Amenorrhea

Dr Neeta Katuwal
4/3/2074
 INTRODUCTION
Absence of menstruation

TYPES
Physiological-Before puberty, pregnancy ,lactation,
menopause
Pathological
-Concealed (Cryptomenorrhea)
- Real –Primary
Secondary
Normal menstrual
function requires
-Female 46XX
-An intact hypothalamic-
pituitary-ovarian-
uterine/vaginal axis
-Support of adrenal and
thyroid
Hypothalamo-Pituitary Ovarian Axis
 Normal Puberty

Thelarche→Adrenarche→Menarche

In normal healthy women, menarche occurs

between the age of 10 and 16 years ,the mean
age being 12.5 years.
 Definition
Primary amenorrhea
• No menarche by 16 years of age in the
presence of secondary sexual
character.
• No menarche by 14 years of age in
absence of secondary sexual character
 Causes of Primary Amenorrhea
A. Hypogonadotropic hypogonadism
a. Hypothalamic causes:
• Delayed puberty/menarche
 Kallman’s syndrome-GnRh deficiency
 Psychcogenic causes, weight loss , stress,
excessive exercises, anorexia nervosa and
malnutrition
Causes of Primary Amenorrhea
A. Hypogonadotropic hypogonadism
contd..
b. Pituitary causes:
 CNS tumors-
craniopharyngioma,prolactinomas,adenomas
 Hypopituitary states-Simmond’s disease,
Forbes Albright syndrome.
c. Systemic diseases like tuberculosis, syphilis
Causes of Primary Amenorrhea
B. Hypergonadotropic hypogonadism (FSH>40
mIU/ml)
▫ Gonadal dysgenesis: Turner’s syndrome (45 X0),
mosaic states (45 X/46XX)
▫ Pure gonadal dysgenesis (46XX or 46XY)
▫ Testicular regression (46 XY)- Swyer syndrome
▫ Gonadotropin receptor mutation (Savage syndrome)
▫ Metabolic-Galactosemia,17 alpha hydroxylase
deficiency-Follicles destroyed
 Causes of Primary Amenorrhea
C. Eugonadotrophic hypogonadism
a. Absence of Mullerian development :
-Mullerian agenesis (Mayer-Rokitansky–Kuster hauser
(MRKH) syndrome)- absence of uterus/vagina
-Androgen insensitivity syndrome(46 XY)/Testicular
feminisation
b. Normal Mullerian development:
-Female or true intersex
-PCOS
 Causes of Primary Amenorrhea
C. Eugonadotrophic hypogonadism

b. Normal Mullerian development contd..

-Dysfunction of adrenal cortex and thyroid
Adrenogenital syndrome (CAH)-21hydroxylase def
(↓cortisol→↑ACTH→↑androgen)
Cretinism (↑TRH→↑Prolactin)
c. Cryptomennorhea
Imperforate hymen, vaginal septum, agenesis of the vagina
d. Tubercular endometritis-uterine synechiae
Hypogonadotrophic
Hypogonadism
 Delayed puberty/Constitutional delay

-Absence of any breast development by age 13 yrs

-5 years between onset of thelarche and menarche
-Delayed production of GnRH from hypothalamus
- Under stature and delayed bone age ( X-ray Wrist
joint)
-Positive family history
- Diagnosis by exclusion and follow up
- Progress spontaneously through puberty
• No drug therapy is required – Reassurance (? HRT)
 Kallman’s syndrome

-GnRH neurones are absent due to partial or

complete agenesis of olfactory bulb
↓GnRH→↓LH,FSH
-anosmia, amenorrhea
Rx-Menstruation and development of secondary
sexual character can be induced with combined
estrogen and progesterone therapy
 Anorexia nervosa

A state of self-imposed starvation.

psychosexual problem where the patient suffers
from the illusion of excessive body fat and distorted
body image.
Minimal fat should constitute 22% of body weight.
Loss >15% causes amenorrhea
Leptin in the fat initiates Release of GnRH
• FSH and LH levels are low, cortisol level is high. .
• RX: Psychotherapy, Nutritional, GnRh
Pituitary adenoma (Prolactinomas)

Prolactin inhibits GnRH pulse secretion.

Gonadotropin levels are suppressed.
There is anovulation and hypogonodotropic
hypogonadism.
RX: Bromocriptine, Surgery
Hypergonadotrophic
hypogonadism
 Gonadal failure/dysgenesis

Turner’s syndrome(45XO) and mosaics

(46,XX/45,XO)
Pure gonadal dysgenesis(46,XX OR 46,XY)
 Bilateral streak gonads
• Elevated FSH(>40mIU/ml) and low estradiol
level(<25 pg/ml)
• Poor secondary sexual character
 Gonadal failure/dysgenesis

Rx
Cyclical estrogen and progesterone
therapy(HRT ) to promote feminization and
secondary sexual character and prevent
osteopeorosois
Gonadectomy indicated in patient with
gonadal dysgenesis with 46 XY as these
male gonads are prone to malignancy
 Testicular feminization or Androgen insensitivity syndrome

