Definition of Amenorrhea Basic Principles in Menstrual Function Evaluation of Amenorrhea Specific Disorders Within Compartments

Compartment I: Disorders of the Outflow Tract or Uterus

Asherman's Syndrome Mllerian Anomalies Mllerian Agenesis Androgen Insensitivity (Testicular Feminization)

Compartment III: Disorders of the Anterior Pituitary

Treatment of Nonfunctioning Adenomas Pituitary Prolactin-Secreting Adenomas The Empty Sella Syndrome Sheehan's Syndrome

Compartment II: Disorders of the Ovary

Turner Syndrome Mosaicism XY Gonadal Dysgenesis Gonadal Agenesis The Resistant Ovary Syndrome Premature Ovarian Failure The Effect of Radiation and Chemotherapy

Compartment IV: Central Nervous System Disorders

Hypothalamic Amenorrhea Weight Loss, Anorexia, Bulimia Exercise and Amenorrhea Eating Disorders and Pregnancy Inherited Genetic Defects Postpill Amenorrhea

Hormonal Therapy

Primary
Absence of menses by age 16

with normal secondary sexual characteristics Absence of menses by age 14 without secondary sexual development

Secondary
In

a previously menstruating female, absence of menses for a length of time equivalent to a total of at least 3 of the previous cycle intervals or for 6 months

Thelarche (breast development)

Requires estrogen

Pubarche/adrenarche (pubic hair development)

Requires androgens

Menarche

Requires: GnRH from the hypothalamus FSH and LH from the pituitary Estrogen and progesterone from the ovaries Normal outflow tract

Neural control
Dopamine (-)

Chemical control
Endorphines (-)

Norepiniphrine (+)

IV. Hypothalamus

Estrogen

Gn-RH III. Ant pituitary FSH, LH II. Ovaries I. Uterus

?
Progesterone

Menses

Physiological amenorrhea.
Pathological amenorrhea .
a) False (cryptomenorrhea)

b) True Ovarian Uterine Pituitary Hypothalamic

40% 5% 20% 35%

 Definition

Periods of life at which the female doesn't have menses.

Causes Before puberty.

Pregnancy (Most common cause of

2ry amenorrhoea) Lactation. Menopause.

Etiology
Before Immature puberty H.P.O

Hormonal profile

Axis

FSH&LH estrogen& progesterone

Etiology
Pregnancy Continuous release of estrogen & progesterone without withdrawal

Hormonal profile 1- B.HCG (pregnancy test) 2- estrogen & progesterone 3- FS H & LH

Etiology Lactation

Hormonal profile

PRL 1) PRL suppress. 2)estrogen Ovarian & function & progesterone suppress GnRH

Etiology
Menopause Exhaustion of ovarian follicles

Hormonal profile
1) FSH >40 I.U/.L
2) estrogen < 50 pg /ml

Definition:
Hidden mestruation; menstruation occurs regularly but no blood escapes outside due to outflow obstruction.

Etiology: Mainly congenital causes:

1-Imperforate hymen (most common cause) 2-Complete transverse vaginal septum 3-Vaginal atresia with functioning uterus 4-Cervical atresia 5-Vaginal aplasia

Step

Exclude pregnancy
Progestational challenge
TSH, PRL

Galactorrhea
PRL Coned down view

Elevated TSH

+ Withdrawal

- Withdrawal

Hypothyroidism

Normal PRL Normal TSH

Step

Cyclic Estrogen & Progestin

II. Anovulation PCOD

+ Withdrawal

- Withdrawal

Evalution of Amenorrhoea

I. End organ problem

Step

Cyclic Estrogen & Progestin

+Withdrawal bleed
Step

-Withdrawal bleed
I. End organ problem

FSH, LH

Low
Step

Normal

High

Coned down view CT, MRI

III & IV. Pituitary Hypothalamic amenorrhea

II. Ovarian failure

Evalution of Amenorrhoea

Compartment I

Compartment II

Ashermans syndrome Anovulation PCOS Ovarian Failure

7%

abnormal karyotype 0.5% normal karyotype 10% Compartment III

Compartment IV

Prolactinoma

7.5% 28% 10% 10% 1%

Anovulation Hypothalamic suppression Weight loss/anorexia Hypothyroidism

Ashermans Syndrome Mullerian Anomalies

Hystrectomy Endometrial Ablation Uterine irradiation Androngen Insesitivity (Testicular Feminization Syndrome) Incomplete Androgen Insesitivity

