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

From the Guidelines

The workup for secondary amenorrhea should begin with a pregnancy test, followed by evaluation for structural abnormalities with a pelvic examination and transvaginal ultrasound, and laboratory testing including thyroid-stimulating hormone (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels, as the most recent and highest quality study suggests that functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea 1. The initial step in the workup is crucial as it helps to identify or rule out the most common cause of secondary amenorrhea.

• A pregnancy test is essential to exclude pregnancy as the cause of secondary amenorrhea.
• A pelvic examination and transvaginal ultrasound are necessary to evaluate for structural abnormalities, such as polycystic ovarian morphology (PCOM), which is found in a high number of patients with FHA 1. Key laboratory tests include:
• TSH to evaluate for thyroid dysfunction
• Prolactin to rule out hyperprolactinemia
• FSH, LH, and estradiol to assess ovarian function and estrogen status If prolactin is elevated, an MRI of the pituitary should be obtained to rule out prolactinoma. For patients with normal prolactin but low estradiol and elevated FSH/LH, premature ovarian insufficiency is likely. If FSH/LH are low or normal with low estradiol, consider hypothalamic amenorrhea or pituitary dysfunction, as suggested by the study on FHA and PCOM 1. Additional testing may include:
• Total and free testosterone, DHEAS, and 17-hydroxyprogesterone to evaluate for hyperandrogenism and polycystic ovary syndrome (PCOS)
• A progesterone challenge (medroxyprogesterone acetate 10 mg daily for 10 days) to determine estrogen status
• Karyotyping for suspected chromosomal abnormalities
• Assessment of bone mineral density if hypoestrogen state is prolonged This systematic approach helps identify the underlying cause of secondary amenorrhea, which is essential for appropriate treatment and management, as emphasized by the study on FHA and PCOM 1.

From the FDA Drug Label

Progesterone capsules are used for the treatment of secondary amenorrhea (absence of menstrual periods in women who have previously had a menstrual period) due to a decrease in progesterone Progesterone capsules may be given as a single daily dose of 400 mg at bedtime for 10 days. The treatment for secondary amenorrhea involves administering progesterone capsules at a dose of 400 mg per day for 10 days.

• The goal of this treatment is to induce withdrawal bleeding in women with secondary amenorrhea due to a decrease in progesterone levels.
• Progesterone capsules are used to provide the necessary progesterone to treat menstrual irregularities. 2

From the Research

Secondary Amenorrhea Workup

The workup for secondary amenorrhea involves a systematic evaluation to identify the underlying cause. According to 3, 4, 5, the following steps should be taken:

• Rule out pregnancy with a pregnancy test
• Measure serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH)
• Consider the patient's medical history, including menstrual onset and patterns, eating and exercise habits, presence of psychosocial stressors, body weight changes, medication use, and chronic illness

Common Causes of Secondary Amenorrhea

The most common causes of secondary amenorrhea include:

• Polycystic ovary syndrome (PCOS)
• Hypothalamic amenorrhea
• Hyperprolactinemia
• Primary ovarian insufficiency As stated in 4, these conditions can be identified through a combination of physical examination, laboratory testing, and medical history.

Laboratory Testing

Laboratory testing for secondary amenorrhea may include:

• Serum hormone levels (LH, FSH, prolactin, TSH)
• Pregnancy test
• Karyotyping (in some cases)
• Serum androgen evaluation (in some cases)
• Pelvic or brain imaging (in some cases) As noted in 5, additional testing should be individualized based on the patient's symptoms and medical history.

Consideration of Thyroid Function

Thyroid function should also be considered in the workup for secondary amenorrhea. According to 6, TSH concentrations are the principal first test to rule out thyroid disease, taking into account trimester-specific reference ranges. However, this is more relevant to pregnancy, and the relevance of measuring free T3 (FT3) during non-pregnant states is unclear.