Lifestyle and exercise modification

As mentioned above, lifestyle modification is an important protocol in treating BPH and ED. Observational studies indicate that there is a positive association between abdominal obesity and BPH,^17,18 and an inverse association between physical activity and BPH.^19,20 Diets high in fats or in calories may encourage abdominal obesity and sympathetic nervous system activity, both of which can increase the risk of BPH. Sympathetic nervous system activation (which is the ‘fight or flight’ arm of the autonomic nervous system) may cause the prostate smooth muscle to contract, resulting in a worsening of lower urinary tract symptoms. Studies suggest that there is no increased risk of BPH with higher caloric intake when accompanied by increased physical activity.¹⁸ With respect to ED, weight loss, physical activity, smoking cessation and decreased sympathetic activity (relaxation) have also been suggested as beneficial treatments.²¹ Dietary sources of caffeine and other diuretics should be reduced, and fluid intake monitored to reduce nocturia and urinary output to the bladder from the kidneys.

Three potential mechanisms for physical activity and decreased risk for BPH and ED may be proposed:

Nutritional hormonal modulation (5-alpha reductase, aromatase, dihydrotestosterone and oestrogen)

Clinicians should consider dietary strategies to modulate hormones, hydroxylation of DHT and maintain healthy cholesterol and cardiovascular states; these strategies include avoiding sources of pesticides,²² increasing fruit consumption, increasing the intake of zinc and essential fatty acid, decreasing butter consumption, avoiding margarine,²³ decreasing coffee consumption²⁴ and keeping cholesterol levels below 200 mg/dL.²⁵

Inconclusive evidence exists regarding protein intake and BPH. Some research demonstrates that a high-protein diet (total calories made up of 44% protein, 35% carbohydrate and 21% fat) can inhibit 5-alpha reductase, while a low-protein diet (10% protein, 70% carbohydrate and 20% fat) may stimulate the enzyme.²⁶ Contrary to this evidence, a large 8-year observational study of 3523 men with BPH suggests that total protein intake is positively associated with BPH, with the association being slightly stronger for animal protein intake than for vegetable protein intake.¹⁸ A second epidemiological study based in China also revealed a correlation between higher animal intake and the incidence of BPH (91.1% in those eating high animal diets as opposed to 11.8% in those not eating animal protein).²⁷

Authors of these studies suggest that a high protein intake may result in a greater osmolar load, which may be one possible mechanism for its detrimental effects on symptoms of BPH. This will increase urinary output and thus impose undue extra burden on an already partially obstructed or strained elimination system.¹⁸ Consistent with an anti-inflammatory approach, a diet high in quality, plant-derived and coldwater fish-based protein sources in moderate amounts seems prudent, given the current evidence.

Zinc supplementation has reduced the size of the prostate (confirmed by rectal palpation, radiography and endoscopy) and reduced overall symptomatology in the majority of patients with BPH in studies conducted in the 1970s as well as recently.²⁸ The clinical efficacy of zinc is probably due to its critical involvement in many aspects of androgen metabolism. High amounts of oestrogen can inhibit intestinal uptake of zinc, whereas elevated androgens increase absorption. Because oestrogen levels are increased in men with BPH, zinc uptake may be low, suggesting a higher functional need for this nutrient and begging the need for additional supplementation.^29,30 However, one case-control study suggested a positive association between zinc levels and BPH.³¹ This deviation from other research may be partially explained by dietary confounding factors.

The relationship between zinc levels and 5-alpha reductase activity in hyperplastic prostates is inconsistent; however, zinc has been shown to inhibit the activity of 5-alpha reductase, and decreases the conversion of testosterone to DHT.^32–35 Zinc can also inhibit specific binding of androgens to the cytosol and nuclear androgen receptors present in high amounts in prostatic tissue.³² These mechanisms suggest that zinc has more of a preventative role by maintaining a nutritional status that discourages prostate hypertrophy. No interventional studies investigating the use of zinc for BPH exist, although observational studies suggest it has a safe and effective role in diminishing the size of the prostate, particularly for prostate cancer, although one study suggests it can increase urinary symptoms.^36–40

