Table 2.
Patient characteristics and results of prospective and retrospective cohort studies analyzing the efficacy of progestin treatment in women with EH
| Author | Year | Study type | Number of patients | Population characteristics | Intervention | Regression of EH | Persistence/progression of EH | Side effects |
|---|---|---|---|---|---|---|---|---|
| Reed [59] | 2009 | CS | 185 | Complex (n = 115) or atypical EH (n = 70) on independent pathology review | Progestin therapy (oral MPA or MGA or NETA) or no therapy | Complex EH: 59% (68/115) with progestins vs. 12% (14/115) with no therapy; Atypical EH: 54% (38/70) with progestins vs. 8% (6/70) with no therapy | 28.4% with progestins vs. 30% with no therapy (complex EH); 26.9% with progestins vs. 66.7% with no therapy (atypical EH); EC G1 in 11/28 follow-up hysterectomies | – |
| Dhar [61] | 2005 | CS | 4 | Endometrioid EC, G1, PR positive | LNG-releasing IUD for at least 6 months | 1/4 | 3/4 | IUD expulsion (n = 3); emergency curettage (n = 1) |
| Wildemeersch [83] | 2003 | CS | 12 | Simple EH (n = 7), EH with atypia (n = 5) | LNG-releasing IUD (14 µg/d) for at least 12 months | 12/12 | One patient developed EC, G1, which regressed in consecutive biopsies | – |
| Mandel-Baum [84] | 2020 | CS | 245 | Atypical hyperplasia on in-house pathology report | Oral progestin therapy (n = 140 MGA; n = 28 MPA; n = 8 others) or LNG-IUD (n = 69) for at least 1 month | 78.7% (LNG-IUD) vs. 46.7% (systemic progestins) | Progression to EC: 4.5% (LNG-IUD) vs. 15.7% (systemic progestins) | Morbidly obese women had higher benefit from LNG-IUD (HR 4.72; 95% CI 2.83–7.89) for CR) |
| Marra [75] | 2014 | CS | 132 | EH without atypia (simple or complex) | Oral progesterone in 2nd half of menstrual cycle for 18 months or no treatment | 95% vs. 75%, p = 0.05, for simple EH; 89% vs. 35%, p < 0.001, for complex EH | Regression rates were dose-dependent: 82%, 98%, and 100% for 100 mg, 200 mg and 300 mg | – |
| Simpson [76] | 2014 | CS | 44 | Atypical EH (n = 19), EC G1 (n = 25) | Oral progestin therapy (n = 140 MGA; n = 28 MPA; n= 8 others) or LNG-IUD (n = 69) for at least 1 month | 24/44 (55%) | 20/44 (45%); 13/44 with regression later recurred; 3/44 were up-staged | – |
| Park [79] | 2013 | CS | 48 | EC G1 with superficial myometrial invasion or EG G2/3 with no myometrial invasion | Oral progestin therapy (n = 14 MGA; n = 34 MPA) for a median of 6 months | 37/48 (77%) | 16/37 (43%) | Median time to CR 17 weeks; No mortality; 10 live births |
| Park [78] | 2013 | CS | 33 | Recurrence after progestin treatment for EC G1: atypical EH (n = 13), EC G1 (n = 20) | Oral progestin therapy (n = 3 MGA; MPA; n = 30) for a median of 6 months | 28/33 (85%) | 5/33 (15%) | No mortality |
| Wildemeersch [85]; Update of [83] | 2007 | CS | 20 | Simple EH (n = 12), EH with atypia (n = 8) | LNG-releasing IUD (20 µg/d) for at 14–90 months | 11/12 | 1/12 had persisting benign EH | – |
| Yang [86] | 2019 | CS | 160 | atypical EH (n = 120), EC stage I without myometrial invasion (n = 40) | Hysteroscopic resection + oral progestin therapy until CR | 148/160 (93%) | 4/160 (2%) | 15 of 60 attempting pregnancy became pregnant |
