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Microsoft powerpoint - whats new in contraception.ppt [compatibility mode]

 This event is sponsored by the Region V Training Project of HCET. What's New in
 Any views or opinions in this presentation are solely those of the presenter and do not necessarily represent those of the funders. Health Care Education and Training, Inc. accepts no liability for the content of the presentation or for the consequences of any actions taken on the basis of the information provided.
Sharon Myoji Schnare
RN, FNP, CNM, MSN, FAANP Member CDC Advisory Board for MEC  Sharon Schnare reports that she is a consultant for Brand names may
Brand names may be noted for
Bayer HealthCare Pharmaceuticals, Inc. and a speaker for Azur Pharma, Bayer HealthCare identification purposes only
Pharmaceuticals, Inc, Jazz Pharmaceuticals, Merch Sharp & Dohme Corp., and Teva Women's Health and off-label use will be noted
Inc. Sharon Schnare agrees to present the following information fairly and without bias.
 The planners report no relationships with businesses or industries that would pose a conflict of interest.  No commercial support was received for this CNE It is estimated that more than a
Contraception has reduced
quarter of pregnancies worldwide are
women's death rates and has
unintended.
been the single most important
Between 1995 and 2000,
factor impacting women's health,
approximately 700,000 women died
education and freedom in the 20
as a result of unintended pregnancy;
and morbidity from pregnancy
affected even more women.
This is why ALL options must be
available to ALL women.
CDC Prepregnancy
CDC Prepregnancy Contraceptive
PRAMS Data
Among Teens w
Among Teens ith Unintended
50.1% teens were not using contraception at
Pregnancies –Pregnancy
Pregnancies –Pregnancy Risk Assessment
time of conception
Monitoring System
22.1% of teens said:
 Approx. 400,000 teens aged 15-19 give
in U.S. Highest
Highest rate
"I did not mind if I got pregnant."
23.6% said partner did not want to use
 Study: Hispanic, White, Black teens in 37
states & NY City (75% of all live births in
31.4% believed they could not get pregnant
at time of conception
THIS IS AMBIVALENCE
Why is Teen Pregnancy
Pregnancy a Problem?
More likely suffer negative social outcomes:
The Good News: Teen
 School drop out
Pregnancy has Declined
 Infants: increased low birth wt.
this year
 Daughters of teen mothers: more likely
to become teen mothers themselves
 Lower academic achievement
(1) PRAMS Data 2012 Contraception is
Contraception not as Effective
Perceptions of Risk
Without Counseling & Education
 SHOW women & men actual methods,
Remind women and men that
encourage them to touch and handle
NO method of
methods. Carry methods in your pocket !
contraception confers a
 Use motivational interviewing style of
counsel-may be more effective.
higher risk of death than
 Realize ambivalence is normal
 Ask women what they want to know; avoid
telling people what to do.
Pill Side-Effects: The "Nocebo"
Should Contraceptive Pills
Should Contraceptive
be Over the
Counter? YES
"nocebo"? Negative placebo effect. Non-specific
complaints caused by negative perceptions of
pill which WE bring up NO evidence for most
Border Contraceptive Access Study N=
complaints! Telling women to expect side effects
>1000 Latina low-income women-9 mo
becomes a "self fulfilling prophecy"; increases
study. Half received Rx (El Paso), other
o uarez, M i
OTC pills
BENEFITS: FAR OUTWEIGH THE DANGERS
Those in US: 60% more likely to stop pills,
Frequency of most pill side-effects are no
than those getting pills in Mexico.
greater than placebo pills!
If given fewer than 6 packs: 80% more likely
Optimistic Counseling Discussion of Beneficial
to to stop pills than those taking OTC pills
Effects of Pills!
Grimes 2011
Potter 2011
Cont…Should Contraceptive
Should Contraceptive
Cont…Should Contraceptive
Should Contraceptive
Over the Counter? YES
the Counter
the U.S.? YES
ACCESS decreases unintended pregnancy.
If progestin-only pills become OTC then
Mexican women using OTC pills in Mexico
safety is much less of a concern
more likely to have health conditions:
With unconscionable politically motivated
HTN, smoking
smoking >34 (more
attacks on
contraceptiv access,
contraindications but no absolute
American women will be forced into third
contraindications 13% vs 9% in Rx grp.)
world conditions, the middle class and
However no medical complications
the poor will suffer and some will die
occurred. PROVIDE YEAR SUPPLY WHEN
ALL contraceptive methods are safer than
POSSIBLE
Potter 2011
WHO and CDC Medical
U.S. (2010) Medical Eligibility
Criteria for Contraceptive Use is
Eligibility Criteria
Criteria
Available
at last…evidence-based
Is changing contraceptive
practice in the U.S and
Medical Eligibility
y Criteria for
Rationale for the Change
Contraceptive Use CDC, 2010
 Risk of VTE first 42 days postpartum 22-84
What's new (Jul
y 8, 2011)
times greater than non-postpartum women
Safety of CHC's during postpartum period
 Risk decreases rapidly post delivery over first
First 21 days postpartum:
Changed from category 3 to category 4 :
 Most women will not ovulate until 42 days
unacceptable risk for all women
postpartum so no clear benefit to CHC
Days 21- 42 Postpartum
 Women can be given Rx at delivery and advised
changed from category 1 to category 2 or 3
to start after 42 days
depending on other risk factors
 Recommendation is not based on any direct
>42 days postpartum: category 1 unless other
medical conditions present
evidence on postpartum use of CHC
Jackson 2011, CDC 2011
Risk Factors for Thrombosis
Related to Pregnancy
Age > or = 35 years
Postpartum
Previous VTE
Transfusion at
BMI > or = 30
Peripartum
Drospirenone: Thrombogenic…or just bad
EURAS European Active Surveillance study
(2000-2004) requested by regulators. 58,674
Thrombosis: It's not just about
enrolled followed for 142,475 person yrs. DRSP
with 30 mcg EE with 2 comparators (Lng &
Estrogen…
COCs) Each
checked q 6
adverse events. Results: no increase risk of
Controversy
Controversy and Chaos in the
VTE, ATE (arterial thrombotic events): MI,
ischemic stroke or mortality between grps.
Progestin World
Adjusted for age, BMI, smoking, HTN, duration
of use, VTE Hx. Showed NO difference between
Lng, DRSP or other COCs
Dinger 2007
Drospirenone and Thrombotic Events
bad press? EURAS data
FDA requested U.S. based study: i3 Ingenix (2001-
Hazard Ratio (HR)
2004): to identify all instances of death,
hospitalization, syncope, arrhythmia,
VTE venous thromboemboli
hyperkalemia, electrolyte disturbances, dialysis
DRSP vs LNG
& MI among DRSP initiators.