• Inherited as X-linked recessive

• Karyotype 46,XY
• Inability of end organs to respond to androgen→↑testesterone
• In pheripheral tissue, Testesterone converted by aromatase to
estradiol- Phenotypically female
• Testes either places in labia or inguinal canal or
intraabdominal
• Produce normal mullerian inhibiting factor so uterus fallopian
tube and upper vagina absent.
• Treatment: Gonadectomy after puberty +HRT
Eugonadotrophic
Hypogonadism
 Mullerian Agenesis
Mayer-Rokitansky-Kuster-
Hauser (MRKH) syndrome 
- Complete agenesis of the
proximal(upper) vagina,
cervix and uterus  
- Normal external genitalia
- Functional ovaries
- Normal karyotype for
females (46, XX)
Congenital adrenal hyperplasia (CAH)

• Inborn error of adrenal steroidogenesis due to

21 hydroxylase deficiency
• Lack of cortisol→ ↑ACTH- → Excess
androgen→Virilisation of female off
spring ,cliteromegaly
• Female intersex, Karyotype XX
• Ambiguity of sex at birth
• Salt wasting
Cryptomenorrhea
Transverse vaginal septum
 AMENORRHOEA
AN APPROACH FOR DIAGNOSIS

• HISTORY
• PHYSICAL EXAMINATION
• INVESTIGATION

Exclude Pregnancy
 APPROACH to Amenorrhea
• History
-Increase or decrease in weight, exercises
-Cyclic abdominal pain
-Galactorrhea, headaches, anosmia, visual field defects
-Symptoms of estrogen deficiency such as hot flushes
or vaginal dryness
-Hx of TB, juvenile DM, Mumps,thyroid disorders
-Family history of PCOD,delayed puberty,testicular
feminizing syndrome
 APPROACH to Amenorrhea
Physical Exam
• Height and weight, Body habitus
• Secondary sexual character
-Tanner stage for maturation status : Breast, axillary, pubic hair
• Genetic or endocrine stigmatas eg webbed neck, wide spaced
nipples
• Evidence of androgen excess, such as acne, hirsutism,
clitoromegaly
• Cushing disease stigmata
• Thyroid enlargement
• Abdominal mass
 APPROACH to Amenorrhea
• External genitalia
-Imperforate hymen, Vaginal septum
-Clitoral hypertrophy

• Internal genitalia
-Absence of vagina, uterus
 APPROACH to Amenorrhea

INVESTIGATION
• Hormonal assay
-LH,FSH
-Prolactin
-TFT
- Testosterone : Mild elevations consistent with the
diagnosis of PCOS. Values exceeding 200 ng/dL are
consistent with the presence of an ovarian tumor
 APPROACH to Amenorrhea
• Imaging
--Pelvic USG to confirm presence of uterus and
normal gonads or evaluate for polycystic ovaries
-CT/MRI of brain to rule out pituitary tumor
• Genetic Karyotyping(strongly indicated if
FSH>40
• Laparoscopy-streak gonads, polycystic ovaries,
ovarian tumor
 Evaluation of Primary Amenorrhea
History and physical examination

Secondary sexual characteristics present ?

No Yes
Measure FSH and LH levels Pelvic USG

FSH /LH Low FSH /LH High Uterus absent Uterus present
or abnormal or normal

Hypergonadotropic
Hypogonadotropic Karyotype analysis Outflow obstruction
hypogonadism
hypogonadism
Yes No
Karyotype analysis 46, XY 46, XX

Further evaluation
CNS; HP
Disorder
Androgen Mullerian
Gonadal Agenesis Imperforate hymen
insensitivity
Failure or transverse
Syndrome
vaginal septum
Treatment of Primary Amenorrhea
Treat underlying cause
• Imperforate hymen-Incision and drainage
• Septate vagina, vaginal atresia-Excision and vaginoplasty
• Kallmann syndrome: HRT, Ovulation induction by GnRH
• Eating disorder: Pshycotherapy,Nutrition
• Pitutory tumor: Bromopcriptine /Surgery
• Thyroid disorder: appropriate medical treatment
• Turner syndrome: HRT
• Testicular feminisation: Gonadectomy,HRT.
 Definition
• Secondary amenorrhea
Absence of menstruation for 6 months or more in
a previously menstruating lady
 Secondary amenorrhea
CAUSES
1. Pregnancy: Most common cause (always consider).
2. Genital tract
-cervical stenosis following electrocauterisation, conization for
CIN, cervical amputation in Fothergill, genital TB
-Vaginal atresia due to scarring following traumatic delivery
-Asherman syndrome following excessive curettage, uterine
infection or endometrial TB, uterine packing in PPH
 Secondary amenorrhea
CAUSES contd..
3.Ovarian causes (60%)
-Polycystic ovarian disease(35%)
-Surgical extirpation
-Radiotherapy
Autoimmune disease (SLE, Rheumatoid arthritis)
Infections-mumps, tb, rarely pyogenic
Premature menopause-premature ovarian failure
Resistant ovarian syndrome-absent FSH receptors
Masculinizing ovarian tumor (Granulosa cell,Theca cell)
 Secondary amenorrhea
CAUSES contd..
4. Hypothalamus
-GnRH deficiency
-Brain tumors
-Anorexia nervosa, stress
-Excessive weight loss in atheletes, ballet dancers
5. Pituitary
-Tumors like prolactinoma ,Cushing ‘s disease
-Sheehan’s syndrome, Si mmond’s disease
-Drugs: tranquilizers, metoclopramide, dopamine blockers,
anti HTN, anti depressant, phenothizine, OCP(Post pill
amenorrhea)
 Secondary amenorrhea
CAUSES contd..
6. Suprarenal causes
-Addison disease
-CAH
• Thyroid disorders (Hypothyroisism→↑TRH→↑Prolactin)
• Diabetes
• Renal and Liver disease-↓excretion of LH and Prolactin,
Impaired meatabolism
• Idiopathic
 Polycystic ovary syndrome

