up
LNG IUS Counseling: Efficacy
• High efficacy
–In clinical studies failure rate about
that of female and male
sterilization
• Continuous contraception for up to
five years
LNG IUS Counseling: Side
Effects
• Possible hormonal side effects
– Mood changes
– Acne
– Headache
– Breast tenderness
– Nausea
• No reported weight gain
Mean Weight Change After Five
Years
Weight gain in kg
3
2,5
2,5
2,4
2
1,5
1
0,5
0
Nova T
LNG IUS
Andersson et al. Contraception 1994;49:5
LNG IUS Counseling: Changes
in Bleeding
• Bleeding characteristics:
• 1 – 4 mo frequent spotting
• 1 – 6 mo reduced duration and amount
of bleeding
• Reduction in menstrual blood loss
• After 12 mo, about 20 % have no
bleeding
Pakarinen et al. Fertil Steril 1997;68:59
LNG IUS Counseling: Absence
of Bleeding
• Local effect
– No proliferation of endometrium
• This is expected. It is not a sign of:
– Pregnancy
– Ovarian or pituitary dysfunction
– Menopause
• Rapid return to menstruation after
removal
LNG IUS Counseling: Health
Benefits
• Reduction of
– Duration and amount of bleeding
– Ectopic pregnancies
– Menstrual pain
• Increase of
– Hemoglobin
– Iron storage
Luukkainen et al. Contraception 1987;36:169
LNG IUS Counseling: Safety
•
•
•
•
•
> Ten years experience in Europe
> Two million users world wide
Few serious side effects
Highly effective
Does not prevent acquisition of STDs
–Condoms advised for women at risk
LNG IUS Counseling: Insertion
• Steps in the insertion process
–Pelvic and speculum exam
–Sensations produced by tenaculum
–Paracervical anesthesia, if needed
–Sensations of IUS as it is inserted
–Measures you will take for her
comfort
LNG IUS Counseling: PostInsertion
• Schedule a follow-up visit at 1 – 3
months post-insertion
–Check for partial or complete
expulsion
–Address any questions or concerns
LNG IUS: Therapeutic
Possibilities
• Range of non-contraceptive benefits,
including:
–Treatment of heavy menstrual
bleeding
–Endometrial protection for women
receiving estrogen replacement
therapy
Menstrual blood loss (ml)
LNG IUS: Treatment of Heavy
Bleeding
400
300
200
100
0
Before
treatment
3
6
12
Months of use
Andersson and Rybo. Br J Obstet Gynaecol 1990;97:690
LNG IUS: Percentage Reduction of
Menstrual Blood Loss
0
-25
LNG IUS
Placebo
-50
Prostaglandin
Synthetase Inhibitor
Combination OCs
-75
-100
Milsom et al. Am J Obstet Gynecol 1991;164:87
Pictorial blood loss
assessment chart score
LNG IUS vs. Endometrial
Resection
500
Levonorgestrel
intrauterine
system
Endometrial
resection
400
300
200
100
0
Baseline
6 months
12 months
Crosignani et al. Obstet Gynecol 1997;90:257
LNG IUS as Alternative to
Hysterectomy
70
Women
Canceling
Hysterectomy
Percent
60
50
40
30
20
10
0
LNG IUS
Medical Therapies
Lahteenmaki et al. BMJ 1998;316:1122
LNG IUS: Hormone
Replacement
• Prevention of endometrial hyperplasia
from estrogen therapy
• “Local is logical”
• Oral progestins can cause depression
• LNG IUS avoids systemic side effects of
oral progestins
Girdler et al. J Womens Health Gend Based Med 1999;8:637
LNG IUS: Hormone
Replacement
• Bleeding is the most common
reason why women discontinue HRT
• LNG IUS suppresses endometrium
• 83 – 88 % have no bleeding/
spotting at 12 months
• 82 % continuation rate at three years
Ettinger. Menopause 1999;6:273
Suhonen et al. Acta Obstet Gynecol Scand 1997;76:145
General Discussion
• New methods are coming to U.S. market
• This should translate into more
contraceptive choices, fewer unintended
pregnancies
• These new methods share the common
advantage of not requiring daily attention
Intrauterine Contraception in the
U.S.
