Management of
Unscheduled Bleeding
Dr.Suma Natarajan MD DGO FAGE
HOD,Ganga Women & Child
Centre
Agenda
• Understanding ‘Unscheduled Bleeding’
• Managing Unscheduled Bleeding - RCOG 2009 and
other guidelines
• Using hormonal contraception with the right dose of
estrogen
Agenda
• Understanding ‘Unscheduled Bleeding’
• Managing Unscheduled Bleeding - RCOG 2009 and
other guidelines
• Using hormonal contraception with the right dose of
estrogen
Etiopathogenesis of Break Through Bleeding
The evidence to date implicates superficial blood vessel fragility within the
endometrium as a consistent problematic feature
Endometrial response to hormonal contraception will reflect circulating sex
hormone concentrations plus the dose and formulation of steroid delivery, the
route of delivery of the steroid, and the timing and duration of administration
Exogenous administration of sex steroids, in the form of hormonal
contraception, will dramatically influence endometrial histology
Scheduled vs Unscheduled bleeding
Scheduled bleeding:
– Menstruation or regular withdrawal bleeding with combined
hormonal contraception (requiring sanitary protection)
Unscheduled bleeding
Frequent
Bleeding
>5 bleeding
episodes
Prolonged
bleeding
1/ more
bleeding
episodes
lasting 14
days
Irregular
bleeding
Spotting
Breakthrough
bleeding
3 -5
episodes
with fewer
than 3
bleeding-free
intervals of
length
14 days
May not
require the
use of
sanitary
protection
Unscheduled
bleeding in
women using
hormonal
contraception
Clinical history
Cervical Cancer Screen
• Identify or exclude some of the
possible underlying causes of
unscheduled bleeding
• If already not tested annually
Unscheduled Bleeding
Preliminary Evaluation
Exclude STI
For e.g. Chlamydia trachomatis the
most commonly treatable bacterial
disease
Pregnancy test
If there has been incorrect method
use (e.g. missed pills, late injection
etc.), drug interactions or illness,
which may alter absorption of oral
methods
Clinical History – What is Relevant?
• Current method of contraception and the duration of use
• Use of medications (incl. OTC) that may interact with hormones
• Risk of sexual transmitted infections
– For those aged <25 years, or at any age with a new partner, or
more than one partner in the last year)
• Bleeding pattern before starting hormonal contraception since
starting and currently
• Any other symptoms suggestive of an underlying cause
– e.g. abdominal or pelvic pain, post-coital bleeding, dyspareunia,
heavy bleeding)
• The possibility of pregnancy
Preliminary Evaluation
Unscheduled Bleeding
Cervical Cancer
History
Pregnancy Test
•
•
•
•
<3 months in a method
Exclude above
Investigations if Requested by woman
Reassure and arrange follow-up
Medical management may be considered
Exclude STI
•
•
•
•
>3 months in a method with symptoms of;
Persistent bleeding
New symptoms or changed bleeding pattern
Failed medical treatment
If requested by the woman
Pain, p/v discharge, dyspareunia
Follow-up Visit
Speculum Examination
Normal
Bleeding
Settled
Speculum and bimanual
Examination
Clinical Finding
Mx as Indicated
Bleeding
persists
Symptoms
No symptoms
Consider further invx to r/o
Endometrial CA, USG etc.
Reassure and Medical Mx
Continue with method
Last accessed on 29th Aug 2011 http://www.fsrh.org/pdfs/UnscheduledBleedingMay09.pdf
Examination or No Examination?
When is it Required?
Providing there has been consistent
and correct use of hormonal
contraception, examination is
warranted to visualize the cervix by
speculum examination
When is it not Required?
