The Roller Coaster of Midlife Steven R Goldstein MDFACOGCCDNCMP RCOGH Professor of Obstetrics amp Gynecology New York University School of Medicine Director of Gynecologic Ultrasound ID: 919785
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Perimenopausal Bleeding: The Roller Coaster of Mid-life
Steven R. Goldstein, M.D..FACOG,CCD,NCMP, RCOG(H)Professor of Obstetrics & GynecologyNew York University School of MedicineDirector of Gynecologic UltrasoundCo-Director of Bone DensitometryNew York University Medical Center
Slide2PERIMENOPAUSE (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.
Slide3“Early” menopausal transition:Variable durationCycle length variable “persistent ≥ 7day difference in length of consecutive cycles”.
Lab testsFSH: variableAMH (Anti- Mullerian Hormone): lowInhibin B: lowAntral follicle count: low
Slide4“Late” Menopausal TransitionDuration 1-2 years.Interval of amenorrhea of ≥ 60 days.Lab tests
FSH: elevatedAMH: lowInhibin B: lowVasomotor symptoms “likely”.
Slide5PERIMENOPAUSE: 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.
Slide6Characterized by oligoovulation Hallmark of ovulation: regular cyclic, predictable menses.Hallmark of anovulation/oligoovulation: irregular timing and length of uterine bleeding.
PERIMENOPAUSE: CLINICAL SEQUELAE
Slide7DYSFUNCTIONAL 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)
MENSES: “A uterine bleed preceded two weeks by ovulation”
Slide8PSYCHOSOCIAL SYMPTOMSDennerstein et al Med J
Aust 1993This menstrual pattern has also been associated with psychosocial symptoms’ exacerbation or initiation, including:Free floating anxietyInability to concentrateSleep disturbancesMood swingsMemory changes
Slide9PSYCHOSOCIAL SYMPTOMS
Obviously it is difficult to distinguish how much of this is hormonally mediated and how much is natural aging or situational.
Slide10DIAGNOSTIC EVALUATION OF ABNORMAL UTERINE BLEEDING Practice Bulletin No. 128. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2012;120:197–206Medical HistoryAge of menarche and menopauseMenstrual bleeding patternsSeverity of bleeding (clots or flooding)Pain (severity and treatment)Medical conditionsSurgical historyUse of medicationsSymptoms and signs of possible hemostatic disorder
Slide11Physical ExaminationGeneral physicalPelvic ExaminationExternal 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
Slide12Laboratory TestsPregnancy test (blood or urine)Complete blood countTargeted screening for bleeding disorders (when indicated)Thyroid-stimulating hormone levelChlamydia trachomatis culture
DIAGNOSTIC EVALUATION OF ABNORMAL UTERINE BLEEDING Practice Bulletin No. 128. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:197–206
Slide13Available Diagnostic or Imaging Tests (when indicated)Transvaginal ultrasonographySaline infusion sonohysterographyHysteroscopy (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
Slide14Available Tissue Sampling Methods (when indicated)Office endometrial biopsyHysteroscopy directed endometrial sampling (office or operating room)
DIAGNOSTIC EVALUATION OF ABNORMAL UTERINE BLEEDING Practice Bulletin No. 128. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:197–206
Slide15FIGO Nomenclature: PALM-COEIN
Adapted from Practice Bulletin No. 128. ACOG Obstet Gynecol 2012;120:197–206
Slide16GYN 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.
Slide17THE STANDARD OF CARE HAS CHANGED!!!!
Slide18BUT HOW MANY CLINICIANS ARE AWARE OF IT?
