What are the uses and dosages of progesterone receptor modulators, such as ulipristal acetate (generic name) and mifepristone (generic name), in clinical contexts like emergency contraception and early pregnancy loss management?

Progesterone Receptor Modulators: Clinical Uses and Dosing

Emergency Contraception

Ulipristal acetate 30 mg as a single oral dose is the preferred progesterone receptor modulator for emergency contraception, providing effective pregnancy prevention for up to 120 hours after unprotected intercourse with sustained efficacy throughout this window. 1, 2

Ulipristal Acetate Dosing and Efficacy

• Single dose of 30 mg orally within 120 hours (5 days) of unprotected intercourse or contraceptive failure 1, 2
• Reduces pregnancy rate from an expected 5.5-5.6% to an observed 1.9-2.2% when taken within the indicated timeframe 1
• Superior to levonorgestrel when administered 72-120 hours post-intercourse, and meta-analyses suggest greater effectiveness throughout the entire 5-day period 2, 3
• Mechanism involves inhibiting or delaying ovulation by postponing LH surge or directly inhibiting follicular rupture 2

Important Clinical Considerations

• Requires negative pregnancy test prior to administration 1
• Menses typically delayed by 2-3 days following treatment 2
• Contraindicated in known or suspected pregnancy 1, 4
• Evidence suggests potential postfertilization effects in addition to ovulation inhibition, which patients should be informed about 4

Pregnancy Termination

Mifepristone is the established progesterone receptor modulator for first-trimester pregnancy termination, initially developed and commercialized specifically for this indication. 5, 6

Mechanism and Clinical Use

• Binds to cytosolic progesterone receptors, preventing gene transcription and causing decidual breakdown 6
• Well tolerated and effective for single-dose first-trimester at-home pregnancy termination 7
• Available in much of the world for this indication 7

Early Pregnancy Loss Management

• Mifepristone can be used up to 7 weeks gestation as an alternative to surgery in select high-risk populations 8
• High-risk patients (cardiac disease, end-stage renal disease) should be managed in experienced centers with emergency support 8
• Avoid misoprostol in women with previous cesarean delivery due to uterine rupture risk 8
• Dilatation and evacuation remains the safest procedure for high-risk patients 8

Uterine Fibroid Management

For preoperative management of uterine fibroids, ulipristal acetate 5-10 mg daily for 3-month courses is recommended based on PEARL trial data, though hepatic safety concerns have emerged with chronic use. 5

Ulipristal Acetate for Fibroids

• Dosing: 5-10 mg daily for 3-month courses 5
• Approved in Europe and Canada for pre-surgical single course (2013) and repeated intermittent treatment (2016) 5
• Effectively controls bleeding, reduces fibroid volume, and achieves amenorrhea 5
• Endometrial changes (PAEC) are benign and reversible within 3 months of discontinuation 5
• Repeated intermittent courses demonstrated sustained efficacy over nearly 2 years 5

Mifepristone for Fibroids

• Dosing: 5-50 mg daily 5
• ACOG notes efficacy in relieving symptoms, reducing fibroid volume, and achieving amenorrhea 5
• Cochrane Review confirmed effectiveness at controlling bleeding and improving quality of life 5
• Not formally indicated for uterine fibroids in any jurisdiction despite demonstrated efficacy 5

Critical Safety Warning

• Chronic SPRM use has been associated with abnormal liver enzymes and rarely hepatic failure; causality remains unclear 7
• This hepatotoxicity concern has significantly impacted clinical availability and use patterns 7
• Monitor liver function tests during extended treatment courses 7

Drug Interactions and Contraindications

CYP3A4 Interactions

• Strong CYP3A4 inhibitors (ketoconazole) increase ulipristal acetate exposure 5.9-fold 1
• CYP3A4 inducers may reduce efficacy of progesterone receptor modulators 1

Hormonal Contraception Interactions

• Ulipristal acetate may reduce efficacy of hormonal contraceptives due to progesterone receptor antagonism 2, 3
• Barrier methods recommended as backup contraception after emergency contraception use 2

Alternative SPRMs in Development

• Vilaprisan is in late-stage clinical development for uterine fibroids 5
• Asoprisnil showed dose-dependent bleeding suppression (5-20 mg daily) but development halted in 2007 5
• Telapristone acetate showed promise in animal models but limited human data 5