Most common endocrine disorder of reproductive-aged

women
Include 2 of the 3 criteria(Rotterdam)
-Amenorrhea/oligo
-Hyperandrogenism
-USG-Polycystic ovaries
• Pathophysiology
 Hypothalamic pituitary abnormality –LH/FSH ratio
 Hyperandrogenism
 Insulin resistance
Pathophysiology PCOS
PCOS
 PCOD
Acanthosis Nigricans
• cutaneous marker of of
insulin resistance
characterized by
thickened, gray-brown
velvety plaques seen in
flexure surface such as
the back of the neck,
axillae, beneath the
breast, the waist
 PCOS
Treatment-Specific need of patient
• Menstrual irregularities: weight reduction, OCP
• Hirsuitism: Antiandrogen-Cyproterone acetate,
spironolactone.OCP’s
• Infertility: wt reduction, ovulation induction-
Clomiphine citrate or gonadotrophins, Insulin
sensitiser-Metformin
• Surgical-Ovarian drilling, diathermy
 Hyperprolactinemia

Prolactin under inhibitory effect of dopamine.

Prolactin inhibits GnRH pulse secretion and ovarian steroidogenesis.
Causes
-Hypothlamic tumor ,pituitary tumor (Pituitary
adenoma:Prolactinoma),head injury
-Hypothyroidism due to stimulatory effect of TSH
-PCOD(20%)
-Liver and chronic renal diseaese
-Drugs: neuroleptics,antidepressants,phenothiazines,anti
HTN,metochlopramide
-
 Hyperprolactinemia contd..
• Normal level of prolactin 25 ng/ml
Treatment
-Treat the cause: stop drug, treat thyroid
disorders
-Drugs: Bromocriptine,Quinagolide
-Macroadenoma(>10mm) and microadenoma
not responding to drug require Transsphenoidal
adenectomy or radiotherapy.
 Hypogonadotropic hypogonadism
• Anorexia Nervosa
-A body mass index (BMI) <17 kg/m² menstrual
irregularity and amenorrhea
-Intense fear of wt gain-Hypothalamic supression
Rx: Increase body wt(Psychiatrist consullt)

• Strenous Exercise
- As in ballet, gymnastics, and long-distance running
- Abnormal GnRH pulsation
 Sheehan’s syndrome

Pituitary necrosis following massive obstetric

hemorrhage is most common cause
 Panhypopituitarism
 Failure of lactation, amenorrhea, signs of
hypothyroidism and cortisol def
Treatment :
Replacement of deficient hormones
 Post pill amenorrhea
-1% following the use of OCP
-some have H-P unusually sensitive to suppression by
these hormone
-Dx made if Spontaneous menses doesn’t resume 6mths of
stopping pills
Treatment
-resumption of menstruation occurs after varying period of
discontinuation
-Changeover to OCP with higher estrogen content helps to
restore
 Secondary Amenorrhea
Progesterone Challenge test
Depends on the presence of estrogen primed
endometrium
Tab Norethiesterone 5mg PO TDS 3 days.
OR
Tab Medroxyprogesterone 10 mg PO OD 5 days
Positive: Withdrawal bleed 2-7 days.(Anovulation)
Negative: Add oestrogen for 25 days and
progesterone 16-25 days of cycle
 Secondary Amenorrhea
MANAGEMENT
Always treat the underlying cause
General Measures
• Obese, PCOS-Weight reduction with intake of
low calorie diet
• Behavioral modification-anorexia
nervosa ,bullemia nervosa
 Secondary Amenorrhea
Medication (Drugs)
• Thyroid replacement if hypothyroid
• Prednisolone-CAH
• Dopamine agonist if hyperprolactinemia
• PCOS: Cyclical estrogen-progesterone or Combined
estrogen-progesterone oral contraceptive pills
• Patients seeking pregnancy may require ovulation
induction with clomiphene citrate, exogenous
gonadotropins, or pulsatile GnRH.
Thank You