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Do any of you use a natural supplement for issues related to enlarged prostate (low urine stream, evening trips to the bathroom), and if so, what is the name of it? Thank you.
 
Defy Medical TRT clinic doctor
Do any of you use a natural supplement for issues related to enlarged prostate (low urine stream, evening trips to the bathroom), and if so, what is the name of it? Thank you.

I would look into a daily PDE5i such as tadalafil (5 mg/day) which is effective for treating symptoms of BPH/LUTS let alone is a healthy addition when it comes to erectile tissue health.




MANAGEMENT OF NON-NEUROGENIC MALE LOWER URINARY TRACT SYMPTOMS (LUTS) - UPDATE MARCH 2021


5.2.5 Phosphodiesterase 5 inhibitors

Mechanism of action:
Phosphodiesterase 5 inhibitors (PDE5Is) increases intracellular cyclic guanosine monophosphate, thus reducing the smooth muscle tone of the detrusor, prostate, and urethra. Nitric oxide and PDE5Is might also alter reflex pathways in the spinal cord and neurotransmission in the urethra, prostate, or bladder [226]. Moreover, chronic treatment with PDE5Is seems to increase blood perfusion and oxygenation in the LUT [227]. Phosphodiesterase 5 inhibitors could also reduce chronic inflammation in the prostate and bladder [228]. The exact mechanism of PDE5Is on LUTS remains unclear.

*Although clinical trials of several selective oral PDE5Is have been conducted in men with LUTS, only tadalafil (5 mg once daily) has been licensed for the treatment of male LUTS.


Efficacy:
Several RCTs have demonstrated that PDE5Is reduce IPSS, storage and voiding LUTS, and improve QoL. However, Qmax did not significantly differ from placebo in most trials.

A recent Cochrane review included a total of sixteen randomized trials that examined the effects of PDE5Is compared to placebo and other standards of care drugs (α1-blockers and 5-ARIs) in men with LUTS [229]. Phosphodiesterase 5 inhibitors led to a small reduction (mean difference (MD) 1.89 lower, 95% CI 2.27 lower to 1.50 lower) in IPSS compared to placebo. There was no difference between PDE5Is and α1-blockers in IPSS. Most evidence was limited to short-term treatment up to twelve weeks and of moderate or low certainty. In earlier [230] and more recent [231] meta-analyses, PDE5Is were also found to improve IPSS and IIEF scores, but not Qmax.

Tadalafil 5 mg reduces IPSS by 22-37% and improvement may be seen within a week of initiation of treatment [232]. A three-point or greater total IPSS improvement was observed in 60% of tadalafil-treated men within one week and in 80% within four weeks [233]. The maximum trial (open-label) duration was 52 weeks [234]. A subgroup analysis of pooled data from four RCTs demonstrated a significant reduction in LUTS, regardless of baseline severity, age, previous use of α-blockers or PDE5Is, total testosterone level, or predicted prostate volume [235]. In a recent post hoc analysis of pooled data from four RCTs, tadalafil was shown to also be effective in men with cardiovascular risk factors/comorbidities, except for patients receiving more than one antihypertensive medication. The use of diuretics may contribute to patients’ perception of a negated efficacy [236]. Among sexually active men > 45 years with comorbid LUTS/BPH and ED, tadalafil improved both conditions [235].

An integrated data analyses from four placebo-controlled clinical studies showed that total IPSS improvement was largely attributed to direct (92.5%, p < 0.001) vs. indirect (7.5%, p = 0.32) treatment effects via IIEF-EF improvement [237]. Another analysis showed a small but significant increase in Qmax without any effect on PVR [238]. An integrated analysis of RCTs showed that tadalafil was not superior to placebo for IPSS improvement at twelve weeks in men ≥ 75 years (with varied effect size between studies), but was for men < 75 years [239]. An open-label urodynamic study of 71 patients showed improvements in both voiding and storage symptoms, confirmed by improvements in BOO index (61.3 to 47.1; p < 0.001), and resolution of DO in 15 (38%) of 38 patients. Flow rate improved from 7.1 to 9.1 mL/s (p < 0.001) and mean IPSS from 18.2 to 13.4 [240].

