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Definition: 

Absence of menstruation when menstrual periods should occur.

• No menstrual period for 6 months in a woman who usually has normal periods OR for a length of time equal to 3 cycle intervals in a woman with less frequent cycles.
• No menstrual period by age 14 in the absence of growth or development of secondary sexual characteristics.
• No menstrual period by age 16 regardless of the presence of normal growth and development with the appearance of secondary sexual characteristics

Common Complaint:

"I have stopped having periods." " I used to have periods and they have now stopped."  "My last menstrual period was months ago."  "I have nipple discharge" "I am 16 and have never had a menstrual period."

Differential Diagnoses:

Pregnancy
Breastfeeding related
Menopause
Norplant related.
Hypothalamic.Suppression of the hypothalamic-pituitary-ovarian axis.

Exercise induced.
Eating disorder such as anorexia nervosa

Endocrine such as hypothyroidism.
Polycystic ovarian disease
Pituitary or ovarian tumor.
Rarely, Mullerian duct agenesis or other chromosomal or developmental defect. 

A young woman who has is Tanners Stage 1 at age 14 or who has had no period by age 16 needs to be referred to an OB-GYN for work up.

Incidence:

Amenorrhea in a woman who has had menstrual periods is quite common at some time during her reproductive life.
Amenorrhea that is a result of agenesis of part of the reproductive system or a chromosomal anomaly is quite rare.

Pathophysiology:

Physiological: Pregnancy, breastfeeding, menopause.

It is important to understand normal, female reproductive physiology.  Please review.  You may click here for menstrual physiology.

Pathogenesis of Compartment I: Disorders of the outflow tract or uterine target organ.
Abnormalities in the systems of this compartment are uncommon. Examples include: Ashermans Syndrome from inadvertent endometrial ablation during D&C (causes 7% of amenorrhea), agenesis or anomalies of the structure of the uterus, tubes or vagina. (there may be appropriate Tanner stage).

Pathogenesis of Compartment II: Disorders of the ovary.
Examples: Abnormal chromosomes such as Turners Syndrome (0.5%), Normal chromosomes(10%) such as in gonadal dysgenesis or agenesis (there may be no or very delayed Tanner stage), premature ovarian failure (premature menopause, before age 40), effect of radiation or chemotherapy, polycystic ovarian disease.

Pathogenesis of Compartment III: Disorders of the anterior pituitary.
Examples: Prolactin tumors (7.5%)

Pathogenesis of Compartment IV: Disorders of the central nervous system (hypothalamic).
Hypothalamic amenorrhea is the most common cause of amenorrhea (28%). There is a deficiency in GnRH pulsatile secretion. Examples include a stressful lifestyle (10%), weight loss as in anorexia or bulimia (10%), extreme exercise, medications such as hormones as in postpill amenorrhea, hypothyroidism (1%), major medical disease such as Crohns, systemic lupus erathematosis

Work Up:

Pregnancy test.  If positive, treat your patient as a pregnant patient.

If pregnancy test is negative, draw a TSH and Prolactin Level, do a Progesterone Challenge Test.

If prolactin elevated >100, do CT of puitary.

If TSH elevated or depressed, treat thyroid disorder

Progesterone challenge test.

Medroxyprogesterone acetate (Provera/Cycrin) 10 mg each day for 5 days OR Progesterone in oil 200 mg IM.

Positive test is any vaginal bleeding. Bleeding usually occurs in 2-7 days. A late vaginal bleed may be associated with ovulation

A withdrawal bleed indicates a functional outflow tract and a uterus primed with endogenous estrogen. The progesterone challenge may repeated once if no bleeding.  If there is withdrawal bleeding, the diagnosis is hypothalamic amenorrhea (Compartment IV).   Drug regimen for progesterone replacement is discussed below under medication heading.

No withdrawal bleed after progesterone challenge.

Progesterone and estrogen challenge. Drug regimen discussed below under medication heading. This differentiates patients with target organ outflow tract dysfunction from those with inadequate endometrial proliferation.

Click here for pathophysiology of Polycystic Ovarian Syndrome

Click here for Work up and Treatment of Polycystic Ovarian Syndrome

Click here for Antepartum work up of pregnant woman.

Click here for Dysfunctional Uterine Bleeding

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Treatment for Hypothalmic Amenorrhea (Compartment IV):

Progesterone therapy for hypothalamic amenorrhea

• Minimal therapy requires monthly administration of progesterone.
• Medroxyprogesterone acetate (Provera//Cycrin) 10 mg for 10 days each month.
• * New Medicantion. Micronized progesterone (Prometrium).  100 mg, 2 q day in above regemin.
• Low dose oral contraceptive pills
• Clomiphene citrate for women desiring pregnancy
• Treat for six months to counter unopposed estrogen effect on the endometrium.  Then discontinue treatment and assess for return of regular menstrual periods.
• Hormone replacement therapy for perimenopausal women.

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