Definition
Amenorrhoea literally means absence of menustration. It is a sympto and not a disease.

Introduction
Amenorrhea is generally taken as a symptom of a disease but it is a normal condition of physiology. If we assume that amenorrhea is a symptom of a disease, then it will be difficult to identify the normal and abnormal concepts. For example –Puberty is one of a physiological condition. Before that amenorrhea is a normal condition. If we say that it is a symptom of disease, every girl before puberty we have to consider as a patient, which is totally wrong. Same thing will happen in the case of pregnancy, lactation period and menopausal conditions.

So here we are going to study amenorrhea as a normal condition of physiology as well as pathological condition of it which is really symptom of disease. We will study define, classify all the type of amenorrhea. We also study the normal and abnormal concept according to its type.

Today’s life is very fast, mental exertion is tremendously affecting on life and physical and mental condition of women. The menstruation cycle started at earlier age. As the age of marriage increased and obesity both the things affecting on the pregnancy. So we must be aware of the faint line in normal and abnormal conditions according to situation and for that we must know each and every type of amenorrhea.

Classification

A) Physiological

i) Primary
ii) Secondary

- During Pregnancy
- During Lactation

B) Pathological

a) Concealed
b) Acquired

As per classification it is clear that physiological amenorrhea is the normal condition of female body and pathological amenorrhea is the abnormal.

Physiological:

Primary
-The pituitary gonadotrophins are not adequate enough to stimulate the ovarian follicles for effective steroidogenesis.
- Oestrogen level is not sufficient enough to cause bleeding from the endometrium.

Secondary
- During pregnancy-Large amount of oestrogens and chorionic gonadotrophins secreted from the trophoblasts suppress the pituitary gonadotrophins no maturation of the ovarian follicles.
- During lactation-High level of prolactin inhibits ovarian response to response to FSH no follicular growth hypooestrogenic state no menstruation. In case of no breast feed the menstruation returns by 6th week. In case of breast feed menstruation may be suspended until the baby stops breast feeding.
- Following menopause-Few responsive follicles in the ovaries for the gonadotrophins to act. As a result cessation of oestrogen production from the ovaries with elevation of pituitary gonadotrophins

Pathological

Concealed (Cryptomenorrhea) - There is periodic shedding of the endomectrium and bleeding but the menstrual blood fail to come out the genital track due to obstruction in passage. It is again divided into 2 parts, namely

- Congenital
It is caused by

1) Imperforate hymen
2) Transverse vaginal septum
3) Atresia of upper-third of vagina and cervix

- Acquired (Cryptomenorrhea)

1) Stenosis of the cervix following amputation, deep cauterisation and conisation.

Patho-physiology
If the site of obstruction is low down in vagina, the accumulated blood results in haematocolpos haematometra haematosalpinx. If the obstruction is at the cervix, it will produce haematometra haematosalpinx. Haematocolpos produce marked elongation of the urethra retention of urine.

Clinical Features
Periodic pain in lower abdomen, haematocolpos associated with retention of urine

- Abd.Exam. - An uniform globular mass in hpyo gastrium.
- Vul.Exam. - Bulging hymen.
- Rect.Exam. - Fullness of vagina and uterine mass.

Treatement-Cruciate incision of the hymen and drainage of blood. Dilatation of the cervix in stenosis.

Real amenorrhoea-

Primary amenorrhoea

- Definition: No menstruation by 16 years of age is primary amenorrhoea.The upper age limit is 15 years.

Causes:

Disorders of hypo thalamo-pitutary-ovarian axis.
Delayed puberty.
Kallman’s syndrome.
Central nervous systems.
Galactosemia
Developmental defect of genital track.
Imperforate hymen.
Transverse vaginal septum.
Atresia upper third of vagina and cervix.
Complete absence of vagina.
Absence of uterus.
Abnormal chromosomal pattern.
Turner’s syndrome (45 X).
Various mosaic status 45 X/46 X X.
Pure gonodal digenesis (46 X X or 46 X Y).
Androgen insensitivity syndrome (46 X Y).
Partial deletions of the X chromosome (46 X X)
Deletion of (X q^-) amenorrhoea but no somatic abnormalities
Deletion of (X p^-) somatic features.
Dyes function of thyroid and adrenal cortex.
Adrenogenital syndrome.
Cretinism.
Metabolic disorders.
Juvenile diabetes.
Abnormal loss or gain in weight in short span of time.
Systemic illness.
Malnutrition, anaemia.
Weight loss-tuberculosis.
Unresponsive endometrium.
Congenital.
Tubercular.

reatment of primary Amenorrhoea-scope is very limited

1) Development anomalies: Vaginal reconstruction means to creat an avascular space between bladder and rectum. Pantancy is maintained by mould or graft –using skin and amnitoc membranes .This is done ideally prior to or soon after marriage.

