contraception updates amr nadim, md professor of obstetrics & gynecology ain shams faculty of...
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Contraception Updates
Amr Nadim, MDProfessor of Obstetrics & Gynecology
Ain Shams Faculty of MedicineMaternity & 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 OptionsHormonal Methods
•Progestin Only Injectables / Oral Contraceptives
•Combined Injectable / Oral Contraceptives
•Intrauterine Systems
•Implants
•Patches
•Vaginal rings
Contraceptive OptionsNon-Hormonal Methods
IUD
Barriers
NFP methods
Contraceptive OptionsSterilization Methods
Tubal Occlusion
Tubal ligation
Vas Ligation
What are the concerns of any couple What are the concerns of any couple about the method of family planning about the method of family planning they need?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
Hennekens CH. Epidemiology in Medicine. 1987.
CausalityWeigh
pros and cons
Degree towhich
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
Absoluterisk
Absoluterisk
reduction
Relativerisk
Absolute Risk
NY Academy of Medicine. 2005. Misselbrook D. Fam Practice. 2002.
• The percentage of people in a group who experience a discrete event
Number of People With Event
Total # of People At Risk
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
NY Academy of Medicine. 2005.
• 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
Example of Absolute Risk Reduction• Of 100,000 women on 2nd generation OCs,
15 will develop VTE per year
Absolute risk
15 per 100,000 woman-years
Absolute riskreduction
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
Grimes DA. Lancet. 2002. Hennekens CH. Epidemiology in Medicine. 1987.
Exposure Outcome
Odds Ratio
• Used to identify an association between exposure and outcome in a case-control study
• Similar to relative risk
Hennekens CH. Epidemiology in Medicine. 1987.
Exposure Outcome
Relative Risk: Example 1
Absolute risk
3rd Generation OCs
30 per 100,000 woman-years
Absolute risk
2nd Generation OCs
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
Relative risk < 1
Decreased risk in exposed group
Hennekens CH. Epidemiology in Medicine. 1987.
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
Relative risk = 20 / 10 = 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%
Grimes DA. Lancet. 2002.
more…
Relative Risk: Example 2 (continued)
• Interpretation:
Grimes DA. Lancet. 2002.
more…
“The risk of cesarean delivery with elective induction of labor is 2 times that associated with spontaneous labor.”
“The risk is twice as high.”
Or, alternatively stated:
Relative Risk: Example 2 (continued)
Graph of relative risk of 2
0.1
1
10
Re
lativ
e r
isk
(log
sca
le) Increased risk
Decreased risk
Grimes DA. Lancet. 2002.
Relative Risk: Example 3
= 0.5
Rate with prophylactic antibiotics
6%
Rate without prophylactic antibiotics:
12%
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
0.1
1
10
Re
lativ
e r
isk
(log
sca
le) Increased risk
Decreased risk
Grimes DA. Lancet. 2002.
Comparing Relative Risks of 2 and 0.5
Zone of increased risk
Zone of reduced risk
2
0.5
0.1
1
10
Re
lativ
e R
isk
(lo
g s
cale
)
Grimes DA. Lancet. 2002.
Comparative Risks of VTE
Shulman LP. J Reprod Med. 2003. Chang J. In: Surveillance Summaries. 2003.
Inci
den
ce o
f VT
E p
er
100
,000
wo
ma
n-ye
ars
0
20
40
60
Pregnancy High-dose OC
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
O’Connor A, Legare F, Stacey D. BMJ. 2003.
Clarify situation
Provide information
Clarify patient’s values
Screen for implementation problems
A Final Thought
“Two times a very rare event is still a very rare event.”
David Grimes, MD2006
WHO Eligibility Criteria for Contraceptive UseWHO Eligibility Criteria for Contraceptive UseWHO Eligibility Criteria for Contraceptive UseWHO Eligibility Criteria for Contraceptive Use
CategoryCategoryDescriptionDescriptionWhen clinical When clinical judgment is judgment is
availableavailable
When clinical When clinical judgment is judgment is
limitedlimited
11No restriction for No restriction for
use use Use the method under Use the method under
any circumstances any circumstances Use the methodUse the method
22Benefits generally Benefits generally
outweigh risks outweigh risks Generally use the Generally use the
method method
33Risks generally Risks generally
outweigh benefitsoutweigh benefits
Use of method not Use of method not usually recommended, usually recommended, unless other methods unless other methods
are not are not available/acceptable available/acceptable
Do not use the Do not use the methodmethod
44Unacceptable Unacceptable
health riskhealth riskMethod not to be used Method not to be used
Source: WHO, 2004.Source: WHO, 2004.
