Transcript 48e19bf616d9411ba5b605c7c6fede8e

Perimenopausal Bleeding:
The Roller Coaster of Mid-life
Steven R. Goldstein, M.D..FACOG,CCD,NCMP, RCOG(H)
Professor of Obstetrics & Gynecology
New York University School of Medicine
Director of Gynecologic Ultrasound
Co-Director of Bone Densitometry
New York University Medical Center
PERIMENOPAUSE (DEFINED)
Harlow, Siobán D., et al. Executive summary of the Stages of Reproductive
Aging Workshop+ 10: addressing the unfinished agenda of staging
reproductive aging. Climacteric 2012: 15.2 : 105-114.
• The STRAW+10 system for reproductive aging in
women defined “perimenopause” as the “early”
and “late” menopausal transition.
“Early” menopausal transition:
• Variable duration
• Cycle length variable “persistent ≥ 7day difference
in length of consecutive cycles”.
• Lab tests
– FSH: variable
– AMH (Anti- Mullerian Hormone): low
– Inhibin B: low
• Antral follicle count: low
“Late” Menopausal Transition
• Duration 1-2 years.
• Interval of amenorrhea of ≥ 60 days.
• Lab tests
– FSH: elevated
– AMH: low
– Inhibin B: low
• Vasomotor symptoms “likely”.
PERIMENOPAUSE:
CLINICAL SEQUELAE
• Some have likened perimenopause as the mirror
image of adolescence.
• Corollary to this: one is the coming onto the
reproductive years, the other the coming off.
PERIMENOPAUSE:
CLINICAL SEQUELAE
• Characterized by oligoovulation
– Hallmark of ovulation: regular cyclic, predictable menses.
– Hallmark of anovulation/oligoovulation: irregular timing
and length of uterine bleeding.
MENSES: “A uterine bleed
preceded two weeks by
ovulation”
• DYSFUNCTIONAL UTERINE BLEEDING (DUB): erratic
estrogen production without ovulation resulting in
unpredictable bleeding.
• Thus bleeding associated with oligo-or anovulation
will be characterized by its irregular nature (heavy,
light, with or without cramps, longer or shorter
intervals)
PSYCHOSOCIAL SYMPTOMS
Dennerstein et al Med J Aust 1993
• This menstrual pattern has also been associated with
psychosocial symptoms’ exacerbation or initiation,
including:
– Free floating anxiety
– Inability to concentrate
– Sleep disturbances
– Mood swings
– Memory changes
PSYCHOSOCIAL SYMPTOMS
• Obviously it is difficult to distinguish how much of
this is hormonally mediated and how much is natural
aging or situational.
DIAGNOSTIC EVALUATION OF
ABNORMAL UTERINE BLEEDING
Practice Bulletin No. 128. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2012;120:197–206
Medical History
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Age of menarche and menopause
Menstrual bleeding patterns
Severity of bleeding (clots or flooding)
Pain (severity and treatment)
Medical conditions
Surgical history
Use of medications
Symptoms and signs of possible hemostatic disorder
DIAGNOSTIC EVALUATION OF
ABNORMAL UTERINE BLEEDING
Practice Bulletin No. 128. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2012;120:197–206
Physical Examination
• General physical
• Pelvic Examination
– External
– Speculum with Pap test, if needed
– Bimanual
DIAGNOSTIC EVALUATION OF
ABNORMAL UTERINE BLEEDING
Practice Bulletin No. 128. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2012;120:197–206
Laboratory Tests
• Pregnancy test (blood or urine)
• Complete blood count
• Targeted screening for bleeding disorders (when
indicated)
• Thyroid-stimulating hormone level
• Chlamydia trachomatis culture
DIAGNOSTIC EVALUATION OF
ABNORMAL UTERINE BLEEDING
Practice Bulletin No. 128. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2012;120:197–206
Available Diagnostic or Imaging Tests (when indicated)
• Transvaginal ultrasonography
• Saline infusion sonohysterography
• Hysteroscopy (preferably office-based)
DIAGNOSTIC EVALUATION OF
ABNORMAL UTERINE BLEEDING
Practice Bulletin No. 128. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2012;120:197–206
Available Tissue Sampling Methods (when indicated)
• Office endometrial biopsy
• Hysteroscopy directed endometrial sampling (office
or operating room)
FIGO Nomenclature: PALM-COEIN
Abnormal Uterine Bleeding (AUB)
-Heavy menstrual bleeding (AUB/HMB)
-Intermenstrual bleeding (AUB/IMB)
PALM: Structural Causes
Polyp (AUB-P)
Adenomyosis (AUB-A)
Leiomyoma (AUB-L)
Submucosal myoma (AUB-Lsm)
Other myoma (AUB-Lo)
Malignancy & hyperplasia
(AUB-M)
COEIN: Nonstructural Causes
Coagulopathy (AUB-C)
Ovulatory dysfunction (AUB-O)
Endometrial (AUB-E)
Iatrogenic (AUB-I)
Not yet classified (AUB-N)
Adapted from Practice Bulletin No. 128. ACOG Obstet Gynecol 2012;120:197–206
GYN ISSUES
• Obviously these are FINAL diagnoses. Thus when
such patients present, the diagnostic challenge is
structural vs. non-structural.