Zinc is also involved in the regulation of prolactin secretion, leading to increased uptake of testosterone and subsequent rise in DHT in the prostate.^41–43 Natural (from beer, stress and tryptophan)^44,45 and pharmaceutical prolactin antagonists (bromocriptine)⁴⁶ have been shown to reduce many of the symptoms of prostatic hyperplasia. However, this strategy can have severe side effects, particularly pertaining to cardiovascular and neurological systems, including severe changes in mood.^47,46

A 100 g serving of soybeans or soy products contains 90 mg of beta-sitosterol, which has been shown to decrease cholesterol; this is a potential mechanism for soy’s effect on BPH. The cholesterol-lowering effects of phytosterols are well documented,^48,49 while also showing an effect on treating BPH.⁹ One double-blind study⁵⁰ in 200 men using beta-sitosterol (20 mg) or placebo three times daily demonstrated an increase in the maximum urine flow rate from a baseline of 9.9 mL/s to 15.2 mL/s and a decrease in mean residual urinary volume of 30.4 mL from 65.8 mL in the beta-sitosterol group. No changes were observed in the placebo group. An increased consumption of soy and soy foods is associated with a decrease in the risk of prostate cancer,^51,52 which is associated with the incidence of BPH. Phytoestrogens in soy (isoflavonoids, genistein and daidzein), as well as Trifolium pratense are implicated due to their effect on oestrogen receptors^51,53 and inhibition of 5-alpha reductase.⁵⁴ Other sources of beta-sitosterols such as Hypoxis hemerocallidea may also be of benefit, although many of these studies are lacking in the rigour of reporting including dose and method of extraction as well as adverse-event reporting.⁵⁵ Clinical use of these substances may be most appropriate for men with BPH in the ‘watchful waiting’ stage of the condition⁵⁶ with clinically effecting doses of beta-sitosterol ranging from 60–130 mg daily.^57,58

One study⁵⁹ suggested that 60 mg twice daily of the dried, ground flowers of Opuntia spp. over 2 to 6 months was effective at reducing urinary urgency and the sensation of a full bladder, although this remains to be repeated in other studies and stands as preliminary evidence.

The diet should be as free as possible from environmental toxins such as pesticides and other contaminants because many of these compounds (such as dioxin, polyhalogenated biphenyls, hexachlorobenzene and dibenzofurans) increase 5-alpha reduction of steroids.²⁶ Diethylstilbestrol produces changes in rat prostates histologically similar to BPH.⁶⁰ While cadmium is a known antagonist of zinc and can influence testosterone levels through effects on the activity of 5-alpha reductase, its concentration in, and effects on, the prostate are unclear. Several studies have produced conflicting results.^61,62

Herbal hormonal modulation (5-alpha reductase, aromatase, dihydrotestosterone and oestrogen)

During the 1990s, botanical medicine in Germany and Australia were considered ‘first-line’ treatments for BPH and accounted for greater than 90% of all drugs in the medical management of BPH.⁶³ In Italy, plant extracts accounted for roughly 50% of all medications prescribed for BPH, while alpha-blockers and 5-alpha reductase inhibitors account for only 5.1% and 4.8%, respectively.⁶⁴

Clinical success with any of the botanical treatments of BPH may be determined by the degree of obstruction as indicated by the residual urine content.^1,22 For mild LUTS symptoms and residual urine levels less than 50 mL, the results are usually excellent. For levels between 50 and 100 mL, the results are usually quite good. Residual urine levels greater than 100 mL will be more difficult to produce significant improvements in the customary 4- to 6-week period without co-management using other therapies including pharmaceuticals, and with botanical medicine adding little to the overall reduction in symptoms within a 4–6 week period. One small (n = 40) but well-designed clinic-based research study investigating the open use of phytotherapy for LUTS/BPH demonstrated a statistically significant superiority of phytotherapy use (as both adjuvant to pharmacological treatment or as a stand-alone) over use of alpha-blockers to reduce urinary retention, and improve erectile and ejaculatory dysfunction.⁶⁵ Adulteration and/or contamination in herbal products for erectile dysfunction is relatively widespread^66,67 particularly in ‘commercial’ natural health products in some countries. As with usual prescriptions, clinicians should ensure that patients are accessing high quality products.