New Methods
Single-rod Implant
LNG IUS
PatchVaginal Ring
Monthly Injectable
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 ProgestogensCyproterone 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 effects-
less 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 progestogen-only 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 YUZPEPregnancy rate 1.1% 3.2%
Efficacy rate(pregs.prevent-ed vrs pregs.expected)
85% 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 IUS are not affected by broad spectrum antibiotics.
The only drugs known to have a clinicallysignificant 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 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.”
World Health Organization. 2003
WHO, 2003
Unmet Need for Contraceptive Method
Highly effective
SafeNo daily
motivationRapidly
reversible
Implant Systems6-Rod
Norplant2-Rod Jadelle
1-Rod Implanon
Contraceptive Implant Track Record
1966Implant R&D
Population Council. www.popcouncil.orgOrganon Data on File
1968Ongoing clinical trails
1985 WHO acceptance
1990Norplant launch US
1993Norplant launch UK
more…
Contraceptive Implant Track Record (continued)
Population Council. www.popcouncil.orgOrganon Data on File
1998 Implanon enters international market
2002 Jadelle approved but not marketed in US
2002 Norplant removed from US
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
Reinprayoon D, et al. Contraception. 2000.Diaz S. Contraception. 2000.
• Highly effective• Not motivation dependent• Can be used during
lactation • Discreet, virtually invisible• Rapidly reversible
more…
Features of Contraceptive Implants (continued)
Reinprayoon D, et al. Contraception. 2000.Diaz S. Contraception. 2000.
• Stable hormone levels • Extended protection• Contain no estrogen• Safe
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
ANON. Obstet Gynecol. 2007
ClassProgestin-only
RouteSubdermal
FormulationImplantable rod; 68 mg etonogestrel
Bioavailability~100%
MetabolismHepatic via CYP3A4
Half-life~ 25 h
ExcretionPrimary urine; some fecal
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
more…
Inject local anesthetic just under skin
Remove applicator, maintain sterility
Verify implant is within needle of applicator
Remove needle cover
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)
more…
Press the obturator support to break seal of applicator
Insertion Steps Overview (continued)
Palpate to verify correct insertion
Turn obturator 90 degrees and fix with one hand (c)
With other hand, pull needle out (d)
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
Press down on proximal end of rod
Inject local anesthetic under distal end of rod (b)
more…
Removal Steps Overview (continued)
Close with steri-strip closure
Use scalpel to make 2–3 mm incision over distal end (c)
Gently push rod toward incision, then grasp with mosquito forceps (d)
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 women16
Woman-cycles of use16 cycles
Cumulative pregnancy rate
Limited 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 women1,417
Woman-cycles of use2,440
Cumulative pregnancy rate1%
Shangold et al. Obstet Gynecol 2000;95:S36
History of Intrauterine Contraception
1909: Grafenberg develops ring-shaped IUD device
1962: 1st international conference on IUDs; designs for plastic spiral and plastic loop presented
1967: "T" shaped device developed
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.
more…
History of Intrauterine Contraception (continued)
1980: LNG IUD tested in randomized clinical trials
1968: Contraceptive action of intrauterine copper reported
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.
2001: LNG IUD available in the U.S.
Today:Only 2% of US women use IUDs
Mosher WD, et al. 2004.
Comparison of Copper IUDsComparison of Copper IUDsComparison of Copper IUDsComparison of Copper IUDs
11stst Year Failure Year Failure per 100 womenper 100 women
Recommended Recommended
LifespanLifespan
TCu 380A 0.312 years
Multiload Cu 2501.23 years
Multiload Cu 3751.45 years
TCu 2002.33 years
Nova T3.35 years
Source: : FHI clinical trials, 1985-1989..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 actinomyces-
like 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
Adapted from Farley T, et al. Lancet. 1992.
1.6
9.25
<21 days of use 21 days - 8 years of use
Rate per 1,000 woman yearsN = 20,000 women
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
Tubal infertility by previous copper T IUD use and presence of chlamydia antibodies, nulligravid women
Hubacher D, et al. NEJM. 2001.
