Many medications have been used in the treatment of benign enlargement of the prostate during the 1960s, 1970s, and 1980s, including progestational agents, amino acids, spironolactone, candicidin, nystatin, flutamide, bromocriptine, alpha-adrenergic blockers, Serenoa repens (Saw palmetto extracts), and mepartricin. 

Finasteride and dutasteride are 5-alpha reductase inhibitors decrease levels of dihydrotestosterone, which contributes to prostate enlargement, have been increasingly used in the treatment of benign prostatic hyperplasia.

There is some evidence suggesting that non-hormonal therapies (i.e., medication that do not directly affect male hormones like testosterone or dihydrotestosterone) can reduce prostate volume, particularly in the context of benign prostatic hyperplasia [1].

Beta-sitosterol is a plant phytosterol commonly found in various plant extracts, structurally similar to cholesterol that is believed to exert several beneficial effects on prostate health.

The exact mechanism by which beta-sitosterol affects benign prostatic hyperplasia remains somewhat unclear, but it is thought to work through multiple pathways. These include anti-inflammatory properties, inhibition of pro-inflammatory cytokines, and modulation of growth factors that influence cell proliferation within the prostate. Additionally, beta-sitosterol may help improve smooth muscle tone in the prostate and bladder, thus contributing to reduced lower urinary tract symptoms [1-6]. Beta-sitosterol has been recognized and studied as early as the 1930s (Sandqvist & Hok, 1930; Sandqvist & Bengtsson, 1931; Bengtsson, 1935; Waflis & Chakravorty, 1937) [2].

Clinical Evidence

Several randomized controlled trials have investigated the use of beta-sitosterol in benign enlargement of the prostate, with promising results supporting its role in symptom management and potential prostate volume reduction. In 1995, Berges et al. from Germany conducted a landmark double-blind, placebo-controlled study that demonstrated the efficacy of beta-sitosterol in alleviating symptoms of benign enlargement of the prostate.

The study included 200 patients with symptomatic benign enlargement of the prostate treated with either 20 mg daily or placebo. Treatment with beta-sitosterol was associated with increased peak flow, and reduction of mean residual urinary volume.

In this trial, patients receiving beta-sitosterol showed significant improvements in urinary flow rates and symptom scores compared to those on placebo, without major side effects.

Although the study did not specifically measure changes in prostate volume, the improvements in symptoms were suggestive of a positive effect on prostate size [3].

In 1997, Klippel et al. from Germany reported a multicentric, placebo-controlled study that confirmed the benefits of beta-sitosterol in reducing the lower urinary tract symptoms associated with benign enlargement of the prostate.

The study included 177 patients who had benign enlargement of the prostate. The patients were treated with either 130 mg free beta-sitosterol (phytosterol) daily for 6 months or placebo.

The study reported not only improved urinary symptoms but also noted a reduction in prostate size in a subset of patients. This reduction in prostate volume is thought to be due to the anti-inflammatory effects of beta-sitosterol, which may help to decrease prostatic edema and slow the proliferation of prostate cells [4].

In 1998, a study by Kobayashi et al. suggested that beta-sitosterol could reduce prostate volume in addition to relieving symptoms of benign enlargement of the prostate.

The study included twelve patients who had symptoms of urinary outlet obstruction caused by benign enlargement of the prostate. The patients were treated with sitosterol 180 mg daily in 2 or 3 divided doses for 3 months. Treatment was associated with marked symptomatic improvement. However, the peak flow rate and residual urine volume showed slight but not considerable improvement [5].

In 1999, Wilt et al. from the United States conducted a systematic review of available clinical trials and concluded that beta-sitosterol was effective in improving urinary symptoms in benign enlargement of the prostate.

The review included 4 studies involving 519 patients with benign enlargement of the prostate. Compared with placebo, beta-sitosterol was associated with symptomatic improvement and improved flow parameters. However, beta-sitosterol did not decrease prostate size.

The review, which included studies from the 1990s, found that beta-sitosterol had a moderate effect on both symptom relief and quality of life, with no significant adverse effects. Importantly, although a direct correlation between beta-sitosterol and prostate volume reduction was not universally observed, many studies reported symptomatic improvement that may imply secondary effects on prostate size [6].

Impact on Prostate Volume

While most studies have focused primarily on the symptomatic benefits of beta-sitosterol, there is emerging evidence suggesting that beta-sitosterol may have some role in reducing prostate volume.

The exact mechanism behind this effect remains speculative, but it is believed that beta-sitosterol’s anti-inflammatory and cell growth-modulating properties could contribute to a decrease in the size of the prostate gland.

For example, the reduction in inflammation within the prostate may decrease prostatic edema and tissue growth, leading to a smaller gland and improved urinary function.

In one of the studies reviewed by Wilt et al. (1999), it was suggested that patients who experienced significant symptomatic relief also had a corresponding reduction in prostate size, indicating that the benefits of beta-sitosterol might extend beyond symptom management to include structural changes in the prostate. However, more robust and targeted studies are needed to confirm these findings and elucidate the mechanisms involved.

Safety and Tolerability

Beta-sitosterol is generally well-tolerated with a favorable safety profile. Most clinical studies, including those conducted by Berges et al. (1995) and Klippel et al. (1997), reported minimal adverse effects, with the most common being mild gastrointestinal discomfort. The absence of major side effects is one of the key advantages of beta-sitosterol over conventional pharmacological therapies like 5-alpha-reductase inhibitors and alpha-blockers, which can cause sexual dysfunction or hypotension, respectively.

Beta-sitosterol monotherapy appears to be a safe and effective treatment option for managing the symptoms of benign enlargement of prostate. While the evidence for its ability to reduce prostate volume is still limited, several studies suggest that it may have beneficial effects on prostate size, likely through anti-inflammatory and growth-modulating mechanisms. Further research, particularly studies that directly measure changes in prostate volume, and is needed to fully establish its role in reducing prostate size. Nevertheless, beta-sitosterol offers a promising alternative or adjunct to traditional therapies, especially for patients seeking a natural treatment with minimal side effects.

1. Al-Mosawi AJ. Benign prostate hypertrophy: An educational ultrasound images and pharmacotherapy mini-review. Journal of Medical Clinical Case Reports. 2024; 6: 1-4.
2. Rosenheim O, Webster TA. The metabolism of beta-sitosterol. Biochem J. 1941; 35: 928-31.
3. Berges RR, Windeler J, Trampisch HJ, Senge T. Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Lancet. 1995; 345: 1529-32.
4. Klippel KF, Hiltl DM, Schipp B. A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto Study group. Br J Urol. 1997; 80: 427-32.
5. Kobayashi Y, Sugaya Y, Tokue A. Clinical effects of beta-sitosterol (phytosterol) on benign prostatic hyperplasia: preliminary study. Hinyokika Kiyo. 1998; 44: 865-8.
6. Wilt TJ, MacDonald R, Ishani A. beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review. BJU Int. 1999; 83: 976-83.