The preventive effect of metformin on progression of benign prostate hyperplasia: A nationwide population-based cohort study in Korea

Abstract

Metformin, a first-line treatment for type 2 diabetes mellitus (T2DM), has recently been recognized for its pleotropic anti-proliferative, anti-cancer, and anti-aging effects. Contrary to the studies characterizing metformin effects in prostate cancer, little is known about these effects in BPH progression. With the Sample Cohort DB data during 2007 and 2017 from the Health Insurance Review and Assessment Service (HIRA) in South Korea, we investigated the preventative effect of metformin on BPH progression. The study population consisted of 211,648 BPH naïve patients that were diagnosed with BPH in 2009 and a follow-up occurrence of prostatectomy until 2017 that was defined as progression of BPH. These patients were divided into three treatment groups: without T2DM, T2DM without metformin, and T2DM with metformin. The hazard ratio in the T2DM with metformin group was 0.86 for prostatectomy compared to the group without T2DM (CI = 0.77–0.96, P value = 0.007) after adjusting for confounding factors such as age, comorbidity, residential area, level of hospital, and category of BPH medications. The T2DM with high-dose metformin group had a significantly lower risk of prostatectomy with hazard ratio of 0.76 (CI = 0.62–0.92, P value = 0.005) in stratified analysis. Our results suggest that metformin may improve BPH progression based on the reduced risk of prostatectomy, although T2DM effects on BPH were unclear. Future observational studies and prospective trials are needed to confirm the effects of metformin on BPH progression.

The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review

“…In humans, an earlier retrospective cohort study conducted in the USA did not find any association between thiazolidinediones or metformin (adjusted HR for metformin use, 0.99; 95% CI, 0.94–1.03) and BPH while compared to sulfonylureas [ 87 ]. However, a later retrospective cohort study conducted in Korea using the Health Insurance Review & Assessment Service suggested that diabetes patients who used metformin had a reduced risk of BPH progression indicated by the occurrence of prostatectomy during follow-up while compared to a group without T2DM (HR, 0.86; 95% CI, 0.77–0.96; p=0.007) [ 88 ].…”

Metformin mitigates PLCε gene expression and modulates the Notch1/Hes and androgen receptor signaling pathways in castration‑resistant prostate cancer xenograft models

“…Similarly, Hankinson et al ( 15 ) reported that metformin treatment in patients with type 2 diabetes reversed metabolic conditions by decreasing the androgen levels, thereby leading to high levels of androgen stimulating prostate growth, proliferation and tumorigenesis. Although the antitumor properties of metformin are not obvious in the early stages of prostate cancer development, the drug could be effective in decreasing the mortality of patients with prostate cancer by significantly improving the parameters of metabolic syndrome after ADT, and it could exhibit a therapeutic effect on some patients with asymptomatic or mild metastatic CRPC ( 23 , 24 ). There is potential for metformin to be used as a monotherapy or an adjuvant agent in ADT, or in external therapy or other chemotherapies.…”

Anti-aging properties of metformin

“…In the case of the estrogen-β receptor, the pro-apoptotic response was increased. Results of this study are very promising, but more research is needed to rule out the effects of other medications used by patients and other confounding factors [14].…”