J Gynecol Oncol.  2019 Nov;30(6):e90. 10.3802/jgo.2019.30.e90.

Long-term outcomes of progestin plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer patients

• Mitsuhashi A
• Habu Y
• Kobayashi
• Kawarai Y
• Ishikawa H
• Usui H
• Shozu M

• KMID: 2458897
• DOI: http://doi.org/10.3802/jgo.2019.30.e90

Abstract

OBJECTIVE
The present study investigated long-term outcomes of medroxyprogesterone acetate (MPA) plus metformin therapy in terms of control of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC), and post-treatment conception.
METHODS
We retrospectively analyzed 63 patients (42 with EC; 21 with AEH) who underwent fertility-sparing management using MPA plus metformin. MPA (400 mg/day) and metformin (750-2,250 mg/day) were administered to achieve complete response (CR). Metformin was administered until conception, even after MPA discontinuation.
RESULTS
Of the total patients, 48 (76%) had a body mass index (BMI) ≥25 kg/m² and 43 (68%) showed insulin resistance. Sixty-one patients (97%) achieved CR within 18 months. CR rates at 6, 8-9, and 12 months were 60%, 84%, and 90%, respectively. During a median follow-up period of 57 months (range, 13-115 months), relapse occurred in 8 of 61 patients (13.1%) who had achieved CR. Relapse-free survival (RFS) in all patients at 5 years was 84.8%. Upon univariate analysis, patients with BMI ≥25 kg/m² had significantly better prognoses than did those with BMI <25 kg/m2 (odds ratio=0.19; 95% confidence interval=0.05-0.66; p=0.009). Overall pregnancy and live birth rates per patient were 61% (19/31) and 45% (14/31), respectively.
CONCLUSIONS
MPA plus metformin is efficacious in terms of RFS and post treatment conception. Moreover, metformin may be more efficacious for patients with BMI ≥25 kg/m².

Keyword

Endometrial Cancer; Atypical Endometrial Hyperplasia; Fertility Preservation; Medroxyprogesterone Acetate; Metformin; Insulin Resistance

MeSH Terms

Body Mass Index
Endometrial Hyperplasia*
Endometrial Neoplasms*
Female
Fertility Preservation
Fertilization
Follow-Up Studies
Humans
Insulin Resistance
Live Birth
Medroxyprogesterone Acetate
Metformin*
Pregnancy
Prognosis
Recurrence
Retrospective Studies
Medroxyprogesterone Acetate
Metformin