R i
e i nsurance claims, medi
dical records
DRSP vs CHC
Risk of VTE: >40 yrs, DM, HTN, Hx MI, arrhythmia;
ATE (arterial thrombotic events-stroke, MI)
BUT suggested no difference in incidence
DRSP vs LNG
of VTE between users of DRSP and other
DRSP vs CHC
Seeger 2007, Eng 2008
Dinger 2007
MEGA Study Study listed
Lidegaard Re-analysis Lidegaard 2011
insert by
insert by FDA
s and time extension of Danish retrospective
cohort study
national
database hospital
national
discharge and
database hospital
9 8,010,290
0 woman-y
man-y ars
Compared to
Relative Risk
Odds Ratio
DVT event
s compared to levonorg
e + 30-40 mcg of EE:
Comparison
3.7 — 8.4
5.3 — 10
Drospirenone + 30 μg EE
196 v 123
2.12 (1.68 to 2.66)
4.7 — 10
Desogestrel + 30 μg EE
168 v 123
2.20 (1.74 to 2.77)
2.9 — 13.7
Gestodene + 30 μg EE
575 v 123
2.07 (1.70 to 2.52)
van Hylckama Vlieg 2009 FDA Funded Study Continued
Continued FDA study
endpoints
y exposure CHCs
Retrospective cohort study data from 2 US HMO
e to the combined comparator CHCs group
sites and Medicaid data from WA and TN 2001-
2007 835,826 women, ages 10-55 years
All Users
drospirenone/ethinyl estradiol tablets (DRSP)
0.99 (0.58, 1.69)
1.74 (1.42, 2.14)
0.37 (0.11, 1.25)
0.85 (0.59, 1.23)
estradiol transdermal patch
patch (NGMN)
63, 2.74)
17, 2.07)
03, 1.56)
51, 1.26)
etonogestrel/ethinyl estradiol vaginal ring (ETON)
1.72 (0.61, 4.83)
1.56 (1.02, 2.37) 0.62 (0.08, 4.72)
1.31 (0.71, 2.40)
group of 4 common COCs with progestins: LNG, NETA,
New Users
NGM with EE doses ranging from 20-35 mcg (COMP)
2.01 (1.06, 3.81)
1.77 (1.33, 2.35)
0.25 (0.03, 1.95)
0.88 (0.52, 1.53)
group of COCs with LNG and EE 30 mcg (LNG2)
1.07 (0.36, 3.23)
1.35 (0.90, 2.02)
1.07 (0.56, 2.05)
1.65 (0.38, 7.12) 1.35 (0.90, 2.02)
0.96 (0.29, 3.14)
Problems with Progestin
Problems with Progestin
 Technical design flaws especially with
Bias in prescribing: Newer products
using data collected for other purposes
considered safer (or riskier)
Difficulty validating diagnosis coding
depending on when prescribed
billing v
chart rev
Prescribing for secondary indications
or perceived advantages like
 Lumping various CHC's as comparison
antiandrogenic effects to women with
 Including rarely prescribed drugs and
conditions that may affect risk (PCOS
drugs not relevant to US prescribers
linked to obesity etc.)
Problems with Progestin
 Has a greater thrombotic risk in CHC with some
progestins been firmly established? NO
Diagnostic bias: when patient or
Multiple studies with various methods,
strengths and weaknesses and varying
clinician thinks an OC may cause
thrombosis this can lead to more
 Will w
ev get level
level I evi
idence to
question? NO
Events too rare to do a prospective
 Will we ever get consensus on this question?
More and better comparable studies needed
Result of FDA inquiry: Label
Result of FDA inquiry: Label
Change DRSP containing COC's
Change DRSP containing COC's
New Yasmin label approved
Safety Announcement 4/10/2012
February 2012 by the FDA
"FDA has concluded that drospirenone
containing birth control pills may be associated
Added r
eference
reference to
data from
higher risk f
blood clot t
FDA funded study
progestin-containing birth control pills."
No specific indication that FDA
New labeling approved April 2012 by
considers drospirenone more of a
the FDA for all drospirenone
risk than other COC's
FDA SA 2012
Lable added reference to
reference
No Increase in VTE Risk with:
from FDA funded study
ormone re easi
ng an copper
Øjvid 2009
From: Yasmin Prescribing Information April 2012
Thrombotic Risk with
Combination
Putting VTE Risk in Perspective:
 Risk of VTE with patch appears to be
200,000 new cases diagnosed in U.S./
equivalent to risk of COCs with
each year
norgestimate, some studies show equal
2/3 VTE's are DVTs; DVTs have 6%
risk (3)(5)(6)(8); while
hile other
data suggest
suggest a
higher risk (4)(9) Stroke and MI were so rare
that risks could not be estimated
1/3 are pulmonary emboli (12%
However, the risk of VTE with the
transdermal combination patch is still less
40% of VTEs are idiopathic
than the risk associated with pregnancy
Nelson 2011
VTE and COC's
When is the Greatest Risk of VTE?
VTE risk pregnancy: 98.5 per 100,000
women yrs, BUT rises to 511.2 per
 In the 1st 3 to 12 mos of COC use, then
100,000 women-yrs in postpartum period!
Risk of PE during pregnancy: 10.6 per
 Obese users have 3 fold increased risk
 ACOG recommends women over 35 with
rogen con i
During Postpartum the risk rises to 159.7
contraception with caution; however US MEC
per 100,000 women-yrs.!
rates obesity as Cat 2
VTE risk is reversible within 30 days after
 Smokers 18-39 yrs who DID NOT use COC's
had 2X VTE risk; smokers who did: 8.8 X higher
risk
Nelson 2011
Nelson 2011
Risk Factors for VTE
e echnolog
 Obesity: >1/3 adult women have BMI>30
 Age, smoking, hypertension
Thrombophilias: factor V Leiden accounts for
30% of ALL DVT's
Other clotting defects: prothrombin factors
Deficiences in antithrombin, protein C,
Protein S
With these defects the VTE risk may be 120-150
/100,000 a year
Nelson 2011
Antimicrobial, Antifungals and
Morbidly Obese Women
Antiparasitics Medications: Impact on
Y Gastric Bypass
Efficacy CDC MEC
Broad spectrum antibiotics:
Pregnancy should be avoided for 12-18 mos
Antifungals: All
post surgery
Etonogestrel (ENG) implant (Implanon
subcutaneous delivery unaffected by
Rifampicine or Rifabutin
malabsorptive surgery (N=3)
Cat 3 for CHC's and POP
ENG serum levels decreased with wt loss, but
Cat 1 for MPA injection
remained above level necessary for effective
Cat 2 for Implant
contraception for at least 6 mos
Cat 1 for IUDs
Contraception for Women w
Contraception for
DMPA Injection: Postpartum
UNcomplicated Organ Transplant
Breastfeeding < 1 mo PP
Breastfeeding 1 mo or more PP
Postpartum < 21 days
Postpartum 21-42 days with other risk
factors for VTE
Uncomplicated All methods: 2
More than 42 days PP
U.S. Med Eligibility Criteria for Contraceptive Use
June 2012
Magnetic Resonance Imaging
and IUDs and Implants
YES is safe for women with IUDs,
implants, microimplants
(inserted during hysteroscopy
Correia L et al. Magnetic resonance imaging and gynecological
devices. Contraception 2012.
