Amenorrhea

Absence of menstruation (for 6 months)

Types

Primary amenorrhea

Menstruation has not occurred by the age of 14 in the absence of secondary sexual characters or by the age of 16 even if the secondary sexual characters are present.

Secondary amenorrhea

Periods have not occurred for 6 months or a time equivalent to length of three previous cycles.

Major Causes of Amenorrhea

Outflow tract

Congenital                                                                    Acquired

Complete androgen resistance                       Asherman syndrome (intrauterine synechiae)

Imperforate hymen                                          Cervical stenosis

Müllerian agenesis

Transverse vaginal septum

Primary ovarian insufficiency

Congenital                                                                                 Acquired

Gonadal dysgenesis (other than Turner syndrome)          Autoimmune destruction    

Turner syndrome or variant                                                   Chemotherapy or radiation

Pituitary

Autoimmune disease

Cocaine

Cushing syndrome

Empty sella syndrome

Hyperprolactinemia

Infiltrative disease (e.g., sarcoidosis)

Medications

Antidepressants

Antihistamines

Antihypertensives

Antipsychotics

Opiates

Other pituitary or central nervous system tumor

Prolactinoma

Sheehan syndrome

Hypothalamic

Eating disorder

Functional (overall energy deficit)

Gonadotropin deficiency (e.g., Kallmann syndrome)

Infection (e.g., meningitis, tuberculosis, syphilis)

Malabsorption

Rapid weight loss (any cause)

Stress

Traumatic brain injury

Tumor

Other endocrine gland disorders

Adrenal disease

Adult-onset adrenal hyperplasia

Androgen-secreting tumor

Chronic disease

Constitutional delay of puberty

Cushing syndrome

Ovarian tumors (androgen producing)

Polycystic ovary syndrome (multifactorial)

Thyroid disease

Physiologic

Breastfeeding

Contraception

Exogenous androgens

Menopause

Pregnancy

Relevant history and associations

History	Associations
Chemotherapy or radiation	Impairment of specific organ (e.g., brain, pituitary, ovary)
Family history of early or delayed menarche	Constitutional delay of puberty
Galactorrhea	Pituitary tumor
Hirsutism, acne	Hyperandrogenism, PCOS, ovarian or adrenal tumor, CAH, Cushing syndrome
Illicit or prescription drug use	Multiple; consider effect on prolactin
Menarche and menstrual history	Primary versus secondary amenorrhea; new disease
Sexual activity	pregnancy
Significant headaches or vision changes	Central nervous system tumor, empty sella syndrome
Temperature intolerance, palpitations,  diarrhea, constipation, tremor, depression, skin changes	Thyroid disease
Vasomotor symptoms	Primary ovarian insufficiency, natural menopause
Weight loss, excessive exercise, poor nutrition,  psychosocial stress, diets	Functional hypothalamic amenorrhea

General Examinations

Abnormal thyroid examination	Thyroid disorder
Physical examination Anthropomorphic measurements; growth charts	Multiple; Turner syndrome, constitutional delay of puberty
Body mass index	High: PCOS                                                                                  Low: Functional hypothalamic amenorrhea
Dysmorphic features (webbed neck, short stature, low hairline)	Turner syndrome
Male pattern baldness, increased facial hair, acne	Hyperandrogenism, PCOS, ovarian or adrenal tumor, CAH, Cushing syndrome

Pelvic examinations

Absence or abnormalities of cervix or uterus	Rare congenital causes
Clitoromegaly	Androgen-secreting tumor, CAH
Presence of transverse vaginal septum or imperforate hymen	Outflow tract obstruction
Reddened or thin vaginal mucosa	Decreased endogenous estrogen
Striae, buffalo hump, central obesity, hypertension	Cushing syndrome
Tanner staging abnormal	Turner syndrome, constitutional delay of puberty, rare causes

          Laboratory testing

1.     Full blood count     -Chronic disease

2.     Estradiol

3.     Follicle-stimulating hormone and luteinizing hormone

             High: Primary ovarian insufficiency, Turner syndrome

             Low: Functional hypothalamic amenorrhea

             Normal: PCOS, Asherman syndrome, multiple others

4.     Free and total testosterone; dehydroepiandrosterone sulfate

             High: Hyperandrogenism, PCOS, ovarian or adrenal tumor, CAH, Cushing 5.               

5.       karyotyping

             Abnormal: Turner syndrome, rare chromosomal disorders

6.     Pregnancy test

              Positive: Pregnancy, ectopic pregnancy

7.     Prolactin

               High: Pituitary adenoma, medications, hypothyroidism, other neoplasm

8.     Thyroid-stimulating hormone

             High: Hypothyroidism

              Low: Hyperthyroidism

9.     Diagnostic imaging

a.Magnetic resonance imaging of head or sella

            Tumor (e.g., microadenoma)

 b. Pelvic ultrasonography

              Morphology of pelvic organs

10.        Progesterone challenge test

Oral progestogen for 5 to 10 days

If withdrawal bleeding- anovulation

If no withdrawal bleeding add estrogen to progetagen

If bleeding occurs- estrogen deficiency may be due to primary ovarian problem or central problem (both can be differentiated by FSH/LH ) measurement .

If still no bleeding – asherman syndrome

                                    Mullerian abnormalities

Treatment

Directed to the cause and depends on the patient`s current desire to fertility.

1.     Treatment of feeding disorder and normalization of body weight

2.     Correction of thyroid disorder

3.     Surgical correction of outflow tract obstruction

4.     Removal of space occupying pitutiray /brain tumor

5.       Hysterescopic resection of intrauterine adhesions