This document provides a differential diagnosis for primary amenorrhea, which is the absence of menstruation by age 16. It lists various potential etiologies categorized as anatomic abnormalities of the genital tract, hypergonadotropic hypogonadism indicating gonadal failure, and hypogonadotropic hypogonadism where the hypothalamus-pituitary axis is affected. It further discusses an approach to evaluating a patient with primary amenorrhea through history, exam, and targeted laboratory and imaging tests to arrive at a diagnosis and guide treatment.

1. PRIMARY AMENORRHOEA
Prof. M.C.Bansal
MBBS., MS., FICOG., MICOG.
Founder Principal & Controller,
Jhalawar Medical College & Hospital Jjalawar.
MGMC & Hospital , sitapura ., Jaipur

2. DIFFERENTIAL DIAGNOSIS OF PRIMARY
AMENORRHOEA
A. Anatomic abnormalities of the genital outflow tract
1. Müllerian dysgenesis (Rokitansky–Küster–Hauser syndrome)
2. Distal genital tract obstruction
a. Imperforate hymen
b. Transverse vaginal septum
B. Hypergonadotropic (follicle–stimulating hormone >30
mIU/mL) hypogonadism (gonadal “failure”)
1. Gonadal dysgenesis with stigmata of Turner syndrome
2. Pure gonadal dysgenesis
a. 46,XX
b. 46,XY
3. Early gonadal “failure” with apparent normal ovarian
development

3. • C. Hypogonadotropic (luteinizing hormone and
follicle–stimulating hormone <10 mIU/mL)
hypogonadism
• 1. Constitutional delay
• 2. Isolated gonadotropin deficiency
• a. Associated with midline defects (Kallmann
syndrome)
• b. Independent of associated disorders
• c. Prader–Labhart–Willi syndrome
• d. Laurence–Moon–Bardet–Biedl syndrome
• e. Many other rare syndromes
• 3. Associated with multiple hormone deficiencies
• 4. Neoplasms of the hypothalamic–pituitary area
• a. Craniopharyngiomas
• b. Pituitary adenomas
• c. Other

4. • 5. Infiltrative processes (Langerhans cell–type
histiocytosis)
• 6. After irradiation of the central nervous system
• 7. Severe chronic illnesses with malnutrition
• 8. Anorexia nervosa and related disorders
• 9. Severe hypothalamic amenorrhea (rare)
• 10. Antidopaminergic and gonadotropin–releasing
hormone–inhibiting drugs(especially psychotropic
agents, opiates)

5. • 11. Primary hypothyroidism
• 12. Cushing syndrome
• 13. Use of chemotherapeutic (especially alkylating)
agents
• II. Asynchronous pubertal development
• A. Complete androgen insensitivity syndrome (testicular
feminization)
• B. Incomplete androgen insensitivity syndrome

6. DISCUSSION

7. Central signals Peripheral
HYPOTH signals
GABA, ALAMUS
NPY,GLUTAMATE Leptin, Ghrelin
Kisspeptin-
GPR54 system
GnRH
ANT. PITUITARY
FSH LH

8. FSH LH
OVARY
GRAN THE
Aromatisation
Androgen
of androgens
production
ESTRADIOL
INHIBIN
Follicular growth
Mid cycle LH peak

9. • WHO divides patients into groups based on endogenous
oestrogen production, follicle-stimulating hormone
(FSH) levels, prolactin levels, and hypothalamic-pituitary
dysfunction.
• This classification is a guide that eliminates several
diagnoses based on initial information. However, further
work-up is still required.
• Group I: low oestrogen, low FSH, and no hypothalamic-
pituitary pathology, leading to a diagnosis of
hypogonadotrophic hypogonadism.
• Group II: normal oestrogen, normal FSH, and normal
prolactin, leading to a diagnosis of polycystic ovary
syndrome.
• Group III: low oestrogen and high FSH, leading to a
diagnosis of gonadal failure.

10. APPROACH TO A CASE OF PRIMARY
AMENORRHOEA
HISTORY & CLINICAL EXAM
ASYNCHRONOUS IMMATURE MATURE SECONDARY
DEVELOPMENT SECONDARY SEXUAL SEXUAL
BREAST > PUBIC HAIR CHARACTERISTICS CHARACTERISTICS
ANDROGEN
FSH , PROLACTIN DISTAL GENITAL
INSENSITIVITY
TRACT OBSTRUCTION,
MULLERIAN AGENESIS

11. FSH , PROLACTIN
HIGH FSH LOW OR NORMAL FSH HIGH PROLACTIN
KARYOTYPE PITUITARY FUNCTION CHECK T4, TSH
TESTING
SELLAR X-RAY
NORMAL HIGH TSH
NORMAL ABNORMAL
NORMAL ABNORMAL TSH
MRI OR CT
• 46, XX • 45,XX OR •CONSTITUIONAL
GONADAL 46,XY DELAY
HYPOTHYROIDISM
DYSGENE • MOSAIC •ISOLATED
SIS GONADAL GONADOTROPIN
• PREMATU DYSGENES DEFICIENCY
RE IS •MALNUTRITION
• HYPOPITUITARISM
OVARIAN •CHRONIC
• CNS TUMOR
FAILURE ILLNESS