2) Cromosomal abnormalities- In gonadal dysgensis short term use of oestrogen+progesterone for development of breast. The gonads of XY gonadal dysgensis should be removed for increased development of seminoma.

In androgen insensitivity syndrtome the ectopic gonads are to be removed to avoid malignancy. After that substitution therapy is indicated for secondary sex characters.

Hormone replacement therapy (premarin 0.625 mg daily)

Hypothalamo-pitutary ovarian axis defect-

GnRH analogues and pulsatile administratation ofGnRH for ovulation. Oestrogen and progestin therapy for menstruation. Sergical excision or radiotherapy for Hypothalamic-pituitary tubours.

4) Thyroid and adrenal dysfunction-

Thyroid replacement theary for cretinism.
Surgical removal of clitoris for Adrenogenital syndrome
Corticosteroid therapy for hydroxylase deficiency.

5) Metabolic and nutritional-

Antidiabetic in diabetes
Antitubercular in tuberculosis.
Correction of Anemia, improvement of nutrition for menstruation.

6) Unresponsive endometrium-

Adhesiolysis and IUCD insertion for Uterine synechiae (T)
Electcautery for Hystreoscopic release of adhesion.High dose oestrogen +progestin for (monthly)for withdrawal of bleed.

Secondary Amenorrhoea

Definition - When there is absence of period for 6 monthes or more following normal menstruation is called secondary Amenrrhoea.

Etiology of secondary Amenrrhoea

- Uterine factors
Tubercular endometritis
Destruction of the endometrium or inhabitation of ovarian function by tubercular toxin.

- Postradion
Destruction of the endometrium

- Synechiae
Intrauterine adhesions - visecocortcal reflex - ameorrhoea

- Surgical removal
Ablation of endometrium by laser,resetoscope.

2) Ovarian Factors

Polisystic ovarian syndrome

Tonically elevated LH - Incresed androgen production from the theca (PCOS) cells and stroma of the ovaries - Decrease SHBG - increased unbound oestrogens and androgens - Pitutary sensitivity to GnRH is increased - Preferential Increased production of LH, decreased production of FSH Due to inhibin. Disturbed adrenal function is also Implicated in androgen excess. A state of hyperandrogenism produces amenorrhoea by its anti-oestrogenicaction.

- Premature ovarian failure
Absence of follicle or accelerated rate of depletin of follicle in the ovaries.
- Resistent overian syndrome (Savages syndrome)
- Follicles are present but are resistant to gonadotrophins (defect in FSH receptor)
- Hyperoestrogenic state
The oestrogen level remains high and there is no function.
- Persistant follicles in metropathia
As such so long as endometrial support is not lost,amenorrhoea continues.
- Feminizing tumor of the ovary (Granulose cell tumour)
Masculinising tumor of the ovary (Sertoli –leydig cell tumour)
Androgen excess opposes the effect of oestrogen on the endrometrium .
- Hypo-oestrogenic state
- Ablation of the ovaries
Removal of site of oestrogens.
- Pelvic radiation
Makes the ovaries unresponsive to genadotrophins.
- Persistant follicles in metropathia

As such so long as endometrial support is not lost, amenorrhoea continues.

- Feminising tumour of the ovary (Granulosa cell tumour)
Masculinising tumour of the ovary (Sertoli –leydig cell tumour)
Androgen excess opposes the effect of oestrogen on the endrometrium .
- Hypo-oestrogenic state
- Ablation of the ovaries

Removal of site of oestrogens.
- Pelvic radiation
Makes the ovaries unresponsive to genadotrophins.