2010-New Quadriphasic COC
Cont… Cycle Control with
Dienogest (DNG) (19-nortestosterone-
ith estradiol
estradiol a
v lerate (E2V)
Estradiol valerate /dienogest (aka Natazia®
(US) Qlaira ® (EU)
 Ist 2 days: 3 mg estradiol valerate (E2V)
19-nortestosterone-derived DNG (dienogest)
alone (primes endometrium)
an antiandrogenic progestin
Then 5 days of 2 mg E2V with DNG 2 mg
with estradiol valerate (E2V)
 Then 5 days of 2 mg E2V with DNG 2 mg
No clinically relevant effects on most
 Dose of DNG is raised the next 17 days to
3 mg while E2V dose stays at 2 mg
 Then 2 active pills contain only E2V 1 mg
Nelson 2010, Borgelt 2012
 2 placebo pills end the 28 day cycle
Oral Contraceptive
Two New Drospirenone Combined
Dienogest + Estradiol va
COC's with Folate
Showed superior bleeding profile to EE 20 mcg
FDA approved two new
with Lng 100 mcg pills
drospirenone (DRSP) containing
67% reduction in bleeding compared with typical
pills with folate
OC reduction
of 35% to 43%
 Beyaz 24/28
pills with 2
Low discontinuation rate
New Drug application (NDA) requested indication
 Safyral 21/28 pills with 30 mcg EE & 3 mg
for "prolonged menstrual bleeding …" BUT
approved by FDA 5/6/2010 only for
contraception.
Levomefolate calcium 0.451 mg per tablet
in all 28 pills in both brands
Fraser 1991, Jensen 2011, Nelson 2010 The "Chewable" Pill
Norethindrone 0.8 mg
WHAT'S NEW ON THE
Ethinyl estradiol 25 mcg
Ferrous fumarate 75 mg (no therapeutic
value: Prenatal dose is 325 mg/d)
24 active pills and 4 "inactive pills"
which contain iron
iPhone app available as pill reminder
(Generess Fe)
New Injectable Contraceptive:
Injectable
Progestin-Only Patch
In Phase 2 trials
Levonorgestrel butanoate suppresses
ovulation for up 5-6 months after
Progestin-only (levonorgestrel)
single injection of 50 mg; 12.5 mg
Benefits women with contraindications
ose… nhibited ovulati
to estrogen:
another 2-3 months
Migraine with aura
CCNT: Contraceptive Clinical Trial
Network investigation potential
Postpartum or nursing mothers
Garza 1991, Jensen 2011 New Transdermal Combination
Transdermal
Progestin-Nestorone Vaginal Ring
on the Horizon PHASE 3
T IALS COMPLET
LS COMPLET D
Potent 19-norprogesterone derivative, neutral
metabolic effects (not active orally); can be used
Using 50 mcg gestodene, a
in gel, ring or spray formulas
synthetic progestin from the 19-
nortestosterone family and ethinyl
2 Phase 3 trials completed
estradiol 20 mcg
Vaginal r
eleasing
releasing 150 mcg/d n
estorone
nestorone wi
15 mcg/d of EE
Patch is applied once/week: 21 days
21 days on, 7 days off regimen
on and 1 week off
The same ring reinserted every month
Inhibits ovulation
Heger-Mahn 2004, Jensen
for 1 year
Sitruk-Ware
Developed by Population Council
Natural Progesterone as a
New Oral Contraceptive
e pill…On the
Horizon: Nomegestrol Acetate
Estradiol with nomegestrol acetate (NOMAC)
Designed for lactating women
19-norprogesterone derivative-lacks affinity for
steroid receptors other than progesterone
10 mg/d progesterone release vaginal
receptors: antiestrogenic and antigonadotropic
effects on
ndometrium
endometrium without androgen
Effective for 3-4 months
Treatments: dysmenorrhea, heavy menstrual
No effects on breast-feeding or infant
bleeding, premenstrual syndrome
Combined with estrogen for OC, inhibits ovulation
& follicle development
Nath 2010, Massai 2005
2011 Jensen, Lello 2011
Oral Contraceptives:
Contraceptive Vaccines Naz 2011
Treatment for Hirsutism?
OFF LABEL
Who can use
Prospective RCT comparing 2 drospirenone
FSH: follicle
(1) 21/7 grp: 3 mg DRSP+0.03 mg EE
stimulating
Luteinizing
Female Causes impotency
lab animals,
N=50 (24 and 23 pts in each grp) 6 mo study
Both grps comparable effects; well tolerated
HCG: Human
Women and
Successful in
chorionic
women. Difficult to
(T & free T decreased significantly; SHBG
increased; no change in DHEAS levels)
Zona pellucida
Female animals,
Causes irreversible
Wildlife/dogs PZP
Oner 2011
dogs, primates,
Can Nurse Clinicians Perform
Manual Vacuum Aspiration (MVA)?
Vaginal Contraceptive Ring
Study from India determined that
nurses performing MVA's are as
safe as physician coll
lleagues.
Nurse provided MVA's increases
access to safe abortions
Shireen J et al Contraception 84(2011) 615-21
Extended use Vaginal Ring
Teaching Women How to
Ring: It's easy!
No hormone-free interval
 Hand a ring sample to her- "soft, small"
Potential for break through
 Quick demonstration of insertion and
removal technique(s) and positions ("Ring
Macarena")
Probably continuous 30 day
 Assure her that vast majority of women
find it very easy to use and she will too.
LARC: Long-acting Reversible
Methods that are as effective as
surgical sterilization, yet reversible.
IUD's (copp
p er and levonor
Implant
Cost effective, reduce need for clinic
visits, safe
AVOID PLASTIC INSERTER
Implant and IUCs effective for 3, 5 or
10+ years.
OFF LABEL SM Schnare
Gestrinone and Mifepristone for
Gestrinone
and Mifepristone for
OFF LABEL
EMERGENCY
 Double-blind controlled trial N=998 with
499 in each arm; unprotected intercourse
within 72 hrs.
WHAT'S NEW?
 Pregnanc
y rate for 10 mg
g gestrinone
progestin not available in U.S.): 2.5%
 Pregnancy rate for 10 mg mifepristone:
Wu 2010 Obst Gynecol
Cheng 2012 Cochrane Database
Syst Rev
Emergency Contraception
Contraception
Cu IUD for Emergency
What's on the Horizon?
Mifepristone 25-50 mg superior to Lng IUD
Emergency placement of Cu-IUD:
and Yuzpe (combined COC regimens)
significantly more effective (99%)
Ulipristal acetate may be more effective
than EC pills.
than Lng IUD
Lng IUD more effective than Yuzpe
May also prevent pregnancy after
COPPER IUD MOST EFFECTICE EC and
ONLY METHOD TO PROVIDE ONGOING
Can be placed within 120 hrs of UPIC
CONTRACEPTION WHEN LEFT IN SITU
(only 0.23 preg/100 women)
Cheng Cochrane Database Syst Rev. 2012
Cheng 2008
Richardson Clin Ther. 2012
What's New:
IUD UPDATE and
Frameless (FibroPlant) LNG-IUD reduces
menstrual blood loss in women
NEWER USES
with/without heavy menstrual bleeding
Releases 14 mcg LNG/day for contraception
Amenorrhea occurred in 80% of women
Andrade 2009
Smaller devices may be beneficial for
Jensen 2011
Lng IUD: What's New?
