Transcript Amenorrhea

Amenorrhea
Dr. Afaf Ibrahim AlNoury
Associate professor of
OBS & GYN
King Abdul Aziz University
Welcome….
Amenorrhea
Few problem in gynecologic
endocrinology are as
challenging or taxing to the
clinician as amenorrhea.
Definition of amenorrhea
Any patient fulfilling the following criteria should be
evaluated as having the clinical problem of amenorrhea:
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3.
No period by age 16 regardless of the presence of
normal growth and development with the appearance
secondary sexual characteristics.
No period by age 14 in the absence of growth or
development of secondary sexual characteristics.
In a woman who has been menstruating , the absence of
periods for a length of time equivalent to a total of at
least 3 of the previous cycle intervals or 6 months of
amenorrhea.
It is useful to employ a diagnostic evaluation that
segregates causes of amenorrhea into the following
compartments:
 Compartment I:
Disorders of the outflow or uterine target organ.
 Compartment II:
Disorders of the ovary.
 Compartment III:
Disorders of the anterior pituitary.
 Compartment IV:
Disorders of central nervous system (hypothalamic)
factors.
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environment
Compartment IV
Central
nervous
system
Hypothalamus
Gn RH
Compartment III
Anterior
Pituitary
Compartment II
LH
FSH
Ovary
Compartment I
progesterone
Estrogen
Uterus
menses
Evaluation of amenorrhea
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A careful history and physical examination should seek the
following:
evidence for psychological dysfunction or emotional stress,
family history of apparent genetic anomalies , signs of a
physical problem with a focus on nutritional status, abnormal
growth and development, the presence of a normal reproductive
tract , and evidence for CNS disease. A patient with amenorrhea
is then exposed to a combined therapeutic and laboratory
dissection according to the depicted flow diagrams.
Step 1
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The initial step in the workup of the amenorrheic patient
after excluding pregnancy begins with a measurement of
thyroid-stimulating hormone (TSH), aprolactin level , and
a pregestational challenge.
Amenorrhea
TSH
Prolactin
Presentational challenge
Elevated TSH
+ withdrawal bleed
hypothyroidism
Normal prolactin
Normal TSH
An ovulation
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There are two rare situations associated with a negative
withdrawal response , despite the presence of adequate
levels of endogenous estrogen. In both situations, the
endometrium is decidualized and , therefore , it will not
be shed following the withdrawal of exogenous progestin.
Polycystic ovaries.
Specific adrenal enzme deficiency.
All anovulatory patients require therapeutic
management.
Minimal therapy of anovulatory women requires the
monthly administration of a progestational agent.
If , at any time , an anovulatory patient fails to have
withdrawal bleeding on a monthly progestin program ,
this is a sign (providing the patient is not pregnant ) that
she has moved to the negative withdrawal bleed category.
Step 2
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Orally active estrogen is administered in quantity
and duration certain to stimulate endometrial
proliferation and withdrawal bleeding provided
that a completely reactive uterus and patent
outflow tract exist.
If there is no withdrawal flow , the diagnosis of a
defect in the compartment I systems
(endometrium , outflow tract) can be made with
confidence.
If withdrawal bleeding does occur , one can
assume that compartment I system have normal
functional abilities if properly stimulated by
estrogen.
Step 3
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This step involves an assay of the level of
gonadotropins in the patient.
Step 3 is designed to determine whether the lack of
estrogen is due to a fault in the follicle (compartment II)
or in the CNS-pituitary axis (compartments III and IV).
Clinical state
Serum FSH
Serum LH
5-20 IU/L , with the ovulatory
midcycle peak about 2 times
the base level
5-20 IU/L , with the
ovulatory midcycle peak
about 2 times the base level
Hypogonadotropic state:
prepubertal, hypothalamic
, or pituitary dysfunction
Less than 5 IU/L
Less than 5 IU/L
Hypogonadotropic state:
prepubertal, hypothalamic
, or pituitary dysfunction
Greater than 20 IU/L
Less than 40 IU/L
Normal adult female
High Gonadotropins
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High gonadotropins accompanied by ovaries not contain follicles
)overian failure)
There are rare situation in which high gonadotropins can be
accompanied by ovaries that contain follicles.
On rare occasions , tumors can produce gonadotropins.
A single gonadotropin deficiency.
Due to a gonadotropin-secreting pituitary adenoma.
Duing the perimenopausal period
In the resistant or insensitive ovary syndrome
Secondary amenorrhea caused by premature ovarian failure can be
due to autoimmune disease.
Calactosemia is a rare inherited autosomal recessive disorder of
galactose metabolism due to a deficiency of galactose-1-phosphate
uridyl transferase.
The final rare clinical situation is that associated with specific
enzymatic deficiencies the 17-hydroxylase deficiency (P450c17) is
present in both ovaries and the adrenal gland.
The need for chromosome evaluation
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All patients under the age of 30 who have been assigned the
diagnosis of ovarian failure on the basis of elevated gondotropins
must have a karyotype determination.
The presence of mosaicism with a Y chromosome requires excision
of the gonadal areas because the presence of any testicular
component within the gonad carries with it a significant chance of
malignant tumor formation.
Normal conadotropins
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Why is it that hypoestrogenic (negative progestational withdrawal)
patients will frequently have normal circulating levels of FSH and
LH as measured by immunoassay.
The molecules are qualitatively altered and biologically inactive.
Another very rare possibility is an inherited disorder of
gonadotropin synthesis leading to the production of
immunologically active but biologically inactive hormones.
Low Gonadotropins
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If the gonadotrpin assay is abnormally low , or in
the normal range , one final localization is
required to distinguish between a pituitary
(compartment III) or CNS-hypothalamic
(compartment IV) cause for the amenorrhea.
