Perimenopausal bleeding

Perimenopausal bleeding
comprehensive evaluation to save
uterus.

Veerendrakumar CM
MD.,DNB

Professor
Dept of OBG,VIMS,Bellary.
11/14/2013

Prof.Veerendrakumar,VIMS, Bellary.

1

READ/LISTEN/TALK to


Not to contradict & Confute.
Nor to believe & take it for granted.
Nor to find & discourse.
But to weigh & consider.
Francis Bacon

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2

Litigant and evidence based world..
Don’t simply knock off the uterus.
 Uterus is a marker of FEMINITY.
 Make all efforts to save it




Comprehensive evaluation can offer
specific treatment.

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Perimenopausal bleeding


It is 3-5 years period before menopause
with increase frequent irregular
anovulatory bleeding followed by
episodes of ammenorrhea and
intermittent menopausal symptoms.

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low resource …


basic investigations for abnormal uterine
bleeding (AUB) –
bearing in mind issues of effectiveness and
cost effectiveness.

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

Ideally, the evaluation is comprehensive,
considering each of the potential
etiological domains as defined by FIGO
PALM-COEIN system for Causes.
International Journal of Gynecology and Obstetrics
113 (2011) 3–13

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Figo classification of causes of AUB

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

the extent of investigations will be
significantly influenced by the

technologies available and the time allotted
for a consultation.

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

investigations should be performed only if
they will make a material difference to the
management approaches that can be
offered.

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AUB


heavy menstrual bleeding (HMB),
intermenstrual bleeding (IMB), and
irregular menstrual bleeding are very
common.

Semin Reprod Med 2011;29(5):383–390

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Medications that can be associated
with abnormal uterine bleeding
Anticoagulants
 Antidepressants (SSRIand tricyclics)
 Hormonal contraceptives
 Tamoxifen
 Antipsychotics
 Corticosteroids
 Herbs: ginseng,chasteberry,danshen


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Systematic investigation



Determination of the clinical impact of
the symptom with HMB



Evaluation of the patient for the
underlying cause

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Assesmeent of blood loss..
Frequency of changing "menstrual protection"
items, use of "double" protection;
 changing menstrual protection at night; selfconsciousness about odor; inability to contain
"gushes" of menstrual
 flow; embarrassment at being unable to contain
"gushes" of flow, and preparations and rituals to
prevent embarrassing episodes.


NICE Guideline 44; Heavy menstrual bleeding.
Women Health 2010;50(2): 195–211
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Pelvic examination


pelvic signs are picked up with low
sensitivity and specificity in most situations,
especially when influenced by obesity and
the nervous patient.

postgraduate training improves the accuracy
of this examination,
Int J Gynaecol Obstet 2005;88(1):84–88



it is of great value in the evaluation of the
cervix.
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Labortatory assesment


Evaluation for coagulopathies that may
contribute to HMB (AUB-C) is important
in any setting

Ann Hematol 2005;84(5):339–342
Fertil Steril 2005;84(5):1345–1351

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Acquire knowledge and clinical
skills to Comprehensively
evaluate the uterus
1. assessment of the endometrium for the
presence of hyperplasia or malignancy;
2.visualization of the endometrial cavity and cervical
canal for localized Lesions and
3.evaluation of the structure of the uterine wall for
adenomyosis, leiomyomas, and,

more rarely, arteriovenous malformations.
Semin Reprod Med 2011;29(5):391–399
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Ultrasound


TVUS is undoubtedly the primary imaging
modality



highly dependent on the skill and
experience of the ultrasound operator
and contemporary machine !!!

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TVUS


…an excellent tool for the
determination of whether further
investigation with curettage or some
form of endometrial biopsy is
necessary
Am J Obstet Gynecol. 2003 Feb;188(2):401-8.

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Typically, endometrial thickness is actually
measured and reported as the sum of the
two adjacent layers of endometrium, in
essence a double thickness,
a measurement called


the Endometrial Echo Complex, or EEC.

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as long as the EEC thickness is ≤12 mm
(in premenopausal women), there is a
very low incidence of
endometrial hyperplasia or neoplasia.


Ultrasound Obstet Gynecol 1998;11(5):337–342

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Who should undergo
endometrial sampling?








