LabMed

Secondary Amenorrhea Associated with Polycystic Ovarian Syndrome

At a Glance

Approximately 1% of women of reproductive age experience secondary amenorrhea, cessation of menses. In women who previously experienced regular menstrual cycles, secondary amenorrhea is the absence of menstruation for 6 months. In women who had previously experienced irregular menstrual cycles, secondary amenorrhea is the absence of menstruation for 12 months. Secondary amenorrhea is a symptom caused by many pathological states, including pregnancy, polycystic ovary syndrome (PCOS), Cushing’s syndrome, hypopituitarism, hypothyroidism, and hyperprolactinemia. Some patients do not demonstrate an obvious etiology for their amenorrhea; however, the diagnostic evaluation should lead to the correct diagnosis if the problem is approached in a logical, stepwise manner.

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder among women of reproductive age. Clinical presentation of PCOS is characterized by irregular menses or amenorrhea, infertility, hirsutism, and metabolic disturbance often manifesting as type II diabetes mellitus, insulin resistance, or metabolic syndrome accompanied by obesity.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Laboratory diagnosis of PCOS is complicated. Although initial tests may suggest PCOS, further testing is needed to exclude other diagnoses.

In diagnosing the underlying cause of amenorrhea, the first step should always be to rule out pregnancy with a negative urine or serum hCG result. Next, levels of thyroid-stimulating hormone (TSH), prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) should be ordered. The combination of normal prolactin (rules out prolactinemia), normal TSH (rules out hypothyroidism), elevated LH, and normal FSH (LH/FSH ratio > 2.5) suggests PCOS.

The next step involves testing levels of total and free testosterone, sex-hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA-S). Moderately elevated testosterone and DHEA-S suggest PCOS. However, highly elevated levels of testosterone may indicate an ovarian tumor, and highly elevated levels of DHEA-S may indicate an adrenal tumor. SHBG is typically low in PCOS patients.

If all of the results are consistent with PCOS, then exclusion of other etiologies is necessary. Late-onset congenital adrenal hyperplasia can present very similarly to PCOS, and levels of 17-hydroxyprogesterone should be measured to exclude this diagnosis.

Finally, once a diagnosis of PCOS is made, patients should be screened for insulin resistance as a comorbidity (Table 1).

Table 1.

Test Results Indicative of the Disorder
hCG Prolactin LH FSH Total testosterone Free testosterone DHEA-S SHBG 17- hydroxyprogesterone
Negative Normal Elevated Normal Moderately elevated Moderately elevated Moderately elevated Decreased Normal

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

LH

Levels can appear falsely elevated in patients who are taking anticonvulsants, naloxone, or clomiphene.

Levels can appear falsely decreased in patients who are taking oral contraceptives (or other hormonal treatments) or digoxin.

FSH

Levels can appear falsely elevated in patients who smoke or take cimetidine, clomiphene, digitalis, or levodopa.

Levels can appear falsely decreased in patients who are taking oral contraceptives (or other hormonal treatments) or phenothiazines.

Testosterone

Levels can appear falsely elevated in female patients who are taking oral contraceptives (or other hormonal treatments), anticonvulsants, barbituates, or clomiphene.

Levels can appear falsely decreased in patients who are taking steroids.

SHBG

Levels can appear falsely elevated in patients with liver disease, hyperthyroidism, or anorexia, and in those who take oral contraceptives (or other hormonal treatments).

Levels can appear falsely decreased in patients with hypothyroidism or Cushing's disease and in patients who take steroids.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

There are measurement issues, including lack of accuracy and precision at the low concentrations of testosterone seen in women, children, and hypogonadal men. Additionally, methods of measuring testosterone levels are not harmonized, and results from different laboratories may appear discordant, further complicating the interpretation of results.

A consensus statement from ten professional medical organizations and the Centers for Disease Control was published in October 2010, outlining all the issues with current testosterone testing and making recommendations for improvement.

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