APPROACH TO AMENORRHOEA

DR. K. KADWA
DEFINITION:

Primary - No menses by 16 years (normal 2°sexual

characteristics)
-14yrs absence 2°sexual characteristics

Secondary - Prev. menstruated

- No menses – 3 cycles or 6/12

Oligomenorrhoea
- Infrequent, irregularly timed episodes of
bleeding
- intervals > 35 days
Primary
- mainly – genetic or Anatomic abnormality
- Chromosomal and gonadal dysgenesis – 50%
- Cong. Abn. – Female reproductive organs
20%
- Hypothalamic hypogonadism 20%
- Other 10% ( Reindollar et
al )

Secondary - Pregancy most common

- Ovarian dx 40%
- Hypothalamic dysfunction 35%
- Pituitary disease – 19%
- Uterine disease – 5%
- Other 1% ( Reindollar et
al )
Basic
- Hypothalamic – Pituitary – ovarian axis

- End organ

- Drugs
 HPO Axis
 Ovarian & Endometrial Axis
- Follicular + Luteal
- Proliferative + secretory

 Hyperandrogenism
◦ increased androgen production and action vs
 Virilisation
◦ Development of male secondary sexual characteristics in women

 Galactorrhoea
◦ Inappropriate or nonpueperal lactation vs
 Hyperprolactinaemia
 14 years and no secondary sexual characteristics
 16 years with normal development and no menses
 Amenorrhoea for 3-6 months
 Hyperandrogenism regardless of duration of menstrual

dysfunction
 Dysmorphic features
 Signs of endocrinopathy
- Functional (excercise, Anorexia, stress)
- Cong ↓ GnRH (kallman’s syndrome)
- Constitutional delay – puberty
- Pituitary Prolactinomas
- Empty Sella syndrome
- Infiltrative lesions – lymphoma, sarcoid, TB)
- Trauma , Radiation
- Sheehans Syndrome
- Hypothyroidism → hyperprolactinaemia
• Psycho-neuroendocrine
– Stress (MBChB V)
– Pseudocyesis
– Undernutrition
• Anorexia nervosa and strenuous exercise
• GnRH deficiency / Kallmann’s Syndrome
– Hypo gonodotrophic , hypo gonadism
– Primary amenorrhoea, delayed puberty, anosmia
• HT compression or destruction → hypo pituiatarism
– Craniopharyngyomas
– TB
– Sarcoidosis
Pituitary gland:
- Due to Primary Ovarian Failure

- Lack of E2, Inhibin A & B

- Lack – Negative feedback – pituitary

- ↑ FSH
Gonadal causes:
 Turners Syndrome
• Webbed neck
• High arched palate
• Low set ears
• Low posterior hairline
• Epicanthal folds
• Micrognanthia
• Increased carrying angle of
arms
• Shield like chest
• Wide spaced nipples
• CVS: coarctation of aorta
• Renal abnormalities
• Shortened fourth and fifth digit
• Lymphoedema at birth
• IUGR
MOST COMMON :
PCOS
ROTTERDAM CRITERIA :
 20 follicles of 2-9mm (older machines >12)
 Large volume ovaries >10ml
 Dense stroma
 Peripheral follicle distribution
 Rosary bead appearance
 PRIMARY OVARIAN  INSULIN RESISTANCE
PATHOLOGY
 Alterations in GnRH pulsations lead to ↑ LH  Insulin resistance (IR) with hyperinsulinemia
production are common findings
 Abundant LH drives the theca cells to produce
androgens, but FSH concentrations and
 IR in PCOS women is tissue-selective.
conversion of androgens to estradiol are  Resistance primarily in skeletal muscle,
insufficient, resulting in failure to select a adipose tissue, and liver
dominant follicle, thus chronic anovulation  Sensitivity to insulin persists in the adrenal
 AMH, secreted by granulosa cells, plays a gland and ovary.
major role in governing this balance because  Insulin as well as IGF-1 can synergize with LH
it inhibits transition from primordial to to ↑ theca cell androgen production
primary follicles.  Insulin ↓ the hepatic synthesis of SHBG, ↑
 PCOS is characterized by increased growth of circulating free androgens
small follicles but subsequent growth arrest  pancreatic beta cell secretory dysfunction has
leading to the typical polycystic morphology. been described in a subset of women with
 Theca cells obtained from women with PCOS PCOS
retain their phenotype with increased
androgen secretion from
increased CYP17A1 expression or P450c17
activity
 Treat underlying symptoms
 Prevent TOD
 Lifestyle modifications

◦ - health diet, exercise, optimise BMI

 AUB - COC or Mirena or Depot
 Hirsutism – Antiandrogens
 Acne
 Prevent/Rx HPT,DM/IR, ↑cholesterol
 Fertility Rx