• In the past, blind endometrial sampling (D&C, Vabra
aspirator, suction piston biopsy instruments) were
standard procedures.
THE STANDARD OF CARE
HAS CHANGED!!!!
BUT HOW MANY
CLINICIANS ARE AWARE
OF IT?
HIGHLIGHTS OF NEWEST ACOG
BULLETIN
Practice Bulletin No. 128. American College of Obstetricians
and Gynecologists. Obstet Gynecol 2012;120:197–206
“DIAGNOSIS OF AUB IN REPRODUCTIVE
AGED WOMEN”
ACOG PRACTICE BULLETIN
JULY 2012
“One third of outpatient visits to the gynecologist
are for AUB and it accounts for more than 70% of
GYN consults in the perimenopausal and
postmenopausal years ”
ACOG PRACTICE BULLETIN
JULY 2012
“AUB most frequently occurs in women 19-39 as a
result of pregnancy,structural lesions (polyps,
myoma), anovulatory cycles (e.g.PCOS),hormonal
contraception and
endometrial hyperplasia.EM
carcinoma is less common but may occur in this age
group”
ACOG PRACTICE BULLETIN
JULY 2012
“In women aged 40 to menopause AUB may be due
to anovulatory bleeding which represents normal
physiology in response to declining ovarian function.
It may also be due to EM carcinoma or hypeplasia,
EM atrophy or leimyomas”
BASIC COURSE IN
HISTOLOGY
• HORMONAL STATUS OBVIOUSLY EFFECTS
ENDOMETRIAL THICKNESS
• THE ENDOMETRIUM CONSISTS OF A BASALIS
AND A FUNCTIONALIS
• ESTROGEN CAUSES THE FUNCTIONALIS TO
PROLIFERATE
PROLIFERATIVE EM
• Characterized by abundant mitoses
• In the following slide taken from a nysterectomy
specimen done in the proliferative phase note the
AMOUNT (or HEIGHT) of glandular tissue
• PROGESTERONE (OR IN SEQUENTIAL HORMONE
THERAPY THE USE OF A PROGESTIN) WILL CONVERT
AN ESTROGEN PRIMED ENDOMETRIAL FUNCTIONALIS
TO A SECRETORY PHASE
SECRETORY EM
• The following slide is also from a hysterectomy
specimen but done in the luteal phase
• Note the thickness of the functionalis as well as the
way the glands line up
• AFTER SHEDDING OF THE FUNCTIONALIS THE BASAL
ENDOMETRIUM THAT REMAINS IS INITIALLY QUITE
THIN AND APPEARS AS A THIN ECHOGENIC LINE ON
TV U/S
SINCE THERE IS NO”NORMAL’ WIDTH OF
ENDOMETRIAL THICKNESS…
WHAT IS THE PROPER USE OF THE ENDOMETRIAL
ECHO CLINICALLY?
ANSWER
THE HIGH NEGATIVE PREDICTIVE VALUE OF A THIN
DISTINCT ECHO IN PATIENTS WITH BLEEDING WHEN
U/S IS PERFORMED JUST AS THE BLEEDING ENDS
ACOG PRACTICE BULLETIN
JULY 2012
“The primary imaging test of the uterus for the
evaluation of AUB is transvaginal ultrasonography.”
ACOG PRACTICE BULLETIN
JULY 2012
“If transvaginal ultrasonographic images are not
adequate or further evaluation of the cavity is
necessary, then sonohysterography (also called saline
infusion
sonohysterography)
or
hysteroscopy
(preferably in the office setting is recommended).”
ACOG PRACTICE BULLETIN
JULY 2012
“An office endometrial biopsy is the first-line
procedure of tissue sampling in the evaluation of
patients with AUB.”
