AMENORRHEA Ludmila Barbakadze Ivane Javakhishvili Tbilisi State University Assistant Professor Medical Doctor at Archil Khomassuridze Institute of Reproductology ,Tbilisi , Georgia.

1. AMENORRHEA
Ludmila Barbakadze
Ivane Javakhishvili Tbilisi State
University Assistant Professor
Medical Doctor at Archil Khomassuridze
Institute of Reproductology ,Tbilisi ,
Georgia.

2. Definition: the absence of menstrual bleeding
• Physiologic states of Amenorrhea: prepubertal
age, pregnancy, lactation and postmenopausal
females.
• Non-Physiologic occurs in 5% of reproductive
age women. In the absence of pregnancy, the
challenge is to determine the exact cause of
absent menses.
• Amenorrhea might be Primary and
Secondary

3. .
• Primary amenorrhea - is the absence of menses by
age 16 years, in the presence of normal growth and
secondary sexual characteristics. If by age 14
menses has not occurred and the onset of puberty,
such as breast development, is absent, a workup for
primary amenorrhea should start.
• Secondary amenorrhea - is defined as the cessation
of an established menses – for 3 months in a
woman with a regular cycle or 6 months in a
women with history of irregular cycle.

5. Causes of primary amenorrhea
• First , it is imperative to rule out pregnancy. Additional
diagnoses of primary amenorrhea usually result from a
genetic or anatomic abnormality.
• The relative prevalence of primary amenorrhea includes:
• hypergonadotropic hypogonadism (48.5% of cases),
• hypogonadotropic hypogonadism (27.8%), and
• eugonadism (pubertal delay with normal gonadotropins;
23.7%).
• The hypergonadotropic hypogonadism category includes
patients with abnormal sex chromosomes (ie, Turner
syndrome), who make up 29.7% of all primary
amenorrhea cases, and
• those with normal sex chromosomes. The latter group
includes both patients who are 46,XX (15.4%) and those
who are 46,XY (3.4%).

6. Causes of secondary amenorrhea
• Disorders associated with a low or normal FSH, which account for 66% of cases of secondary
amenorrhea, include the following:
• Weight loss/anorexia
• Chronic anovulation including PCOS
• Hypothyroidism
• Cushing syndrome
• Pituitary tumor, empty sella, Sheehan syndrome
Disorders in which the FSH is high (12%) include the following:
• 46,XX spontaneous POI
• Premature ovarian failure due to abnormal karyotype (45,X mosaic/ring chromosome)
• Pure gonadal dysgenesis
• Disorders associated with a high prolactin level make up 13% of cases. Anatomic disorders (ie,
Asherman syndrome) account for 7%.
Hyperandrogenic states as a cause of secondary amenorrhea (2%) include the
following:
• Polycystic ovarian syndrome (PCOS)
• Ovarian tumor
• Non-classic CAH
• Undiagnosed
• Iatrogenic
• Antipsychotics
• Cancer chemotherapy
• Antidepressants
• Blood pressure drugs
• Allergy medications.

8. Hypothlamic dysfunction (20-30%)
• hypogonadotropic hypogonadism leads to low
gonadotropin (FSH/LH) levels.

9. Types of amenorrhea based on HPO axis etiology
• Hypothalamic amenorrhea (20-30%)
• Hypothalamic dysfunction results in decreased GnRH
secretion, which affects the pulsatile release of
pituitary gonadotropins, LH and FSH, causing
anovulation.
• A common cause of amenorrhea is functional
hypothalamic amenorrhea. Functional hypothalamic
amenorrhea can be caused by eating disorders,
exercise, or high levels of prolonged physical or mental
stress (depression).
• Hypothyroidism, hyperthyroidism, or any severe
chronic medical condition may result in amenorrhea.

10. • Idiopathic hypogonadotropic hypogonadism leads to low
gonadotropin (FSH/LH) levels. When this occurs with
anosmia, it is diagnosed as Kallmann syndrome, the
signs of which include midline facial defects, renal
agenesis, and neurologic deficiencies. Kallmann
syndrome most commonly occurs as an X-linked
recessive disorder caused by a KAL1 defect.
• In some female athletes excessive exercise and
disordered eating cause severe suppression of GnRH,
leading to low estradiol levels. This female characterized
by low energy availability with or without disordered
eating, amenorrhea, and osteoporosis.
• Anorexia nervosa is a serious psychiatric disease with
severe medical complications including primary
amenorrhea (15%), osteopenia (52%), and osteoporosis
(35%).

11. Pituitary amenorrhea
• A deficiency in FSH and LH may result from GnRH receptor gene
mutations. Women with these mutations presented with amenorrhea, low
FSH and estradiol levels and high LH levels.
• Primary amenorrhea caused by hyperprolactinemia is a rare condition
characterized by the onset of thelarche and pubarche at appropriate ages
but arrest of pubertal development before menarche. Hyperprolactinemia is
associated with suppression of the GnRH from the hypothalamus and
subsequent inhibition of LH and FSH, suppressed gonadal function and
galactorrhea.
• Prolactinomas are the most common cause of persistent
hyperprolactinemia. Prolactinomas are more commonly noted in secondary
amenorrhea.
• Brain injury or cranial irradiation may also result in amenorrhea. Other
pituitary causes include empty sella syndrome, pituitary infarct,
hemochromatoses, and sarcoidosis.
• Treatment: HRT. Hypoth-pituitar region imaging to role out CNS lesions.