Immediate Post-placental
Placement of IUDs
Look for smaller version of the
Expulsion rates appear higher than
Greater use of post-
Early F/U to identify expulsions
placental placement of
Grimes Cochrane Database Syst Rev. 2010
No increase in excessive bleeding
or endometritis Welkovic Contraception. 2001
Offer LARC Contraceptives
Broader Use of Cu IUD
OFF LABEL
OFF LABEL
Immediately
Immediately Post Abortion
Immediate post abortion (copper)
Data: Having a previous abortion does not deter
IUD insertion is safe Can decrease
repeat unintended pregnancy and
Women are more likely to choose IUD or implant if
offered i mmediately
immediately post abortion
with women without Hx of recent AB. Offer
LARC methods IMMEDIATELY post AB…don't
Higher expulsion rates: typical rate 1-
wait for another visit!
3%, post abortion rate: 5-6%
In clinic: Candidates for IUDs should
have them placed on same day visit
Grimes 2004, Goodman 2008
Broader Use of Lng IUD
OFF LABEL
OFF LABEL
Broader Use of Lng
Broader Use of
 Nulliparous women & adolescents (smaller IUCs
 Prevent iron deficiency anemia
will be available)
 Endometrial polyp & fibroid protection for
 With previous history of PID
women using tamoxifen. In lieu of endometrial
Levonorgestrel (Lng) IUD: Treatment of:
ablation for uterine bleeding and an alternative
idiopathic menorrhagia (19)(20)(29) and pelvic pain
due to endometriosis (15)(17)(18) or adenomyosis
 Menopausal women- inhibit hyperplasia with
(14) or dysmenorrhea (14)(20) chronic pelvic pain
estrogen therapy (a smaller version of the Lng
(16) protection against ectopic pregnancy Naz 2011
IUD is in progress)
and for HRT
 Immediate postpartum & post abortion-
regardless of lactation status
Lethaby 2005, Luukainen 1995,Vilos 2009, Petta 2005, Abou-
Setta 2006, Manetta 2008, Sheng 2009, Bahamondes 2007
Toivonen 2009, Chin 2009, Gardner 2000, Roman 2008, Grimes 2007, Hayes 2007 Lng IUC as Therapy for
Lng IUD: Endometrial Protection
with Tamoxifen &
OFF LABEL
OFF LABEL
Prospective, non-randomized 12
 122 postmen-1 yr tamoxifen use- randomized to
month VERY SMALL STUDY
endometrial surveillance or Lng IUD with
surveillance x 12 months
N=11 symptomatic women with
 Baseline-all women showed only benign
v ginal septum
Pelvic pain, deep dyspareunia,
 Lng IUD-protective against tamoxifen, initial
dysmenorrhea greatly improved. Size of
bleeding resolved, no new polyps, 13% fewer
endometriomas significantly reduced per
fibroids
 Lng IUD may be used with ERT to inhibit
Fedele 2001
Gardner 2009, Wan 2011
Cu and Lng IUDs Lower Risk of
IUDs may lower cervical
cancer risk
Endometrial Cancer OFF LABEL
May reduce risk of cervical cancer by 45%
Mechanism of action of Cu IUD unknown;
may be related to alteration in
Protective affect occurred in 1st year and
endometrium & preferred for recent
continued up to 10 yrs (>15,000 women)
breast cancer; Lng IUD is used with
Squamous cell ca reduced by 44%
tamoxifen tx
Adenosquamous risk reduced
Lng IUD prevents endometrial hyperplasia
Castellsagué X et al. Lancet Oncol 2011(pooled analysis of 26 in peri & post menop women on estrogen
and used in tx of non-atypical hyperplasia
Copper IUDs: possible protection against
May be effective for atypical hyperplasia,
endometrial cancer Grimes, Nelson. Contraceptive
and 1I endometrial cancer as well.
Contraceptive Tech 2011
Lng IUD: Treatment for Menorrhagia
Risk of PID Reduced with
OFF LABEL
 RCT: PID rates in Lng IUD vs. Nova-T (Cu)
Systematic review: Lng IUD use for
Salpingitis significantly lower in Lng IUD vs.
menorrhagia- 9 studies showed
Nova-T users at 3 and 5 yrs.
statistically significant reduction in blood
7 yr randomized study, PID rates did not
loss (74% to 97%
differ between devices and mild to
e increases in h
bin levels
 1 study- 64% women with menorrhagia
occurred in users of BOTH IUDs
(given Lng IUD) cancelled surgery vs 14%
AND…Continuation rates were similar:
of controls
29.4% for the CuT380A IUD and 24.9% for
the Lng IUD
 Acceptance and continuation of Lng IUD
for HRT has been high Stewart 2001, Luukkainen
Toivonen 1991, Andersson 1994, Sivin 1999 IUD's, Implant: Duration of Efficacy
Lng IUD, approved duration-5 yrs,
some studies show efficacy to 7 yrs
PAIN MANAGEMENT
Implant approved for 3 yrs; but stable
FOR IUD PLACEMENT
etonogestrel up
36 months
OFF LABEL
Dean, Schwarz Intrauterine contraceptives. In:Hatcher, Trussell, Nelson et al Contraceptive Tech: 20th rev ed. NY: Ardent Media; 2011;149.
Raymond E. Contraceptive implants. In:Hatcher, Trussell, Nelson et al Contraceptive Tech: 20th rev ed. NY: Ardent Media; 2011;195.
Pain Management for IUC Placements
Paracervical block (PCB) generally
not indicated; may not reduce
overall pain
May be useful for difficult
placements or cervical dilation.
PCB is used for ALL IUC
placements in Finland.
Paracervical Anesthetic Block
Paracervical Block (PCB) for IUC
Placement or Difficult Removal
Anatomy: Cervical nerve innervations
Have adequate visibility of cervix. Lift
from Lee-Frankenhäuser plexus,
cervix with tenaculum and apply
located l ateral to th
the juncti
tion of th
anesthetic g
gel to injection
cervix and uterus. Sensation is
Use a needle extender to reach the
carried to the spinal cord at the T10-
T12 and L1 segmental nerves.
Paracervical Anesthetic Block Cont…
Paracervical Anesthetic Block Cont…
 At each site the needle depth should only
As you slowly instill 1% lidocaine NO
be 2-3 mm; just cover the bevel of the
epinephrine, the area around the
needle in the tissue
e p will bl
anch; a good sign.
 Avoid uterine arteries at 3:00 and 9:00
There is resistance with the injection
 Use sites 4:00 OR 5:00 and 7:00 OR 9:00
and often two thumbs are needed for
Prior to instillation, ASPIRATE to assure
the needle is not in a vessel.
PCB Complications are Very
Cont… Paracervical Anesthetic Block
Paracervical Anesthetic
 Watch the lower vagina to assure the
lidocaine is not pooling…this means the
Hypersensitivity to lidocaine (ask
needle bevel is not covered & lidocaine is
leaking. If this occurs, advance the needle
Bleeding from injection sites
slightly, ASPIRATE TO ASSURE NOT IN
(usually very minor)
VESSEAL, THEN CONTINUE WITH THE
INSTILLSTION.
