What labs and dosage of medroxyprogesterone (Provera) are used to evaluate and correct amenorrhea?

Laboratory Evaluation and Management of Amenorrhea

For patients with amenorrhea, a systematic laboratory evaluation should include LH, FSH, estradiol, prolactin, TSH, and a pregnancy test, followed by a progesterone challenge with medroxyprogesterone acetate 10 mg twice daily for 5-10 days to determine estrogen status and endometrial responsiveness. 1, 2

Initial Laboratory Evaluation

The initial laboratory workup for amenorrhea should include:

• Pregnancy test (first step in all cases of secondary amenorrhea)
• Hormone panel (ideally collected between days 3-6 of cycle if cycling):
  • LH and FSH levels (LH/FSH ratio >2 suggests PCOS)
  • Estradiol
  • Prolactin (>20 μg/L is abnormal)
  • TSH and free T4 (to rule out thyroid dysfunction)
  • Total and free testosterone (elevated levels >2.5 nmol/L suggest hyperandrogenism)
  • Anti-Müllerian hormone (AMH) - helpful to assess ovarian reserve 3, 1

Imaging Studies

• Transvaginal ultrasound - more sensitive than transabdominal for identifying:
  • Endometrial thickness (correlates with bleeding response to progesterone) 4
  • Polycystic ovarian morphology
  • Structural abnormalities 1
• Pituitary MRI - if clinical features or laboratory results suggest hypothalamic-pituitary abnormality, especially with elevated prolactin levels 1, 5

Progesterone Challenge Test

After ruling out pregnancy and assessing baseline hormones, a progesterone challenge test helps determine estrogen status and endometrial responsiveness:

• Medication: Medroxyprogesterone acetate (Provera) 10 mg orally twice daily for 5-10 days 6, 4
• Interpretation:
  • Withdrawal bleeding occurs: Indicates adequate estrogen levels, patent outflow tract, and responsive endometrium
  • No bleeding: Suggests hypoestrogenism, outflow tract obstruction, or endometrial pathology 2

Diagnostic Algorithm Based on Lab Results

1. Elevated FSH/LH (>40 mIU/mL):

   • Suggests primary ovarian insufficiency
   • Consider karyotype testing to rule out Turner syndrome 3

2. Low/normal FSH and LH:

   • With elevated prolactin: Evaluate for prolactinoma, medication effects, or hypothyroidism
   • With normal prolactin: Consider functional hypothalamic amenorrhea (FHA)
     • Assess for low energy availability, excessive exercise, stress
     • Check BMI (<18.5 kg/m² suggests energy deficiency) 1

3. Normal FSH/LH with LH/FSH ratio >2:

   • Suggests PCOS
   • Check androgens and insulin resistance markers
   • Evaluate for polycystic ovarian morphology on ultrasound 3, 1

Management with Medroxyprogesterone (Provera)

For therapeutic management of amenorrhea when withdrawal bleeding is desired:

• Standard dosage: Medroxyprogesterone acetate 10 mg orally twice daily for 5-10 days 4
• Efficacy: Withdrawal bleeding occurs in approximately 93% of women with adequate estrogen levels and responsive endometrium 4
• Timing: Can be administered at any time in anovulatory women without regular cycles
• Follow-up: Withdrawal bleeding typically occurs within 2-7 days after completing the course

Special Considerations

• Functional hypothalamic amenorrhea: Address underlying energy balance issues before hormonal therapy 1
• PCOS: May require combined hormonal contraceptives for cycle regulation 1
• Hyperprolactinemia: Requires treatment of underlying cause (medication adjustment, prolactinoma treatment) 5
• Primary ovarian insufficiency: Patients can maintain unpredictable ovarian function and should not be presumed infertile 2

Common Pitfalls to Avoid

• Failing to rule out pregnancy before initiating workup
• Missing functional hypothalamic amenorrhea in normal-weight women (can occur without obvious weight loss if energy expenditure exceeds intake) 1
• Confusing isolated polycystic ovarian morphology with PCOS (polycystic ovaries occur in 17-22% of general female population) 3, 1
• Not considering medication effects (antiepileptics, hormonal contraceptives, antipsychotics) 1

By following this systematic approach to laboratory evaluation and progesterone challenge testing, the underlying cause of amenorrhea can be identified and appropriate treatment initiated to address both the hormonal imbalance and any associated health risks.