Assesment of Amen or Rhea

8/14/2019 Assesment of Amen or Rhea

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Dr. Mohammed AbdallaDr. Mohammed Abdalla

ASSESSMENT OF A CASEASSESSMENT OF A CASE

OFOF

AMENORRHEAAMENORRHEA


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AMENORRHEAAMENORRHEA

Amenorrhea is the absenceAmenorrhea is the absence

or abnormal cessation ofor abnormal cessation of

menstruation.menstruation.


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Primary amenorrhea

is defined either as absence of menses by

age 14 years with the absence of growth

or development of secondary sexual

characteristics .

OR as absence of menses by age 16

years with normal development of

secondary sexual characteristics.


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PHYSIOLOGY

Circulating estradiol stimulates growth of the

endometrium. Progesterone, produced by

the corpus luteum formed after ovulation,

transforms proliferating endometrium into

secretory endometrium. If pregnancy does

not occur, this secretory endometrium

breaks down and sheds as a menstrualblood.


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the age of the first menses varies by

geographic location, as demonstrated by a

World Health Organization study

comparing 11 countries, which reported a

median age of menarche of13-16 years

across centers.

PHYSIOLOGY


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The number of primordial follicles in the

human ovary peaks during the fifth

gestational month at approximately 7

million. After this initial pool is in place, no

additional primordial follicles are formed. In

some cases, loss of menstrual regularity is

an early sign of declining fertility andimpending premature ovarian failure

PHYSIOLOGY


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by age 20 years, women have established

regular and persistent patterns of menstrual

cycle length with little variation .

on an individual basis Relatively stable and

predictable menstrual cycle length continuesuntil age 40 years.

PHYSIOLOGY


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In the first year after menarche, the fifth

percentile for menstrual cycle length is 23 days

and the 95th percentile is 90 days.

By the fourth year after menarche, the 95thpercentile for cycle length has declined from 90

days to approximately 50 days.

by 7 years after menarche, cycles are morestable; the fifth percentile in cycle length is 27

days, and the 95th percentile is 38 days.

PHYSIOLOGY


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How common is it?

Secondary amenorrhoea (prevalence about 3%)

primary amenorrhoea (prevalence about 0.3%)

Between 10 and 20% of women complaining of

infertility have amenorrhoea [Franks, 1987].

Up to 50% of competitive runners (training 80 miles

per week) and up to 44% of ballet dancers have

amenorrhoea [Balen, 1999a].


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Etiology ofEtiology of PRIMARY

amenorrhoea


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Secondary sexual

characteristics present Pregnancy

Constitutional delay

Genito-urinary malformation, e.g. imperforate hymen,

transverse vaginal septum, absent vagina with or

without a functioning uterus

Androgen insensitivity: XY female or testicularfeminization

Resistant ovary syndrome


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Secondary sexual

characteristics absent Hypothalamic dysfunction, e.g. chronic illness, anorexia,

weight loss, 'stress'

Gonadotrophin deficiency, e.g. Kallman's syndrome Hydrocephalus

Tumours of the hypothalamus or pituitary

Hypopituitarism Hyperprolactinaemia

Gonadal failure, e.g. ovarian dysgenesis/agenesis,

premature ovarian failure

Hypothyroidism


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Ambiguous external genitalia

Congenital adrenal hyperplasia

Androgen-secreting tumour

5-Alpha-reductase deficiency


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Turner's syndrome

Turner's syndrome is caused by either a

complete absence or a partial abnormality of

one of the two X chromosomes. About 50%

have mosaic forms such as 45X/46XX or45X/46XY.

Features :( short stature, web neck,

lymphoedema, shield chest with widely spaced

nipples, scoliosis, wide carrying angle,

coarctation of the aorta, and streak ovaries.)


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Constitutional delay

In this condition there is no anatomical

abnormality and endocrine

investigations show normal results.

It is caused by immature Pulsatile release

of gonadotrophin-releasing hormone;

maturation eventually occursspontaneously.