Infection (very rare)
 Wait 10 min for full anesthetic effect
Etonogestrel Progestin Implant
(Nexplanon replaces Implanon)
 Flexible, white ethylene vinyl acetate rod with
68 mg etonogestrel, subdermal implant 4 cm x 2
mm Action: Inhibits ovulation
 Effective for 3 years. Releases 60-70 mcg/day in
 Inserted subdermally between the biceps and
triceps muscles
Now radio-opaque (visible on X-ray or CT
scan) and new inserter
Must be inserted and removed only by clinicians
completing a training program
Does Etonogestrel (ETG) Implant Effect
(ETG) Implant
Cervical Neoplasia and
ETG Implant does not affect carbohydrate
Condoms marginally effective at
metabolism after 12 months in healthy
preventing abnormal cytology by
preventing HR-HPV or persistence of
Use of low dose combined OC's may cause
slight insulin resistance & rise in fasting
insulin levels, however glucose levels are
Hormonal contraceptives may increase
unchanged or reduced-
HPV acquisition; but risk not as great
Non-randomized, open label, prospective
as that of women with high parity
controlled trial. N=40
Curry 2012, Nelson 2011
Oderich 2012
Do COCs Impact HIV Acquisition?
Update to USMEC 6/22/12
HIV uninfected women using either
COCs or injectable progestins were
not at any significantly increased risk
COC/P/R POP DMP
for acquiring HIV compared with
High risk for HIV women who used other non-barrier
methods. Contraceptive Technology 2011
 Questionable link with epithelial ovarian
cancer in premenopausal women
according to WHI? WHO Collaborative Study Neoplasia
What's Else is New in
Steroid Contraceptive Lancet 1991
 May actually have a protective affect
against according to Women's CARE
Study (CDC)
 Breast cancer is rare among
premenopausal women. Strom Contraception 2004
Newest Progestin: In Clinical
MANAGING SPOTTING
 Nestorone similar to progesterone
 Population Council: in clinical trials as a
AND BLEEDING WITH
intra-vaginal ring (2 1/4 inches)
 Also evaluated as transdermal metered
dose spray and gel
 May be efficacious for men when used
(36) 2010 (37) 2007
Managing Challenging Idiopathic Spotting-
Managing Challenging Idiopathic Spotting-
Bleeding with Implant
Bleeding with Hormonal
OFF LABEL
OFF LABEL
RCT: effect of mifepristone with EE on
Continuous use, no pill free interval
ovulatory function in women with
Spotting or light bleeding (short-term
treatment): Nonsteroidal anti-inflammatory
mg bid with
(NSAIDS) Ibuprofen 600-800 mg qd x
Would this regimen work as well with IUD
Mefenamic acid (Ponstel®)
idiopathic bleeding? No data
Doxycycline 100 mg bid x 1-2 wks
 Heavy-prolonged bleeding
NSAIDS
Hormonal: Ethinyl estradiol or add CHC
Cont…Managing Challenging Idiopathic Spotting-
Effects of hormonal
Bleeding with
Hormonal Contraceptiv s
contraception on vaginal flora
 Tranexamic acid (Lysteda®) synthetic
derivative of lysine. Antifibrinolytic-
Compared to COC's, contraceptive
inhibits activation plasminogen to
vaginal ring showed an increase in
degradation of fibrin;
the number of lactobacilli in vaginal
inhibits endometrial plasminogen
flora…this could be protective.
activator; prevents break down of clots
 Dose: 1,300 mg (two 650 mg tabs) tid for max. 5
days during menses.
De Seta et al. Effects of hormonal contraception on
Consider as second line treatment to Lng IUD for
vaginal flora. Contraception 2012.
treatment of heavy menstrual bleeding Naz 2011
Health Benefits of Combined Oral
OFF LABEL
Health Benefits of
Protects against ovarian, endometrial
cancer and possibly colorectal carcinoma
Decreases dysmenorrhea, menorrhagia,
anemia, c
clic mood problems (PMS),
protects against ectopic pregnancy and
All methods of
contraception are safer than
AND…reduces acne…and as an aside…it
reduces death.
Maguire 2011
Health Benefits of Progestin-
Health Benefits of
Only Pill and Lng IUD
POP: Lactation not disturbed (Cat 2 MEC)
 Fewer seizures
OFF LABEL
Lng IUD: decreases menstrual blood loss,
 Fewer sickle cell crises
menorrhagia, PID, endometriomas,
 Decreased pain from endometriosis
adenomyosis, endometrial hyperplasia,
 Reduced risk ectopic
polyps, chronic pelvic pain, fibroids,
 Decreased risk pelvic inflammatory
provides progestin for HRT and reduces
endometrial polyps in women using
 No estrogen
 Benefits women with myomas
OFF LABEL
Fraser 2010
Cont…Health Benefits of
Emergency Contraception:
Contraception:
Medroxy rogesterone acetate
New: Ulipristal acetate "ELLA"
Culturally acceptable (method not
 Progesterone receptor modulator
 More effective than Lng EC on days 4-5
postcoital Dose: 30 mg
 Advise to abstain or use a barrier method
Works for obese women
to end of current menstrual cycle.
 HA (18%)
Absence of menstrual bleeding and
 Abdominal pain (12%)
improved menstrual symptoms
 Nausea (12%)
 R/O ectopic
Minimal drug interactions
OFF LABEL
Contraceptive technology Update 5/2010, CDC 2010 Contraception for Women with
Cancers and Contraception
Breast: benign disease and family
 Copper T380A IUD first line for women
history of cancer-all methods
with history of hormonally mediated
Current Breast Cancer: all categor
 Lng IU
ble in women using
4, except Cu IUD is 1
tamoxifen, or have non-hormonally
mediated cancers.
Past breast cancer and no evidence
of current disease for 5 yrs: all
 Women with IUD's can undergo CT and MI
category 3, except Cu IUD is 1
OFF LABEL
Cervical Cancer and Contraception
"Quick Start" and Combined
OFF LABEL
Cervical cancer awaiting treatment:
 Conventional OC initiation may delay start
for several weeks.
CHC, P/R: 2; POP: 1
 Up to 25% of women do not begin
ETG Implant:
method. No
difference in
bleeding
parameters.
Cu and Lng IUDs: Initiation-4,
Westhoff C, et al. Fertil Steril. 2003.
Initiate OC during office visit !
Applicable to Pills, Patch, Ring, DMPA,
CIN: same as above, except Cu IUD
IUD insertion, Implant
is 1 and Lng IUD is 2
Advise backup method first 7 days
DMPA Initiation or Late Injections
CONTRACEPTION FOR
Use a backup method for first 7 days
post injection to allow time for
cervical mucus to thicken to inhibit
sperm m
WHAT S NEW
NEW OVER THE
OFF LABEL
RAINBOW?
Zieman M et al. 2007-2009 Managing Contraception for
Your Pocket. Tiger, GA: Bridging the Gap; 2007.
Men's Use of Contraception
Transdermal Gel for Male
In 2002 male methods accounted for
32% of contraceptive use in the U.S.
Population Council and National
Institute of Health are working on
Vasectomy 9%
Condom use: 18%
testosterone gel for male
Periodic abstinence: 1%
Darroch 2008
tiv Trans
d rmal Gel for MEN
rmal Gel for
Contraception for Men
Testosterone transdermal gel with
Let men know that hormonal
nestorone 8mg significantly reduced
sperm concentration to 1 million/mL or
contraceptives are over the
less after a 20 wk tx
horizon!
effective methods
methods their
adult range in the men. Adverse events:
partner can use & help with cost
Ilani et al. A new combination testosterone and nestorone
Cu IUD EC with men
transdermal gels for male hormonal contraception. J
Clin Endocrinol Metab.