0,1
1
10
Odd
s R
atio
Fertility Rates in Parous Women After Discontinuation of Contraceptive
Pre
gnan
cies
(%
)
Months After Discontinuation
0
20
40
60
80
100
0 12 18 24 30 36 42
IUC
OC
Diaphragm
Other methods
Vessey MP, et al. Br Med J. 1983.Andersson K, et al. Contraception. 1992.Belhadj H, et al. Contraception. 1986.
Safety: IUDs May Be Used by HIV- Positive Women• No increased risk of
complications compared with HIV-negative 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
Backman T, et al. Obstet Gynecol. 2005.
Age Group (y)
LNG users: Incidence rate per 100,000
woman-years
Average Finnish population:
Incidence rate per 100,000 woman-
years
30–3427.225.5
35–3974.049.2
40–44120.3122.4
45–49203.6232.5
50–54258.5272.6
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 LNG IUD
Women who don’t want hormonal
contraception or want contraception for
more than 5 years
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
WHO. Medical Eligibility Criteria for Contraceptive Use. 2004.
more…
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
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.
Copper T IUD LNG IUD
Within 48 hours postpartum
OR
After 4 weeks once uterus is involuted
6 weeks postpartum
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 parametersChi I-C, et al. Contraception. 1989; Mirena label. 2006.Shaamash AH, et al. Contraception. 2005.
Checklist for STI Risk Assessment
Circle appropriate answerYesNo
Is the client < 25 years old? 1 0
Is she currently living apart from her husband or partner?
1 0
During the last year, has she had bleeding between periods or bleeding or spotting within 24 hours after sex?
1 0
Is her school education < secondary level?
1 0Morrison CS, et al. Contraception. 2007.
more…
Checklist for STI Risk Assessment (continued)
How many different sexual partners has she had during the last 3 months?
None
0One
> One
If she has had one or more partners, how often has she used a condom in the last 3 months?
Never used condoms01
Sometimes used condoms11
Always used condoms00Morrison CS, et al. Contraception. 2007.
Scoring STI Risk Assessment
Recommended action
Low cervical infection
population (<10%)
High cervical infection
population
(=10%)
Counsel/refer for IUD insertion without any reservations
If score is
0–2If score is 0
Consider presumptive treatment for chlamydia/ gonorrhea (if available) or counsel/refer to use another contraceptive
If score is 3+If score is 1+Morrison CS, et al. Contraception. 2006.
Levonorgestrel Intrauterine System (LNG IUS)
32 m
m Steroid reservoirlevonorgestrel 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;43:447Videla-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;49:56Luukkainen et al. Contraception
1987;36:169
LNG IUS: EfficacyFive-Year Cumulative Pregnancy Rates per 100 Women by Age and
IUD Type
0 0,1 0,1 0,2
2,9
1,5
0,80,6
0
0,5
1
1,5
2
2,5
3
<=25 26 - 30 31 - 35 36+
Age (Years)
LNG IUS
Nova T
Luukkainen and Toivonen. Contraception 1995;52:269
LNG IUS: Comparison to Sterilization
Andersson et al. Contraception 1994;49:56Peterson et al. Am J Obstet Gynecol
1996;174:1161
5-year gross cumulative failure rate per 100 women
0,5
1,41,3
0,6
0
1
2LNG IUS
Nova T
All Sterilization
Post PartumSalpingectomy
LNG IUS: Return to Fertility
0
20
40
60
80
100
3 6 9 12MonthsC
um
ula
tive
pre
gn
an
cy r
ate
(%
)
LNG IUS
Copper IUD
Andersson et al. Contraception 1992;46:575Belhadj et al. Contraception 1986;34:261
Plasma Concentrations of Levonorgestrel
0
1000
2000
3000
4000
5000
6000
7000
Pla
sma
con
cen
trat
ion
s (p
g/m
L)
LNG IUS Implant Mini-pill Combined OCs
Nilsson et al. Acta Endocrinol 1980;93:380Diaz et al. Contraception 1987;35:551
LNG IUS: Endometrial Effect
Days of cycle
Months
Changes in the endometrium during normal menstrual cycle
Ovulation
LNG IUS: Endometrial Effect
Days of cycle
Months
Endometrium in “resting state” with LNG IUS
Ovulation
Pakarinen et al. Fertil Steril 1997;68:59
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;5:235
LNG IUS: Number of Bleeding Days
Luukkainen and Toivonen. 1992;90
Days
0
2
4
6
0 4 8 12 16 20 24
Months
Copper IUD
LNG IUS
LNG IUS: Bleeding Patterns
• 20 % of women will have no bleeding at all after 12 months