• Unscheduled bleeding in the first 3
months after starting a new hormonal
contraceptive method is common
• Persistent bleeding beyond the first
3 months use
• After taking a clinical history there are
no risk factors for STIs, no concurrent
symptoms suggestive of underlying
causes
• New symptoms or a change in
bleeding after at least 3 months use
• Cervical cancer screen completed
• If requested by the woman
• After a failed trial of the medical
management available
• If there are other symptoms such as
pain, dyspareunia or post-coital
bleeding
• Cervical cancer screen
Some women may be happy to continue
with the method after this initial
assessment but follow-up should be
planned as bleeding may persist
Agenda
• Understanding ‘Unscheduled Bleeding’
• Managing Unscheduled Bleeding - RCOG 2009 and
other guidelines
• Using hormonal contraception with the right dose of
estrogen
Expected Bleeding Patterns with Hormonal
Contraception
Before starting hormonal contraception, women should be advised about
the expected bleeding patterns, both initially and in the longer term
Medical Eligibility Criteria (U.K MEC) on use of Hormonal
Contraception in women with different vaginal bleeding patterns
Vaginal Bleeding patterns
Hormonal
Contraceptives
Progesterone only
Pills
Progesterone only
injections
Irregular bleeding without heavy
bleeding
1
2
2
Heavy or prolonged bleeding
(includes
regular or irregular)
1
2
2
Unexplained vaginal bleeding
(suspicious
of serious pathology) before
evaluation
2
2
3
Medical Eligibility Criteria (MEC)
1: A condition for which there is no restriction for the use of the contraceptive method
2: A condition for which the advantages of using the method generally outweigh the theoretical or proven risks
3: A condition where the theoretical or proven risks usually outweigh the advantages of using the method
4: A condition that represents an unacceptable health risk if the contraceptive method is used.
Management of Unscheduled Bleeding in Women on
Hormonal Contraception: RCOG 2009 Guidelines
Combined Hormonal
Contraception
• In general, continue with the
same pill for at least 3 months
as bleeding may settle in this
time
• Use a COC with a dose of EE
to provide the best cycle
control
Progesterone only Pill
Users
• May try a different POP
although there is no
evidence that changing the
progestogen type or
increasing the dose
improves bleeding
• May consider increasing the
EE dose up to a max. of 35
μg
• May try a different COC but
no evidence one better than
any other in terms of cycle
control
• No evidence changing
progestogen dose or type
improves cycle control but
may help on an individual
basis
• No evidence to support the
use of two POPs per day to
improve bleeding
Progestogen only
implants, injectable/
IUS
• A first-line COC (3035μg EE) may be
considered for up to 3
months continuously or in
the usual cyclical regimen
(unlicensed)
• No evidence reducing
injection interval for
DMPA improves bleeding,
however the injection can
be given up to 2 weeks
early
• Mefenamic acid 500 mg
twice (or as licensed use
up to three daily) for 5
days for women with
bleeding on DMPA to
reduce the duration of the
bleeding interval, no
long-term benefit
More Evidence on Management of Unscheduled Bleeding in
women using hormonal contraception
•
Unscheduled bleeding is less common with combined (E & P) methods than with
progestogen-only methods
•
Any unscheduled bleeding with COC use usually settles with time and therefore
changing to another COC in the first 3 months is not recommended
•
Women should use a COC with the lowest dose of EE to provide good cycle
control. Cycle control may be better with COCs containing 30–35 μg EE than 20
μg EE
•
Data does not support increasing the dose of EE in women already using a 30
μg COC
•
A Cochrane review concluded there was insufficient evidence to recommend the
use of a biphasic and triphasic COC to improve bleeding patterns
Agenda
• Understanding ‘Unscheduled Bleeding’
• Managing Unscheduled Bleeding - RCOG 2009 and
other guidelines
• Using hormonal contraception with the right dose of
estrogen
Breakthrough (Unscheduled) Bleeding
– Annoying
– Inconvenient
– Primary reason reported for brand/strength switching
Women who experience BTB are
substantially more likely to discontinue OCs
than women without these problems
Unintended Bleeding: Major Cause of
Discontinuation
• A survey of 1657 women
• Frequency & reason for discontinuation
• 46% discontinued the use of OCPs in 6 months;
– 12% Unintended bleeding
– 7% Nausea
– 5% Weight gain
– 5% Mood changes
– 4% Breast tenderness
– 4% Headache
– 9% clinician recommended
>4/5th of women who discontinued oral contraceptives
remained at risk of unintended pregnancy either failed
to adopt another method or adopted a less effective method
n= 293
Rosenberg MJ et al Am J Obstet Gynecol 1998;179:577-82
Is it important to consider the Estrogen
dose in OCPs?