| Pal [74] | 2018 | CS | 32 | atypical EH (n = 17), EC G1/2, stage I (n = 15) | LNG-IUD for 6 months | 80% (atypical EH) vs. 67% (EC G1) vs. 75% (EC G2) | 3/32 | 1/5 became pregnant and delivered |
| Scarselli [87] | 2010 | CS | 34 | EH without atypia (n = 30), atypical EH (n = 4) | LNG-IUD (20 µg/day) for 5 years (range 12–60 months) | 32/34 | 2/32 persistence; after mean follow-up of 17 years 9 had hysterectomy with EH in 5/9 cases | |
| Buttini [88] | 2009 | CS | 57 | EH without atypia (n = 41), EH with atypia (n = 16) | LNG-IUD (n = 26), oral progestin (n = 10), hysterectomy (n = 21) | 21/26 (LNG-IUD) vs. 9/10 (progestin) | 2/32 persistence; 0/57 developed EC | 1 LNG-IUD removed for side effects |
| Varma [89] | 2008 | CS | 105 | EH without atypia (n = 96), EH with atypia (n = 9) | LNG-IUD for 2 years | 96% (90/94) after 1 year; 90% (94/105) after 2 years; 88/96 (92%) for EH without atypia and 6/9 (67%) for EH with atypia | 1 case of EC | – |
| Gallos [90] | 2013 | CS | 344 | Complex EH without atypia or EH with atypia | Oral progestins (n = 94) or LNG-IUD (n = 250) | 95% (237/250) for LNG-IUD vs. 84% (79/94) for oral progestins (OR 3.04; 95% CI 1.4–6.8) | 8 cases of EC | Hysterectomy rates were 55/250 (22%) for LNG-IUD vs. 35/94 (37%) for oral progestins |
| Gallos [91]; Update of [90] | 2013 | CS | 219 | Complex EH without atypia or EH with atypia who achieved CR after progestin treatment | Oral progestins or LNG-IUD | – | 21/153 (14%) for LNG-IUD vs. 20/66 (30%) for oral progestin; 2 cases of EC | Hysterectomy rates lower for LNG-IUD (20% vs. 32%) |
| Cholakian [92] | 2016 | CS | 60 | EH with atypia (n = 25); EC G1 (n = 35) | MGA (n = 42); MPA (n = 11); LNG-IUD (n = 22); multiple regimens possible | – | – | Median weight change greater for MGA vs. LNG-IUD (+ 2.9 vs. + 0.05 kg); BMI < 35 gained more weight vs. BMI ≥ 35 (+ 2.3 vs. − 0.7 kg/month); for BMI ≥ 35, MGA had more weight gain than LNG-IUD (+ 2.2 vs. − 5.4 kg) |
| Kim [93] | 2016 | CS | 75 | EH without atypia (n = 60); EH with atypia (n = 15) | LNG-IUD for 12 months | 95% (36/38) after 12 months | 1 case with residual EH | – |
| Marnach [94] | 2017 | CS | 94 | Endometrial intraepithelial neoplasia | LNG-IUD | 87% (no atypia); 62% (with atypia); 22% (adenocarcinoma) | – | – |
| Haoula [95] | 2011 | CS | 51 | EH without atypia (n = 32); EH with atypia (n = 19) | LNG-IUD for 12 months | 97% (31/32) for EH without atypia after 24 months; 84% (16/19) for atypical EH | 2 cases of persistence | – |
| Kim [96] | 2013 | CS | 16 | EC G1, < 2 cm | LNG-IUD + oral MPA (500 mg/day) for 3 months | 88% (14/16); median time to CR 9.8 months | No case of progression | No treatment-related complications |
| Pooled analysis | - | CS (n = 21 including two Updates) | 1087 | – | – | LNG-IUD with higher rates vs. oral progestins in 7 studies | Progression to EC lower with LNG-IUD in 2 studies; regression rates dose-dependent with oral progestins in 1 study | Hysterectomy rates lower for LNG-IUD in 2 studies; more weight gain for MPA/MGA than LNG-IUD in 1 study |