What causes Benign Prostatic Hyperplasia (BPH)? Many believe it is closely linked to aging and hormonal changes. BPH is most common in men over the age of 50 because, as men age, various risk factors accumulate that contribute to the growth of prostate cells. The balance between the growth and death of prostate cells is disrupted, leading to hyperplasia. Hormonal changes also play a role. Testosterone in men is converted into dihydrotestosterone (DHT), which stimulates the growth of prostate cells. In the prostate, testosterone is mainly converted into DHT, contributing to BPH. Estrogen is also a factor— as testosterone levels decrease, estrogen levels rise, which can promote the proliferation of prostate cells. Other contributing factors include obesity and lack of exercise, both of which lead to metabolic disorders. However, today I want to focus on the effects of insulin on prostate tissue. Why does insulin trigger cellular proliferation, and how do growth factors like IGF-1 stimulate prostate cells?

Insulin resistance

Diabetes significantly increases the risk of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Insulin plays a crucial role, particularly in cases of BPH without an apparent cause. Primarily, insulin regulates blood sugar levels, while also influencing overall metabolic health and hormonal balance.

Conditions associated with insulin resistance, such as obesity and type 2 diabetes, contribute to an increased risk of BPH due to hormonal changes and inflammation. Over time, insulin resistance can lead to elevated insulin levels in the blood, a condition known as hyperinsulinemia, which independently promotes the development of BPH.

Insulin resistance alters the body through several biological pathways. Metabolic syndrome, arising from diabetes or insulin resistance, has been linked to the onset of BPH. Factors such as high blood sugar, elevated blood lipids, and obesity create an environment that may stimulate prostate cell growth. Additionally, obesity is closely related to insulin resistance; excess weight and elevated insulin levels encourage prostate cell growth. Numerous studies support the connection between diabetes and BPH, highlighting the importance of addressing insulin resistance in managing these conditions.

Growth factors play a significant role in prostate cell growth. Insulin, particularly in the context of hyperinsulinemia, stimulates the release of insulin-like growth factor 1 (IGF-1). Elevated levels of IGF-1 contribute to excessive prostate growth, leading to benign prostatic hyperplasia (BPH). In addition to IGF-1, high insulin levels promote the release of other mitogenic and anti-apoptotic agents, which bind to insulin receptors and stimulate prostate growth.

The levels of IGFs and their binding proteins in both prostate tissue and blood are associated with the risk of developing BPH. Because insulin and IGF-1 share structural similarities, insulin can also bind to IGF receptors on prostate cells, activating these receptors and inducing growth and cellular proliferation. Dysregulation of the IGF axis may contribute not only to BPH symptoms but also to the progression of prostate cancer.

At the genetic level, insulin and obesity influence sex hormones. Hyperinsulinemia can increase the transcription of genes and the translation of proteins. It is also associated with reduced levels of sex hormone-binding globulin, leading to increased free sex hormones entering the prostate, which may promote growth. Research has shown that alterations in sex steroid metabolism can cause hormonal changes that impact the prostate.

Chronic inflammation is another critical factor in this context. Inflammation can adversely affect prostate tissues, and chronic conditions stemming from high insulin levels, obesity, and metabolic disorders can lead to prostate enlargement. Local accumulation of pro-inflammatory substances, such as interleukin-1, interleukin-8, and macrophages, due to systemic inflammation and oxidative stress, can further contribute to the development of BPH.

1) Differentiation. 2011 Nov-Dec;82(4-5):261-71. doi: 10.1016/j.diff.2011.04.004. Epub 2011 May 4. Diabetes, growth hormone-insulin-like growth factor pathways and association to benign prostatic hyperplasia. Zongwei Wang 1, Aria F Olumi

2) Stromal Insulin-Like Growth Factor Binding Protein 3 (IGFBP3) Is Elevated in the Diseased Human Prostate and Promotes ex Vivo Fibroblast-to-Myofibroblast Differentiation Get access Arrow
Natalie Sampson, Christoph Zenzmaier, Martin Heitz, Martin Hermann, Eugen Plas, Georg Schäfer, Helmut Klocker, Peter Berger
Endocrinology, Volume 154, Issue 8, 1 August 2013, Pages 2586–2599,

3) Jangir RN, Jain GC. Diabetes mellitus induced impairment of male reproductive functions: a review. Curr Diabetes Rev. 2014;10:147–57. doi: 10.2174/1573399810666140606111745.

Vitamin D

So, what should we focus on? The answer is vitamin D. Low levels of vitamin D are directly linked to insulin resistance and benign prostatic hyperplasia (BPH). Therefore, it’s essential to ensure adequate vitamin D supplementation.

Vitamin D plays a crucial role in regulating various hormones, including insulin. Sufficient levels of vitamin D in the body improve insulin sensitivity, counteracting insulin resistance. Reducing the risk of insulin resistance is vital for preventing associated complications like BPH. Additionally, vitamin D may enhance insulin signaling pathways, which promotes better glucose metabolism and further impacts insulin sensitivity.

Vitamin D also serves a protective role in prostate health. Vitamin D receptors (VDR) are present in prostate cells, and researchers believe that vitamin D influences cell growth and differentiation through these receptors. Low vitamin D levels in prostate cells may increase the risk of prostate enlargement and other related issues.

The combination of low vitamin D levels, obesity, and metabolic syndrome is particularly concerning, as these conditions can lead directly to insulin resistance. Maintaining adequate vitamin D levels may support overall metabolic health and influence the risks associated with both BPH and insulin resistance. Furthermore, vitamin D has anti-inflammatory properties that can help mitigate the chronic inflammation often seen in these conditions. Reducing inflammation can benefit prostate health and lower the risk of BPH.

The general recommended dietary allowance (RDA) for vitamin D is around 800-1000 IU per day for adults. However, individuals with type 2 diabetes, metabolic syndrome, or insulin resistance may benefit from higher doses. Optimal blood levels of vitamin D typically range from 30-50 ng/mL. If you are concerned about insulin resistance, a supplement dosage of 1000-2000 IU may be helpful. Keep in mind that dosages can vary based on individual needs and current vitamin D levels. If you are considering doses above 4000 IU to improve insulin sensitivity, it is advisable to consult your doctor to discuss your current health.

Conclusion

Insulin is indirectly related to BPH, particularly through insulin resistance, the activation of IGF-1, chronic inflammation, and metabolic disorders. Managing insulin resistance through healthy diet and lifestyle habits can help reduce the risk of BPH.