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Androgen insensitivity syndrome

(AIS)

formerly known as testicular feminization,

46XY

failure of normal masculinization of the external

genitalia in chromosomally male individuals. This

failure of virilization can be either complete (CAIS) or

partial (PAIS), depending on the amount of residual

receptor function. affected individuals have normal testes with normal

production of testosterone and normal conversion to

dihydrotestosterone (DHT), which differentiates this

condition from 5-alpha reductase deficiency.


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5-alpha-reductase deficiency

(5-ARD)

inability to convert testosterone to the more

physiologically active dihydrotestosterone (DHT).

Because DHT is required for the normal

masculinization of the external genitalia in utero, genetic males with 5-ARD are born with ambiguous

genitalia (ie, male pseudohermaphroditism).

The described clinical abnormalities range frominfertility with normal male genital anatomy to

underdeveloped male with hypospadias to

predominantly female external genitalia, most often

with mild clitoromegaly.


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Measuring the clitoris is an effective method

for determining the degree of androgen

effect. The clitoral index can be determined

by measuring the glans of clitoris in theanteroposterior and transverse diameter. A

clitoral index greater than 35 mm2 is

evidence of increased androgen effect. Aclitoral index greater than 100 mm2 is

evidence of virilization.

5-alpha-reductase deficiency

(5-ARD)


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Imperforate hymen

Imperforate hymen represents the most common and

most distal form of vaginal outflow obstruction.

Clinical presentations range from an incidental finding

on physical examination of an asymptomatic patient

to discovery on an evaluation for primary amenorrhea

or abdominal or back pain.

The differential diagnosis of uterovaginal obstruction

includes disorders of vaginal development, such as

transverse vaginal septum or complete vaginal

agenesis, Duplication anomalies of the uterovaginal

tract often involve one tract that is decompressed and

one that is obstructed.


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Imperforate hymen


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Etiology ofEtiology of secondary

amenorrhoea


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No features of androgen excess present

Physiological, e.g. pregnancy, lactation, menopause Iatrogenic, e.g. depot medroxyprogesterone acetate contraceptive

injection, radiotherapy, chemotherapy

Systemic disease, e.g. chronic illness, hypo- or hyperthyroidism

Uterine causes,e.g. cervical stenosis, Asherman's syndrome (intra-

uterine adhesions)

Ovarian causes, e.g. premature ovarian failure, resistant ovary

syndrome

Hypothalamic causes, e.g. weight loss, exercise, psychological distress,

chronic illness, idiopathic

Pituitary causes, e.g. hyperprolactinaemia, hypopituitarism, Sheehan's

syndrome

Causes of hypothalamic/pituitary damage, e.g. tumours, cranial

irradiation, head injuries, sarcoidosis, tuberculosis


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Features of androgen excess present

Polycystic ovary syndrome

Cushing's syndrome

Late-onset congenital adrenal hyperplasia

Adrenal or ovarian androgen-producing tumour


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Polycystic ovary syndrome

This condition is characterized by hirsutism, acne,

alopecia, infertility, obesity, and menstrual

abnormalities (amenorrhoea in 19% of cases).

Ultrasound examination of the ovaries typically shows

multiple, small peripheral cysts. up to a third of women in

the general population have polycystic ovaries on

ultrasound examination [DTB, 2001].

Endocrine abnormalities include increased serum

concentrations of testosterone, prolactin, luteinizing

hormone (LH) (with normal follicle-stimulating hormone

[FSH] levels), and insulin resistance with compensatory

hyperinsulinaemia.


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Menopause/ovarian failure occurring before the

age of 40 years is considered premature.

Auto-immune disease is the most common cause;auto-antibodies to ovarian cells, gonadotrophin

receptors, and oocytes have been reported in 80%

of cases.

Before puberty or in adolescents, ovarian failure is

usually due to a chromosomal abnormality, e.g.

Turner mosaic, or previous radiotherapy, or

chemotherapy

Premature ovarian failure


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Ovarian failure (premature

(menopause

chromosomal

anomaliesautoimmune

disease

If the woman is under 30, a

karyotype should be

performed to rule out any

mosaicism involving a Y

chromosome.

it is prudent to screen for thyroid,

parathyroid, and adrenal

dysfunction

If a Y chromosome is found the

gonads should be surgically

excised.