◦ OI first line(if patent tubes)/IUI/IVF

 Psychological symptoms
- Other causes of Hyperandrogenism

- CAH, Cushings

- Drugs, Tumours
- Congenital / Acquired

- Congenital
- Imperforate hymen

- Transverse vaginal septum

- Vaginal agenesis

- Mayer – Rokitansky – Küster – Hauser

Syndrome

- Disorders of sexual differentiation

Imperforate Hymen
Acquired

- Asherman’s syndrome

- TB endometrium, Bilharzia
Asherman’s Syndrome (HSG, Hysteroscopy)
- Complete Androgen
Insensitivity Syndrome
- 46 XY female
- X-linked recessive
disorder
- Defect – androgen
receptor
-breast development,
scanty Axillary, pubic hair
- External genitalia –
Female
- Gonads testes (MIF) – no
Mullerian structures
5 Alpha reductase deficiency

- 46 XY
- neonates – Female/ambigous genitalia
- failure -testosterone → dihydrotestosterone ( more potent form)
- peripubertal virilization occurs
• Hypothalamic hypogonadism
• Gonadal dysgenisis
• Müllerian anomaly
• Androgen insensitivity

• Disorders of genital differentiation.

• 1. Hypothalamic amenorrhoea

• 2. PCOS

• 3. Ovarian failure

• 4. Hyperprolactinaemia
History

- Pubertal development

- Neonatal/childhood health (CAH)

- Symptoms of virilisation

- Changes – weight, diet, exercise, stress

- Galactorrhoea, headaches, visual disturbances

History

- Symptom of ovarian failure

- Thyroid dx symptoms

- other endocrine symptoms

- Obstetric catastrophe – PPH, evacs, sepsis

- PMHx

- Drugs – injectables or drugs ↑ prolactin

- Height & BMI (↑ PCOS, ↓ Hypothalamic)

- Features of Turner Syndrome or other phenotypes

- Pubertal dev. (Tanner – Breast, pubic hair)

TANNER STAGING
- Features of Endocrinopathies
– Acne, hirsuitism

- Acanthosis nigricans

- Striae (purple) etc

- Abdomen
– masses (Androgen secreting tumours)

- Haematometra
- Ambiguous genitalia

- Cliteromegaly

- Imperforate hymen

- Presence or absence of Mullerian structures

 EXCLUDE PREGNANCY

 Guided by physical examination

 Initial bloods : FSH , LH

TSH
Hirsutism/hyperandrogenism – testosterone (rest of profile), SHBG, FAI
PRL

Primary Amenorrhoea

- guided by physical examination

- Absent/poor breast development or short (?Turners) → FSH if increased -KARYOTYPE

- Imperforate hymen or? Absent Mullerian structures

- Pelvic U/S – need to confirm presence or absence of uterus

- Uterus absent, then karyotype
- 46 XX → Mullerian Anomaly, also investigate renal
system
- 46 XY – AIS or 5 & reductase deficiency (Virilization
at puberty)

- Uterus present & normal 2° sex characteristics

- endocrine evaluation as for secondary amenorrhoea

Secondary Amenorrhoea

- exclude pregnancy

- Endocrine evaluation
- TSH, Prolactin

- Increased TSH=Hypothyroidism

- Increased prolactin-MRI Pituitary or other cause

- Rileys test : Provera 5-10mg daily for 5 days

- Withdrawal bleed=Anovulation
- no withdrawal bleed = End-organ pathology or
Oestrogen deficiency
- COC – if bleeds = end organ is normal, oestrogen
deficiency
- Hypogonadotrophic/Hypergonadotrophic
- FSH,LH

- Increased FSH (on 2 occassions)=Primary Ovarian failure

- Investigate cause of POF

- Low or normal FSH

=Hypogonadotrophic/normogonadotrophic

- MRI OR investigate ie anorexia etc

Secondary Amenorrhoea

- If signs of hyperandrogenism

- DHEAS, 17 alpha-hydroxyprogesterone, Testosterone,

SHBG, Free Androgen Index, +/- 24HR Urine cortisol

- U/S-PCO, Androgen secreting tumour

CT Abd – Adrenal tumour

- Congenital Adrenal Hyperplasia
Aims :
- treat – treatable causes

- hyperprolactinaemia, Thyroid problems

- or surgically ie imperforate hymen/asherman’s

- Prevent complications ie osteoporosis

- Help with Fertility if desired

- Psychological & emotional support

- Primary Ovarian Failure
 Hormone Replacement therapy or COC

- Hypothalamic – if no organic cause

• Diet counselling, ↓ exercise & stress
• COC

- Hyperandrogenism
• Rx symptom ie Fertility, hirsuitism, periods

- If Y Chromose - gonadectomy
- Amenorrhoea/Oligomenorrhoea-cause for psychological
distress

- Mostly due to anxiety-Fertility

- Proper investigations necessary to prevent complications (eg.

Macroprolactinomas )

- Management mainly-treat cause or assist with fertility