Download - Amenorrhea

04.11.2014

1

[email protected]@yoldemir.com

EVALUATION ANDEVALUATION ANDTREATMENT OFTREATMENT OFAMENORRHEAAMENORRHEA

Tevfik Tevfik YoldemirYoldemir, , MD, BBAMD, BBA

Marmara Marmara UniversityUniversityDepartmentDepartment of of ObstetricsObstetrics andand GynecologyGynecology

DivisionDivision of of ReproductiveReproductive EndocrinologyEndocrinology andand InfertilityInfertility

DefinitionDefinition

Primary amenorrhea: failure of menarche Primary amenorrhea: failure of menarche by by age 16age 16

Secondary amenorrhea: absence of Secondary amenorrhea: absence of menstruation for menstruation for 3 months 3 months in a woman in a woman withwith previousprevious spontaneousspontaneous mensesmenses

www.yoldemir.comwww.yoldemir.com

ClassificationClassification

1. 1. GonadalGonadal failurefailure

2. 2. ChronicChronic anovulationanovulation

WithWith estrogenestrogen presentpresent

WithWith estrogenestrogen absentabsent

3. Defects of female reproductive tract3. Defects of female reproductive tract


ClassificationClassification


GonadalGonadal failurefailure --11

GonadalGonadal (ovarian) failure is associated with (ovarian) failure is associated with increased increased gonadotropinsgonadotropins, and, and the term the term hypergonadotropichypergonadotropichypogonadismhypogonadism is used. is used.

The development of amenorrheaThe development of amenorrhea and and hypoestrogenismhypoestrogenismassociated with elevated associated with elevated gonadotropinsgonadotropins beforebefore the age the age of 40of 40 defines ovarian failure. defines ovarian failure.

Cessation of ovarian function as aCessation of ovarian function as a result of loss of germ result of loss of germ cells and follicles in the ovary can occur at any age,cells and follicles in the ovary can occur at any age,however, even in however, even in uteroutero, such as in , such as in gonadalgonadal dysgenesisdysgenesisor ovarian agenesis.or ovarian agenesis.



When ovarian failure occurs before puberty, the When ovarian failure occurs before puberty, the presentation is that of apresentation is that of a phenotypic female with primary phenotypic female with primary amenorrhea and lack of secondary sexualamenorrhea and lack of secondary sexual developmentdevelopment..

When it occurs after pubertal development, the When it occurs after pubertal development, the presentationpresentation is is secondary amenorrhea with the primary secondary amenorrhea with the primary complaint being hot flashescomplaint being hot flashes..

GonadalGonadal dysgenesisdysgenesis can be associated with normal or can be associated with normal or abnormal abnormal karyotypeskaryotypes..

Women harboring Y chromosome material have an Women harboring Y chromosome material have an increased risk ofincreased risk of gonadalgonadal tumors, and the gonads should tumors, and the gonads should be be removedremoved. .


04.11.2014

2


Rare causesRare causes of ovarian failure include 17of ovarian failure include 17--hydroxylase hydroxylase deficiency, resistant ovary syndrome,deficiency, resistant ovary syndrome, autoimmune autoimmune disorders associated with disorders associated with galactosemiagalactosemia, and iatrogenic, and iatrogeniccauses secondary to chemotherapy or radiation therapy. causes secondary to chemotherapy or radiation therapy.

The diagnosis ofThe diagnosis of ovarian failure should be suspected in ovarian failure should be suspected in all cases of primary amenorrhea andall cases of primary amenorrhea and sexual infantilism sexual infantilism and in women with secondary amenorrhea who developand in women with secondary amenorrhea who develophot flashes and other signs of estrogen deficiency. hot flashes and other signs of estrogen deficiency.

This diagnosis is confirmedThis diagnosis is confirmed by documenting an by documenting an increasedincreasedfolliclefollicle--stimulating hormone (stimulating hormone (FSHFSH) in) in the menopausal the menopausal range (30range (30--40 IU/L).40 IU/L).


ChronicChronic AnovulationAnovulation withwithEstrogenEstrogen PresentPresent --11 Women with chronic Women with chronic anovulationanovulation who experience who experience withdrawal menstrualwithdrawal menstrual bleeding after a bleeding after a progestin challenge progestin challenge and exhibit and exhibit normal FSH normal FSH levels are said tolevels are said to be in a chronic be in a chronic estrous cycle because of a cyclic production of estrogen. estrous cycle because of a cyclic production of estrogen.