AUB and an EEC >12 mm should be sampled.
age >45 years;
obesity (>90 kg)
a history of chronic anovulation,
infertility, or diabetes;
a family history of endometrial cancer; and
prolonged exposure to unopposed estrogens or
tamoxifen.
Am J Obstet Gynecol 1999;181(3):525–529



Colorectal cancer affected families with AUB
regardless of age
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Endometrial sampling


Histological assessment of the
endometrium requires a biopsy or
curettage to evaluate for endometrial
hyperplasia or malignancy (AUB-M).

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

Office endometrial sampling has a
reasonably high accuracy and detects 67
to 96% of endometrial carcinomas.



J Reprod Med 1995;40(8):553–555

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

insufficient tissue obtained for diagnosis
has been reported in 4 to 20% of cases.
Gynecol Obstet Invest 1994;37(4):260–262

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D and C left to Oblivion ???

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Récamier's operation ( D &C )
named after French gynecologist who
designed curette.

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Options

D&C

Endomet
biopsy

USG

Hysteroscopy
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Dilatation and curettage alone should not be
used as a diagnostic tool.
suggested that D&C does not give additional diagnostic
information over and above a hysteroscopy with
endometrial biopsy and it is not therapeutic in cases of
heavy menstrual bleeding



NICE clinical guideline 44

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Heavy menstrual bleeding


28



D&C should no longer be used as
the first-line method of investigating
PMB in most cases.



Scottish Intercollegiate Guidelines 2011

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

it is limited in its ability to access the tubal
cornua of the uterus.



Hysteroscopy with biopsy provides more
information than dilatation and curettage
alone and rivals the combination of salineinfusion sonohysterography and endometrial
biopsy in its ability to diagnose polyps,
submucous fibroids, and other sources of
abnormal uterine bleeding.

Am Fam Physician. 2004 Apr 15;69(8):1915-1926.
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

Hysteroscopy with directed biopsy is
more sensitive in disclosing all types of
uterine lesions than dilatation and
curettage.



Curettage done after hysteroscopy and
directed biopsy does not improve the
detection of endometrial cancer

Eur J Gynaecol Oncol. 2007;28(5):400-2.

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

We support hysteroscopy as a
routine alternative to dilatation and
curettage in the diagnosis of
postmenopausal bleeding
J Obstet Gynaecol. 2001 Jan;21(1):67-9

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D&C missed 58% (25/43) of polyps,
 50% (5/10) of hyperplasias,
 60% (3/5) of complex atypical Hyperplasias, and
 11% (2/19) of endometrial cancers.


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



The limitations of D&C are due to the
blindness of the sampling procedure.

George Vorgias,etal 10/14/2003; Medscape General Medicine. 003;5(4)

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

dilatation a



YOU SHOULD NOT BE OFFERED…



oral progestogens for use only in the second
half of your menstrual cycle



drugs called danazol and etamsylate
D and C, which involves scraping out the womb
lining – as a treatment or test on its own
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Endometrial Biopsy (EMB)
Safe, simple office procedure

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Both EB and D& C


ineffective at diagnosing focal lesions.
Polyps (AUB-P) are frequently missed (up
to 50%) by blind techniques, which may
include cases of focal atypical hyperplasia
and carcinoma especially in
premenopausal cases.
Cancer 2000;89(8):1765–1772

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Structural abnormalities
P –Polyp
 A-Adenomyosis
 L-Leiomyoma
 M-Malignancy- endometrial hyperplasia
and endometrial carcinoma.


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

advanced TVUS developments have
improved our ability to detect and define
certain structural lesions.

-saline infusion sonography (SIS),
-color-flow Doppler assessment, and
-3D imaging techniques.

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Endometrial Polyp
3D Ultrasound

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Saline infusion sonogram (SIS)
Sonohysterography.
 Hysterosonography,
 Transvaginal sonography (TVS) with fluid
contrast augmentation
 Saline infusion sonogram (SIS)


Parson, J Clin Ultrasound 1993
Goldstein J Ultrasound Med 2001;
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SIS






Performed during proliferative phase
Not later than 10 days
Post menopuasal bleeding – any time
Women on HRT time it during withdrawal
or during progesterone phase
Bleeding not a contraindication but clot can
make interpretation difficult. But doppler can
differentiate cavitory lesions.

‘standard for the performance of saline
infusion sonohysterography. J Ultrasound
Med 2003
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SIS
If a focal lesion is identified on SIS, that
lesion can be treated with hysteroscopy.
 Those patients who do not have a focal
lesion can be spared hysteroscopy in
many cases.


