Mechanism of Endometrial Protection by Progestin-Containing IUDs
The levonorgestrel-releasing intrauterine device (LNG-IUD) protects the endometrial lining through direct local suppression of endometrial growth, making the endometrium insensitive to ovarian estradiol and causing profound atrophy of the endometrial glands and stroma. 1
Primary Mechanism of Action
The LNG-IUD releases levonorgestrel directly into the endometrial cavity, creating high local progestin concentrations that fundamentally alter endometrial physiology:
- Local progestin delivery causes strong suppression of endometrial proliferation, rendering the endometrium unresponsive to circulating estradiol despite normal ovarian function 1
- This endometrial suppression results in glandular atrophy and decidualization of the stroma, which is the histologic basis for protection against hyperplasia 2
- The mechanism is primarily local rather than systemic, which explains why LNG-IUDs have minimal effects on ovulation while providing robust endometrial protection 1
Clinical Manifestations of Endometrial Protection
The protective effects translate into measurable clinical outcomes:
- Menstrual blood loss decreases by approximately 90% from baseline within the first year of use, reflecting the degree of endometrial suppression 1
- Many women develop amenorrhea due to profound endometrial atrophy, which is a marker of effective endometrial protection 3
- Endometrial thickness is significantly reduced on transvaginal ultrasound, providing an imaging correlate of the suppressive effect 4
Evidence of Therapeutic Efficacy
The protective mechanism is so robust that LNG-IUDs are used therapeutically for endometrial pathology:
- In women with endometrial hyperplasia without atypia, disease regression occurs in 85-93% of cases with LNG-IUD use, demonstrating reversal of pathologic proliferation 3
- Meta-analysis shows LNG-IUD achieves 91.3% resolution/regression rates for endometrial hyperplasia compared to 68.6% with systemic progestins (OR 3.42,95% CI 1.86-6.30), indicating superior local endometrial effects 5
- In tamoxifen users, LNG-IUD reduces the risk of endometrial polyps (OR 0.28,95% CI 0.15-0.55) and hyperplasia (OR 0.14,95% CI 0.02-0.80), protecting against tamoxifen-induced endometrial stimulation 2
Comparison to Systemic Progestins
The local delivery mechanism provides advantages over oral progestins:
- LNG-IUD demonstrates higher treatment success and lower failure rates (19.2% vs 32.3%, OR 0.34) compared to systemic progestins for endometrial hyperplasia 5
- Hysterectomy rates are significantly lower with LNG-IUD (9.3% vs 24.1%, OR 0.41) compared to oral progestins, reflecting better disease control 5
- Side effects are fewer with LNG-IUD compared to oral medroxyprogesterone acetate, with higher patient satisfaction rates, due to minimal systemic absorption 4
Important Caveats
- During the first 2-3 months of use, irregular spotting is common before endometrial suppression is fully established, which should not be interpreted as treatment failure 1
- The protective effect requires the device to remain in situ; removal results in rapid return of normal endometrial proliferation and menstrual bleeding 1
- For women with uterine fibroids, expulsion rates may be higher (11% vs 0-3%), potentially compromising endometrial protection if unrecognized 3, 6