Amenorrhea

oleh Dr. H M A ASHARI SpOG (K)

Physiology of menstruation
Normal endometrial shedding ensues as a consequence of progestagen withdrawal in an endometrium primed by both estrogen & progestagen.
Estrogen & progestagen are secreted by the ovary under the influence of pituitary gonadotrophins (FSH & LH), which in turn are stimulated by hypothalamic GnRH

Aksis Hipothalamushipofisisovarium-uterus

Two cells two gonadotrophins theory

Menstruation
Spontaneous, revealed menstruation therefore requires:
Hypothalamic GnRH secretion Pituitary FSH & LH secretion Ovarian estrogen & progestagen secretion Endometrium Patent cervix & lower genital tract

Disorders at any the above levels will have the potential to disrupt menstruation

CNS-Hypothalamus-Pituitary Ovary-uterus Interaction

Neural control
Dopamine (-)

Chemical control
Norepiniphrine (+) Endorphines (-)

Hypothalamus

Estrogen

Gn-RH Ant. pituitary FSH, LH Ovaries Uterus

?
Progesterone

Menses

Amenorrhea
Amenorrhea is a sign of a disorder not a diagnosis Because any abnormality of menstruation may be associated with pregnancy, pregnancy always must be ruled out as a cause for the absence of menses

Definitions
Primary amenorrhea Failure of menarche to occur when expected in relation to the onset of pubertal development No menarche by age 16 years with signs of pubertal development. No onset of pubertal development by age 14 years. Secondary amenorrhea

Absence of menstruation for 3 or more months in a previously menstruating women of reproductive age.

Common causes of primary amenorrhea

The Practice Committee of the American Society for Reproductive Medicine FERTILITY AND STERILITY VOL. 82, SUPPL. 1, SEPTEMBER 2004

Common causes of secondary amenorrhea

The Practice Committee of the American Society for Reproductive Medicine FERTILITY AND STERILITY VOL. 82, SUPPL. 1, SEPTEMBER 2004

Causes of amenorrhea
Physiological
Prepuberty, pregnancy, lactation, postmenopause

Pathological prevalence: 3-4%

Local genital causes
Congenital--eg, testicular feminisation Acquired--eg, Asherman's syndrome

Hypothalamic
Congenital--eg, Kallmann's syndrome Acquired--eg, weight loss, craniopharyngioma

Pituitary
Tumour--eg, prolactinoma Infarction--eg, Sheehan's syndrome

Ovarian
Congenital--eg, gonadotrophin-receptor defect, resistant ovary syndrome Acquired--eg, radiation

Causes of amenorrhoea

William L. Ledger*, Jonathan Skull Current Obstetrics & Gynaecology (2004) 14, 254260

Disorders leading to amenorrhea

Site of disorder
Hypothalamus Pituitary Endocrine-thyroid Ovary

Diagnosis
Hypothalamic hypogonadism (rare) Weight-related amenorrhea (common) Pituitary adenoma (common) Sheehans syndrome (rare) Hypothyroidism (rare) Gonadal dysgenesis (rare) PCOS (common) POF (rare)

Investigations
FSH, LH & E2 all low FSH, LH & E2 low PRL raised, FSH, LH & E2 low LH, FSH & E2 low TSH raised, T4 low or normal FSH, LH high, E2 low LH high, FSH normal, androgens high normal FSH, LH high, E2 low

Muellerian tract
Genital tract

Absence of uterus (rare)

Imperforate hymen (common) Ashermans syndrome or endometrial fibrosis (rare)

Ultrasound & progesterone challenge

Physical examination & ultrasound HSG & AAFB testing

Amenorrhea & androgen excess

Amenorrhea can be divided into 2 groups:
amenorrhea without evidence of associated androgen excess
hypothalamic-pituitary dysfunction (stress, weight loss, exercise) Hyperprolactinemia Non-gonadal endocrine disease Systemic illness

Amenorrhea with evidence of androgen excess (eg, hirsutism, virilization, sexual ambiguity)
PCOS Cushings syndrome Congenital adrenal hyperplasia (late onset)

AMENORRHOEA
AN APPROACH FOR DIAGNOSIS
HISTORY PHYSICAL EXAMINATION ULTRASOUND EXAMINATION Exclude Pregnancy Exclude Cryptomenorrhea

Clinical evaluation
History
Emotional stress, family history of possible genetic anomalies or diabetes, galactorrhea, symptoms of thyroid disorder, weight loss, hirsutism or menopausal symptoms

Physical examination
Body dimensions & habitus Distribution & extent of terminal androgen-stimulated body hair Extent of breast development (Tanner) & the presence or absence of any breast secretions External & internal genitalia, with emphasis on evidence of exposure to androgens & estrogens

Basal concentrations of FSH, LH, TSH & prolactin Pelvic ultrasound

Estrogen + progestin challenge test?

Method:
Oral conjugated estrogen, 2,5 mg daily for 25 days + oral MPA 5-10 mg for the last 10 days of estrogen therapy

Induce bleeding if the endometrium is normal Determine with certainty if the outflow tract is intact

Cryptomenorrhea
Outflow obstruction to menstrual blood Imperforate hymen Transverse vaginal septum with functioning uterus Isolated vaginal agenesis with functioning uterus Isolated cervical agenesis with functioning uterus
Intermittent abdominal pain Possible difficulty with micturition Possible lower abdominal swelling Bulging bluish membrane at the introitus or absent vagina (only dimple)

Imperforate hymen

Uterovaginal anomalies

Embryology of the female urogenital tract

Noncommunicating vertical fusion defect of the transverse vaginal septum

Modified FerrimanGallwey (FG) hirsutism scoring system for nine body areas

Facial hirsutism in a 17-year-old woman with PCOS

Gross & cut appearance of typical polycystic ovaries. Multiple small follicular cysts are apparent in the cut section

Prolactinoma

Coronal CT scan of patient with prolactinoma (left) shows a large suprasellar adenoma (arrow). CT scan of same patient (right), made after 2 weeks of treatment with bromocriptine (2,5 mg, 3 times a day) shows significanct regression in size

Once Pregnancy and cryptomenorrhea are excluded:

The patient is a bioassay for endocrine abnormalities

Four categories of patients are identified

1. Amenorrhea with absent or poor secondary sex Characters 2. Amenorrhea with normal 2ry sex characters 3. Amenorrhea with signs of androgen excess 4. Amenorrhea with absent uterus and vagina

Diagnostic workup for amenorrhea

Veldhuis JD. Hospital Practice 1988;23:40-56

Investigation of women with amenorrhea

AMENORRHOEA , By: Baird, David T., Lancet, 00995355, 07/26/97, Vol. 350, Issue 9073

Suggested flow diagram aiding in the evaluation of women with amenorrhea

The Practice Committee of the American Society for Reproductive Medicine FERTILITY AND STERILITY VOL. 82, SUPPL. 1, SEPTEMBER 2004

Conclusions
Amenorrhea is a symptom not a diagnosis. Comprehensive history and clinical examination in conjunction with a few carefully chosen investigations are sufficient to make an accurate diagnosis in the vast majority of cases. Successful management depends not only on identification of the underlying cause, but also on the needs and concerns of the individual woman. The absence of menses in itself has no deleterious effect on health, but amenorrhea may be a presenting symptom of an underlying disorder (eg, pituitary tumor or hypo-estrogenism) that requires treatment.