Objective After successful progestin therapy for endometrial hyperplasia (EH), the risk of relapse remains. We aimed to assess if immunohistochemical (IHC) expression of progesterone receptor isoforms, PR‐A and PR‐B, in endometrial glands and stroma in pre‐treatment endometrial biopsies was related to relapse of EH. Design and setting Biopsy material originated from women with low‐risk and medium‐risk EH recruited to a recent Norwegian multicentre randomised trial. Participants (n = 153) had been treated for 6 months with three different progestin regimens. Population One hundred and thirty‐five of the 153 women achieved therapy response and underwent follow up for 24 months after therapy withdrawal. Fifty‐five women relapsed during follow up. Pre‐treatment endometrial biopsies from 94 of the 135 responding women were available for IHC staining. Methods Immunohistochemical staining was performed separately for PR‐A and PR‐B and IHC expression was evaluated in endometrial glands and stroma by a histological score (H‐score) using light microscopy. Main outcome measure Immunohistochemical expression of PR‐A and PR‐B in endometrial glands and stroma in women with or without relapse of EH. Results Low PR‐A in endometrial glands (P = 0.013) and stroma (P < 0.001), and high PR‐B in endometrial glands (P = 0.001) in pre‐treatment endometrial biopsy have a statistically significant association with relapse of EH. Women with a pre‐treatment ratio of PR‐A:PR‐B ≤ 1 have a higher risk of relapse (71%) compared with women with a ratio of PR‐A:PR‐B > 1 (19%; P < 0.001). Conclusion Immunohistochemical expression of PR‐A and PR‐B in pre‐treatment endometrial biopsy proves valuable as a predictor of relapse in EH. Tweetable abstract Pre‐treatment endometrial expression of PR‐A and PR‐B is a valuable predictor of relapse in endometrial hyperplasia.

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