Amenorrhea Flashcards
(27 cards)
Cryptomenorrhea
Cryptomenorrhea- in cryptomenorrhea, there is periodic shedding of endometrium and bleeding but the menstrual
blood fails to come out from the genital tract due to obstruction in the passage
Physiological types of amenorrhea
- Before Puberty- pituitary gonadotropins are not adequate enough to stimulate ovarian follicles for effective
steroidogenesis → estrogen levels are insufficient to cause bleeding from the endometrium - During Pregnancy- Large amount of estrogens & chorionic gonadotropins secreted from trophoblasts suppress
pituitary gonadotropins → no maturation of ovarian follicles. - During Lactation- High level of prolactin → inhibits ovarian response to FSH → no follicular growth →
hypoestrogenic state → no menstruation. - Following Menopause- No more available responsive follicles in ovaries to produce hormones
causes of amenorrhea
congenital causes
1. Imperforate hymen
2. Transverse vaginal septum
3. Atresia of upper-third of vagina and cervix.
4. Rarer causes include absence of vagina with or without (Rokitansky’s syndrome) a functioning uterus
Acquired cause- usually cause 2° amenorrhoea. Are rare due to
1. Cervical stenosis following amputation, conization or deep cauterization.
2. Stenosis of the cervix following amputation, deep cauterization and conization.
3. Secondary vaginal atresia following neglected and difficult vaginal delivery
4. Asherman’s syndrome & endometrial resection or ablation
Pathology of cryptomenorrhoea
There is only accumulation of blood in uterine cavity resulting in hematometra.
In neglected cases, blood may enter the tubes whose fimbrial ends get blocked resulting in distension of the tubes by
blood → hematosalpinx
Clinical features of crytopmenorrhoea
Pts aged about 13-15 (congenital type) with H/O any of
mentioned etiological factors, C/O:
Amenorrhea dated back from the events.
Periodic lower abdominal pain.
Hematocolpos is associated with urinary problems to extent of retention of urine
Pelvic exam reveals offending lesion in vagina/ cervix. Uterus is symmetrically enlarged, uniform globular
mass in the hypogastrium. Vulval inspection reveals bulging hymen.
DRE confirms the fullness of the vagina and uterine mass
Management of cryptomenorrhoea
i) Cruciate incision of hymen& drainage of blood.
(ii) Dilatation of cervix in stenosis.
(iii) In cases of secondary atresia of the vagina, reconstructive surgery
Primary amenorrhea
Is defined as the absence of menstruation by age of 14 years in the absence of secondary sexual
characteristics, or the absence of menstruation by age 16 years in the presence of secondary sexual
characteristics (breast development, pubic hair, growth acceleration)
Normal upper age limit for menarche is 15 years.
Median age of menarche is 10-15 years, Mean is 13years & weight 51.1kg.
As a general rule, failure of devt. of any secondary sexual characteristic by age of 14 years should be investigated
In the presence of secondary sexual characteristics, menstruation should occur within 2yrs of the establishment of
this development. Failure to do so would warrant investigation
Causes of primary amenorrhea
Are grouped as disorders of; uterus or outflow tract, ovary, pituitary, hypothalamus/CNS & endocrine.
Most common cause is gonadal dysgenesis, such as in Turner syndrome- 40% and Müllerian agenesis (MayerRokitansky-Küster-Hauser Syndrome) is 2nd
- 15%
Hypothalamic/pituatory Causes of primary amenorrhea
hypothalamic/pituatory causes (Hypogonadotropic hypogonadism)
1. Delayed puberty- delayed GnRH pulse reactivation.
2. Hypothalamic dysfunction- Gonadotropin deficiency due to
- Stress
-Weight loss- a minimum of 17% body fat is required for the onset
on menarche & 22% for the maintenance of resumption of normal menstrual function
-Excessive exercise- exercise induced amenorrhea (occur in 6-18% of recreational runners)
-Eating disorder - Anorexia nervosa,
-Chronic disease (e.g. TB), diabetes
-Medication- antipsychotic, Antiepileptics
3. Kallmann’s syndrome- Inadequate GnRH pulse secretion — reduced FSH & LH.
4. Pituitary tumours-
a. Adenomas (micro- or macroadenomas) of which prolactinoma is most common- galactorrhea, headaches, or
↓↓peripheral vision
b. craniopharyngioma → reduced GnRH secretion → reduced FSH & LH
5. Hyperprolactinaemia – (10-40% of women with hyperprolactinaemia presents with amenorrhoea)
6. Pituitary necrosis, e.g. Sheehan’s syndrome (due to prolonged hypotension following major obstetric
haemorrhage).