3)Pitutary factors
- Adenoma (Prolactinoma)
Microdenoma usually associated with hyperprolactinaemia . It either inhibits ovarian steroidogenesis directly or inhibits pituitary gonadotrophins release.

- Cushings disease
ll

- Acromaly
ll

- Sheehans syndrome
There is partial or complet destruction of the pituitary by is chaemia caused by venous thrombosis folling severe postpartum haemorrhage and shock .The principal hormones affected ar4e groth hormone, gonatrophiins ,TSH,adrano-cortcophins and prolaction.

- Simmonds disease
ll

4) Hypothalamic factor

- Psychogenic shock ,stress, anoerexia nervosa, strenuous exercise, pseudocyesis.
Inhiabit the realease of GnRH or affect dopamine metabolism. There is low level of oestrogen and LH but FSH level remains normal.

- Congenital malformation
Lead to hypogonadotrophic hypogonadism. There may be hyperprolactinemia due to altered dopamine inhabitation. Tumours of the hypothalamus or pituitary needs surgical excition or radiotherapy.

- Trauma :Accidents, surgery, or radiotherapy
ll
- Infection :Tubercular or sarcoid granulomas.
ll
- Tumors: Craniopharyngioma, meningimoa.
ll

5) Adrenal factors
- Adrenal tumor or hyperplasia
Androgen excess opposes the effect on oestrogen on the endometium.
- Cushings syndrome
ll

6) Thyroid factors
- Hyopothyroid state
Raised TSH and hyperprolactinaemia by direct action of TRH on the galactophore cells in the pituitary.

7) Genaeral disease
- Malnutrion, tuberculosis, chronic nephritis diabetes
Probably affecting the hypothalamo-pitutary axis.

8) Iatrogenic
- Contraceptive pills
Supression of GnRH release
- Psychotrophic phenothiazinederivativedrugs
Dopamine receptor blocking agents raise the prolaction level.
- Antihypertensive drugs
Dopamine depleting agents raise the prolaction level.

Management
1) No abnormality detected:
- only assurance is given
- If anxious then-Oral combined steroidal contraceptive for at least 3 months
- If low endogenousoestrogen :Ethanil oestradial 0.02 mg or conjugated equine oestrogen 1.25 mgdaily for 25 days.
- If anxious for fertility: Husband semen analysis and evaluation of woman tubal factor prior to ovulation using clomiphene or gonatrophins.

2) Cases with detectable cause:
- Anxiety and stress- phychotherapy
- Systematic illness and malnutrition- Improve heath states.
- Exercise indused- limitation of activity.

3) Polycystic ovarian disease: Primarily to correct the biochemical abnormality
Weight reduction in obecity

If fertility not concerned :
- Androgen excess—Combined oral contraceptive pills.
- GnRH agonists—Luprolide 3.75 mg IM or Goserelin3.6 mg SCfor every 4 weeks.
- Hirutism—Cyproterone and other.

If patient waiting for pregangy:

- Ovulation induction by clomiphene with or without dexamethasone
- If PCOS and obesity –Clomiphen+Metforfin 500 mg thrice daily.

If PCOS+resistant to medical therapy :

- Endoscopic cauterization or carbon-di-oxide laser vaporization

4)Hyperprolactinaemia Inappropriate galactorrhoea:

- Bromocriptine 1.25 mg orally at bed time—for first week—increased gradually
- If medical therapy fails –Transnasal—Transphennoidal excision.

5) Premature ovarian failure:
- In postmenapausal health hazards—HRT judiciousaly
- Autoimmun disorders—corticosteroids
- In far and remote fertility potentiality—administraition of sequential oestrogen and progesterone
- IVF with donors oocytewith total replacement
- In the presence of ‘Y’ chromosomes - Gonadectomy for avoiding malignancy

6) Adranal disordes:
- Pitutary tumor—transphenoidal pituitary micro surgery—irradiation
- Aderrnal tumor—simple adrenalectomy
- To block excess cortisol—amnioglutethimide
- Adult onset adrenal hyperplasia--Dexamethasone replacement therapy—0.25-0.5 mg

7) Hypothyroid state—thyroxine

8) Hyperandrogenic state—oral contraceptives

9) uterine synechiae—adhesiolysis—insertion of IUD—oral contraceptive pills

10) Ovarian tumor - surgery