Diagnostic Evaluation of Amenorrhea

Introduction to Progesterone Challenge Test

The progesterone challenge test is used to evaluate women with amenorrhea, determining endometrial estrogen status and outflow tract patency, and differentiating between functional hypothalamic amenorrhea and polycystic ovarian syndrome, as recommended by the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine 1

The test serves two purposes: assessing estrogen status and evaluating outflow tract patency, helping to distinguish between functional hypothalamic amenorrhea and polycystic ovary syndrome, with a strength of evidence level of moderate, according to the Endocrine Society 1
A positive test (withdrawal bleeding occurs) indicates adequate endogenous estrogen production and outflow tract patency, suggesting polycystic ovary syndrome or other causes of anovulation with estrogen production, as stated by the American College of Obstetricians and Gynecologists 1
A negative test (no withdrawal bleeding) may indicate a hypoestrogenic state or outflow tract obstruction, requiring further evaluation, with a strength of evidence level of low, according to the Society for Reproductive Endocrinology and Infertility 1

The progesterone challenge test has limited reliability, as up to 60% of women with functional hypothalamic amenorrhea may still have withdrawal bleeding despite lower estrogen levels, highlighting the need for complementary tests, as recommended by the American Society for Reproductive Medicine 1
Endometrial thickness is a more reliable indicator of response to progesterone withdrawal than the test alone, with a thickness of ≤1.5mm predicting absence of bleeding with 94% sensitivity and 93% specificity, according to the Endocrine Society 1
A thicker endometrium is strongly associated with a more predictable withdrawal bleed response, and factors such as insulin resistance, body composition, and weight can influence hormone metabolism and bleeding response 1

For women requiring cyclic progesterone therapy, the American College of Obstetricians and Gynecologists recommends oral micronized progesterone 200-300 mg daily for 12-14 days of the month 2
The timing of withdrawal bleeding following progesterone withdrawal is primarily determined by endometrial thickness, endogenous estrogen levels, and the specific progesterone formulation and dosage used, with most women experiencing bleeding within 2-7 days after discontinuation 1

Women with polycystic ovary syndrome (PCOS) typically have positive withdrawal bleeding due to chronic estrogen exposure, while women with hypothalamic amenorrhea may have variable responses depending on estrogen status 1
Endometrial thickness measurement by ultrasound may be more reliable than the progesterone challenge test alone for assessing endometrial response 1