ACOG PRACTICE BULLETIN
JULY 2012
“Endometrial biopsy has high overall accuracy in
diagnosing endometrial cancer when an adequate
specimen is obtained and when the endometrial
process is global”
ACOG PRACTICE BULLETIN
JULY 2012
“If the cancer occupies less than 50% of the surface
area of the endometrial cavity, the cancer can be
missed by a blind endometrial biopsy sample.”
ACOG PRACTICE BULLETIN
JULY 2012
“A positive test result is more accurate for ruling in
disease than a negative test result is for ruling it out.”
ACOG PRACTICE BULLETIN
JULY 2012
“These tests are only an endpoint when they reveal
cancer or atypical complex hyperplasia.”
ACOG PRACTICE BULLETIN
JULY 2012
“Persistent bleeding with a previous benign pathology,
such as proliferative endometrium, requires further
testing to rule out nonfocal endometrial pathology or a
structural pathology, such as polyp or leiomyoma.”
NOW THE STANDARD OF CARE CORROBORATES THAT
A NEGATIVE BLIND BIOPSY IS NOT A STOPPING POINT.
CLINICIANS CAN STILL BEGIN WITH A BIOPSY BUT
UNLESS IT IS MALIGNANT (OR COMPLEX ATYPICAL
HYPERPLASIA) THE ENDOMETRIAL EVALUATION IS
NOT COMPLETE!
SALINE INFUSION
SONOHYSTEROGRAPHY (SIS)
THE NEXT FOUR SLIDES ARE SONOHYSTEROGRAMS OF
PERIMENOPAUSAL WOMEN WHO ALL PRESENTED
WITH IRREGULAR BLEEDING
TREATMENTS
• ANATOMIC LESIONS will usually be removed
(polyps, submucous myomas)
• Complex atypical hyperplasias and malignancy
almost always require hysterectomy (remember we
are dealing with perimenopause so PRESUMABLY
childbearing is complete)
• DYSFUNCTIONAL UTERINE BLEEDING (DUB) and
HEAVY MENSTRUAL BLEEDING (HMB) are usually
treated expectantly or hormonally
• Thus some women however will require
hormonal cycle control
• This is not the same as hormone
replacement
THE KEY TO DIAGNOSIS IS…
IS THERE STILL OVARIAN FUNCTION (albeit
erratic & pulsatile) …or NOT?
The key to successful hormonal treatment in
perimenopause is SUPPRESION of ovarian
function (i.e. ultra low dose birth control pills
in non smokers with normal blood pressure)
Traditional HRT does not suppress ovarian
function and thus may make perimenopausal
bleeding symptoms worse!
BIRTH CONTROL PILLS: SO
MISUNDERSTOOD !!!
BIRTH CONTROL PILLS:
CANCER REDUCING AGENTS
• OVARIAN CANCERS
• UTERINE CANCERS
• BREAST CANCERS (? In the low doses
currently being employed)
WHAT IS “NATURAL”?
Women stop being “natural” when they do
not have 8 children, nurse them all for 12-15
months (no bottles or formula in nature) and
probably would have had 3 miscarriages along
the way
WOMEN ARE HAVING TOO
MANY CYCLES!
• Reproductive life roughly 40 years (age 11-51)
• 13 lunar months in each calendar year results
in ~ 520 cycles
• Typical patient: 2 children, nurses 3 mos each
= 24 cycles eliminated
• That leaves 496 cycles !!!
LEFT TO NATURE...
• 8 kids x 9 months =
72
• 8 kids x 15 months =
120
• 3 miscarriages x 3 mos = 9
201
• Leaves maybe 320 cycles
… for those women whose bleeding symptoms
are significant enough
USE OF BIRTH CONTROL PILLS…
• Suppresses erratic, pulsatile ovarian function
takes the hormonal component “ off the
table”
• For most women this gives incredible
improvement, and can allow them to drift
into menopause without major surgical
intervention
IN SUMMARY
• Perimenopause is characterized by oligo and
anovulation resulting in often erratic
pulsatile estradiol production
• Perimenopause is also a time of increasing
incidence of STRUCTURAL reasons for AUB
(polyps, myomas, adenomyosis, hyperplasias
and even occassional malignancies)
IN SUMMARY
• Adequate
diagnostic
measures
can
distinguish between structural vs. non
structural causes
• Pathologies are often not global so blind
biopsy (when negative) is not an end point
• Increasingly TV U/S, sonohysterography and
office hysteroscopy will be employed
IN SUMMARY
• Appropriate treatment mandates adequate
and proper diagnosis
• Structural lesions are usually approached
surgically
• Non structural lesions are usually treated
expectantly or hormonally