Amenorrhoea😊

Primary Amenorrhea

• Müllerian anomalies (≈ 47%) > gonadal dysgenesis (≈ 20.5%) > hypogonadotropic hypogonadism (≈ 14.7%)

Definition

1. 13 years and no Menarche and no Breast budding (Tanner stage 1)

2. 15 years and no menarche but Breast budding present (Tanner stage ≥ 2)

3. No menarche by 3 years of thelarche

Initial Work-up

1. Physical exam > UPT > USG > Hormone level > Karyotyping

2. EPUHK

3. Physical Examination:
• Assess breast development
• Check for pubic hair
• Palpate gonads (if suspecting gonadal dysgenesis)

4. Urine Pregnancy Test (UPT):
• Should be done in all cases of primary amenorrhea

5. Ultrasonography (USG):
• To determine the presence or absence of the uterus

6. Hormone Levels:
• FSH
• LH
• Estrogen

7. Karyotyping:
• Performed after initial assessment to identify chromosomal abnormalities

Compartment-Wise Causes and Classification

Note

• When FSH, LH, Oestrogen, Androgen = Normal
  ⇔ Height, pubic hair and breast Normal

Cryptomenorrhoea: Hidden Menstruation

• Definition: Hidden menstruation.

• Clinical Features:
• Cyclic abdominal pain monthly.

• Local Exam Differentiation (Outflow Obstructions):
• Imperforate Hymen:
• Most common cause.
• Tensed, bulging hymen.
• Cough impulse present.
• Transverse Vaginal Septum (TVS):
• Hymen not tensed/bulging.
• Cough impulse absent.
• Vaginal Atresia:
• Absence of vaginal opening.

• Per Rectal (PR) Exam:
• Bulky uterus (hematometra).
• Hematocolpus.

Mullerian Agenesis /
Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome

Gonadal Dysgenesis

• Hormonal Profile:
• FSH: Increased
• LH: Increased
• Estrogen (E): Decreased
• Androgen: Decreased

• Common features for Turners, Sweyers and Kallman
• Estrogen (E): Decreased
• Androgen: Decreased

Feature	Description
Breast development	Absent
Pubic hair	Decreased/Absent

• Diagnosis: Hypergonadotropic hypogonadism

Kallmann's Syndrome

• Gene Involved: Kal 1 gene

• Stature: Normal

• Defect → GnRH neurons → In olfactory epithelium → Fail to migrate to Hypothalamus

• Patient Complaints (P. c/o):
• Primary amenorrhea
• Infertility
• Delayed puberty

• Associated Feature: Anosmia

• Diagnosis: Hypogonadotropic hypogonadism

• Hormonal Profile:
• FSH: Decreased
• LH: Decreased
• Estrogen (E): Decreased
• Androgen: Decreased

• Demographics:
• Seen in both males and females
• Most common in: Males

• Management (Mx): Pulsatile GnRH

Turner's Syndrome

• Basic defect: 45, X0

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• Turner Mosaicism:
• 45 XO; 46XX (two cell lines present).
• Secondary amenorrhea
• Cardiac abnormalities
• Hearing loss → cholesteatoma
• insulin resistance
• ↑↑ r/o GONADOBLASTOMA
• Prophylactic gonadectomy is done

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Features

• Primary amenorrhea

• IQ: Usually normal.

• Sensorineural hearing loss

• Amenorrhea (Primary)

• Barr body absent

• ↑↑ Autoimmune Diseases
• Diabetes.
• Hashimoto's thyroiditis.
• Coeliac disease.
• NOT SLE → (SLE in Klinefelters)

Horseshoe kidney

• Turner’s syndrome

• Edward’s syndrome

• Risk of → Wilms T 2

• Edward turned above Horse

• Cystic hygroma

• Short stature

• High Arched Palate

• Nipples are widely spaced on a shield-shaped chest

• Webbed neck
• Due to lymphedema → Post resolution of cystic hygroma
• Webbed neck is associated with more chances of Cardiovascular malformations

• Low posterior hairline

• ↑↑ FSH, LH → Hypergonadotropic hypogonadism

• ↑↑ Carrying angle → Cubitus Valgus

• Short 4th metacarpal & Madelung
• [Short 5th distal phalanx → Downs]

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• Female with absent Barr body = Turner
• Normal males: 1-1 = 0 Barr body
• Normal females: 2-1 = 1 Barr body
• Turner syndrome females: 1-1=0

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Cardiac Anomaly: 

• Bicuspid aortic valve (most common) > Coarctation of aorta.

• Most common cause of death → Coarctation of aorta

Ovaries: 

• Rudimentary ovary / Streak ovary.

• Uterus Present

Dysgenetic/Undescended Testes (45XO/46XY):

• Increased malignancy risk.