Discuss state paternity laws with
2012Contraceptive Technology Update. May 2010
men for their protection
Male Contraception: Where are we at?
Male Contraception: The Challenges
 Goal: Reducing sperm count to low
Progestins (cyproterone, etonogestrel)
enough levels to ensure infertility. Recent
also suppress gonadotropins and
studies have reduced counts to 1 million
sperm per mL in 80-90% of subjects.
Testosterone therapies involve injections
or implants along with progestins.
 Side effects: weight gain, mood changes,
Studies on-going.
acne, sweating, libido change.
Amory 2008
Mommers 2008
Male Contraception: Is Ultrasound
Male Contraception: New Possibilities?
No new male contraceptives have emerged
in the past century…but that's changing!
US treatments to inhibit spermatogenesis.
RISUG (Vasalgel™): reversible inhibition of
Post US sperm counts in dogs showed no
sperm under guidance
sperm. US intensity is that used by
(not yet approved)
therapists to treat
injuries 15
Polymer gel coats vas deferens lumen-kills
sperm & blocks lumen.
treatment has 4-6 mos contraceptive
effect. The transducer is placed directly
Flushing vas with dimethyl sulfoxide (DMSO)
or sodium bicarbonate solution to reverse
on testes; painless.
Gates Foundation is funding FHI
Tulsiani 2010, Male Contraception Information Project
Male Contraception Information Project
Indonesian herb: Gandarusa
Can nurse practitioners perform
1. Research supported by Indonesian Gov't
. urrently in cli
linical trials with 350
Both scalpel and Non-scalpel
couples Male Contraception Information Project 2012
Gamendazole: Research supported by NIH
(100% effective in rats & monkeys)
Less bleeding
Less infection
Male Contraception Information Project
Hormonal Contraception….
2 Generation Progestins
Progestins, Progestins, Progestins
1st Generation Progestins
More potent, longer half-lives, more
androgenic activity: avoid in those
with hirsutism, acne, dyslipidemia
Lynestrenol (not in US)
Norethynodrel (not in US)
3 Generation Progestins
4 Generation Progestin
Drospirenone…parent drug is
spironolactone, a potassium
Gestodene (not in US)
sparing d
Less androgenic activity, allows
greater expression of estrogens.
Significant increase in SHBG
Labeling : For cystic acne
birth control method
sex hormone binding globulin
oral contraceptive pills
combined hormonal contraceptives
depo medroxyprogesterone acetate
sexually transmitted infection
bilateral tubal ligation
v nous thromboembolism
 NET-EN norethindrone enanthate
 IUD: intrauterine
deep vein thrombosis
 IUC: intrauterine
 PE pulmonary
 Lng IUD levonorgestrel intrauterine device
 CDC MEC
Centers for Disease Control
 Cu IUD copper IUD
Contraceptive Medical Eligibility Criteria
bone mineral density
Abou-Setta AM et al. Levonorgestrel-releasing intrauterine device Centers for Disease Control and Prevention (CDC). U S. Medical Eligibility (LNG-IUD) for symptomatic endometriosis following surgery. Criteria for Contraceptive Use, 2010. MMWR Recomm Rep. 2010 Jun 18;59(RR-4):1-86.
Cochrane Database Syst Rev. 2006 Oct 18;(4):CD0005072.
Centers for Disease Control and Prevention (CDC). Update to CDC's U.S. Ageno W et al. Circulation 2008;117 Jan (1):93-102.
Medical Eligibility Criteria for Contraceptive Use, 2010: revised Amory JK. Progress and prospects in male contraception. Curr recommendations for the use of contraceptive methods during the postpartum period. MMWR Morb Mortal Wkly Rep. 2011 Jul Opin Endocrinol Diabetes Obes. 2008 Jun;15(3):255-60.
Andersson K et al. Levonorgestrel-releasing and copper-releasing Centers for Disease Control and Prevention (CDC). Prepregnancy (Nova T) IUDs during five years of use: a randomized contraceptive use among teens with unintended pregnancies resulting hs - Pregnancy Risk Assessment (PRAMS), 2004-2008. MMWR Morb Mortal Wkly Rep. 2012 Jan Andrade A, Wildemeersch D. Menstrual blood loss in women using the frameless FibroPlant LNG-IUS. Contraception. 2009 Feb; Cheng L, Gülmezoglu AM, Piaggio G, Ezcurra E, Van Look PF. Interventions for emergency contraception. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD001324.
Bahamondes L, Petta CA, Fernandes A, Monteiro I. Use of the Chin J et al. Levonorgestrel intrauterine system for endometrial protection levonorgestrel-releasing intrauterine system in women with in women with breast cancer on adjuvant tamoxifen (Review). The endometriosis, chronic pelvic pain and dysmenorrhea. Cochrane Collaboration. 2009 issue 4.
Contraception. 2007 Jun;75(6 Suppl):S134-9. Ciangura C et al. Etonogestrel concentrations in morbidly obese women following Roux-en-Y gastric bypass surgery: three case reports. Contraception 2011 84:649-51. Cole A. et al. VTE, MI and stroke among transdermal contraceptive Dinger J. Oral contraceptives and venous thromboembolism: old system users. Obste Gynecol 2007;109(2 Pt 1):339-46.
questions revisited. J Fam Plann Reprod Health Care. Cole JA et al. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Dore DD, Norman H, Loughlin J, Seeger JD. Extended case- Gynecol. 2007 Feb;109(2 Pt 1):339-46.
control study results on thromboembolic outcomes among Contraceptive technology Update. May 2010:Vol.31(5):49-60. transdermal contraceptive users. Contraception. 2010 May;81(5):408-13. Epub 2010 Jan 22. Creinin MD et al. Progesterone receptor modulator for emergency contraception: a randomized controlled trial. Obstet Gynecol ELLA-ulipristal acetate package insert. Watson Pharma, Inc. 2010.
Eng PM, Seeger JD, Loughlin J, Clifford CR, Mentor S, Walker AM. Curry AB et al. Hormonal contraception, condom use and abnormal cervical cytology in collage women. J Lower Genital Tract address potential confounding in a cohort study of Disease. Apr 2012 thromboembolism in oral contraceptive initiators matched on claims-based propensity scores. Pharmacoepidemiol Drug Saf. Darroch JE. Male fertility Control-where are the men? Contraception. 78. 2008: 7-17. FDA Office of Surveillance and Epidemiology. 2011. Combined Dinger JC et al. The safety of a drospirenone-containing oral hormonal contraceptives (CHCs) and the risk of cardiovascular contraceptive: Final results from the European Active disease endpoints. Surveillance Study (EURAS) on oral contraceptives based on 142,475 women-years of observation. Contraception FDA Safety Announcement 5/21/2011. Fraser IS. Non-contraceptive benefits of intrauterine hormonal systems. http://www.fda.gov/Drugs/DrugSafety/ucm257164.htm (FDA sa1 2010 Contraception (82) 396-403. Gardner FJ et al. Endometrial protection from tamoxifen-stimulated changes by levonorgestrel-releasing intrauterine system; a randomised FDA Safety Announcement 9/26/2011. controlled trial.Lancet. 2000 Nov 18;356(9243):1711-7.
http://www.fda.gov/Drugs/DrugSafety/ucm273021.htm (FDA sa2 Gardner FJ, Konje JC, Bell SC, Abrams KR, Brown LJ, Taylor DJ, Habiba M. Prevention of tamoxifen induced endometrial polyps using a levonorgestrel releasing intrauterine system long-term follow-up of a FDA Transcript for the December 8, 2011 Joint Meeting of the randomised control trial. Gynecol Oncol. 2009 Sep;114(3):452-6. Advisory Committee for Reproductive Health Drugs and the Garza-Flores J et al. Long-acting hormonal contraceptives for women. J ty and Risk Managem o . 1991;40:697-704. Grigoryan OR et al. Use of the NuvaRing hormone-releasing system in late reproductive-age women with type 1 diabetes mellitus. Gynecol mittee/UCM288721.pdf (FDA ac 2011) Endocrinol. 2008 Feb;24(2):99-104.
