Table 1

Characteristics of included studies ordered by date of publication

Author (year)	Region	Design	Total No of patients	No of patients in treatment groups	Intervention dosage	Age at diagnosis (years)*	Histological diagnosis, n (%)	Reported outcomes	Median follow-up (months)	Study period
Matsuo et al (2020)21	USA	Retrospective, single institution	245	Prog: 194 (140 oral, 54 IUD)	MPA, MA, NE, Depo, LNG-IUD; dosages not specified	36 (30–43) for oral progestin; 36 (29.8–44.3) for IUD	AEH	Remission	9.0	2003–2018
Matsuo et al (2020)21	USA	Retrospective, single institution	245	Prog+M: 51 (36 oral, 15 IUD)	As above, metformin; dosages not specified	35 (27–41) for oral progestin; 34 (29-39) for IUD	AEH	Remission	9.0	2003–2018
Acosta-Torres et al (2020)17	USA	Retrospective, multi-institution	92	Prog: 58	MA 80–160 mg daily, MPA 10–40 mg daily, prometrium 400 mg daily, or LNG-IUD 52 mg	36 (31–39)	AEH: 33 (56.9%); EC: 25 (43.1%)	Remission, relapse, live births, 5 year recurrence free survival	28.4	1999–2018
Acosta-Torres et al (2020)17	USA	Retrospective, multi-institution	92	Prog +M: 34	As above, metformin 500–1000 mg daily	32 (29–35)	AEH: 21 (61.8%); EC: 13 (38.2%)		28.4	1999–2018
Yang et al (2020)14	China	Randomized trial (open label), single institution	150	Prog: 74	MA 160 mg daily	33.4±5.2	AEH: 62 (83.8%) EC: 12 (16.2%)	Remission, relapse, pregnancy, live births, adverse effects	33.4, until Feb 2019	2013–2017
Yang et al (2020)14	China	Randomized trial (open label), single institution	150	Prog +M: 76	As above, metformin 500 mg three times a day	32±4.5	AEH: 61 (80.3%); EC: 15 (19.7%)	Remission, relapse, pregnancy, live births, adverse effects	33.4, until Feb 2019	2013–2017
Mitsuhashi et al (2019)	Japan	Retrospective, single institution	86	Prog: 23	MPA 400 mg daily	35 (28–45)	EC†	Remission, relapse, 5 year recurrence free survival, pregnancy rates, live birth rates, adverse effects	57	2009–2017
Mitsuhashi et al (2019)	Japan	Retrospective, single institution	86	Prog +M: 63	MPA 400 mg daily, metformin 750–2250 mg daily	35 (26–44)	AEH: 21 (33.3%); EC: 42 (66.7%)		57	2009–2017
Zhou et al (2015)19	China	Retrospective, single institution	32	Prog: 23	MPA 250 mg daily, or MA 160 mg daily	30.4 (20-40)	AEH: 13 (40.6%); EC: 19 (59.4%)	Remission, relapse, pregnancy, live births	32.5	2006–2013
Zhou et al (2015)19	China	Retrospective, single institution	32	Prog +M: 9	As above, metformin 250 mg three times a day	30.4 (20-40)	AEH: 13 (40.6%); EC: 19 (59.4%)	Remission, relapse, pregnancy, live births	32.5	2006–2013
Shan et al (2014)20	China	Randomized trial, single institution, pilot study	16	Prog: 8	MA 160 mg daily	34±7.1	AEH	Remission, relapse, pregnancy rates, live birth rates, adverse effects	12, until Jan 2014	2012–2013
Shan et al (2014)20	China	Randomized trial, single institution, pilot study	16	Prog +M: 8	As above, metformin 500 mg three times a day	36.4±4.2	AEH		12, until Jan 2014	2012–2013

*Mean±SD, or median with IQR.
†Twenty-three patients with endometrial carcinoma were used as historical controls, with study period from 1996 to 2017.
AEH, atypical endometrial hyperplasia; Depo, intramuscular depo-medroxyprogesterone acetate; EC, endometrialcarcinoma; LNG-IUD/IUD, levonorgestrel intrauterine device; MA, megestrol acetate; MPA, medroxyprogesterone acetate; NE, norethindrone; Prog, progestin therapy; Prog+M, progestin and metformin combined therapy.