• Gonadectomy recommended.

• Most common gonadal tumour: Gonadoblastoma.

• Most common gonadal malignancy: Dysgerminoma.

• Mnemonic: CLOWNS
• C → Cardiac, cubitus valgus
• L → Lymphedema
• O → Fibrosed ovaries
• W → Webbed neck
• N → Normal intelligence
• S →Short stature, with short 4th metacarpal and shield chest

Management Strategies

• NO GONADECTOMY

• Growth Hormone (GH):
• Administered only till 8 years old.

• Hormone Replacement Therapy (HRT):
• Oestrogen alone for 1 year.
• Followed by Oestrogen + Progesterone.
• Continued till normal menopause age.

• Pregnancy:
• Relative contraindication.
• Increased risk of cardiac disease.

Comprehensive Investigations

• Echocardiography (Echo): For cardiac anomalies.

• Renal Ultrasound (USG): For renal anomalies (horseshoe-shaped kidney).

• Thyroid Profile: TSH, T3, T4.

• Metabolic Screening:
• Complete Blood Count (CBC).
• Lipid Profile.
• Fasting Glucose.

• Organ Function Tests:
• Renal Function Tests (RFT).
• Liver Function Tests (LFT).

• Audiometry: For sensorineural hearing loss.

• Anti-Endomysial Antibodies: Increased risk of coeliac disease.

• Karyotyping: Definitive diagnostic investigation.

Comparison: Noonan Syndrome vs Turner Syndrome

Feature	Noonan Syndrome	Turner Syndrome
Inheritance	Autosomal dominant	No inheritance pattern
Karyotype	Normal (microscopic deletion)	45, XO
Sex affected	Both boys and girls	Only girls
Intelligence	Intellectual disability present	Normal intelligence
Puberty	Delayed puberty, fertility preserved	Infertile (streak ovaries, rudimentary uterus)
Facial Features	Antimongoloid slant of eyes, low-set ears	Webbed neck (higher CHD risk)
Congenital Heart Disease	More common; Pulmonary stenosis (supravalvular)	Less common, (A/w webbed neck) Bicuspid aortic valve > Coarctation of the aorta (death)

• Children with Noonan syndrome
• More CHD than Turner syndrome

• Webbed neck in Turner
• Higher chance of CHD

• Antimongoloid slant
• Treacher-Collins syndrome
• !st pharyngeal arch defect



• Noonan syndrome
• Cri du chat syndrome
• Mnemonic:
• Teacher (Treacher collin) Noonil (Noonan) Mangalam (Antimongoloid) vayikkum

Cri du chat syndrome

• Chromosome 5

• Hypotonia

• Shrill cry

• Microcephaly, Mental retardation

• Anti mongoloid facies

Secondary Amenorrhea

Definition

• Absence of menstruation for 3 months (90 days) in a previously normally menstruating female.

Common Causes

• Most Common: Pregnancy (check UPT).

• Thyroid Disorders (check TSH).

• Increased Prolactin levels (check Prolactin level).

• LH, FSH & Estrogen levels.

Specific Causes and Findings

Note:

• In entire Gyni, there are two conditions where LH high, FSH normal (LH > FSH)
1. PCOS → Secondary amenorrhea
2. AIS → Primary amenorrhea

Diagnosis of POI:

• Both FSH and LH ↑↑, but FSH > LH

• FSH levels.
• (N): 1–10 IU.
• Suggestive: ≥ 25 IU.
• Diagnostic: ≥ 40 IU.

• AMH
• Glycoprotein hormone
• Gene for MIS/AMH
• Chromosome 19
• Produced by
• Sertoli cells at 7 weeks
• Granulosa cells of preantral and small antral follicles
• Function: Regression of Mullerian Duct in males.
• Best test for Ovarian reserve
• Done any day
• 1 - 3 = Normal
• High AMH
• > 3: PCOS
• > 3.3: High risk of OHSS
• Good outcome of IVF
• Low AMH
• <1 = Suggestive of POI (Poor Ovarian reserve)
• <0.5 = Diagnostic of POI

• Mnemonic: Ammachi (AMH ↓↓) ayi FISH POI

Pituitary Apoplexy

Definition

• Acute infarction/haemorrhage of the pituitary gland in a patient with
• undiagnosed pituitary adenoma.

• Sheehan's + Prolactinoma

Precipitating Factors

• Postpartum hemorrhage

• Hypertension.

• Diabetes Mellitus (DM).

Presentation

• History: PPH (Postpartum Hemorrhage).

• Clinical Features (C/F):
• Postpartum shock f/b
• Headache & visual disturbance (due to pressure from adenoma).
• Hypotension & Hypoglycemia (due to decreased cortisol).