Grimes DA et al. Cochrane systematic reviews of IUD trials: lessons Fedele L, Bianchi S, Zanconato G, Portuese A, Raffaelli R. Use of learned. Contraception. 2007 Jun;75(6 Suppl):S55-9.
a levonorgestrel-releasing intrauterine device in the treatment of Grimes DA, Schulz KF. Nonspecific side effects of oral contraceptives: rectovaginal endometriosis. Fertil Steril. 2001 Mar;75(3):485-8.
nocebo or noise? 2011 Contraception 83;5-7.
Fraser IS, McCarron G. Randomized trial of 2 hormonal and 2 Gronich N, Lavi I, Rennert G. Higher risk of venous thrombosis associated prostaglandin inhibiting agents in women with a complaint of with drospirenone-containing oral contraceptives: a population-based cohort study. CMAJ. 2011 Dec 13;183(18):E1319-25.
menorrhagia. Aust N Z J Obstet Gynaecol. 1991;31:66-70.
Hatcher et al Contraceptive Technology 19th Ed 2007. Hayes JL et al. A pilot clinical trial of ultrasound-guided Jejeebhoy SJ, Kalyanwala S, Zavier AJ, Kumar R, Mundle S, Tank J, postplacental insertion of a levonorgestrel intrauterine device. Acharya R, Jha N. Can nurses perform manual vacuum aspiration Contraception. 2007 Oct;76(4):292-6.
(MVA) as safely and effectively as physicians? Evidence from India. Contraception. 2011 Dec;84(6):615-21.
Heger-Mahn D, Warlimont C, Faustmann T, Gerlinger C, Klipping Jensen JT. The future of contraception: innovations in contraceptive C. Combined ethinylestradiol/gestodene contraceptive patch: agents: tomorrow's hormonal contraceptive agents and their clinical two-center, open-label study of ovulation inhibition, acceptability implications. Oct 2011. Supplement: Am J Obstet Gynecol.
and safety over two cycles in female volunteers. Eur J Jick S et al. Further results on the risk of nonfatal venous Contracept Reprod Health Care. 2004 Sep;9(3):173-81.
thromboembolism in users of the contraceptive transdermal patch Heikinheimo O et al. Double-blind, randomized, placebo-controlled compared to users of oral contraceptives containing norgestimate and estradiol. Contracept ion. 2007 Jul;76(1):4-7.
insertion of the levonorgestrel-releasing intrauterine system. Jick SS et al. Risk of non fatal VTE in women using a contraceptive Contraception. 2010 (In press) transdermal patch and oral contraceptives containing 35 mcg EE and Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ 3rd. Trends in the incidence of venous Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in thromboembolism during pregnancy or postpartum: a 30-year women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case- population-based study. Ann Intern Med. 2005 Nov control study using United States claims data. BMJ. 2011 Apr Jackson E, Curtis K, Gaffield M. Risk of venous thromboembolism Johnson JV et al. Effects of oral and transdermal hormonal contraception during the postpartum period: a systematic review. Obstet on vascular risk markers: a RCT. Obstet Gynecol 2008;111(2Pt.1):278- Lello S. Nomegestrol acetate: pharmacology, safety profile and therapeutic Manetta LA et al. Uterine ultrasonographic changes during endometriosis efficacy. Drugs 2010;70:541-59.
treatment: a comparison between levonorgestrel-releasing intrauterine Lethaby AE et al. Progesterone or progestogen-releasing intrauterine devices and a gonadotroppin0releasing hormone agonist. Ultrasound systems for heavy menstrual bleeding. Cochrane Database Syst Rev. Med Biol. 2008 Dec;34(12):1914-8.
2005 Oct 19;(4):CD002126.
Martinez F, Avecilla A.Combined hormonal contraception and VTE. Eur J Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal Contracept Reprod Health Care 2007;12(2):97-106.
contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009 Aug 13;339:b2890. Martinez F, Avecilla A.Combined hormonal contraception and VTE. Eur J Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Contracept Reprod Health Care 2007;12(2):97-106.
Risk of venous thromboembolism from use of oral contraceptives Massai R et al. Extended use of a progesterone-releasing vaginal ring in ens an oestrogen doses: D nursing women: a phase II clinical trial. Contraception 2005; 2 study, 2001-9. BMJ. 2011 Oct 25;343:d6423.
Milsom I et al. A comparison of flurbiprofen, tranexamic acid, and a Luukkainen T, Toivonen J. Levonorgestrel-releasing IUD as a method of levonorgestrel –releasing intrauterine device in the treatment of contraception with therapeutic properties. Contraception. 1995 idiopathic menorrhagia. Am J Obste Gynecol 1991; 164:879-883.
Mommers E et al. Male hormonal contraception: a double-blind, placebo- Luukkainen T. The levonorgestrel intrauterine system: therapeutic aspects. Steroids. 2000 Oct-Nov;65(10-11):699-702.
controlled study. J Clin Endocrinol Metab. 2008 Jul;93(7):2572-80.
Maguire K, Westhoff C. The state of hormonal contraception today: Nath A et al. Progesterone vaginal ring for contraceptive use during established and emerging noncontraceptive health benefits. Am J lactation. Contraception 2010;82:248-34.
Obstet Gynecol. 2011Oct;205(4 Suppl):S4-8.
Naz RK. Contraceptive vaccines: Success, status, and future perspective. Male Contraception Information Project Am J Reprod Immunology 2011 66:2-4.
Nelson AL, Cwiak C. Combined Oral Contraceptives (COCs). In: Hatcher Potter JE, McKinnon S, Hopkins K, Amastae J, Shedlin MG, Powers DA, RA et al, editors. Contraceptive technology 20th revised edition. Ardent Grossman D. Continuation of prescribed compared with over-the- Media Inc. 2011. p. 249-313.
counter oral contraceptives. Obstet Gynecol. 2011 Mar;117(3):551-7.41. Novikova N et al. Effectiveness of levonorgestrel emergency contraception Rabe E et al. Efficacy and safety of great saphenous vein sclerotherapy given before or after ovulation—a pilot study. Contraception. 2007 using standardised polidocanol foam (ESAF): a randomised controlled multicentre clinical trial. Eur J Vasc Endovasc Surg 2008;35:238-45.