This is achieved by imaging evaluation of the
sella turcica for signs of abnormal.
Galactorrhea
TSH
Prolactin coned-down
view of sella Turcica
Amenorrhea
TSH
Prolactin
Progestional challenge
Elevated TSH
hypothyroidism
+ withdrawal
- withdrawal
Normal prolactin normal
TSH
Prolactin > 100 or
abnormal coned-down view
Anovulation
+Withdrawal bleed
FSH , LH assay
MRI
normal
low
Abnormal coned - view
Estrgen and progestin cycle
Coned-down view
of sella turcica
Hypothalamic
amenorrhea
- Withdrawal bleed
End organ
problem
High
Ovarian
failure
Compartment I: Disorders of the Outflow
Tract or Uterus
A Sherman's syndrome
Mullerian Anomalies
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Imperforate hymen
Obliteration of the vaginal orifice , and lapses in
continuity of the vaginal canal.
The cervix or the entire uterus may be absent.
The uterus be present , but the cavity absent.
The endometrium may be congenitally,lacking.
Mullerian Agenesis
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Lack of mullerian development (mayer-Rokitansky-kuster
syndrome) is the diagnosis for the individual with primay
amenorrhea and no apparent vagina.
Androgen insensitivity (feminization)
Differences between mullerian agenesis and Testicular feminization
Mullerian agenesis
Testicular Feminization
Karyotype
46,xx
46,xy
Not known
Maternal x-linked recessive; 25%
risk of affected child,25% risk of
carrier
Sexual hair
Normal female
Absent to sparse
Testosterone leve
Normal female
Normal to slightly elevated male level
Other anomalies
Frequent
Rare
Normal incidence
5%incidence of malignant tumors
Heredity
Conadal neoplasis
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The male pseudohermaphrodite is a genetic and gonadal male with failure of
virilization.
Transmission of this disorder is by means of an x-linked recessive gene that is
responsible for the androgen intracellular receptor.
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Clinically , the diagnosis should be considered in:
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A female child with inguinal hernias because the testes are
frequently partially descended.
A patient with primary amenorrhea and an absent uterus.
A patient with absent body hair.
This syndrome is marked by a unique combination:
1.
2.
3.
Normal female phenotype.
Normal make karyotype. 46 .XY.
Normal or slightly elevated mate blood testosterone levels and
a high LH.
Compartment II: Disorders of the Ovary
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Problems in gonadal development can present with either primary or
secondary amenorrhea from 30 to 40% of primary amenorrhea cases
have gonadal streaks due to abnormal development:gonadal
dysgensis. These patients can be grouped according to the following
karyotypes:
50%-45,x
25%-Mosaics
20%-46,xx
Turner syndrome
Mosaicism
XY conadal Dysgenesis
Conadal agenesis
The resistant Ovary syndrome
Premature Ovarian Failure
Compartment III : disorders of the Anterior Pituitary
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Hypogonadism and delayed puberty deserve brain evaluation by
MRI.
Compartment IV:Central Nervous System Disorders
Hypothalamic Amenorrhea
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Patients with hypothalamic amenorrhea (hypogonadotropic hypogonadism )
have a deficiency in GnRH pulsatile secretion.
Hypothalamic problems are usually diagnosed by exclusion of pituitary
lesions and are the most common category of hypogonadotropic
amenorrhea , a functional suppression of reproduction ,often a
psychobiologic response to life events.
The degree of GnRH suppression determines how these patients present
clinically.
Mild duppression can be associated with a marginal effect on reproduction ,
specifically an inadequate luteal phase.
Moderate suppression of Gn RH secretion can yield anovulation with
menstrual irregularity , and profound suppression is manifested by
hypothalamic amenorrhea.
Weight loss, anorexia , bulimia
Diagnosis of Anorexia Nervosa
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Onset between ages 10 and 30.
Weight loss of 25% or weight below normal for age and height.
Special attitudes:
Denial.
Distorted body image.
Unusual hoarding or handing of food.
At least one of the following:
Lanugo.
Bradycardia,
Overactivity,
Episodes of overeating (bulimia),
Vomiting , which may be self disorder
Amenorrhea
No known medical illness.
No other psychiatric disorder.
Other characteristics:
constipation.
Low blood pressure .
Hypercarotenemia.
Diabetes insipidus.
Exercise and Amenorrhea
Stress
↑CRH
↑Endorphins
↓ GnRH
↑ Somatostatin
↑ACTH
↓ TRH
↑ Corticol
↓ TSH
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↓ T4
↓ T3
Inherited Genetic Defects
1- Amenorrhea and Anosmia , kallmann’s syndrome.
2- Molecular Explanations for Hypogonadotropic Amenorrhea.
3-Adrenal Hypopasia.
Postpill Amenorrhea
Hormone Therapy:
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The patient who is hypoestrogenic and who is not a candidate
for induction of ovulation deserves hormone therapy.
This includes patients appropriately and diagnosed as having
gonadal failure, patients with hypothalamic amenorrhea , and
postgonadectomy patients.
* periodic measurements of bone density are worthwhile to assess adequacy of
hormonal treatment and to provide evidence of lifestyle and dieting changes.
Note:
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It is not enough to provide hormone therapy when
disturbed mensrual function is secondary to
psychobiologic stress responses. appropriate support and
counseling are necessary to help patients develop coping
mechanisms other than extreme dieting and exercise.
All available skills and resources should be utilized to
promote healthy attitudes and healthy behaviors.
The presence of amenorrhea in athletes and recreational
exercisers should be regarded as a sign of negative
balance, a condition requiring appropriate interventions.
Thank you and
best regards