Pekonen et al. J Clin Endocrinol Metab 1992;75:660Luukkainen 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;357:273Andersson 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 FindingStrength 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 FindingStrength of conclusion
Prevents anemiaA
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
SymptomsConsider
Return of menstruationExpulsion
Fever/chillsInfection
Continuous bleeding and/or pain after first month post-insertion
Perforation, infection, or partial expulsion
LNG IUS: Possible Complications (cont)
SymptomsConsider
Irregular bleeding and/or pain in every cycle
Dislocation or perforation
Missing stringDislocation 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 thousand
Andersson et al. Contraception 1994;49:56
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
2,5 2,4
0
0,5
1
1,5
2
2,5
3
Wei
gh
t g
ain
in k
g
Andersson et al. Contraception 1994;49:56
Nova T LNG IUS
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 storageLuukkainen 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: Post-Insertion• 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
LNG IUS: Treatment of Heavy Bleeding
Andersson and Rybo. Br J Obstet Gynaecol 1990;97:690
0
100
200
300
400
Before treatment
3 6 12
Months of useMen
str
ual b
lood
loss (
ml)
LNG IUS: Percentage Reduction of Menstrual Blood Loss
-100
-75
-50
-25
0
LNG IUS
Placebo
ProstaglandinSynthetase Inhibitor
Combination OCs
Milsom et al. Am J Obstet Gynecol 1991;164:879
LNG IUS vs. Endometrial Resection
500
400
300
200
100
0
Baseline 6 months 12 months
Crosignani et al. Obstet Gynecol 1997;90:257
Pic
tori
al b
lood
loss
assessm
en
t ch
art
score
Levonorgestrel intrauterine systemEndometrial resection
LNG IUS as Alternative to Hysterectomy
Lahteenmaki et al. BMJ 1998;316:1122
0
10
20
30
40
50
60
70
LNG IUS Medical Therapies
Perc
ent
Women Canceling Hysterectomy
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 IUSCopper IUD
20 mcg
levonorgestrel/daycopper ions
Approved for
5 years
Approved for
10 years
Approved 2000Approved 1988
PID Incidence Rate for All IUDs by Time Since Insertion
Farley et al. Lancet 1992;339:785
0
2
4
6
8
1 2 3 4 5 6 7 8 9 10 11 12
Month (first year)
2 3 4 5 6 7 8
Year
Time Since Insertion
Combined WHO clinical trial data for all IUDs - 22,908 IUD insertions(per 1,000 woman-years)
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;60:57 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
Use of Contraception by U.S. Women Physicians
0
20
40
Sterilization IUD Pills
% o
f Wom
en U
sing
Met
hod
Women MDs General Population
Frank. Obstet Gynecol 1999;94:666
Incidence* of Ectopic Pregnancy
LNG IUS0.20
Copper IUD0.34
No method1.20-1.60
All U.S. women2.00
* Per 1,000 woman-yearsAndersson 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 Contraception- Diaphragms 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 hours- need 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: 85-95%
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 sex-must 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 MethodsMethods for accessing the fallopian
tubes
• Laparotomy
• Mini-laparotomy
• Vaginal posterior colpotomy
• Laparoscopy
• Hysteroscopy
Tubal Sterilization: FDA-Approved Methods
• Partial salpingectomy• Clips• Silicone rings• Electrocoagulation• Micro-insert
The most widely used occlusion methods are typically performed on the isthmic portion of the fallopian tube:
Electrocoagulation
Uterotubal Junction Device
Hossenian, 1976
Intra-tubal DeviceHamou, 1982
Hysteroscopic Sterilization Techniques
Chemical
Hysteroscopic Sterilization Techniques (continued)
P-Block DeviceBrundin, 1981
OvaPlug1981
Transcervical Sterilization Methods
EndoscopeEfficiency
ContinuousFlow
Technology
AdvancedCardiologyTechnology
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 long-term 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 micro-inserts into proximal fallopian tubes
Micro-Insert: Design
ARHP. Clinical Proceedings. May 2002.
Micro-Insert length = 4 cm
Inner Coil Material: Stainless Steel
Fiber Material: PET
Dynamic Expanding Superelastic Outer Coil Material: Nitinol
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.