What is the workup for secondary amenorrhea (absence of menstruation)?

From the Guidelines

The workup for secondary amenorrhea should begin with a pregnancy test, as pregnancy is the most common cause, and if negative, a systematic approach includes measuring TSH, prolactin, FSH, and estradiol levels to identify the underlying cause, as suggested by recent studies 1, 2. The initial evaluation should include a thorough medical history, physical examination, and laboratory tests to rule out other causes of amenorrhea.

• A pregnancy test should be performed to rule out pregnancy as the cause of secondary amenorrhea.
• Measurement of TSH, prolactin, FSH, and estradiol levels can help identify the underlying cause of amenorrhea, such as hypothyroidism, hyperprolactinemia, or polycystic ovary syndrome (PCOS) 2.
• A progesterone challenge test (medroxyprogesterone acetate 10 mg daily for 5-10 days) can help determine if estrogen levels are adequate and if the outflow tract is patent, as recommended by recent guidelines 3, 4.
• If withdrawal bleeding occurs, anovulation is likely the cause, and further evaluation for PCOS or other causes of anovulation should be performed.
• If no bleeding occurs, estradiol levels should be checked, and low levels may suggest hypogonadotropic hypogonadism or ovarian failure, while normal levels may suggest outflow tract obstruction. Additional testing may include:
• Pelvic ultrasound to evaluate the uterus and ovaries
• Assessment for PCOS by checking total testosterone, DHEAS, and 17-hydroxyprogesterone
• MRI of the pituitary to rule out prolactinoma in patients with elevated prolactin
• Karyotyping to rule out premature ovarian failure in patients with elevated FSH The workup should also include evaluation for other medical conditions that can cause amenorrhea, such as thyroid disorders, adrenal disorders, and significant weight changes, as highlighted in recent studies 1, 2. Management depends on the underlying cause and the patient's reproductive goals, ranging from lifestyle modifications to hormone replacement therapy or specific treatments for conditions like PCOS or hyperprolactinemia, as recommended by recent guidelines 3, 4.

From the FDA Drug Label

The workup and treatment of candidates for clomiphene citrate therapy should be supervised by physicians experienced in management of gynecologic or endocrine disorders. Patients should be chosen for therapy with clomiphene citrate only after careful diagnostic evaluation Impediments to achieving the goal of therapy must be excluded or adequately treated before beginning clomiphene citrate. The plan of therapy should be outlined in advance Patients selected for clomiphene citrate therapy should be evaluated in regard to the following: Estrogen Levels. Primary Pituitary or Ovarian Failure. Endometriosis and Endometrial Carcinoma. Other Impediments to Pregnancy. Uterine Fibroids Pelvic examination is necessary prior to the first and each subsequent course of clomiphene citrate treatment. The workup for secondary amenorrhea includes:

• Careful diagnostic evaluation
• Excluding impediments to achieving pregnancy
• Evaluating estrogen levels
• Assessing for primary pituitary or ovarian failure
• Evaluating for endometriosis and endometrial carcinoma
• Checking for other impediments to pregnancy such as thyroid disorders, adrenal disorders, hyperprolactinemia, and male factor infertility
• Evaluating for uterine fibroids
• Performing a pelvic examination prior to the first and each subsequent course of clomiphene citrate treatment [5] [6]

From the Research

Diagnostic Approach for Secondary Amenorrhea

The diagnostic approach for secondary amenorrhea involves a systematic evaluation, including a detailed history, physical examination, and laboratory assessment of selected serum hormone levels 7, 8.

• The initial workup should include a pregnancy test and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone 7, 8.
• A thorough history should include menstrual onset and patterns, eating and exercise habits, presence of psychosocial stressors, body weight changes, medication use, galactorrhea, and chronic illness 8.
• The physical examination should identify anthropometric and pubertal development trends 8.

Common Causes of Secondary Amenorrhea

Secondary amenorrhea can be attributed to various causes, including:

• Polycystic ovary syndrome (PCOS) 7, 8
• Hypothalamic amenorrhea 7, 8
• Hyperprolactinemia 7
• Primary ovarian insufficiency (POI) 7, 8, 9
• Pregnancy should be excluded in all cases 7, 8

Additional Testing and Considerations

Additional testing, including karyotyping, serum androgen evaluation, and pelvic or brain imaging, should be individualized 8.

• Patients with primary ovarian insufficiency can maintain unpredictable ovary function and may require hormone replacement therapy, contraception, or infertility services 8.
• Functional hypothalamic amenorrhea may indicate disordered eating and low bone density 8.
• Patients with PCOS should undergo screening and intervention to attenuate metabolic disease and endometrial cancer risk 8.