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 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.

Hyperprolactinemia is frequently due to a prolactinoma, a benign tumor of the pituitary gland that results in excess production of prolactin. However, the most common cause of hyperprolactinemia is the use of prescription drugs.

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

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. If TSH, LH, and FSH are normal but prolactin is elevated, then the amenorrhea is due to hyperprolactinemia.

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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?

Drugs that block the effects of dopamine or decrease dopamine stores can cause the pituitary to secrete prolactin. These drugs include estrogen therapies, tricyclic antidepressants, opiates, amphetamines, hypertension drugs (e.g., reserpine, verapamil, methyldopa), and some drugs used to treat gastroesophageal reflux (cimetidine).

Different laboratories may use immunoassays utilizing different antibodies with differing specificities, leading to discordant results. Patients may also have circulating heterophilic antibodies, resulting in false-positive results in some serum assays. Furthermore, prolactin immunoassays are often subject to the “hook effect,” in which high levels of prolactin in the sample can lead to falsely low results because of saturation of the antibody. Therefore, if clinical symptoms are present and levels of prolactin are unexpectedly low, the clinician should suspect the “hook effect” and request that the laboratory dilute the patient’s sample and repeat the testing.

What Lab Results Are Absolutely Confirmatory?

A serum prolactin level of at least 5000 mIU/L is likely due to a prolactinoma, whereas levels 1000-5000 mIU/L may be due to other causes. Prolactinoma as the cause of hyperprolactinemia is confirmed by MRI.