What baseline laboratory assessments and follow‑up tests should be obtained before and during systemic progestin therapy to monitor for adverse effects?

Laboratory Monitoring for Systemic Progestin Therapy

Baseline Assessment Before Initiating Progestin Therapy

No laboratory tests or physical examinations are required before starting progestin-only therapy in healthy women. 1, 2

Essential Pre-Treatment Requirements

• Blood pressure measurement is NOT required for progestin-only methods (unlike combined hormonal contraceptives where it is mandatory). 1, 2, 3
• Weight/BMI measurement is optional but may be useful for baseline monitoring of potential weight changes during therapy. 1, 2
• Medical history focusing on contraindications is the most important pre-treatment assessment—specifically screening for current breast cancer, active thromboembolic disease, undiagnosed vaginal bleeding, and known or suspected pregnancy. 1

Tests That Are NOT Required at Baseline

The following investigations are Class C (non-essential) and should not delay progestin initiation in healthy women: 1, 2, 3

• Glucose testing
• Lipid panel
• Liver enzyme tests (ALT, AST)
• Hemoglobin/complete blood count
• Thrombogenic mutation screening
• Cervical cytology (Pap smear)
• Clinical breast examination
• Pelvic/bimanual examination (except for IUD placement)
• STI or HIV screening (unless risk-based indications exist)

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Follow-Up Monitoring During Progestin Therapy

For Contraceptive Progestin Use

No routine laboratory monitoring or follow-up testing is required during ongoing progestin-only contraception. 1

• Clinical follow-up should focus on patient-reported symptoms, bleeding patterns, and satisfaction with the method rather than laboratory parameters. 1
• Endometrial monitoring is not indicated for routine progestin contraceptive use. 1

For Therapeutic Progestin Use (Non-Contraceptive Indications)

The monitoring strategy depends on the specific clinical indication:

Endometrial Hyperplasia or Early-Stage Endometrial Cancer (Fertility-Sparing)

Endometrial sampling (biopsy or D&C) every 3 to 6 months is mandatory to assess treatment response and detect progression. 1

• Discontinue progestin therapy and proceed to hysterectomy if:

  • Documented progression on biopsy 1
  • Endometrial cancer persists after 6 to 12 months of therapy 1
  • Childbearing is complete 1

• Pregnancy testing should be performed if attempting conception during treatment intervals. 1

• Imaging (pelvic MRI or ultrasound) may be indicated if extrauterine disease is suspected. 1

Uterine Fibroids (Selective Progesterone Receptor Modulators like Ulipristal Acetate)

Endometrial thickness measurement by ultrasound is NOT clinically indicated during treatment courses. 1

• Baseline endometrial biopsy is recommended as part of the workup for abnormal uterine bleeding but is not specifically required before initiating ulipristal acetate if already performed. 1
• Post-treatment endometrial biopsy is not routinely required unless clinically indicated (e.g., persistent bleeding, concern for pathology). 1
• Alert the pathologist that the patient has been treated with a SPRM when submitting any endometrial specimens, as progesterone receptor modulator-associated endometrial changes (PAEC) are benign and reversible but may be misinterpreted. 1
• Rapid increase in fibroid size, particularly in perimenopausal women, warrants investigation to exclude sarcoma. 1

Hormone Replacement Therapy (Progestin Component)

Repeat laboratory testing at 3 months after starting therapy is recommended to assess response, then every 3 to 6 months during the first year, followed by annual monitoring if stable. 4

• Liver function tests (ALT, AST) should be monitored, particularly with oral formulations, though low-dose progestins show minimal hepatic effects. 4
• Lipid panel monitoring may be indicated, as progestins can modestly affect HDL-cholesterol depending on the specific agent (medroxyprogesterone acetate decreases HDL-C more than micronized progesterone). 5

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Critical Pitfalls and Caveats

Contraindications That Require Clinical Assessment (Not Laboratory Tests)

Screen for these conditions via history, not routine lab work: 1

• Current or history of breast cancer
• Active or recent thromboembolic disease (stroke, MI, PE, DVT)
• Active smoking (particularly relevant for combined hormones, less so for progestins alone)
• Undiagnosed vaginal bleeding (requires evaluation before starting therapy)

Avoid Unnecessary Barriers to Access

Do not delay progestin initiation while awaiting unnecessary tests (e.g., Pap smear, pelvic exam, breast exam, or routine labs in healthy women), as this creates barriers and increases the risk of unintended pregnancy or untreated symptoms. 1, 2

Special Populations Requiring Additional Evaluation

Women with known medical conditions (e.g., diabetes, hypertension, liver disease, thrombophilia) may require individualized assessment and additional testing based on the U.S. Medical Eligibility Criteria for Contraceptive Use. 1, 2

Pregnancy Testing Strategy

If pregnancy status is uncertain, the benefits of starting progestin therapy generally outweigh the risk; initiate treatment and schedule a follow-up pregnancy test in 2 to 4 weeks. 1, 2