7. Isolated gonadotropin deficiency
Hypergonadotropic hypogonadism Causes of primary amenorrhea
hypergonadotropic hypogonadism
1. Gonadol dysgenesis
2. Primary ovarian failure.
3. Resistant ovarian syndrome and ovarian disorders such as PCOS
4. Galactosemia: Due to premature ovarian failure
5. Enzyme deficiency (17 α hydroxylase deficiency) - characterized by ↓cortisol & ↑ACTH, ↑mineralocorticoids
production. There is htn with hypernatremia & hypokalemia. Individual may be 46 XX or 46 XY with primary
amenorrhea & no secondary sexual characters.
6. Others — Gonadotropin receptor mutations – rarely FSH and/or LH levels are high as respective receptor may
be absent or mutated
Abnormal chromosomal pattern Causes of primary amenorrhea
abnormal chromosomal pattern
1. Turner’s syndrome (45 X). Various mosaic states 45 X/46 XX.
2. Pure gonadal dysgenesis (46 XX or 46 XY) - Phenotypically female with streak gonads. Stature is average
with some secondary sexual characters.
3. Androgen insensitivity syndrome (aka Testicular feminization syndrome), 46 XY.
4. Partial deletions of the X chr (46 XX) - When part of one X chr is missing- deletion of long arm of X chr (Xq–
leads to streak gonads and amenorrhea but no somatic abnormalities. Deletion of short arm of X chr (Xp–)
usually leads to somatic features similar to Turner’s syndrome.
Developmental defect of vagina/genital tract Causes of primary amenorrhea
Imperforate hymen
Vaginal agenesis
Mullerian agenesis; is a congenital malformation where Mullerian ducts fail to develop resulting in an absent
uterus & variable malformations of vagina.
Transverse vaginal septum.
Atresia upper-third of vagina and cervix
Complete absence of vagina
Absence of uterus in MRKH syndrome
ovarian disorder Causes of primary amenorrhea
. Gonadol dysgenesis
1. PCOS (Anovulation)
2. Premature ovarian failure (POF) - is defined as onset menopause before 40yrs of age. It is usually unexplained,
but may be due to chemotherapy, radiotherapy, autoimmune disease or chromosomal disorders (e.g. Turner’s
45XO/46XX)
3. Resistant ovary syndrome
4. Ovarian insensitivity syndrome (Sarage’s syndrome)
5. Chemotherapy and radiation injury
uterine anomaly Causes of primary amenorrhea
- Unresponsive endometrium due to congenital uterine synechiae
- Uterine adhensions- ( asherman’s syndrome is the presence of intrauterine synechiae or scarring preventing
normal growth of endometrium typically from previous infection (endometritis) or endometrial curettage - Androgen insensitivity
- Mullerian agenesis- syndrome often referred to as Mayer-Rokitansky-Kuster-Hauser syndrome is themost
common of primary amenorrhoea
Endocrine disorders Causes of primary amenorrhea
Dysfunction of thyroid
1. Cretinism/hypothyroidism
2. Hyperthyroidism
Dysfunctions of adrenal cortex
3. Adrenogenital syndrome- Androgen insensitivity syndrome (AIS)
4. Congenital adrenal hyperplasias
5. Cushing syndrome
Others
1. Androgen secreting tumours
2. 5α-Reductase deficiency
3. Partial androgen receptor deficiency
4. True hermaphrodite
5. Absent mullerian inhibitors
Secondary Amenorrhea
It is the absence of menstruation for 6 months or more in a woman of reproductive age in whom normal menstruation
was established, and previously menstruating and which is not due to pregnancy, lactation or menopause
Incidence of secondary amenorrhea is 0.7%
It might be temporary ( Pregnancy) or permanent (menopause, Sheehan syndrome)
May occur as a normal physiological event such as before puberty, during pregnancy, lactation or menopause, or as a
feature of a systemic or gynaecological disorder
Most causes of secondary amenorrhoea can also cause primary amenorrhoea, if they occur before the menarche
Common cause of secondary amenorrhoea is pregnancy and polycystic ovary syndrome -PCOS- (which is a
condition that is associated with hypersecretion of androgens).