TheThe ovarian follicles of women with this disorder do not ovarian follicles of women with this disorder do not secrete large amountssecrete large amounts of estrogen, but instead secrete of estrogen, but instead secrete androgens, such as androgens, such as androstenedioneandrostenedione, which, which are converted are converted in peripheral tissues by in peripheral tissues by extraglandularextraglandular aromatasearomatase into theinto theweaker estrogen, weaker estrogen, estroneestrone. .

This condition may be due to problems primarilyThis condition may be due to problems primarily in the in the ovary or in the hypothalamicovary or in the hypothalamic--pituitarypituitary--gonadalgonadal feedback feedback loops. loops.


ChronicChronic AnovulationAnovulation withwithEstrogenEstrogen PresentPresent --22

TheThe consequence is that these women consequence is that these women fail to ovulate fail to ovulate and and produce estrogen andproduce estrogen and do not experience cyclic withdrawal do not experience cyclic withdrawal bleeding. The primary cause of chronicbleeding. The primary cause of chronic anovulationanovulation with with estrogen present is estrogen present is PCOSPCOS..

PCOS is a complex disorder (probably inherited and PCOS is a complex disorder (probably inherited and related to insulin resistance)related to insulin resistance) characterized by the characterized by the development of development of hirsutismhirsutism or androgen excessor androgen excess;; obesityobesity; ; andand menstrualmenstrual disturbancesdisturbances, , includingincluding amenorrheaamenorrhea, , oligomenorrheaoligomenorrhea, , or dysfunctional uterine bleeding at the or dysfunctional uterine bleeding at the time of expected pubertytime of expected puberty. . The clinical picture varies, and The clinical picture varies, and laboratory tests may be helpful, but arelaboratory tests may be helpful, but are only supportive in only supportive in confirming the diagnosis. confirming the diagnosis.


ChronicChronic AnovulationAnovulation withwithEstrogenEstrogen PresentPresent --33

In most women with PCOS,In most women with PCOS, plasma luteinizing hormone plasma luteinizing hormone (LH) levels are elevated at the same time the(LH) levels are elevated at the same time the plasma FSH plasma FSH levels are normal or low. Some have suggested that a levels are normal or low. Some have suggested that a ratio ofratio of LH to FSH of greater than 2 to 3 may be a useful LH to FSH of greater than 2 to 3 may be a useful laboratory distinction. laboratory distinction.

TheThe evaluation of a single sample of evaluation of a single sample of gonadotropinsgonadotropins may may lead to the wrong diagnosis,lead to the wrong diagnosis, however, and only 80% of however, and only 80% of women may exhibit this finding. In addition,women may exhibit this finding. In addition, most women most women with PCOS have moderately with PCOS have moderately elevated serum androgen elevated serum androgen levels.levels.


An ultrasound showing An ultrasound showing multiple superficial small follicles multiple superficial small follicles surrounding thesurrounding the surface of the ovary in a surface of the ovary in a ringlikeringlike pattern pattern associated with increased associated with increased stromalstromal density in a woman density in a woman with amenorrhea supports the diagnosis.with amenorrhea supports the diagnosis.

As stated previously, the diagnosis of PCOS is not based As stated previously, the diagnosis of PCOS is not based on pathologicon pathologic changes in the ovaries or plasma hormone changes in the ovaries or plasma hormone abnormalities, but is primarilyabnormalities, but is primarily based on the clinical based on the clinical evidence of chronic evidence of chronic anovulationanovulation with varying degreeswith varying degrees of of androgen excess and menstrual disturbances.androgen excess and menstrual disturbances.


ClinicalClinical characteristicscharacteristics of PCOSof PCOS


04.11.2014

3

ChronicChronic AnovulationAnovulationwithwith EstrogenEstrogen AbsentAbsent --11

Women with chronic Women with chronic anovulationanovulation with estrogen absent with estrogen absent owing to low orowing to low or absent estrogen production fail to absent estrogen production fail to experience withdrawal bleeding or experienceexperience withdrawal bleeding or experience only vaginal only vaginal spotting after a progestin challenge. spotting after a progestin challenge.

Usually the Usually the FSH levelFSH level is normal or lowis normal or low; this is an important ; this is an important point because evaluating the FSH levelpoint because evaluating the FSH level alone (if within the alone (if within the normal range, e.g., 4normal range, e.g., 4--8 IU/8 IU/mLmL) does not confirm the) does not confirm the cause cause of amenorrhea. of amenorrhea.