The liposterolic extract of the fruit of Serenoa repens, native to Florida in the USA, has been shown to significantly improve the signs and symptoms of BPH in numerous clinical studies. The mechanism of action is postulated to be related to inhibition of DHT binding to both the cytosolic and the nuclear androgen receptors, inhibition of 5-alpha reductase, interference with intraprostatic oestrogen receptors and an anti-inflammatory effect.¹⁰ As a result of this multitude of effects, positive results have been produced in numerous double-blind clinical studies. However, different extracts of S. repens (permixon) may have more of an anti-inflammatory mechanism of action in modulating BPH;^63,66–70 clinicians should be mindful of these differences in therapeutic action from the myriad of extraction methods used in natural health products and the multifaceted effects of herbal medicines, particularly S. repens.⁶⁸

Synthesis research, including systematic reviews of clinical trials, has previously reported excellent results using S. repens.^71,72 One examination of 21 randomised, controlled trials involving a total of 3139 men (including 18 double-blind trials) demonstrated that men treated with S. repens experienced decreased urinary tract symptom scores, less nocturia, better urinary tract symptom self-rating scores and peak urine flow improvements compared with men receiving placebo.⁷¹ This analysis also showed that, matched up with men receiving the DHT inhibitor finasteride (Proscar), men treated with S. repens had similar improvements in urinary tract symptom scores and peak urine. A related review also reported that adverse effects due to S. repens were mild and infrequent with erectile dysfunction appearing more frequently with finasteride (4.9%) than with S. repens (1.1%).⁷² However, a recent update to this Cochrane review, which included nine new studies comparing S. repens to either placebo or finasteride, demonstrated no significant benefit for treating any symptoms of BPH except nocturia.⁷³ The large variability in patient population, severity of disease and extraction or source of S. repens, as demonstrated by a lack of heterogeneity between studies and wide confidence intervals for outcomes, highlights some of the challenges in herbal medicine research when applying research results to individuals. At the same time, these results indicate that clinical success in using serenoa for BPH is variable, with the greatest likelihood for improvement occurring in men with mild to moderate symptoms receiving treatment within the first 4–6 weeks of onset.

Overall, it can be stated that some men with mild to moderate BPH experience some improvement in symptoms during the first 4 to 6 weeks of therapy using S. repens. All major symptoms of BPH are improved, especially nocturia. And despite an efficacy profile similar to finasteride for mild to moderate severity, serenoa has a lower risk profile and is less expensive.⁷⁴ The most common side effect is gastrointestinal distress, and this is easily remedied by taking S. repens with food.

Cernilton®, a proprietary combination of water-soluble and acetone-soluble extract of Secale cereale, has been used to treat prostatitis and BPH for years in Europe.^75,76 Several short clinical studies and one systematic review suggest it to be beneficial in the treatment of BPH,^77–83 with patients reporting moderate improvement. Patients who respond typically have reductions of nocturia and diurnal frequency of around 70%, as well as significant reductions in residual urine volume. The extract has been shown to exert some anti-inflammatory action and produce a contractile effect on the bladder while simultaneously relaxing the urethra.⁸⁴

In one study, the clinical efficacy of Cernilton® in the treatment of symptomatic BPH was examined over a 1-year period.⁷⁶ Seventy-nine males of an average age of 68 years (range 62 to 89), with a mean baseline prostatic volume of 33.2 cm², were administered 63 mg Cernilton® pollen extract twice daily for 12 weeks. Average urine maximum flow rate increased from 5.1 to 6 mL/s. Average flow rate increased from 9.3 to 11 mL/s. Residual urine volume decreased from 54.2 mL to less than 30 mL. Urgency and discomfort improved by 76.9% with dysuria, incomplete emptying, intermittency, delayed or prolonged voiding all having 60–70% improvement. Nocturia improved by 56.8%. Overall, 85% of the test subjects experienced benefit, 11% reporting ‘excellent’, 39% reporting ‘good’, 35% reporting ‘satisfactory’ and 15% reporting ‘poor’ as a description of their outcome.