Whilst hyperandrogenism of PCOS may lead to hirsutism, acne & alopecia these pts do not have signs of virilization
(clitoromegaly, deepening of voice, increased muscle bulk)
Causes of secondary amenorrhea
Any abnormality involving hypothalamic-pituitary-ovarian (HPO) axis or genital outflow tract
1) Pregnancy: most common cause
2) Hypothalamic-pituitary dysfunction
a) Psychogenic: anxiety, anorexia nervosa, pseudocyesis (false pregnancy)
b) Functional: obesity, extreme wgt loss, dieting or exercise
c) Medication or drug induced: psychoactive drugs (antidepressants), marijuana
d) Neoplasms: prolactinomas, craniopharyngioma
Others: head injury or chronic medical illness- lead to state of estrogen defic (hypogonadotropic hypogonadism)
Alteration of pulsatile GnRH, inhibiting FSH and LH
No folliculogenesis = no ovulation
No sex hormone production = no endometrial growth or menstruation
State of chronic estrogenism: anovulation or oligoovulation
a) Idiopathic
b) Polycystic ovarian syndrome (PCOS) is subset of anovulation
c) Adrenal hyperplasia
d) Thyroid dysfunction (hypo- or hyperthyroidism)
e) Obesity
Ovarian dysfunction or failure
1. Turner syndrome (45 ,X)
2. Premature ovarian failure (PMOF)
i. Idiopathic
ii. Iatrogenic (chemotherapy, radiation, surgery)
iii. Autoimmune processes (Blizzard syndrome)
iv. Fragile X premutation
Abnormal genital outflow tract
a) Uterine synechiae/ Asherman syndrome- presence of intrauterine adhesions (causes are intrauterine infection
or vigorous dilation and curettage) is most common anatomic cause of secondary amenorrhea
b) Cervical stenosis
Metabolic disorders
a) Juvenile diabetes.
Systemic illness
a) Weight loss
b) Malnutrition, anemia
c) Tuberculosis.
d) Sarcoidosis Resulting in an infiltrative process in the hypothalamo-hypophyseal region
Drugs:
a) Progestogens, or HRT.
b) Dopamine antagonists (psychoactive drugs) -Dopamine is a negative feedback inhibitor of prolactin release, so
these medications lead to increased prolactin secretion.
c) Antidepressants, (e.g., tricyclics), antipsychotics (e.g., risperidone and haloperidol), and some antiemetics (e.g.,
metoclopramide) are in this category. Also SSRIs & MAOIs induce amenorrhea → ↑Prolactin
History taking of primary amenorrhea
The following guidelines may be of help:
Pregnancy is the common cause of amenorrhea. R/O Possibility of preg even in 1° amenorrhea
a) No -16 yrs of age in the presence of normal secondary sex characters
b) No- period by the age of 14 in the absence of growth or development of secondary sex characters.
Absence of breast devt or pubertal growth by 14 yrs is abnormal. & requires investigation.
Breast development, pubertal growth spurt, and adrenarche are delayed or absent in persons with hypothalamic
pituitary failure.