Laboratory evidence of autoimmune

phenomenon is much more prevalent

than clinically significant disease


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autoimmune related dysfunction

The most common association is with thyroidThe most common association is with thyroid

disease, but the parathyroids and adrenals can alsodisease, but the parathyroids and adrenals can also

be affected.be affected.

Several studies have shown laboratory evidence ofSeveral studies have shown laboratory evidence ofimmune problems in about 15-40% of women withimmune problems in about 15-40% of women with

premature ovarian failure.premature ovarian failure.

In general, ovarian biopsy is not indicated inIn general, ovarian biopsy is not indicated in

patients with premature ovarian failure since nopatients with premature ovarian failure since no

clinically useful information will be obtained.clinically useful information will be obtained.


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Hyperprolactinaemia

A prolactinoma is the commonest cause of

hyperprolactinaemia (60% of cases).

Other causes include non-functioning pituitary adenoma

(disrupting the inhibitory influence of dopamine on prolactin

secretion);

dopaminergic antagonist drugs (e.g. phenothiazines,

haloperidol, clozapine, metoclopramide, domperidone,

methyldopa, cimetidine); primary hypothyroidism

(thyrotrophin-releasing hormone stimulates the secretion of

prolactin), or it may be idiopathic.

Prolactin acts directly on the hypothalamus to reduce

the amplitude and frequency of pulses of gonadotrophin-

releasing hormone.


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Weight-related amenorrhoea

A regular menstrual cycle is unlikely to

occur if the body mass index (BMI) is less

than 19 (normal range 20-25). Weight loss may be due to illness, exercise,

or eating disorders, among which anorexia

nervosa lies at the extreme end of thespectrum.


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Post-pill' amenorrhoea

This is defined as absence of menstruation

for 6 months following cessation of the

combined oral contraceptive pill. It probably results from A transient inhibition

of gonadotrophin-releasing hormone .


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Progestogen-associated amenorrhoea

Depot medroxyprogesterone acetate inhibits the secretion of

gonadotrophins and thus suppresses ovulation.

After 1 year of use, 80% of women have amenorrhoea or very scanty,

infrequent vaginal bleeding.

There is partial oestrogen deficiency in women who use depotmedroxyprogesterone acetate.

The progestogen-only pill leads to reversible long-term

amenorrhoea in a minority of women, due to complete suppression of

ovulation.

The levonorgestrel-releasing intra-uterine device commonly

results in amenorrhoea after a few months. This is thought to be

mainly a local effect, but suppression of ovulation can occur in some

women (in some cycles).


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ASSESSMENT of primaryASSESSMENT of primary

amenorrheaamenorrhea

TSH elevated


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TSH elevated

hypothyroidismNormal

bone age

delayed

constitutional delayNormal

LH, FSH, and prolactin levels

elevated

karyotype.

low or within

reference rang

head MRI

45,XO, the cause is gonadal dysgenesis

46,XX, the primary cause is ovarian failure

pituitary tumor or a

brain lesion

drug use, an eating

disorder, athleticism,

or psychosocial

stress.

If puberty delayed


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If the pregnancy test result is negative

TSH and prolactin levels

progestin challenge

within reference range

consider anovulatory cycles

PCO

E2 /progestin challenge

outlet obstruction obtain FSH and LH levels.

low or within reference range

head MRI.

exclude chronic disease,

anorexia nervosa, or

psychosocial stress.

high

karyotype

Turner synd.

karyotype is normal (46,XX),

the cause is ovarian failure

elevatedhypothyroidism and

hyperprolactinemia

+VE-VE

If puberty

not delayed

+-


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genital tract

abnormalitieskaryotype

If the karyotype is 46,XY If the karyotype is 46,XX

testosterone levels

male range

female range

androgen insensitivity.

testicular regression

or gonadal enzyme deficiency.

mllerian agenesis

(ie, Rokitansky-Kuster-Hauser

syndrome).