A systematic review conducted in 2000 compiling two placebo-controlled studies, two comparative trials (both lasting 12 to 24 weeks) and three double-blind studies of 444 men showed that, although Cernilton® did not improve urinary flow rates, residual volume or prostate size compared with placebo or the comparative study agents, it did improve self-rated urinary symptom scores and reduced nocturia compared with placebo.⁸¹ Again, this review highlights some of the variability in evidence for the use of this herbal extract with the chances of clinical success in using this as a stand-alone treatment remaining unclear.

Extracts from the bark of Pygeum africanum used in research studies are fat-soluble sterols and fatty acids. Virtually all of the research on pygeum has featured a pygeum extract standardised to contain 14% triterpenes including beta-sitosterol and 0.5% n-docosanol. The suggested therapeutic action has been suggested to be due, in part, to the inhibition of growth factors EGF, bFGF and IGF-I, which are responsible for the prostatic overgrowth.^85,86

Clinical trials totalling more than 600 patients have demonstrated pygeum extract to be effective in reducing the symptoms and clinical signs of BPH, especially in early cases.^86,87 The research studies suggest pygeum having a superiority in objective parameters, especially urine flow rate and residual urine content, over saw palmetto. However, as the two extracts have somewhat overlapping mechanisms of actions, they can be used in combination.

Lepidium meyenii (maca) is a root belonging to the brassica family traditionally known for its aphrodisiac properties in both men and women.⁸⁸ A recent randomised, double-blind placebo-controlled trial demonstrated a subjective improvement on the International Index of Erectile Function (IIEF-5) and Satisfaction Profile (SAT-P) using 2400 mg/day of dry extract of maca compared to placebo.⁸⁹ Although both groups improved significantly from baseline self-rated psychological performance scores, there was a statistically significant superiority in the maca group in physical and social performance. This represents a small but statistically significant clinical effect from using this dose of maca in men with mild erectile dysfunction. Two other randomised, placebo-controlled studies with limited information suggest that 1.5 and 3 g/day dose of maca can improve erectile dysfunction without altering testosterone levels in men with this disorder.^90,91 Further research is necessary to better determine the mechanism of action, the clinical relevance and optimal dose and constituents in maca for use in erectile dysfunction. No clinical evidence exists for the use of maca for treating BPH.

Extracts of Urtica dioica have also been shown to be effective in the treatment of BPH, although less research evidence exists compared to other botanical medicines. A number of long-term, double-blind studies have shown it to be more effective than a placebo, with no adverse effects reported.^92,93 A randomised, multicentre, double-blind study in 431 patients using extracts of both serenoa and U. dioica found clinical benefit equal to that of finasteride,⁹⁴ with a larger, second study lasting 24 weeks confirming its benefit in reducing residual urine and improving peak flow.⁹² A similar therapeutic action between urtica and serenoa extracts appears to exist in that each interact with binding of DHT to cytosolic and nuclear receptors.⁹⁵ Other in vitro studies also show that lignans found in U. dioica may modulate hormonal effects due to their affinity for sex hormone-binding globulin.⁹⁶

In vitro studies of Epilobium spp. suggest steroid receptor and aromatase inhibition activity as well as potent cyclo-oxygenase-2 (COX-2) and antioxidant potential, so this herb could theoretically be used in BPH.^97,98 Other cell-line research supports this and elucidates the antihyperplastic and potential anticancer action of Epilobium parviflorum extract (oenothein B) as a potent inhibitor of DNA synthesis in a human prostate cell line. Aqueous extracts have also demonstrated plausible COX-2 action,⁹⁹ although ethanolic extracts appear to have the most potential inhibitory action on this enzyme linked to inflammatory pathways.¹⁰⁰ These results have yet to be duplicated in clinical trials.