Primary Amenorrhea is defined as the absence of menses:

• By age 13/14 without normal development of secondary sexual characteristics; OR,
• By age 15/16, with normal secondary sexual characteristics.

In contrast, Secondary Amenorrhea refers to a loss of menses after it has already been established.

The causes of amenorrea are myriad, with an important one being pregnancy.

The most common pathologic causes of Primary Amenorrhea are:

• Chromosomal abnormalities: 50%
• Hypothalamic abnormalities: 20%
• Mullerian agenesis: 5%
• Pituitary abnormalities: 5%

Determining the etiology of Primary Amenorrhea depends on careful history-taking and a targeted physical exam. Key points to address in the history include:

• Potential for pregnancy, current lactation
• Develop of secondary sexual characteristics
  • On a side note, the general order of female sexual development is: breasts, pubic hair, growth spurt, menses; or, “boobs, pubes, grow, flow”
• Lifestyle factors such as stress, nutrition, exercise, weight changes
• Medication: THC, antipsychotics, or irradiation
• Associated symptoms:
  • Hyperprolatinemia: galactorrhea
  • Hyperandrogenism: hair loss/excess, acne, voice change
  • CNS tumor: headaches, visual field deficits, polyuria/polydipsia
  • Family history: Does everyone have relatively late puberty?

In terms of physical exam:

• Vitals, height, weight
• Secondary sexual characteristics: breasts, pubic/axillary hair
• Thyroid: exopthalmos, goiter, abnormal deep tendon reflexes
• Hyperandrogenism: hirsuitism, acne, hair loss
• Hypercortisolemia: striae, hyperpigmentation
• Turner syndrome: webbed neck, low hair line, widely-spaced nipples, short stature
• Pelvic exam: hymen, vaginal septum, ultrasound for uterine anatomy

Laboratory investigations can offer lots of insight:

• βHCG: Gotta rule out this common reason first!
• TSH, PRL: To test for hypo/hyperthyroidism and hyperprolactinemia.
• LH, FHS: For practicality’s sake, these would probably be ordered at the same time as TSH, PRL.
• +/- Androgens (testosterone, DHEAS, 17-alpha-hydroxyprogesterone): May indicate PCOS or androgen-secreting tumor, androhen insensitivity syndrome, or 5-alpha-reductase deficiency.
• +/- Estradiol: These assays lack sensitivity, standardization, and only capture a single time point.

Since chromosomal abnormalities account for half of the pathologic cases of Primary Amenorrhea, karyotyping will be useful for patients who are found to have abnormal uterine anatomy on ultrasound or have elevated FSH, LH. Patients with an absent uterus may be worked-up for abnormal Mullerian development (46XX karyotype and normal female testosterone levels) versus a deficit in masculinization (i.e., androgen insensitivity syndrome, 5-alpha-reductase deficiency). There is a normal uterus, and LH and FSH are high, that means there is nothing feeding back to stop their release; karyotype may reveal Turner syndrome (45XO), while normal karyotype (46XX) may indicate Mullerian agenesis.

The over all treatment goals are to:

• Treat underlying cause:
  • Lifestyle
  • Discontinue offending medications
  • Surgery
• Preserve fertility
• Reduce risk of complications (e.g., remove undescended tests in androgen insensitive patients to mitigate cancer risk).

• Master-Hunter T, Heiman DL. 2006. Amenorrhea: evaluation and treatment; 73:1374.
• The Practice Committee of the American Society for Reproductive Medicine. 2008. Current approach to amenorrhea. Fertility and Sterility;90:S219.
• Welt CK, Barieri RL. Etiology, diagnosis, and treatment of primary amenorrhea. In: UpToDate (Eds: Snyder PJ, Crowley Jr WF, Kirkland JL). Accessed 2013.05.05.