Oderich CL, Wender MC, Lubianca JN, Santos LM, de Mello GC. Impact of Roman H et al. Management of menometrorrhagia in women with and etonogestrel-releasing implant and copper intrauterine device on without pregnancy intention: hierarchy of therapies. J Gynecol Obstet carbohydrate metabolism: a comparative study. Contraception. 2012 Biol Reprod (Paris). 2008 dec; 37 Suppl 8:S405-17.
Feb;85(2):173-6. Øjvid L et al. Hormonal contraception and risk of venous oestrogen-replacement therapy with venous thromboembolism risk. thromboembolism: national follow-up study.BMJ 2009; 1-8.
Lancet 2003;362:428-32. Schwarz EB et al. Contraception for cancer survivors. J Gen Intern Med. Parkin L, Sharples K, Hernandez RK, Jick SS. Risk of venous 2009 Nov;24 Suppl 2:S401-6.
thromboembolism in users of oral contraceptives containing Seeger JD, Loughlin J, Eng PM, Clifford CR, Cutone J, Walker AM. Risk of drospirenone or levonorgestrel: nested case-control study based on UK thromboembolism in women taking ethinylestradiol/drospirenone and General Practice Research Database. BMJ. 2011 Apr 21;342:d2139. other oral contraceptives. Obstet Gynecol. 2007 Sep;110(3):587-93. Petta CA et al. Randomized clinical trial of a levonorgestrel-releasing Sheng J et al. The LNG-IUS study on adenomyosis: a 3–year follow-up intrauterine system and a depot GnRH analogue for the treatment of study on the efficacy and side effects of the use of levonorgestrel chronic pelvic pain in women with endometriosis. Hum Reprod. 2005 intrauterine system for the treatment of dysmenorrhea associated with adenomyosis. Contraception. 2009 mar;79(3):189-93.
Sitruk-Ware RL, Menard J, Rad M, Burggraaf J, de Kam ML, Tokay Toivonen J. The levonorgestrel-releasing intrauterine device. Adv BA, Sivin I, Kluft C. Comparison of the impact of vaginal and Contracpt Deliv Syst. 1994;10(3-4):191-8.
oral administration of combined hormonal contraceptives on Toivonen T. Intrauterine contraceptive device and pelvic hepatic proteins sensitive to estrogen. Contraception. 2007 inflammatory disease. Ann Med. 1993 Apr; 25(2):171-3.
Tulsiani DR, Abou-Haila A. How close are we in achieving safe, Sivin I et al. Prolonged intrauterine contraception: a seven-year affordable and reversible male contraceptives? Endocr Metab randomized study of the levonorgestrel 20 mcg/day (LNg20) and Immune Disord Drug Targets. 2010 Jun;10(2):179-87.
the copper T380 Ag IUDs. Contraception. 1999 Nov;44(5):473- van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. The venous thrombotic risk of oral vaginal rings releas ethinyl estradiol: A 1-years dose-finding trial. Contraception type: results of the MEGA case-control study. BMJ. 2009 Aug Stewart A, Cummins C, Gold L, Jordan R, Phillips W. The Vilos GA et al. the levonorgestrel intrauterine system is an effective effectiveness of the levonorgestrel-releasing intrauterine system treatment in women with abnormal uterine bleeding and in menorrhagia: a systematic review. BJOG. 2001 anticoagulant therapy. J Minim Invasive Gynecol. 2009 Jul- Suvanto-Luukkonen et al. Endometrial morphology during hormone Wan YL, Holland C. The efficacy of levonorgestrel intrauterine replacement therapy with estradiol gel combined to systems for endometrial protection: a systematic review. levonorgestrel-releasing intrauterine device or natural Climacteric. 2011 Dec;14(6):622-32. Epub 2011 Oct 23.
progesterone. Acta Obstet Gynecol Scand. 1998 Aug;77(7):758-63.
MEGA data analys
Weisberg E et al. A randomized study of the effect of mifepristone ltipl Env
Env ronmental and Genetic As
A sessment
of Risk Factors for
alone or in conjunction with ethinyl estradiol on ovarian function Venous Thrombosis Study
in women using the etonogestrel-releasing implant, Implanon®. Contraception 2011;84(6):600-8. Case control study
Westhoff C, Morroni C, Kerns J, Murphy PA. Bleeding patterns Analysis of data collected for thrombosis risk
after immediate vs. conventional oral contraceptive initiation: a men and women
randomized, controlled trial. Fertil Steril. 2003 Feb;79(2):322-9. World Health Organization. Medical eligibility criteria for Patients at anticoagulation clinics in Netherlands
Wu S, Dong J, Cong J, Wang C, VonHertzen H, Godfrey EM. Analysis included women only 18-50 years
Gestrinone compared with mifepristone for emergency contraception: a randomized controlled trial. Obstet Gynecol. 1524 patients 1760 controls (40.5% were
"partners" of patients others random phone
Zieman M et al. 2007-2009 Managing Contraception for Your Pocket. Tiger, GA: Bridging the Gap; 2007.
van Hylckama Vlieg 2009 Lidegaard Re-analysis Lidegaard 2011
Jick Pharmetrics US Drug s and time extension of Danish retrospective
cohort study
national
database hospital
national
discharge and
database hospital
9 8,010,290
0 woman-y
man-y ars
DVT event
s compared to levonorg
e + 30-40 mcg of EE:
 VTE data from prescription and insurance code database women 15-44 yo 2002-2008  Nested case-control and cohort study  Comparison of COC's with drospirenone vs Drospirenone + 30 μg EE
196 v 123
2.12 (1.68 to 2.66)
Desogestrel + 30 μg EE
168 v 123
2.20 (1.74 to 2.77)
Gestodene + 30 μg EE
575 v 123
2.07 (1.70 to 2.52)
Incidence rate 3.1/10,000 yr vs 1.3/10,000 yr Estimates that 2000 women would need to switch to OC
Age adjusted RR 2.8 (2.1-3.8) with levonorgestrel to prevent 1 venous thrombosis a year
Jick 2011
Parkin UK General Practice Israeli Health Provider Study  Retrospective cohort study  Nested case control study 61 cases  Databases of a health care provider in Israel 819,749 woman-years  Database from general practice records 2001-2009 --women 12-44 starting a new  COC's with Drospirenone vs second generation (norgestrel, levonorgestrel) progestins DVT/PE RR 1.43 (1.15-1.78)  COC's containing 30 mcg estrogen and drospirenone vs levonorgestrel  COC's with Drospirenone vs third generation (desogestrel, gestodene, norgestimate) progestin OR 3.3 (1.4-7.6) adjusted for BMI DVT/PE RR 1.65 (1.02-1.78) Incidence 3.1 vs 0.9 cases per 10,000 woman years  No increase RR for arterial thrombosis IRR 2.7 (1.5-4.7) age adjusted Gronich 2011
Parkin 2011
Progestins ALONE have NO impact
Progestins
on clotting system
BUT when some progestins are combined
with estrogen they can modulate the
strength of estrogens production of
extrinsic clotting factors (antithrombin
Pills with 3rd generation progestins
(desogestrel & gestodene) assoc with 2-
fold risk VTE compared with 2nd generation
progestins (Lng & norgestrel)
Nelson 2011

Source: http://www.myhcet.info/MnUpdate/Whats%20New%20in%20Contraception.pdf