A combination of PDE5Is and α-blockers has also been evaluated. A meta-analysis of five RCTs (two studies with tadalafil 20 mg, two with sildenafil 25 mg, and one with vardenafil 20 mg), showed that combination therapy significantly improved IPSS score (-1.8), IIEF score (+3.6), and Qmax (+1.5 mL/s) compared with α-blockers alone [230]. A Cochrane review found similar findings [229]. The effects of tadalafil 5 mg combined with finasteride 5 mg were assessed in a 26-week placebo-controlled RCT [241]. The combination of tadalafil and finasteride provided an early improvement in urinary symptoms (p < 0.022 after 4, 12, and 26 weeks), with a significant improvement of storage and voiding symptoms and QoL. Combination therapy was well tolerated and improved erectile function [241]. However, only tadalafil 5 mg has been licensed in the context of LUTS management while data on combinations of PDE5Is and other LUTS medications is emerging.



Tolerability and safety: Reported adverse effects in RCTs comparing the effect of all PDE5Is vs. placebo in men with LUTS include flushing, gastroesophageal reflux, headache, dyspepsia, back pain, and nasal congestion [230]. The discontinuation rate due to adverse effects for tadalafil was 2.0% [242] and did not differ by age, LUTS severity, testosterone levels, or prostate volume in the pooled data analyses [235].

Phosphodiesterase 5 inhibitors are contraindicated in patients using nitrates, the potassium channel opener nicorandil, or the α1-blockers doxazosin and terazosin. They are also contraindicated in patients who have unstable angina pectoris, have had a recent myocardial infarction (< three months) or stroke (< six months), myocardial insufficiency (New York Heart Association stage > 2), hypotension, poorly controlled blood pressure, significant hepatic or renal insufficiency, or if anterior ischaemic optic neuropathy with a sudden loss of vision is known or was reported after previous use of PDE5Is.



Practical considerations: To date, only tadalafil 5 mg once daily has been officially licensed for the treatment of male LUTS with or without ED. The meta-regression suggested that younger men with low body mass index and more severe LUTS benefit the most from treatment with PDE5Is [230]. Long-term experience with tadalafil in men with LUTS is limited to one trial with a one-year follow-up [234]; therefore, conclusions about its efficacy or tolerability greater than one year are not possible. There is limited information on the reduction of prostate size and no data on disease progression.

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5.2.5 Plant extracts - phytotherapy

Potential mechanism of action:
Herbal drug preparations are made of roots, seeds, pollen, bark, or fruits. There are single plant preparations (mono-preparations) and preparations combining two or more plants in one pill (combination preparations) [216].

Possible relevant compounds include phytosterols, ß-sitosterol, fatty acids, and lectins [216]. In vitro, plant extracts can have anti-inflammatory, anti-androgenic and oestrogenic effects; decrease sexual hormone-binding globulin; inhibit aromatase, lipoxygenase, growth factor-stimulated proliferation of prostatic cells, α-adrenoceptors, 5 α-reductase, muscarinic cholinoceptors, dihydropyridine receptors, and vanilloid receptors; and neutralize free radicals [216-218]. The in vivo effects of these compounds are uncertain, and the precise mechanisms of plant extracts remain unclear.



Efficacy: The extracts of the same plant produced by different companies do not necessarily have the same biological or clinical effects; therefore, the effects of one brand cannot be extrapolated to others [219]. In addition, batches from the same producer may contain different concentrations of active ingredients [220]. A review of recent extraction techniques and their impact on the composition/biological activity of available Serenoa repens based products showed that results from different clinical trials must be compared strictly according to the same validated extraction technique and/or content of active compounds [221], as the pharmacokinetic properties of the different preparations can vary significantly.

Heterogeneity and a limited regulatory framework characterize the current status of phytotherapeutic agents. The European Medicines Agency (EMA) has developed the Committee on Herbal Medicinal Products (HMPC). European Union (EU) herbal monographs contain the HMPC’s scientific opinion on safety and efficacy data about herbal substances and their preparations intended for medicinal use. The HMPC evaluates all available information, including non-clinical and clinical data, whilst also documenting long-standing use and experience in the EU.

European Union monographs are divided into two sections: a) Well established use (marketing authorization): when an active ingredient of medicine has been used for more than ten years and its efficacy and safety have been well established (including a review of the relevant literature); and b) Traditional use (simplified registration): for herbal medicinal products which do not fulfill the requirements for marketing authorization, but there is sufficient safety data and plausible efficacy on the basis of long-standing use and experience. Table 1 lists the available EU monographs for herbal medicinal products.


Table 2: European Union monographs for herbal medicinal products
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Panel interpretation:
Only hexane extracted Serenoa reprens have been recommended for well-established use by the HMPC. A detailed scoping search covering the timeframe between the search cut-off date of the EU monograph and April 2020 will be conducted for the update of the 2021 edition of the Guidelines. Following this, a specific recommendation on phytotherapy will be given.
 
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