LNG IUS
Copper IUD
20 mcg
levonorgestrel/day
copper ions
Approved for
5 years
Approved for
10 years
Approved 2000
Approved 1988
PID Incidence Rate for All IUDs
by Time Since Insertion
Combined WHO clinical trial data for all IUDs - 22,908 IUD insertions
8
(per 1,000 woman-years)
6
4
2
0
1
2
3
4
5
6
7
8
9
Month (first year)
10 11 12
2
3
4
5
6
7
8
Year
Time Since Insertion
Farley et al. Lancet 1992;339:785
Dispelling Myths:
Intrauterine Contraception
• Infections are a frequent problem
• Prevents implantation
• Women are not interested in
intrauterine contraception
Prophylactic Antibiotics?
• Any risk of infection associated with
the IUD relates to insertion
• One woman in 1,000 will develop
PID in the first three months
• Meta-analysis has not shown any
overall benefit of prophylactic
antibiotics
Grimes and Schulz. Contraception 1999;60:5
Walsh et al. Lancet 1998;351:1005
Myth: IUD Prevents
Implantation
• Most evidence now suggests that all
IUDs induce a foreign body reaction
that is spermicidal, preventing
fertilization
• Today’s intrauterine contraceptives
have other mechanisms of action that
prevent fertilization
Alvarez et al. Fertil Steril 1988;49:768
% of Women Using Method
Use of Contraception by U.S.
Women Physicians
Women MDs
General Population
40
20
0
Sterilization
IUD
Pills
Frank. Obstet Gynecol 1999;94:666
Incidence* of Ectopic
Pregnancy
LNG IUS
0.20
Copper IUD
0.34
No method
1.20-1.60
All U.S. women
2.00
* Per 1,000 woman-years
Andersson et al. Contraception 1994;49:56
Sivin. Stud Fam Plann 1983;14:57
Summary
• LNG IUS bleeding patterns:
– 1 – 4 mo frequent spotting
– 1 – 6 mo reduced duration and amount
of bleeding
– > 12 mo, about 20 % have no bleeding
• Treatment of heavy menstrual
bleeding and endometrial protection
with HRT
Gynefix- Frameless IUD
• Developed 1994 in
Belgium- available in
Europe and UK
• Frameless IUD-copper
tubes on a thread with a
knot to anchor to the
fundus
• Reduced risk of
expulsion, pain & heavy
bleeding
• Progestogen device in
development
Female Barrier ContraceptionDiaphragms and
Caps
• Rubber barriers placed into the vagina
•
•
•
•
•
•
•
to cover the cervix prior to sex
Sperm remain in vagina where acid
conditions kill the sperm in a few hoursneed to remain inside for 6 hours.