Imperforate hymen (most common) Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) Transverse vaginal septum Vaginal atresia with functioning uterus Cervical atresia Vaginal aplasia Uterus present but lacking cavity Uterus present but lacking endometrium

Intrauterine synchia following vigorous endometrial curettage, tuberculous endometritis, cesarean section or myomectomy.

Monthly menstrual bleeding in the presence of outflow obstruction leading to collection of menstrual blood .
Vagina becomes distended with blood hematocolpos. Later on uterus becomes distended with blood hematometria. The uterus contract each cycle to overcome the obstruction which is the cause of cyclic colicky abdominal pain

Clinical Picture: Cases with false amenorrhea are usually presented at the age of puberty Symptoms
-Primary amenorrhea. -Progressive abdominal pain . -Cyclic abdominal pain . -Urine retention due to compression on bladder and urethra by distended vagina

Clinical Picture: Signs

-General examination : Normal Secondary sexual characters (breast development, pupic and axillary hair) -Abdominal examination Presence of pelviabdominal mass (due to distended vagina and uterus with blood) which is usually mistaken for pregnancy

Clinical Picture: Vaginal examination

Imperforate hymen
-Intact hymen and complete -Bulging bluish membrane with +ve - impulse on cough -Cross fluctuation in PR examination

Complete transverse vaginal septum

-Intact hymen, incomplete -Septum beyond level of hymen -No impulse on cough

Investigations: Pregnancy test Ultrasound IVU

to detect associated

congenital anomalies in urinary tract

Treatment: Imperforate hymen Partial hymenectomy:

Cruciate incision followed by marsupialization

15% of primary amenorrhea Normal secondary development & external female genitalia Normal female range testosterone level Absent uterus and upper vagina & normal ovaries Karyotype 46-XX 15-30% renal, skeletal and middle ear anomalies

Previously called testicular feminization syndrome Genetically mediated ( X-linked trait ) This is the third most common cause of primary amenorrhea after gonadal dysgenesis and mllerian agenesis Affected individuals have Karyotype 46, XY and have normal testes (undescended) with normal production of testosterone and normal conversion to dihydrotestosterone

Absent cytoplasmic testosterone receptors Due to absence of receptors in target organs, there is a lack of male differentiation of the external and internal genitalia. Therefore, external genitalia remain female and Wolffian duct development fails to take place. Also, Mllerian duct regression is induced by antimllerian hormone which is produced by the Sertoli cells of the fetal testes.

Normal female appearance No female or male internal genitalia Normal female external genitalia Short or absent vaginal pouch Scanty or absent pubic/axillary hair Normal or enhanced breasts

Treatment:
Operative removal of the testicles after puberty due to risk of malignancy (gonadoblastoma) found in 25% of patients Surgical correction of the vagina (artificial vagina)

MA

AIS

Karyotype
Heredity

46, XX
Not known

46, XY
Maternal X-linked recessive, 25% affected, 25% carrier Absent to sparse Normal to slightly elevated male Rare

Sexual Hair Testosterone level Other anomalies

Normal female Normal female Frequent

Gonadal neoplasia

Normal incidence

5% incidence of malignant tumour

1.

Chromosomally abnormal

Gonadal Dysgenesis:

46XX (Pure gonadal dysgeneis) 46XY (Swyers syndrome) 2. The Resistant Ovary Syndrome 3. Premature Ovarian Failure 4. Effect of Radiation & Chemotherapy

Chromosomally normal

Classic turners syndrome (45XO) Turner variants (45XO/46XX),(46X-abnormal X) Mixed gonadal dygenesis (45XO/46XY)

1.

