Management of Unscheduled Bleeding

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Management of Unscheduled Bleeding

• Dr.Suma Natarajan MD DGO FAGE
• HOD,Ganga Women Child Centre

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Agenda

• Understanding Unscheduled Bleeding
• Managing Unscheduled Bleeding - RCOG 2009 and
  other guidelines
• Using hormonal contraception with the right dose
  of estrogen

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Agenda

• Understanding Unscheduled Bleeding
• Managing Unscheduled Bleeding - RCOG 2009 and
  other guidelines
• Using hormonal contraception with the right dose
  of estrogen

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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

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Scheduled vs Unscheduled bleeding

• Scheduled bleeding
• Menstruation or regular withdrawal bleeding with
  combined hormonal contraception (requiring
  sanitary protection)

Unscheduled bleeding
Frequent Bleeding gt5 bleeding episodes
Prolonged bleeding 1/ more bleeding episodes
lasting 14 days
Irregular bleeding 3 -5 episodes with
fewer than 3 bleeding-free intervals of length 14
days
Spotting May not require the use of sanitary
protection
Breakthrough bleeding Unscheduled bleeding in
women using hormonal contraception
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• Clinical history
• Identify or exclude some of the possible
  underlying causes of unscheduled bleeding

• Cervical Cancer Screen
• 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
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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 lt25 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

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Preliminary Evaluation
Unscheduled Bleeding
Cervical Cancer
History
Pregnancy Test
Exclude STI

• lt3 months in a method
• Exclude above
• Investigations if Requested by woman
• Reassure and arrange follow-up
• Medical management may be considered

• gt3 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
Speculum and bimanual Examination
Follow-up Visit
Speculum Examination
Clinical Finding Mx as Indicated
Normal
Bleeding Settled
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
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Examination or No Examination?

• When is it not Required?
• Unscheduled bleeding in the first 3 months after
  starting a new hormonal contraceptive method is
  common
• After taking a clinical history there are no risk
  factors for STIs, no concurrent symptoms
  suggestive of underlying causes
• Cervical cancer screen completed
• Some women may be happy to continue with the
  method after this initial assessment but
  follow-up should be planned as bleeding may
  persist

• 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
• Persistent bleeding beyond the first 3 months use
• New symptoms or a change in bleeding after at
  least 3 months use
• 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

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Agenda

• Understanding Unscheduled Bleeding
• Managing Unscheduled Bleeding - RCOG 2009 and
  other guidelines
• Using hormonal contraception with the right dose
  of estrogen

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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
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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.
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Management of Unscheduled Bleeding in Women on
Hormonal Contraception RCOG 2009 Guidelines
Combined Hormonal Contraception
Progesterone only Pill Users
Progestogen only implants, injectable/ IUS

• 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
• 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

• May try a different POP although there is no
  evidence that changing the progestogen type or
  increasing the dose improves bleeding
• No evidence to support the use of two POPs per
  day to improve bleeding

• A first-line COC (30-35µg 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

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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 3035 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

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Agenda

• Understanding Unscheduled Bleeding
• Managing Unscheduled Bleeding - RCOG 2009 and
  other guidelines
• Using hormonal contraception with the right dose
  of estrogen

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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
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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

gt4/5th 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
1998179577-82
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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
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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 1991819096
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Reducing estrogen dose rationale

• Reduce safety risk
• Maintain endometrial support
• No longer provides contraceptive efficacy

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High-dose estrogen COCs linked to macrovascular
risk
Cerebral thromboembolic risk with oral
contraceptives according to estrogen content
Odds ratio
Progestin only
3040 mcg estrogen
50 mcg estrogen
OC non-users
OCoral contraceptive
Lidegaard Ø et al. BMJ 1993306956963
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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
1977127572258
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• 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)

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20 µg EE or gt 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.

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Irregular bleeding declines to below
pretreatment level with Monophasic Desogestrel
(30 µg EE) and Triphasic Levonorgestrel
Monophasic desogestrel
Triphasic levonorgestrel
45
45
Lachnit
Lachnit
Cullberg
Cullberg
40
40
Dieben
Dieben
35
35
Mall-Haeveli
Upton
30
30
Data on file Organon Int.
Allen
Toogood
25
25
percentage
20
20
15
15
10
10
5
5
0
0
1
2
3
6
9
12
1
2
3
6
9
12
cycle
cycle
Irregular bleeding occurs more in first few
cycles but declines to below pretreatment level
Rekers and Kloosterboer 1988
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• 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.

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Experience of over 1,90,000 cycles!30 µg EE and
150 µg DSG Pill

• 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
• 2-3 fold ? in SHBG levels with fall in
  testosterone levels

BTB at the end of cycles
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
Walling et al 1221 2.9
Fotherby.K. Contraception. 1995 513-12
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30 µg EE dose and Postponement of withdrawal
bleeding Percentage of women without irregular
bleeding
100
90
80
70
60
cumulative percentage of women
50
40
30
Marvelon
20
LNG 150/30
LNG triphasic
10
0
0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
days
(N100)
Hamerlynck et al 1987
Marvelon is available as Novelon in India
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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

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Questions