Use of spermicide is controversial
Failure rates anything from 5-20%-rates
lower in older women and experienced
users
Need to be individually fitted
Last approximately 2 years
Size needs to be checked if weight
gain, failure, or pregnancy
Affected by oil based vaginal lubricants
and treatments eg Antifungal creams
and pessaries
Barriers-The Female Condom
• Lubricated, loose
fitting polyurethane
sheath with 2
flexible rings - one
size fits all
• Lines the vagina
and covers some of
the vulva
• Effectiveness: 8595%
The Female Condom
• Advantages
– Contraception and STI protection
– Can be used with oil based products
– Better heat transmission
– Stronger than latex
– Less “constriction” for partner
– Does not need erection before use
– May provide better protection against herpes
and HPV
• Disadvantages
– Harder to dispose of than male condom
– Requires careful insertion and practise
– Not yet widely available
Latex male condoms
• Cornerstone of safer sexmust be used every time
to provide maximal
protection
• Can be used with other
methods of
contraception- “Double
Dutch”
• Affected by oil based
lubricants and vaginal
medications like
antifungals
Polyurethane Male Condom
• Stronger and thinner than
latex condoms
• Better heat transmission
• Can safely be used with
oil-based lubricants
• Can be used by those
with latex allergies
Permanent Contraception• Inner wire/outer coil with
synthetic fibre between
• Inserted into uterine ends of
Fallopian tubes through
hysteroscope under LA
• Growth of fibroblasts causes
scarring and permanent closure
of the tubes -irreversible
Sterilization: Tubal Ligation
Methods
Methods for accessing the fallopian
tubes
• Laparotomy
• Mini-laparotomy
• Vaginal posterior colpotomy
• Laparoscopy
• Hysteroscopy
Tubal Sterilization:
FDA-Approved Methods
The most widely used occlusion methods are
typically performed on the isthmic portion of the
fallopian tube:
•
•
•
•
•
Partial salpingectomy
Clips
Silicone rings
Electrocoagulation
Micro-insert
Hysteroscopic Sterilization
Techniques
Electrocoagulation
Uterotubal Junction
Device
Hossenian, 1976
Intra-tubal Device
Hamou, 1982
Hysteroscopic Sterilization
Techniques (continued)
Chemical
P-Block Device
Brundin, 1981
OvaPlug
1981
Transcervical Sterilization
Methods
Endoscope
Efficiency
Continuous
Flow
Technology
Advanced
Cardiology
Technology
Transcervical Sterilization:
Advantages to the Provider
• Outpatient procedure
• No general or regional
anesthesia
• Women with certain medical
conditions may be eligible
Transcervical Sterilization:
Disadvantages to the Provider
• Special equipment and training
needed for insertion
• Some women may not be
candidates
• Uncertainty still exists about longterm effectiveness and insurance
coverage
Transcervical Sterilization:
Advantages to the Patient
•
•
•
•
•
•
No incision
Absence of a scar preserves privacy
Less invasive
Less discomfort
Faster recovery
Efficacy
Transcervical Sterilization:
Disadvantages to the Patient
• Another contraceptive method is
required for three months after
insertion
• Non-reversible; some women
may experience regret
New Tubal Occlusion Method:
Micro-Insert Tubal Occlusion
(Essure®)
• FDA approval in November 2002
• Only FDA approved hysteroscopic
method of tubal sterilization available
• Placement of microinserts into proximal
fallopian tubes
Micro-Insert: Design
Fiber Material: PET
Dynamic Expanding
Superelastic Outer
Coil Material: Nitinol
Micro-Insert length = 4
cm
ARHP. Clinical Proceedings. May 2002.
Inner Coil Material:
Stainless Steel
Micro-Insert: Mechanism of
Action
• Expansion of outer coil for acute anchoring
• Space filling/mechanical blockage of tubal
lumen
• Tubal occlusion by tissue in-growth into
and around the micro-insert
• Long-term nature of tissue response not
known beyond 24 months
Essure® Prescribing Information
Male Hormonal Contraception
• Recent trials at Andrology Clinic,
Concord Hospital
• Depo Provera plus testosterone
implants 3 monthly
• Very low sperm count (less than
1 million per ml) in all men on
trial - 80% had no sperm
• Few side-effects
• Similar regime using an oral
progestogen and testosterone
implants being trialed in UK
• Implants and testosterone also
being trialed
The Introduction of a New
Contraceptive Method to the Market
• New contraceptive methods
usually considered
newsworthy
• Consumers increasingly well
informed around options and
their rights to informed choice
• The growing number of
options available makes it
increasingly difficult for health
practitioners to do justice to
the pros and cons of each
method in the available time.
Contraceptive Counselling
• The trend to an increase in available contraceptive
options seems likely to continue along with an
acceptance that the consumer has a right to accurate,
comprehensive and balanced information from their
health provider
• Any clinician attempting to counsel a patient around
contraceptive choice will need to put this counselling
within the broader context of the person’s past
experiences, cultural background and belief systems
• A person will rarely persist with a contraceptive method
they do not feel is right for them - they will simply feel
their practitioner has not heard them
• In the area of contraception the clinician is often the
adviser, sometimes the supplier, but, if they have any
sense at all, never the decider.