Investigations

• All pituitary hormones decreased.

Treatment

1. First Line: 
1. Corticosteroid supplementation.
• Followed by thyroid hormone, sex steroid, vasopressin, and GH replacement as needed.

2. Indications for Surgery: 
1. Progressive visual loss,
2. cranial nerve involvement,
3. loss of consciousness.

Menopause

• Age worldwide: 51 years.

• Age India: 47 years.

• POI/Premature menopause: menopause < 40 yrs (Primary ovarian insufficiency).

• Late menopause: Not achieved at ≥ 55 yrs.

• Diagnosis: clinical, amenorrhea ≥12 months.

Hot Flashes

• Vasomotor symptom.

• Due to: Decreased Estrogen, ↑ FSH

• Imbalance in: Serotonin & norepinephrine.

• More at: Night (night sweats).

• Feeling of: intense heat followed by sweating.

• Severe hot flash: affects daily activities.

• Seen in: Perimenopausal & menopausal Females.

Management:

• 1st line
• HRT: Severe hot flashes.
• If uterus (+) → E+P
• If uterus (-) → E only

• 2nd line:
• SSRI: Fluoxetine.

• SERM approved:
• E + Bazedoxifene.

• Others:
• Phytoestrogens, clonidine, gabapentin, tibolone.

• Drugs not used:
• Clomiphene, raloxifene, tamoxifen.
• All leads to hot flashes

• Mnemonic:
• Hot (HRT) flashes (Fluoxetine) based (Bazedoxifene) fights (Phytoestrogen)
• Between 5 (gabaPentine) clones (Clonidine)

Senile Vaginitis/Genitourinary Syndrome of Menopause

• Due to decreased Estrogen.

• Patient c/o: vaginal dryness, spotting, dyspareunia.

• Management:
• 1st line: Vaginal lubricants.
• 2nd line: HRT (Estrogen cream).

• SERM used: Ospemifene.
• Mnemonic: OsnnuPainwhileFucking (Ospemifene)

• SERMs not used: Clomiphene, Raloxifene, Tamoxifen.

Coronary Artery Disease

• Estrogen is cardioprotective (→ ↑↑ HDL, ↓↓ LDL).

• After menopause CAD risk increases but HRT not given for prevention.
• In females ≥ 60 y:
• HRT slightly increases CAD risk.
• E+P HRT > E only HRT.

Osteoporosis

• Decreased Estrogen, quantitative defect.

• C/o backache.

• M/C fractures: Vertebral > Neck of femur > Colle's fracture.

• Compulsory bone mineral density check: Dexa scan (IOC).

• Management:
• Bisphosphonates: Alendronate (1st line).
• SERM: Raloxifene.
• Others:
• Tibolone,
• teriparatide (PTH analogue),
• strontium,
• denosumab (Rank ligand antagonist).

• Drugs on osteoblasts:
• Teriparatide,
• strontium.

• Mnemonic: Do not (Denozumab) tell (Tibolone) teri (Teriparatide) strongly (Strontium) to Rolex (Raloxifene) → He is the ser (SERM) → Adichodikkum (Osteoporosis)

Hormone Replacement Therapy

• OE HRT → OEstrogen → Ovarian, Endometrial Cancer

• O + P HRT → Oestrogen + B → Ovarian + Breast Ca

• HRT does not increase: Ca cervix risk.
• Note:
• Cervical cancer ↑ by OCP

• HRT does not decrease: CAD.

Common C/I of HRT

• H/O breast cancer.

• H/O thrombosis.

• H/O MI or stroke.

• Active liver disease.

• Undiagnosed vaginal bleeding.

• Severe uncontrolled hypertension.

• Severe increased TG.

• Diabetes with vasculopathy.

• Migraine with aura.

• ≥ 35 years + smoker.

Only Indication

• Severe hot flashes.
• If uterus is present: E + P.
• If uterus is absent: E only.
• M/C estrogen used in HRT: β 17 estradiol.
• HRT is not a contraceptive agent.

E HRT

• Advantage:
1. Decreased Hot Flashes.
2. Decreased Osteoporosis.
3. Decreased Colorectal carcinoma.

• Disadvantage:
1. Increased Endometrial cancer
2. Increased Thrombosis.
3. Increased Ovarian cancer.

E+P HRT

• Advantage:
1. Decreased Hot Flashes.
2. Decreased Osteoporosis.
3. Decreased Colorectal carcinoma.
4. Decreased Endometrial cancer.

• Disadvantage:
1. Increased Thrombosis.
2. Increased Ovarian cancer.
3. Increased Breast cancer.

HRT for Post Menopausal Females

• Maximum 5 years.

For peri menopausal females/Turner syndrome/POI:

• Till normal age of menopause.