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meta-analysis of 5892 women.


Using a double-wall thickness of 5 mm,the
sensitivity for detecting endometrial
cancer was 96%



A thin endometrium of 5 mm or less
had a high negative predictive value, and
this finding would support the diagnosis
of atrophy
JAMA 1998; 280:1510–1517.
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Pipelle curette is “excellent for detecting
endometrial processes when the
pathology is global in nature.”
 When a focal lesion is detected a visually
directed biopsy is indicated.


J Reprod Med 1995; 40:553–555.

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

In postmenopausal women, polyps are
found to be the cause of bleeding in
approximately 30% of cases.

Most of these polyps are benign.
 malignancy in polyps ranges from 0.5% to
1.5%.




Eur J Gynaecol Oncol 2000; 21:180–183.

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

Transvaginal sonography cannot
distinguish endometrial hyperplasia from
benign polyps



both conditions can cause thickening of
the endometrium, are hyperechoic, and
can contain cystic spaces.

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Saline infusion
sonohysterography


can distinguish focal lesions from diffuse
endometrial thickening. Polyps are focal
lesions, which project into the lumen of
the endometrial cavity

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Normal endometrium

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Endometrial polyp

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Multiple polyps
Longitudinal section

Transverse section

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Sub mucous fibroid & polyp

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Blood clot in the cavity
After dislodging with the catheter

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

If the fibroid projects into the lumen
by more than 50% of its surface, then it
can be resected by hysteroscopy, obviating
an abdominal surgical procedure

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Endometrial hyperplasia

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SIS for monitoring the pts on
Tamoxifen


the finding of a normal endometrium on
SIS allowed these patients to avoid
further intervention.
Am J Roentgenol 1997; 168:657–661.

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Future direction


Endometrial biopsy with real time usg
guidance
Dubinsky AJR Am J Roentgenol 2000

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SIS


Saline infusion sonohysterography is a
simple technique that yields additional
information over TVS in evaluation of
endometrial and subendometrial
conditions.

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Clinical impact
SIS added certainty to the
diagnosis in 88% of the patients studied.
 SIS results changed the patients’
treatment in 80% of cases.
 increased diagnostic confidence by 86%.


Radiology 2000; 216:260–264.

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hysteroscopy


In the presence of an abnormally thick
endometrium, when myomas exist
suspiciously close to the EEC or when
abnormal bleeding occurs or persists
despite a normal TVUS, hysteroscopy is
indicated.

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

Endometrial carcinoma and endometrial
hyperplasia (AUB-M), especially those
arising as a field defect, may not always be
clearly recognizable by hysteroscope
alone, which should be performed in
conjunction with endometrial biopsy.



Am J Obstet Gynecol 2007;196(3):243; e1-e5

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SIS v/s Hysteroscopy
SIS is comparable to hysteroscopy in its
sensitivity for the diagnosis of
intracavitary polyps and submucosal
myomas
 In SIS- limited evaluation of the
endocervical canal and the inability to
concurrently remove selected lesions



Fertil Steril 2010;94(7):2720–2725
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One stop clinic..


Office hysteroscopy may be more cumbersome,
involves a steeper learning curve than either
TVUS or SIS, and may also be more
uncomfortable for the patient.



likely to achieve a primary diagnostic role if
narrow, rigid, or flexible scopes are used without
anesthesia or only with local cervical anesthesia
and with low-pressure saline distension in an
"office" situation
Clinical practice guidelines..Eur J Obstet Gynecol

Reprod Biol 2010;

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Low resource settings..
When TVUS (including SIS) and
hysteroscopy are available, it is
recommended they be used in
complementary fashion.
 In this way, hysteroscopy can be used
more selectively to exploit its use as a
therapeutic tool for the performance of
targeted biopsy, polypectomy, or
myomectomy.


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Myometrial evaluation
TVUS is generally useful for the
evaluation of myomas, 3 D may give
additional information.
 TVUS is quite sensitive for the diagnosis
of diffuse adenomyosis.
 Color flow Doppler is of value for the
detection of
 arteriovenous malformations ,vascular
hyperplasias and malignancies. And focal
adenomyosis.


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Therapy


Once malignancy and significant pelvic
pathology have been ruled out, medical
treatment is an effective first-line
therapeutic option for abnormal uterine
bleeding.

