What is a progesterone challenge test?

From the Guidelines

A progesterone challenge test is a diagnostic procedure used to evaluate the presence of estrogen and the integrity of the hypothalamic-pituitary-ovarian axis, and it is suspected to be negative for women with functional hypothalamic amenorrhea (FHA) and positive for women with polycystic ovary syndrome (PCOS) 1.

Key Points

• The test involves administering a progestin, such as medroxyprogesterone acetate, to assess the response of the endometrium to progesterone withdrawal 1.
• The presence of withdrawal bleeding after progesterone withdrawal indicates adequate estrogen levels and a responsive endometrium, while the absence of bleeding suggests either a lack of estrogen or an out-of-phase endometrium.
• Endometrial thickness is a good indicator of the response to progesterone withdrawal, and its measurement can be used in conjunction with the progesterone challenge test 1.
• The progesterone challenge test has been recommended to rule out chronic estrogen exposure, but its use has been questioned due to the high rate of withdrawal bleeding in women with FHA, with up to 60% of women with FHA experiencing a withdrawal bleed after progesterone withdrawal 1.

Diagnostic Considerations

• A focused history and examination, pelvic ultrasound, and focused laboratory evaluation at the initial visit should be the standard approach to diagnose FHA and PCOS 1.
• The diagnosis of FHA should be based on the presence of typical causes, such as excessive exercise, underweight, caloric deficiency, and/or stress, as well as clear signs of estrogen deficiency, including low endometrial thickness 1.

From the FDA Drug Label

These drugs have been used as a test for pregnancy but such use is no longer considered safe because of possible damage to a developing baby. A progesterone challenge test is a test that was previously used to determine if a woman is pregnant, by administering a progestin, such as medroxyprogesterone acetate, and observing the body's response 2.

• The test is no longer considered safe due to the potential risk of damage to a developing fetus.
• Alternative methods for testing pregnancy are now available and recommended instead.

From the Research

Definition and Purpose of Progesterone Challenge Test

• The progesterone challenge test is a diagnostic tool used to evaluate the presence or absence of withdrawal uterine bleeding in response to progesterone administration 3.
• The test is commonly used in women with secondary amenorrhea to determine the cause of their condition and to predict the occurrence of withdrawal bleeding 4, 5.
• The test involves administering progesterone to the patient and observing whether withdrawal bleeding occurs, which can indicate the presence of estrogen and a responsive endometrium 3.

Factors Associated with Withdrawal Bleeding

• Endometrial thickness, as measured by transvaginal ultrasonography, is a significant predictor of withdrawal bleeding after progesterone administration 4, 5, 6.
• Serum estradiol (E2) levels are also associated with withdrawal bleeding, although endometrial thickness is a superior predictor 4.
• The presence or absence of follicles and the state of follicular development in the ovaries are also correlated with the response to the progesterone challenge test 3.

Clinical Applications

• The progesterone challenge test can be used to divide pathologic amenorrhea into two groups, which can be useful for diagnosis and treatment 3.
• The combined use of the progesterone challenge test and endometrial thickness evaluation by transvaginal ultrasonography can be an effective screening tool for preventive endometrial management in postmenopausal women 6.