12. Gonadal failure 35%
• Hypergonadotropic hypogonadism is characterized by gonads
(bands of fibrous tissue in place of the ovary). Synthesis of oვarian
steroids does not occur. Breast development does not occur because of
very low estradiol level. The ext and internal genitalia are fenotipically
normal female. Causes: Terner syndrome (45,XO) > 50% of patients with
gonadal failure. Outher causes are comonly due to other non-inheareted
chromosomal disorders and deletions. Cause of primary amenorrhea.
• Treatment: Replacement hormonal therapy – developes breast tissue
and prevents osteoporosis. The preasense of Y chromosome requires
exciton of ganadal tissue to prevent the 25% incidence of malignancy.

13. Ovarian causes of primary amenorrhea
• Gonadal dysgenesis is characterized by the congenital
loss or underdevelopment of germ cells within the
gonad during organogenesis. The gonads usually
contain only fibrous tissue and are called streak gonads.
In females, the most common form of gonadal
dysgenesis is Turner syndrome (45,X), in which
gonadotropin levels, especially the FSH levels, are high
during early childhood and after age 9-10 years.
• Additional anomalies associated with Turner syndrome
include short stature, webbed neck, coarctation of the
aorta (10%), renal abnormalities (50%), hypertension,
pigmented nevi, short forth metacarpal and
metatarsals, Hashimoto thyroiditis, obesity, and
osteoporosis.[3] Depletion of ovarian follicles causes
amenorrhea.

14. POI
• Spontaneous 46,XX primary ovarian insufficiency (POI),
is hypergonadotropic hypogonadism, characterized by
oligomenorrhea/amenorrhea, estrogen deficiency, and
its associated symptoms such as hot flashes, vaginal
dryness, dyspareunia, and insomnia.
• Autoimmune oophoritis occurs in 3-4% of POI cases.
• Amenorrhea is also seen in pure 46, XX gonadal
dysgenesis and in 46,XY gonadal dysgenesis. These
women have significantly elevated FSH levels due to the
absence of ovarian follicles and reduction in negative
feedback on FSH from estradiol and inhibin A and B.
• Polycystic ovarian syndrome (PCOS) usually presents as
secondary amenorrhea, but in some cases may present
as primary amenorrhea.

15. Congenital and anatomical abnormalities
• Female reproductive tract abnormalities account for about one fifth
of primary amenorrhea cases. Cyclic pelvic pain is common in girls
with disorders of the reproductive tract involving outflow
obstruction.
• Imperforate hymen causes an outflow obstruction. These patients
can have blood in the vagina that collects and can result in a
perirectal mass. Transverse vaginal septum can be anywhere along
the tract between the hymenal ring and cervix.
• Vaginal agenesis, or müllerian dysgenesis (also known as Mayer-
Rokitansky-Kuster-Hauser [MRKH] syndrome) is caused by
agenesis or partial agenesis of the müllerian duct system. It is
characterized by congenital aplasia of the uterus and upper two
thirds of the vagina in women showing normal development of the
secondary sexual characteristics and a normal 46,XX karyotype.The
first sign is primary amenorrhea. It affects 1 of 4500 women. It can
be associated with renal, vertebral, and, to a lesser extent, auditory
and cardiac defects.
• Treatment: creation of neovagina by surgery.

16. enzyme defects
• Complete androgen insensitivity syndrome is
caused by a defective androgen receptor.
Although patients with this syndrome have a
46,XY karyotype the testosterone cannot activate
cellular transcription; therefore, the patient has
female external genitalia. The testes, located
internally and sometimes in the labia or inguinal
area, also produce müllerian-inhibiting
hormone, so all müllerian-derived structures (ie,
the fallopian tubes, uterus, upper third of the
vagina) are absent.

17. Prognosis
• Amenorrhea has been associated with an increased risk of wrist and
hip fractures related to reduced bone density.
• Young women with ovarian insufficiency that is unresponsive to
therapy require hormone replacement to maintain bone density.
• Adolescence is a critical period for bone accretion as over half of
peak bone mass is achieved during the teenage years. Regular
menses is a sign that the ovaries are producing normal amounts of
estrogen, androgens, and progesterone, all of which play an
important role in building and maintaining bone mass. Late
menarche has been associated with a 3-fold increase in the risk of
wrist fracture.
• In some cases, loss of menstrual regularity is an early sign of
declining fertility and impending premature ovarian failure. Also in
some cases, follicle depletion progresses to cause irreversible
infertility.
• Women with PCOS have many long-term health issues, including
higher risk of diabetes and cardiovascular disease, that should be
monitored and treated.

18. Thank you!

19. Hypogonadotropic hypogonadism includes the following:
• Congenital abnormalities
• Endocrine disorders
• Tumor
• Systemic illness (2.6%)
• Eating disorder (2.3%)
• Congenital abnormalities that can cause hypogonadotropic hypogonadism
include the following:
• Isolated GnRH deficiency (8.3%)
• Forms of hypopituitarism (2.3%)
• Congenital central nervous system (CNS) defects (0.8%)
• Constitutional delay (6%)
• Endocrine disorders that can cause hypogonadotropic hypogonadism include
the following:
• Congenital adrenal hyperplasia (CAH) (0.8%)
• Cushing syndrome (0.4%)
• Pseudohypoparathyroidism (0.4%)
• Hyperprolactinemia (1.9%)
• Tumors that can cause hypogonadotropic hypogonadism include the
following:
• Unclassified pituitary adenoma (0.8%)
• Craniopharyngioma (1.1%)
• Eugonadism may result from anatomic abnormalities or intersex disorders. Anatomic
abnormalities include congenital absence of the uterus and vagina (CAUV; 16.2%) and
cervical atresia (0.4%). Intersex disorders include androgen insensitivity (1.5%), 17-
ketoreductase deficiency (0.4%), and inappropriate feedback (5.3%).