1. Amenorrhea Dr. Maysa’ Khadra
A/Professor in Reproductive Endocrinology and Infertility
Dept of Obstetrics and Gynaecology
University of Jordan;
Jordan University Hospital

2. Amenorrhea definition
Primary:
No period by age 14 in the absence of growth or development of secondary sexual characteristics. or
No period by age 16 regardless of the presence of normal growth and development with the appearance of secondary sexual characteristics.

3. Amenorrhea definition
Secondary:
In a woman who is menstruating , it is the absence of periods for a length of time equivalent to a total of at least three previous cycle intervals or six months of amenorrhea
Oligomenorrhea is defined as an interval of more than 35 days between periods

5. differential diagnosis of amenorrhoea
Disorders of outflow
Disorders of the ovary
Disorder of the anterior pituitary
Disorders of the central nervous system

6. Disorders of outflow Asherman’s syndrome Mullerian Anomlies
Cervical stenosis
Imperforate hymen
Transverse vaginal septum
Mullerian agenesis
Vaginal and uterine aplasia- Rokitansky Kuster Hauser syndrome
Androgen insensitivity

7. Cyclical abdominal pain
urinary retention 37-60%
back pain
Constipation
distended bluish membrane at the introitus

8. 46XY karyotype, X-linked recessive
mutations in AR, the gene for the human Androgen Receptor, located at Xq11-12
Undervirilization and/or infertility in XY persons
undescended testis in abdomen or inguinal canals
No uterus or vagina-AMH
no prostate or internal male gentalia
No pubic or axillary hair
normal breast development
25% chance of developing benign testicular tumors and a 4-9% chance of malignancy.

9. Disorders of the ovary Streak ovaries
Turner’s syndrome xo or mosaicism
XY Gonadal dysgenesis
Resistant ovary syndrome
Premature ovarian failure
Polycystic ovarian syndrome
hormone secreting ovarian tumors

10. Genetic mosaicism (46XX/45XO) is most often implicated, nondisjunction (45XO) and partial monosomy (46XX )
XO : primary amenorrhea
Mosaic: premature ovarian failure,
streak gonads and infertility
Horse shoe kidneys-HTN
Hypothyroidism- Hashimoto’s
risk of gonadoblastoma
(45 XO/46 XY)

11. Gonadal dysgenesis
It is characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo. This loss leads to extremely hypoplastic and disfunctioning gonads mainly composed of fibrous tissue, hence the name streak gonads.
absence of both Mullerian inhibiting factor and testosterone
regression of the Wolffian ducts due to absence of testosterone
The absence of Mullerian inhibiting factor will allow the Mullerian ducts to differentiate into the oviducts and uterus
individual will be genotypically male (i.e., XY), yet will possess female-like internal and external reproductive characteristics

12. Gonadal dysgenesis pure gonadal dysgenesis, 46, XX
Swyer syndrome: pure gonadal dysgenesis, 46, XY type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be partially non-functional streaks
Mutation of the SRY gene: When such a gene is defective, the indifferent gonads fail to differentiate into testes in an XY (genetically male) fetus
absence of breasts ( streak gonads), and the presence of a uterus and pubic hair (adrenals)
High risk of malignancy esp. gonadoblastoma, gonads should be removed as cancer may develop in infancy

13. Disorders of the anterior pituitary
Non- functional adenomas
Prolactin secreting adenomas
Empty sella syndrome or compression of pituitary stalk
Sheehan’s syndrome
Galactosemia: Fewer oogonia result as a direct result of the toxic effect of galactose metabolites on germ cell migration to the genital the genital ridge

14. Disorders of the central nervous system
Hypothalamic amenorrhea
weight loss, anorexia, bulimia
Excessive exercise-induced amenorrhea (decreased body fat and elevated endorphins and CRH)
Inherited genetic defects- Kallman’s syndrome

15. Primary amenorrhea- causes
Chromosomal abnormalities (45%)
Physiological delay (20%)
Mullerian agenesis (15%)
imperforate hymen or vaginal septum (5%)
Hypothalamic GRH deficiency (5%)
anorexia nervosa (2%)
Hypopituitarism (2%)
Prolactinoma, hypothyroidism, craniopharyngima, adrenal disease ( < 1%)

17. Primary amenorrhea- 2 questions approach
Has puberty occurred ?
“No”, then “normal stature or short?
“yes”, then
Feminizing or Virilizing

18. Has puberty occurred ? NO Normal to tall GnRH Deficiency
Pure FSH deficiency
FSH low
Pure gonadal dysgenesis
FSH high

19. Has puberty occurred ? NO Short= something else is going on
Hypopituitarism
Turner’s
Hypothyroidism
FSH slightly high, TSH high

20. Has puberty occurred ? Yes Virilizing 46 xx 46 xy
Virlizing female intersex
Congenital adrenal hyperplasia
Virlizing male intersex
Partial androgen insensitivity syndrome
Leydig cell hypoplasia

21. Has puberty occurred ? Yes Feminizing 46,xx 46,xy Idiopathic delay
Mullerian agenesis
Serum testosterone
Complete androgen insensitivity syndrome
Serum testosterone

22. Presentation with primary amenorrhea : feminizing
Uterovaginal agenesis
low transverse vaginal septum
Complete androgen insensitivity
All the entities of secondary amenorrhea:
Pregnancy
Central
Ovarian failure
Uterine
Ovarian or adrenal tumor
metabolic

23. Diagnostic evaluation
When to investigate?
No menarche by years
Investigate earlier if :
Galactorrhea
Short stature
Dysmorphic features
Virilisation
Abnormal pubertal development
Out of keeping with family history of menarche
Symptoms or signs of hypothalamic-pituitary disease
Parent/adolescent concerned

24. Investigations Thorough history and physical exam Estrogen
FSH/LH level
High-ovarian failure(turner’s,chemo, autoimmune)
Low or normal-hypothal-pit axis, constitutional
Thyroid function tests
Karyotype
Bone age
Prolactin
Testosterone, DHEAS, 17-oh Prog, androstenedione
Pelvic US, imaging
“routine bloods” looking for chronic illness