Does the pt. have evidence of normal pubertal development? Breast development signals exposure to estrogen,
and normal pubic or axillary hair signifies androgen production or exposure and BMI, stature & body form;
Is the reproductive tract normal on examination? External genitalia & vaginal examination
Ask Age of menarche, Details of previous menstrual cycle and about sexual activity
Any triggers: - diseases: diabetes or genital TB though rare, may be responsible for primary amenorrhea. Such type
of amenorrhea is usually associated with hypogonadism
Other features: weight loss, emotional stress, excessive
exercise,
Use of contraceptive methods
abnormal loss or gain of weight within a short period is
suggestive of some metabolic disorders
Symptoms of menopause e.g. hot flushes and ask
specifically about galactorrhoea
Difficulty with dates; menstrual calendar X 3 months.
Is any evidence of hirsutism, excess androgens, or excess
cortisol present?
H/O emotional / physical stress, or nutritional problems
Are any signs of a hypothalamic or pituitary problem noted? Ask whether the patient has had any headaches,
seizures, visual field defects, vomiting, changes in sleep or appetite, or galactorrhea. Examine visual fields to elicit
signs of pressure on the optic chiasm
Is pt. taking any medications, or received chemotherapy or radiation therapy?
Family Hx of early menopause, infertility or autoimmune disease, and delayed menarche or androgen insensitivity
syndrome often runs in family
Look out for symptoms of systemic disease
History taking in secondary Amenorrhoea
In secondary amenorrhea, there is altered coordinated function of the hypothalamopituitary ovarian axis by some
pathology.
Meticulous history taking & clinical examinations are mandatory because diagnosis only by clinical exam is hard.
Laboratory investigations either to diagnose or to confirm clinical diagnosis are mostly needed.
Prior exclusion of pregnancy must be hand, regardless of marital status
Mode of onset — whether sudden or gradual preceded by hypomenorrhea or oligomenorrhea.
Sudden change in environment, emotional stress, psychogenic shock, or eating disorder (anorexia nervosa).
Sudden change in weight—loss or gain.
Intake of psychotropic or antihypertensive drugs like reserpine or methyldopa
Intake of COC’s or its recent withdrawal.
History of radiotherapy and chemotherapy or surgery
Appearance of abnormal manifestations either coinciding or preceeding the amenorrhea, such as: Acne, hirsutism
(excessive growth of hair in normal and abnormal sites in female) or change in voice.
Inappropriate lactation (galactorrhea) —abnormal secretion of milk unrelated to pregnancy and lactation.
Headache or visual disturbances.
Hot flushes and vaginal dryness
Obstetric history —
Overzealous postpartum or postabortal uterine curettage leading to synechiae- Ashermans sydrome
Cesarean section may be extended to hysterectomy of which the pt may be unaware.
Severe postpartum hemorrhage, or shock or infection- Sheehan syndrome.
Prolonged lactation - Pt may be amenorrheic since childbirth or she may have 1 or 2 periods, followed by
amenorrhea. Even though pt states that she is not breastfeeding her baby, a pt enquiry may reveal that she puts
baby to the breast at night. This is sufficient to make the patient remain amenorrheic
Medical history- enquire of TB (pulmonary or extrapulmonary), Diabetes, chronic nephritis or overt hypothyroid
Family history- Premature menopause often runs in the family (mother or sisters)
Clinical Examination in primary amenorrhoea
A general inspection- assess BMI, secondary sexual
characteristics (hair growth, breast devt) and signs of
endocrine abnormalities (hirsutism, acne, abdominal striae,
moon-face, and skin changes).
If history is suggestive of a pituitary lesion, an assessment
of visual fields is indicated.
External genitalia and a vaginal exam to detect structural
outflow abnormalities or demonstrate atrophic changes
consistent with hypo-oestrogenism.
Examination of the eye-visual field.
Abdominal examination.
Pelvic examination
Clinical Examination of secondary amenorrhoae
General examination
The following features are to be noted:
Nutritional status.
Extreme emaciation or marked obesity.
Presence of acne or hirsutism.
Discharge of milk from the breasts.
Abdominal examination
Presence of striae associated with obesity may be related to Cushing disease.
A mass in the lower abdomen.
Pelvic examination
Enlargement of clitoris.
Adnexal mass suggestive of tubercular tuboovarian mass or ovarian tumor.
With above methods, either a probable diagnosis is made or no abnormality is detected to account for
amenorrhea.
