1. Current Management of Amenorrhea
25th European Gynecology and
Obstetrics Congress
15th Ulusal Jinekoloji ve Obstetri
Kongresi
Current Management of Amenorrhea
Münire ERMAN MD Prof
Akdeniz University
Antalya, TURKIYE

2. Objective To define amenorrhea To review the common causes
Management of amenorrhea
To evaluate the clinical significance

3. Definition Primary Amenorrhea(0.3%)
No period by age 13 in the absence of growth or development of secondary sexual characteristics.
No period by age 15 regardless of the presence of normal growth and development with the appearance of secondary sexual characteristics(no menstruation by 4 years after thelarche) .
ASRM 2008

4. Definition Secondary Amenorrhea(3%)
In a woman who has been menstruating,
the absence of periods for a length of time
equivalent to a total of at least 3 of the
previous cycle intervals or 6 months of
amenorrhea

6. Normal physiology 6

7. Most common causes 1.Policystic ovary syndrome
2.Hypotalamic amenorrhea
3.Hyperprolactinemik amenorrhea
4.Ovarian failure

8. Primary Amenorrhea Outflow tract anomalies End organ disorders
Central regulatory disorders

9. Outflow tract anomalies
Imperforate hymen
Transverse vaginal septum
Vaginal agenesis
Testicular feminization

10. İmperforate hymen

11. Transverse vaginal septum
Failure of the Mullerian-derived upper vagina to fuse with the urogenital sinus derived lower vagina.

13. Vaginal agenesis

17. Sheep grown in the artificial womb
Flake et al, 2017, Nature Communications

18. Genetic Analysis of Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) Through Ascertainment of a Large Cohort of Families
Fertil Steril 2017, Layman et al

21. Transmyometrial embryo transfer with Towako catheter

22. Testicular feminization (Androgen insensitivity syndrome)
1/50 000
X-link transmisssion
Testis and Mullerian inhibiting factor present
Karyotype 46, XY
testosteron level as in male
Treatment: gonadectomy after puberty (HRT) (germ cell malignancy risk?)
Vaginal reconstruction (dilatation vs Vaginoplasty)
Mongan et al 2015, Best Pract Res Clin Endocrinol Metab. 2015

23. End-Organ Disorders Ovarian failure
Gonadal agenesis with 46XY chromosome

24. Ovarian failure Hypergonadotropic hypogonadism İdiopathic
Steroidogenic enzyme defects
Cholesterol side chain cleavage
17 hydroxylase
17 desmolase
Pure gonadal dysgenesis (Swyer syndrome)
Turner syndrome
Savage syndrome
Mc Cabe , 2014, Pediatr Endocrinol Rev

25. Turner syndrome
Levitsky et al 2015, Curr Opin Endocrinol Diabetes Obes

26. Swyer syndrome (XY gonadal dysgenesis)
Primary amenorrhea
tall stature, lack of secondary sexual characteristics development
female external genitalia, normal vagina and fallopian tubes
hypoplastic uterus, and streak gonads.
Mutation in SRY gene (sex determining region of Y chromosome)
1955, Swyer et al

27. Fertil Steril 2011

28. Central disorders Hypothalamic disorders Pituitary disorders
Adrenal disorders

29. Hypothalamic dysorders
Hypothalamus unable to produce GnRH
Anovulation and amenorrhea
Kallman syndrome (migration of the GnRH neurons are disrupted from olfactory placode to hypothalamus)
Tumor mass effect
Trauma
Sarcoidosis
Tuberculosis
Irradiation
Anorexia nervosa
Hyperprolactinemia
Hypothyroidism

30. Pituitary dysorders Tumors Infiltration of the pituitary
İnfarct of the pituitary
Hemosiderosis

31. 21 hydroxylase deficiency (Late onset CAH)

32. Evaluation of the patient
History
Physical examination
Breast development
Presence of hirsutizm, virilization
ßhCG
FSH
TSH
Prolactin

33. Uterus absent
Uterus present
Breasts absent
Gonadal agenesis in 46XY
Gonadal failure/agenesis in 46XX
Breasts present
Enzyme deficiencies in testesterone synthesis
Testicular feminization
Mullerian agenesis
Disruption of hypothalamic pituitary axis
Hypothalamic,pituitary or ovarian pathogenesis
Congenital abnormalities of the genital tract
Lobo et al, 2007 Fertil Steril

34. Primary amenorrhea(Katz 2007, Lobo R)
Acc to the presence of secondary sexual characteristics in 4 categories
1.No breast develop, presence of
uterus
2. Presence of breast develop, no uterus
3. No breast development, no uterus
4. Presence of breast development and uterus

35. 1. No breast development, uterus present
A)Gonadal failure
B)Hypothalamic failure due to insuff GnRH
C)Pituitary failure

36. 2.Breast development, no uterus
A)Androgen insensitivity(testicular feminization)
B)congenital agenesis of uterus

37. Androgen Insensitivity
Karyotype
46-XY
46-XX
Androgen Insensitivity
(TSF syndrome)
Mullerian
Agenezis
(MRKH syndrome)
Normal breast develop
No sexual hair
Normal breast d
evelopment and
sexual hair

38. 3. No breast development and no uterus
A)17-20 desmolase def
B)agonadizm

39. 4. Breast development and presence of uterus
A)Hypotalamic etiology
B)Pituitary etiology
C)Ovarian etiology
D)Uterine etiology

40. Asherman’s Syndrome

42. Ovarian or adrenal tumor
Amenorrhea+
Hyperandrojenemia
Testosteron, DHEAS, FSH and LH
TEST. >200 ng/dL
DHEAS >700 mg/dL
DHEAS mg/dL
U/S ? MRI or CT
Serum 17-OH
Progesterone levels
Ovarian or adrenal tumor
Adrenal
hyperfunction
Late CAH
Mildly high DHEAS  PCOS (inc LH / FSH)

44. General principles in management
. Restoration of ovulatory function
If not possible HRT and prevention of osteoporosis and atherosclerosis
Progesteron for prevention of endometrial hyperplasia in patients with normal estradiol levels
Vaginal reconstruction in vaginal agenesis
If there is Y chromozome gonadectomy following puberty
(52%) risk of gonadoblastom, disgerminom, and yolk sac tumors

45. SUMMARY Most common causes First lab tests ßhCG,FSH,TSH and prolaktin
1.Policystic ovary syndrome
2.Hypotalamik amenorhea
3.Hyperprolactinemik amenorhea
4.Ovarian failure
First lab tests ßhCG,FSH,TSH and prolaktin