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NSAID
reduced menstrual blood loss by 33% to
55% when compared with placebo,
without a significant difference in adverse
effects.
 added benefit of improving
dysmenorrhea for up to 70% of patients.
 START before the day of menses and
continue for 3-5 days.


Cochrane Database Syst Rev 2007;
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Tranexemic acid
overall reduction in menstrual blood loss
between 40% and 59% from baseline.
 1 gram of tranexamic acid taken orally
every 6 hours during menstruation, but a
single daily dose of 4 grams has also been
found to be effective
 Intravenous tranexamic acid is available
for more acute scenarios, with a dose of
10 mg/kg every 6 hours.


Cochrane Database Syst Rev 2000;4:CD000249.
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

superiority of tranexamic acid to lutealphase progestins and NSAID
BMJ 1996;313:579–82



No statistically significant increase in VTE

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Hormonal..


cyclic luteal-phase progestin therapy is
significantly less effective in treating
“menorrhagia” than NSAIDS, tranexamic acid, or
danazol



In contrast, long-cycle, high-dose oral progestins
have been shown to reduce menstrual losses for
women with heavy menstrual bleeding.



There are no published trials investigating the
impact of DMPA on abnormal uterine bleeding
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

Woman has never learned to live
healthy & happy without
progesterone coverage of estrogen
primed state



Its not simply a Pregnancy Hormone.
But in true sense,
‘A Mother Hormone.’
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LNG-IUS
Maximal Benefits Outweigh Minimal
Risks.


A reduction in menstrual blood loss of
86% at 3 months and 97% at 12 months
was demonstrated in a single-arm study
on the use of the LNG-IUS in women
with menorrhagia,



20-80% become amenorrhic by 12
months.
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

Hurskainen et al. randomized women with
menorrhagia to receive either a hysterectomy or
insertion of the LNG-IUS. The two groups had
similar health-related quality of life scores at 5
years.
JAMA 2004;291:1456–63.



women awaiting hysterectomy,
Over two thirds of the women who had the LNGIUS inserted cancelled their surgery versus just
14.3% in the control group.
BMJ 1998
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

Danazol and gonadotropin-releasing
hormone agonists will effectively reduce
menstrual bleeding, and may be used for
scenarios in which other medical or
surgical treatments have failed or are
contraindicated. (I-C).

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SERM’s – The Designer Estrogens

 SERMs are designed to
act in a specific ways at
each of the receptor sites
 J Clin Oncol 2000 18:3172-3186.

Estrogens

SERMs
Tomoxifine
Droloxifine
Toremifine
Raloxifine

Ormeloxifine

Antiestrogens

J Clin Oncol 2000 18:3172-3186.

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Ideal SERM for DUB


No uterine stimulation



Prevents bone loss



Has no risk for breast cancer



Has a positive effect on lipids &
cardiovascular system



Maintains cognitive function of the brain

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Ormelloxifene

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Weekly twice for 12 weeks
weekly once for 12 weeks
74 of 85 subjects (87%) showed a reduction in
endometrial thickness
Only 8.2% of women needed hysterectomy
J Obstet Gynecol Ind vol. 54, No 1 2004

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

Amenorrhea with the therapy – 18 patients
(42.9%)



ovarian cyst (7.1%), cervical erosion and
discharge (7.1%), gastric dyspepsia (4.8%),
vague abdominal pain (4.8%) and headache
(4.8%)
J. Obstet. Gynaecol. Res. 2009

Ormeloxifene is more effective as compared to MPA in
reducing the blood loss in the treatment of DUB.
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Surgical management
indications-failure to respond to medical therapy,
-inability to utilize medical therapies (i.e.
side effects, contraindications),
-significant anemia,
-impact on quality of life, and
-concomitant uterine pathology (large
uterine fibroids, endometrial hyperplasia).

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2nd generation techniques
recommended


Several non-hysteroscopic ablation
techniques are currently available.



Balloon, microwave, and radiofrequency
ablation devices have a large reported
clinical experience.



avoids the use of operating room resources
and general anaesthetic.
SOGC guidelines 2013
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SOGC GUIDELINES 2013

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HYSTERECTOMY
THE most definitive treatment.
 Consider the least invasive method.


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

From Research to Practice –
Long Way to Go…..
Technology made large populations
possible and large populations today make
technology indispensible

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Perimenopausal bleeding

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