Even with no inappropriate galactorrhea, serum prolactin, TSH estimations and X-ray sella turcica are mandatory
Investigation of primary amenorrhoea
- Pregnancy test.
- Pelvic Ultrasound,
- Imaging; CT, MRI- exclude hypothalamic or pituitary tumours
- Hormonal assay- LH, FSH, prolactin& androgens, oestradiol, testosterone, SHBG
If pelvic anatomy is normal then essentially assess gonadotrophin and prolactin levels, as this would tend to
indicate a hypothalamic cause for amenorrhoea, so-called constitutional delay.
(LH) to FSH ratio may be elevated, e.g. PCOS
In resistant ovary syndrome gonadotrophin levels is elevated.
Elevation of prolactin levels suggests a prolactinoma. - Thyroid function tests.
- Karyotype-. If the uterus is absent the karyotype should be performed, and if this is 46 XX then Rokitansky
syndrome is the most likely diagnosis. If chromosome complement is 46 XY, patient is, by definition, an XY female. - Autoimmune screen: ANA, Anti dsDNA, Anti phospholipids, anti-Ro, anti- Smith
- Hysteroscopy R/O Asherman syndrome
Investigations for secondary Amenorrhoea
To diagnose or confirm offending factor.
To guide mgt protocol either to restore menstruation & or fertility
1) Blood - a. hCG, b. TSH, c. Prolactin level
2) Progesterone challenge test (PCT): administer medroxyprogesterone acetate 10mg by mouth (PO) X 10 days
a. If withdrawal bleeding occurs, there was adequate estrogen to proliferate endometrium
Result is physiologic withdrawal bleeding after exogenous progestin is discontinued
Anovulatory or oligoovulatory
b. No withdrawal bleeding: obtain FSH
High FSH (> 4 0 mlU/mL) = PMOF
Low or normal FSH: administer estrogen followed by progestin withdrawal (can use standard combination
oral contraceptive)
Withdrawal bleeding = hypogonadotropic hypogonadism
No withdrawal bleeding = Asherman syndrome
outline investigation protocol in the even that serum values are normal for secondary amenorrhea
nvestigation protocol
If serum prolactin, TSH estimations and X-ray sella turcica are
normal, then follow the protocols:
Step – I-Progesterone challenge test- if withdrawal bleeding occur, it
proves;
a) Intact hypothalamopituitary ovarian axis
b) Adequate endogenous estrogen (Serum E2 level > 40 pg/mL) which
promote progesterone receptors in endometrium
c) Anatomically patent outflow tract and
d) Responsive endometrium.
In PCOS estimate serum testosterone, prolactin, TSH, oral GTT
and fasting lipid profile
If no withdrawal bleeding- signifies- (i) lack of progesterone
receptors in endometrium or (ii) diseased endometrium.
Step – II- Estrogen–progesterone challenge test — Ethinyl estradiol
0.02 mg or conjugated equine estrogen 1.25 mg is to be taken daily for 25
days. Medroxyprogesterone acetate 10 mg daily is added from day15–25.
No bleeding, it signifies local endometrial lesion such as uterine synechiae which should be confirmed by HSG or
hysteroscopy.
Withdrawal bleeding occurs - indicates presence of responsive endometrium but endogenous estrogen production
is inadequate
Determine whether underlying defect lies in ovary or in pituitary, one is to proceed to step III.
Step – III- Estimation of serum gonadotropins. If level of serum FSH is > 40
mIU/mL, the case is one of premature ovarian failure or resistant ovarian syndrome
Ovarian biopsy is not recommended to confirm the dsis
If, level of FSH is normal or low, it signifies pituitary dysfunction
Whether disturbed pituitary function is primary or secondary to hypothalamus,
one should proceed to step IV
Step – IV GnRH dynamic test -If with GnRH administration, there is rise of pituitary
gonadotropins, it is probably a case of hypothalamic dysfunction.
In primary pituitary disorder, there is no rise of gonadotropins.
If possible, pituitary tumor have to be excluded by X-ray of sella turcica, CT scan
or MRI, even though the prolactin level is normal