Chronic Chronic anovulationanovulation with estrogen absent is a resultwith estrogen absent is a result of of hypogonadotropichypogonadotropic hypogonadismhypogonadism that is secondary to that is secondary to organic or functionalorganic or functional disorders of the central nervous disorders of the central nervous system hypothalamicsystem hypothalamic--pituitary axis.pituitary axis.



It may be clinically helpful but not always practical to It may be clinically helpful but not always practical to subdivide these intosubdivide these into hypothalamic or pituitary causeshypothalamic or pituitary causes..

Hypothalamic tumors orHypothalamic tumors or other destructive disorders of the other destructive disorders of the hypothalamus are hypothalamus are relatively rare causes relatively rare causes ofof amenorrhea amenorrhea and require radiographic evaluation, such as computed and require radiographic evaluation, such as computed tomographytomography (CT) or magnetic resonance imaging (MRI). (CT) or magnetic resonance imaging (MRI).

In women with tumors,In women with tumors, headaches and other neurologic headaches and other neurologic symptoms and signs are often present. Thesymptoms and signs are often present. The most common most common cause of chronic cause of chronic anovulationanovulation with estrogen absent is a with estrogen absent is a functionalfunctional disorder of the hypothalamus or central nervous disorder of the hypothalamus or central nervous system in the presencesystem in the presence of a normal MRI or CT study. of a normal MRI or CT study.



A history of stress or a stressful event oftenA history of stress or a stressful event often can be can be obtained. These events include loss of a loved one, obtained. These events include loss of a loved one, entering a stressfulentering a stressful work environment, or going off to work environment, or going off to college. In these cases, the college. In these cases, the stressstress reducesreduces hypothalamic hypothalamic secretion of secretion of gonadotropingonadotropin--releasing hormone (releasing hormone (GnRHGnRH), ), leadingleading to to reduced reduced gonadotropingonadotropin secretion secretion followed by followed by reduced ovarian estrogenreduced ovarian estrogen secretion, and amenorrhea secretion, and amenorrhea results. This can happen even in women withresults. This can happen even in women with normal normal body body weightweight..



Other causes related to stress and emotional disorders Other causes related to stress and emotional disorders include include weight lossweight loss and dietingand dieting, which is particularly , which is particularly common in teenage girls. common in teenage girls.

The most severeThe most severe form of weight lossform of weight lossinduced amenorrhea induced amenorrhea is in is in anorexia nervosaanorexia nervosa, which is, which is characterized by distorted characterized by distorted attitudes toward eating and weight, selfattitudes toward eating and weight, self--inducedinduced vomiting, vomiting, extreme emaciation, and distorted body images. extreme emaciation, and distorted body images.

Women whoWomen who exercise excessivelyexercise excessively, such as marathon , such as marathon runners, ballet dancers, or extremerunners, ballet dancers, or extreme gym exercisers, and gym exercisers, and who use exogenous steroids to reduce percent body fatwho use exogenous steroids to reduce percent body fatmay develop amenorrhea. may develop amenorrhea.



Amenorrhea is more likely to develop in womenAmenorrhea is more likely to develop in women with a with a previous history of abnormalities in menstruation before previous history of abnormalities in menstruation before the onsetthe onset of excessive exercise or weight loss. of excessive exercise or weight loss.

Women who develop amenorrhea associatedWomen who develop amenorrhea associated with stress, with stress, exercise, or dieting exhibit alterations in the menstrualexercise, or dieting exhibit alterations in the menstrualcycle that are associated with the start of their new cycle that are associated with the start of their new activities. activities.

Later, as theLater, as the disorder progresses, problems in the disorder progresses, problems in the luteallutealphase production of progesteronephase production of progesterone occur followed by occur followed by anovulatoryanovulatory cycles associated with cycles associated with oligomenorrheaoligomenorrhea, and, andfinallyfinally amenorrheaamenorrhea developsdevelops..



In some of these women, a withdrawal bleed after In some of these women, a withdrawal bleed after progestin challengeprogestin challenge may occur in the may occur in the anovulatoryanovulatory phase phase with some estrogen being produced,with some estrogen being produced, but in most women but in most women the the failure to exhibit a withdrawal bleed failure to exhibit a withdrawal bleed after a progestinafter a progestinchallenge suggests that the disease is more severe. If challenge suggests that the disease is more severe. If untreated, it may leaduntreated, it may lead to problems of estrogen to problems of estrogen deficiency, such as osteoporosis. deficiency, such as osteoporosis.