Evolution of COCs characterized by reduction in estrogen dose
FDA approval of Enovid®
Norethynodrel 10 mg + mestranol 150 micrograms
German approval of Anovlar®
Norethisterone 4 mg + ethinylestradiol 50 micrograms
EMEA approval of Minesse®
Gestodene 0.06 mg + ethinylestradiol 15 micrograms
1960 1961
2000
Marked reduction in prescribed COC
estrogen dose 1964 to 1988
Retail oral contraptive prescriptions by estrogen
dose, United States
Gerstman B et al. Am J Pub Health 1991;81:90–96
High-dose estrogen COCs linked to
macrovascular risk
Cerebral thromboembolic risk with oral contraceptives
according to estrogen content
3.5
Odds ratio
3
2.5
2
1.5
1
0.5
0
OC non-users
Progestin
only
30–40 mcg
estrogen
OC=oral contraceptive
Lidegaard Ø et al. BMJ 1993;306:956–963
50 mcg
estrogen
Unopposed estrogen associated with
risk of endometrial cancer
• Women taking estrogen without progesterone have
twice the risk of endometrial cancer versus women
not taking unopposed estrogen
• Risk of endometrial cancer increases with duration of
exposure to estrogen in absence of progesterone
McDonald TW et al. Am J Obstet Gynecol 1977;127:572–258
Main results
•
No differences were found in contraceptive effectiveness for the 13 COC
pairs for which this outcome was reported
•
Compared to the higher-estrogen pills, several COCs containing 20 μg EE
resulted in higher rates of early trial discontinuation overall and due to
adverse events such as;
– Irregular bleeding
–  risk of bleeding disturbances (both amenorrhea or infrequent
bleeding, irregular, prolonged, frequent bleeding, or breakthrough
bleeding or spotting)
20 μg EE or > 20 μg EE ?
Cochrane collaboration
Authors’ conclusions
• While COCs containing 20 μg EE may be theoretically safer, this
review did not focus on the rare events required to assess this
hypothesis. Data from existing randomized controlled trials are
inadequate to detect possible differences in contraceptive
effectiveness.
• Low-dose estrogen (20 μg EE ) COCs resulted in higher rates of
bleeding pattern disruptions.
Irregular bleeding declines to below pretreatment level
with Monophasic Desogestrel (30 μg EE) and Triphasic
Levonorgestrel
Monophasic desogestrel
45
40
Lachnit
Cullberg
35
Dieben
percentage
Mall-Haeveli
30
Data on file
Organon Int.
25
Triphasic levonorgestrel
45
40
Lachnit
Cullberg
35
Dieben
20
15
15
10
10
5
5
12 3
6
9
cycle
12
Allen
Toogood
25
20
0
Upton
30
0
1 2 3
6
9
12
cycle
Irregular bleeding occurs more in first few cycles but declines to
below pretreatment level
Rekers and Kloosterboer 1988
Main results
• Of 21 trials included, 18 examined contraceptive effectiveness: the triphasic
and monophasic preparations did not differ significantly
• No significant differences were found in the numbers of women who
discontinued due to medical reasons, cycle disturbances, intermenstrual
bleeding or adverse events
Authors’ conclusions
• The available evidence is insufficient to determine whether triphasic OCs differ
from monophasic OCs in effectiveness, bleeding patterns or discontinuation rates.
• Therefore, we recommend monophasic pills as a first choice for women
starting OC use.
• Large, high quality RCTs that compare triphasic and monophasic OCs with
identical progestogens are needed to determine whether triphasic pills differ from
monophasic OCs.
Experience of over 1,90,000 cycles!
30 μg EE and 150 μg DSG Pill
BTB at the end of cycles
• 14 Clinical Trials with 19,000 women
and over 1,90,000 cycles
• No pregnancies due to method failure
overall (PI- 0.12)
• Incidence of BTB- 0.1%-6.0%
• Incidence of subjective s/e low
• No significant change in hematological
and metabolic changes
Trial
Number
BTB%
Lanchit and fixon et al
277
2.1
Dieben et al
475
6.0
Wiseman et al
208
5.5
Billota and Favilli et al
13290
0.1
Rekers et al
1690
5.2
Van Trappen et al
219
4.0
1221
2.9
Walling et al
• 2-3 fold  in SHBG levels with fall in
testosterone levels
Fotherby.K. Contraception. 1995; 51:3-12
30 μg EE dose and Postponement of withdrawal bleeding
Percentage of women without irregular bleeding
cumulative percentage of women
100
90
80
70
60
50
40
30
Marvelon
LNG 150/30
LNG triphasic
20
10
0
0
3
6
9
12
15
18
21
24
27
30
33
days
Hamerlynck et al 1987
Marvelon is available as Novelon in India
36
39
42
(N=100)
In Summary
• Examination, investigation or treatment is essential for bleeding
patterns are outside the expected normal patterns. Pre-method
counseling about expected bleeding patterns is helpful
• High-dose estrogen COCs linked to macrovascular risk. Use a
COC with a dose of EE to provide the best cycle control, may
consider increasing the EE dose up to a max. of 35 μg
• Using the Appropriate Low Dose of EE is critical for avoiding
estrogen related side effects, risks, irregular bleeding and
improving compliance
Questions