Slide19“DIAGNOSIS OF AUB IN REPRODUCTIVE AGED WOMEN”HIGHLIGHTS OF NEWEST ACOG BULLETIN
Practice Bulletin No. 128. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:197–206
Slide20“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
Slide21“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
Slide22“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”ACOG PRACTICE BULLETIN JULY 2012
Slide23BASIC COURSE IN HISTOLOGY
Slide24HORMONAL STATUS OBVIOUSLY EFFECTS ENDOMETRIAL THICKNESSTHE ENDOMETRIUM CONSISTS OF A BASALIS AND A FUNCTIONALISESTROGEN CAUSES THE FUNCTIONALIS TO PROLIFERATE
Slide25PROLIFERATIVE EMCharacterized 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
Slide26Slide27Slide28Slide29Slide30PROGESTERONE (OR IN SEQUENTIAL HORMONE THERAPY THE USE OF A PROGESTIN) WILL CONVERT AN ESTROGEN PRIMED ENDOMETRIAL FUNCTIONALIS TO A SECRETORY PHASE
Slide31SECRETORY EMThe 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
Slide32Slide33Slide34AFTER SHEDDING OF THE FUNCTIONALIS THE BASAL ENDOMETRIUM THAT REMAINS IS INITIALLY QUITE THIN AND APPEARS AS A THIN ECHOGENIC LINE ON TV U/S
Slide35SINCE THERE IS NO”NORMAL’ WIDTH OF ENDOMETRIAL THICKNESS… WHAT IS THE PROPER USE OF THE ENDOMETRIAL ECHO CLINICALLY?
Slide36ANSWERTHE HIGH NEGATIVE PREDICTIVE VALUE OF A THIN DISTINCT ECHO IN PATIENTS WITH BLEEDING WHEN U/S IS PERFORMED JUST AS THE BLEEDING ENDS
Slide37“The primary imaging test of the uterus for the evaluation of AUB is transvaginal ultrasonography.”ACOG PRACTICE BULLETIN JULY 2012
Slide38“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
Slide39“An office endometrial biopsy is the first-line procedure of tissue sampling in the evaluation of patients with AUB.”
ACOG PRACTICE BULLETIN JULY 2012
Slide40“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
Slide41“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
Slide42“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
Slide43“These tests are only an endpoint when they reveal cancer or atypical complex hyperplasia.”ACOG PRACTICE BULLETIN JULY 2012
Slide44“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.”ACOG PRACTICE BULLETIN JULY 2012
Slide45NOW 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!
Slide46SALINE INFUSION SONOHYSTEROGRAPHY (SIS) THE NEXT FOUR SLIDES ARE SONOHYSTEROGRAMS OF
PERIMENOPAUSAL WOMEN WHO ALL PRESENTED WITH IRREGULAR BLEEDING
Slide47Slide48Slide49Slide50Slide51TREATMENTSANATOMIC 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
Slide52Thus some women however will require hormonal cycle control This is not the same as hormone replacement
Slide53THE KEY TO DIAGNOSIS IS…
IS THERE STILL OVARIAN FUNCTION (albeit erratic & pulsatile) …or NOT?
Slide54The 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)
Slide55Traditional HRT does not suppress ovarian function and thus may make perimenopausal bleeding symptoms worse!
Slide56BIRTH CONTROL PILLS: SO MISUNDERSTOOD !!!
Slide57BIRTH CONTROL PILLS:CANCER REDUCING
AGENTSOVARIAN CANCERSUTERINE CANCERSBREAST CANCERS (? In the low doses currently being employed)
Slide58WHAT IS “NATURAL”
?
Slide59Women 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
Slide60WOMEN ARE HAVING TOO MANY CYCLES!Reproductive life roughly 40 years (age 11-51)
13 lunar months in each calendar year results in ~ 520 cyclesTypical patient: 2 children, nurses 3 mos each = 24 cycles eliminatedThat leaves 496 cycles !!!
Slide61LEFT TO NATURE...8 kids x 9 months = 728 kids x 15 months = 120
3 miscarriages x 3 mos = 9 201Leaves maybe 320 cycles
Slide62… for those women whose bleeding symptoms are significant enough
Slide63USE 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
Slide64IN SUMMARYPerimenopause 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)
Slide65Adequate diagnostic measures can distinguish between structural vs. non structural causesPathologies are often not global so blind biopsy (when negative) is not an end pointIncreasingly TV U/S, sonohysterography and office hysteroscopy will be employed
IN SUMMARY
Slide66Appropriate treatment mandates adequate and proper diagnosisStructural lesions are usually approached surgicallyNon structural lesions are usually treated expectantly or hormonally
IN SUMMARY