After a reductionAfter a reduction of stress or exercise and increased of stress or exercise and increased weight gain, reversal from amenorrheaweight gain, reversal from amenorrhea to to ovulatoryovulatorymenstrual cycles may occur requiring no further menstrual cycles may occur requiring no further treatment.treatment.


04.11.2014

4


Other chronic debilitating diseases, such as acquired Other chronic debilitating diseases, such as acquired immunodeficiencyimmunodeficiency syndrome, syndrome, malabsorptionmalabsorption, or cancer, , or cancer, may result in may result in hypogonadotropichypogonadotropic hypogonadismhypogonadism..

A relatively rare cause of hypothalamic amenorrhea in A relatively rare cause of hypothalamic amenorrhea in women iswomen is due to due to KallmannsKallmanns syndromesyndrome, which has been , which has been shown to be associated withshown to be associated with defects in olfactory bulb defects in olfactory bulb development. development. GnRHGnRH neurons develop in the sameneurons develop in the same rostralrostralpart of the brain as the olfactory bulbs, and women with part of the brain as the olfactory bulbs, and women with KallmannsKallmanns syndrome exhibit not only low syndrome exhibit not only low gonadotropinsgonadotropinsand amenorrhea but alsoand amenorrhea but also lack of the sense of smell, or lack of the sense of smell, or anosmiaanosmia. .



The most common causes of amenorrhea associated with The most common causes of amenorrhea associated with the pituitarythe pituitary are disorders associated with are disorders associated with increasedincreasedprolactinprolactin secretionsecretion. Women. Women present with amenorrhea plus present with amenorrhea plus galactorrheagalactorrhea associated with an increasedassociated with an increased prolactinprolactin level. level.

In women with amenorrhea and elevated In women with amenorrhea and elevated prolactinprolactin levels,levels,imaging of the pituitary is required, and a imaging of the pituitary is required, and a thyrotropinthyrotropin level level is obtained.is obtained.

HyperprolactinemiaHyperprolactinemia and and galactorrheagalactorrhea may be associated may be associated with with antidepressantantidepressant drugs or recent breastfeedingdrugs or recent breastfeeding. Most . Most women with women with hyperprolactinemiahyperprolactinemia do not exhibit do not exhibit demonstrable pituitary tumors. demonstrable pituitary tumors.



Women with Women with prolactinprolactin levelslevels greater than 50 greater than 50 gg/L have /L have about a about a 20% chance 20% chance of of presenting with a pituitarypresenting with a pituitary tumortumor

WWomen who have 100 omen who have 100 gg/L /L prolactinprolactin have a have a 50% risk50% risk. .

WWomen with greater than 200 omen with greater than 200 gg/L /L prolactinprolactin have an have an approximatelyapproximately 90% to 100% 90% to 100% chance of harboring a chance of harboring a prolactinprolactin--secreting tumorsecreting tumor


Defects of the female Defects of the female reproductive tractreproductive tract --11

Some of these defects maySome of these defects may be developmental, and some be developmental, and some may be due to iatrogenic causes. Women withmay be due to iatrogenic causes. Women with anatomic anatomic defects have normal ovaries and ovarian function and defects have normal ovaries and ovarian function and developdevelop secondary sexual characteristics. secondary sexual characteristics.

Ovulation can be proven by changes inOvulation can be proven by changes in the the basal body basal body temperaturetemperature or by or by elevated serum progesterone levels elevated serum progesterone levels in in thethe lutealluteal phase. phase.

These women also have a normal female 46,XX These women also have a normal female 46,XX karyotypekaryotype. The. The logical approach to the evaluation and logical approach to the evaluation and classification of anatomic defects isclassification of anatomic defects is to start from the to start from the lowest entry at the opening of the reproductive tract andlowest entry at the opening of the reproductive tract andmovemove upwardupward





Anatomic causes include Anatomic causes include labial agglutination labial agglutination oror labial labial fusionfusion and and imperforate hymenimperforate hymen. .

If the obstruction is farther up intoIf the obstruction is farther up into the vagina, it is the vagina, it is known as a known as a transverse vaginal septumtransverse vaginal septum. Rarely, a . Rarely, a completecomplete absence of the cervix may be suspectedabsence of the cervix may be suspected. .