Gonadal Dysgenesis:
Is a spectrum of disorders with associated hypergonadotropic Hypogonadism. It is characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo. This loss leads to extremely hypoplastic (underdeveloped) and dysfunctioning gonads mainly composed of fibrous tissue, hence the name streak gonads.

1.

Gonadal Dysgenesis:

1.

Gonadal Dysgenesis:

Characters of ovarian dysgenesis: amenorrhea, stunted growth, genital atrophy and absence of secondary sex characters

Classic Turners

Turner Variant Female Streak - Short - Normal XX/XO or abnormal X

True gonadal Dysgenesis Female Streak Tall Nil 46-XX(Pure) 46-XY (Swyer)

Mixed Dysgenesis Ambiguous - Streak - Testes Short XO/XY

Phenotype Gonad Height Somatic stigmata Karyotype

Female Streak Short Classical XO

Classic (45, XO)

Mosaic (46, XX/45, X0)

The term premature ovarian failure (POF) describes a stop in the normal functioning of the ovaries in a woman younger than age 40. This is sometimes called premature menopause, but premature ovarian failure is actually much different than menopause.

Pituitary Tumors Non functioning adenomas Hormone-secreting adenoma Prolactinoma Cushings disease Acromegaly Primary hyperthyroidism Craniopharyngioma Meningioma Glioma Infarction Surgical or Radiological ablation Sheehans syndrome Diabetic vasculitis

Prolactin Secreting Adenoma

Galactorrhoea

Prolactin Secreting Adenoma

Most common pituitary tumor 50% identified at autopsy Disruption of the reproductive mechanism S/S increased PRL Amenorrhea

Galactorrhea For macroadenomas

Headache Visual field defect Treatment Medical : dopamine agonist

Surgical for macroadenomas that do not respond to dopamine agonist

Sheehans Syndrome:

Postpartum hemorrhage Acute infarction and necrosis Hypopituitarism= early in the PP period Failure of lactation Loss of pubic and axillary hair Deficiencies :
GH, Gonadotropins (FSH,LH), ACTH, TSH (infrequency)

Hypothalamic Amenorrhoea Weight loss, Anorexia Nervosa, Bulimia. Exercise Induced Amenorrhoea Inherited Genetic Defects

Kallmanns Syndrome

Adrenal Hypoplasia Postpill Amenorrhoea

Deficiency in GnRH pulsatile secretion. Normal height Normal external and internal genital organs (infantile) Low FSH and LH MRI to R/O intra-cranial pathology. 30-40% anosmia (Kallmanns syndrome) Sometimes constitutional delay Treat according to the cause (HRT), potentially fertile.

1o or 2o Amenorrhea is often first sign A body mass index (BMI) <17 kg/m menstrual irregularity and amenorrhea Hypothalamic suppression Abnormal body image, intense fear of weight gain, often strenuous exercise Mean age onset 13-14 yrs (range 10-21 yrs) Low estradiol risk of osteoporosis Bulemics less commonly have amenorrhea due to fluctuations in body wt, but any disordered eating pattern (crash diets) can cause menstrual irregularity. Treatment : body wt. (Psychiatrist referral)

Common in women who participate in sports (e.g. competitive athletes, ballet dancers) Eating disorders have a higher prevalence in female athletes than non-athletes Hypothalamic disorder caused by abnormal gonadotrophin-releasing hormone pulsatility, resulting in impaired gonadotrophin levels, particularly LH, and subsequently low oestrogen levels

 Post-pill

amenorrhea is not an entity Depot medroxyprogesterone acetate Up to 80 % of women will have amenorrhea after 1 year of use. It is reversible (oestrogen deficiency) A minority of women taking the progestogen-only pill may have reversible long term amenorrhoea due to complete suppression of ovulation