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Breastdevelopment,pubertal growth spurt,

and adrenarche are delayed orabsent in persons with

hypothalamic pituitaryfailure.


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adrenarche occurs normally, whileestrogen-dependent breast development and the

pubertal growth spurt are absent or delayed.

isolated ovarian insufficiency

or failure


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Secondary AmenorrheaSecondary Amenorrhea


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If the history and physicalIf the history and physical

exam are suggestive of aexam are suggestive of acertain etiologycertain etiology ::

for the sake of efficiency and cost-for the sake of efficiency and cost-effectiveness, the workup caneffectiveness, the workup can

sometimes be more directed accordingsometimes be more directed according

to history.to history.( in 85% of cases)


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In patients that will not demonstrate anyIn patients that will not demonstrate any

obvious etiology for their amenorrheaobvious etiology for their amenorrhea

on history and physical exam. Theseon history and physical exam. These

patients can be worked up in a logicalpatients can be worked up in a logicalmanner using a stepwise approach.manner using a stepwise approach.


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How do I assess my patient with

secondary amenorrhoea?

Risk of pregnancy

Associated symptoms, e.g. galactorrhoea, hirsutism, hot flushes, dry

vagina, symptoms of thyroid disease

Recent change in body weight

Recent emotional upsets Level of exercise

Previous menstrual and obstetric history

Previous surgery, e.g. endometrial curettage, oophorectomy

Previous abdominal, pelvic, or cranial radiotherapy Family history, e.g. of early menopause

Drug history, e.g. progestogens, combined oral contraceptive,

chemotherapy

History


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Height and weight: calculate body mass index if appropriate.

Signs of excess androgens, e.g. hirsutism, acne

Signs of virilization, e.g. deep voice, clitoromegaly in addition to

hirsutism, and acne Signs of thyroid disease .

Acanthosis nigricans: this hyperpigmented thickening of the skin folds

of the axilla and neck is a sign of profound insulin resistance. It is

associated with polycystic ovary syndrome (PCOS) and obesity.

Breast examination for galactorrhoea.

Fundoscopy and assessment of visual fields if there is suspicion of

pituitary tumour.

Pelvic examination.

How do I assess my patient with

secondary amenorrhoea?Examination


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Preg.test

TSH ,PROLACTIN,

Prog.challenge test

withdrawal

bleeding

without withdrawal

bleeding

hypoestrogenic compromisedoutflow tract.

++ve.est,progest,

challenge test -ve.est,progest

challenge test

FSH>30-40Normal FSH

HSG OR hysteroscopyasherman

FSH low

repeatRepeat+serum, est.

level

PROF

hypothalamic-

pituitary failure

anovulation

-VE


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Raised testosterone/androgen level.This group includes women with

polycystic ovary syndrome (mildly raised level), and women with

androgen-secreting tumours of the ovary or adrenal gland, late-onset

congenital adrenal hyperplasia, or Cushing's syndrome.Raised gonadotrophins (follicle-stimulating hormone [FSH] and

luteinizing hormone [LH]) with a low estradiol level. This group

includes women with premature ovarian failure and resistant ovary

syndrome.

Hyperprolactinaemia.This group includes women with prolactinomasand hypothyroidism.

Low gonadotrophins (FSH and LH) with a low estradiol level.This

group includes women with amenorrhoea secondary to exercise, low

weight, and stress.

Normal or mildly raised gonadotrophin levels with normal

estradiol levels. This group includes women with polycystic ovary

syndrome (PCOS) or other mild disorders of gonadotrophin regulation or

action.


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Endometrial hyperplasia:women with amenorrhoea but

no associated oestrogen deficiency are at increased risk of

endometrial hyperplasia and endometrial carcinoma .

Infertility:women with amenorrhoea generally do not

ovulate.

Psychological distress:amenorrhoea often causes

considerable anxiety, Many women have concerns about

loss of fertility, loss of femininity, or worry about an

unwanted pregnancy. The diagnosis of Turner's syndrome,

testicular feminization, or developmental anomaly can be

traumatic for both girls and their parents .

Complications and prognosis


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Assesment of Amen or Rhea

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