Women with all of these conditionsWomen with all of these conditions often present with often present with increasing abdominal pain, which is the result of increasing abdominal pain, which is the result of accumulationaccumulation of blood behind the obstruction. In such of blood behind the obstruction. In such instances, the pain is cyclicinstances, the pain is cyclic and predictable in nature and predictable in nature associated with the onset of menstruation. If theassociated with the onset of menstruation. If thediagnosis is delayed, endometriosis, adhesions, and diagnosis is delayed, endometriosis, adhesions, and infertility may resultinfertility may result


04.11.2014

5

www.yoldemir.comwww.yoldemir.com www.yoldemir.comwww.yoldemir.com

www.yoldemir.comwww.yoldemir.com www.yoldemir.comwww.yoldemir.com

Differential Diagnosis ofDifferential Diagnosis of pphenotypichenotypicFemale with Female with ssecondaryecondary SexualSexualDevelopmentDevelopment andand No No UterusUterus



RReproductiveeproductive tract defects may be due to iatrogenic tract defects may be due to iatrogenic causes,causes, such as scarring and such as scarring and stenosisstenosis of the cervix after of the cervix after dilation and curettage, dilation and curettage, conizationconization,, laser, or loop laser, or loop electrosurgical excision procedures to treat cervicalelectrosurgical excision procedures to treat cervicaldysplasia. dysplasia.

Destruction of the Destruction of the endometriumendometrium after a vigorous curettage after a vigorous curettage afterafter postpartum hemorrhage or therapeutic abortion or postpartum hemorrhage or therapeutic abortion or after infection associatedafter infection associated with a missed abortion results in with a missed abortion results in scar tissue or uterine scar tissue or uterine synechiaesynechiae ((AshermansAshermans syndrome). syndrome).

The diagnosis of this defect is rare in the absence of a The diagnosis of this defect is rare in the absence of a previousprevious surgical procedure or pregnancy. surgical procedure or pregnancy.


04.11.2014

6

Defects of the female Defects of the female reproductive tractreproductive tract --55 The diagnosis of female reproductive tractThe diagnosis of female reproductive tract defects is defects is established by history and physical examination. Labial established by history and physical examination. Labial agglutination,agglutination, fusion, imperforate hymen, and transverse fusion, imperforate hymen, and transverse vaginal septum are easilyvaginal septum are easily recognized. recognized.

An ultrasound can be obtained to confirm the location of An ultrasound can be obtained to confirm the location of thethe blockage and presence or absence of the uterus. blockage and presence or absence of the uterus.

To evaluate and confirm theTo evaluate and confirm the diagnosisdiagnosis of of AshermansAshermanssyndromesyndrome, , sonohysterographysonohysterography, , officeoffice hysteroscopichysteroscopicprocedure, or occasionally procedure, or occasionally hysterosalpingographyhysterosalpingography may be may be indicated. indicated.

AA laparoscopy may be required to confirm the final laparoscopy may be required to confirm the final diagnosis of the reproductivediagnosis of the reproductive tract anomaly, particularly tract anomaly, particularly with regard to with regard to fundalfundal appearanceappearancewww.yoldemir.comwww.yoldemir.com

CLINICAL EVALUATION OF CLINICAL EVALUATION OF AMENORRHEA AMENORRHEA --11


CLINICAL EVALUATION OF CLINICAL EVALUATION OF AMENORRHEA AMENORRHEA --22WhenWhen toto evaluateevaluate

1. No 1. No mensesmenses byby ageage 16 16

2. No 2. No evidenceevidence of of sexualsexualdevelopmentdevelopment (i.e., (i.e., breastsbreasts) ) bybyageage 1414

3. 3. IfIf sexualsexual ambiguityambiguity ororvirilizationvirilization is is presentpresent

4. If the patient or4. If the patient or familyfamily is is greatlygreatly concernedconcerned

InitialInitial physicalphysical examinationexamination

1. 1. DegreeDegree of of maturationmaturation of of thethebreastsbreasts, , pubicpubic andand axillaryaxillary hairhair, , andand externalexternal genitaliagenitalia

2. 2. CurrentCurrent estrogenestrogen statusstatus

3. Presence 3. Presence oror absenceabsence of a of a uterusuterus


CLINICAL EVALUATION OF CLINICAL EVALUATION OF AMENORRHEA AMENORRHEA --33 FSH FSH elevatedelevated

FSH FSH lowlow oror normalnormal



FSH normalFSH normal

EvaluationEvaluation of of outflowoutflow tracttract




04.11.2014

7


Download - Amenorrhea

Top Related