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2023年5月11日 星期四

Male enhancement pills are not only for taking before sexual activity - A discussion on the long-term effectiveness of PDE-5 inhibitors and low-dose daily Tadalafil tablets

 

In 1998, the introduction of Viagra opened a new chapter in the treatment of male erectile dysfunction. 

After that, various medications have been introduced, and many treatments other than drugs have also come out one by one.

 

The most well-known medications taken before sexual activity belong to the phosphodiesterase type 5 inhibitor (PDE-5 inhibitor) category. 

The four globally commonly used PDE-5 inhibitors are Sildenafil (Viagra), Vardenafil (Levitra), Tadalafil (Cialis), and Avanafil (Spedra). 

In terms of efficacy, they are all quite good, with about 60-80% of people able to effectively improve their erection status and even successfully complete sexual intercourse

 

Because they are taken before sexual activity, many people believe that these medications are only for emergency use and just "temporary solutions, not permanent cures”.

 

But is it really so?

 

 

In fact, according to research, this type of medication can increase the production of VEGF, leading to an increase in the amount of cGMP and proliferation of endothelial cells.

 

In animal experiments, long-term use of PDE-5 inhibitors can improve endothelial cell function, reduce vascular inflammatory factors, and protect the endothelial tissue of blood vessels.

It can significantly improve or prevent the intracavernous structural alterations caused by age, diabetes or surgical damage.

 

In the treatment of male erectile dysfunction, clinical studies have shown that continuous use of PDE-5 inhibitors on a daily basis can significantly improve erectile function and the peak systolic velocity (PSV) of penile cavernous arteries, compared to as-needed use. 


For men undergoing low-intensity shockwave therapy (Li-SWT), combining daily low-dose Tadalafil 5mg (Cialis) with Li-SWT can yield better results than Li-SWT alone.

 

For men undergoing sexual function rehabilitation after radical prostatectomy, long-term use of PDE-5 inhibitors is an essential part of treatment, and is considered both standard and first-line therapy due to its efficacy, ease of use, good tolerability, excellent safety, and positive impact on quality of life.

 

 

In addition to treating erectile dysfunction, PDE-5 inhibitors have been shown to effectively treat benign prostatic hyperplasia and lower urinary tract symptoms (LUTS). 

They can reduce smooth muscle tone of the detrusor, prostate, and urethra, and may also alter reflex pathways in the spinal cord and neurotransmission in the urethra, prostate, or bladder. 

Furthermore, long-term treatment with PDE-5 inhibitors appears to increase blood perfusion and oxygenation in the lower urinary tract and may reduce chronic inflammation in the prostate and bladder.

 

 

A variety of PDE-5 inhibitors are currently available, and the aforementioned research results are not limited to a specific drug. 

However, for the treatment of male erectile dysfunction, prostatic hypertrophy and lower urinary tract symptoms in the form of continuous daily use, only low-dose Tadalafil 5 mg daily tablets are approved by European Medicines Agency (EMA) and Taiwan FDA.

 

 

Summary of key points:

1.    PDE-5 inhibitors (ED drugs) are not just for short-term use before sexual activity. Long-term use can significantly improve erectile function and can be used in combination with other ED treatments for better efficacy. They are also a standard first-line treatment for sexual function rehabilitation after prostate surgery.

2.    PDE-5 inhibitors can also be used to treat benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Low-dose Tadalafil 5mg daily tablet is the only PDE-5 inhibitor currently approved by the health department for daily use.

 

References:

https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/management-of-erectile-dysfunction

 

https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts/chapter/disease-management

 

The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway

https://pubmed.ncbi.nlm.nih.gov/17226792/

Type 5 phosphodiesterase (PDE5) and the vascular tree: From embryogenesis to aging and disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333613/

in vitro treatment of dermal papillae with sildenafil induces VEGF and platelet derived growth factor A (PDGFA) secretion, increased dermal proliferation and neoangiogenesis 

https://pubmed.ncbi.nlm.nih.gov/30292404/

Behr-Roussel, D., et al. Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis. Eur Urol, 2005. 47: 87. 

https://pubmed.ncbi.nlm.nih.gov/15582254/

Ferrini, M.G., et al. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology, 2006. 68: 429. 

https://pubmed.ncbi.nlm.nih.gov/16904479/

Ferrini, M.G., et al. Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. Biol Reprod, 2007. 76: 915.

https://pubmed.ncbi.nlm.nih.gov/17287493/

Kovanecz, I., et al. Chronic daily tadalafil prevents the corporal fibrosis and veno-occlusive dysfunction that occurs after cavernosal nerve resection. BJU Int, 2008. 101: 203. 

https://pubmed.ncbi.nlm.nih.gov/17888043/

Vignozzi, L., et al. Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. J Sex Med, 2006. 3: 419. 

https://pubmed.ncbi.nlm.nih.gov/16681467/

The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med, 2022. 19: 106. 

https://pubmed.ncbi.nlm.nih.gov/34866029/

Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year: a randomized trial

https://pubmed.ncbi.nlm.nih.gov/17187165/

Impact of Phosphodiesterase Type 5 Inhibitors on Endothelial Function

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2312340/

 

壯陽藥不是只有辦事前才能吃-淺談PDE-5抑制劑的長期療效及低劑量他達拉非(Tadalafil)每日錠

 

1998

威而鋼的問世開啟了男性性功能障礙治療的新篇章

除了多種藥物陸續上市

許多藥物以外的治療方式也一一問世


目前較廣為人知、辦事前吃的藥物

皆屬於第五型磷酸二酯酶抑制劑phosphodiesterase type 5 inhibitor, PDE-5 inhibitor

全球常用的共有四種:SildenafilViagra威而剛)、VardenafilLevitra樂威壯)、TadalafilCialis犀力士)、Avanafil Spedra賽倍達

效果(Efficacy)來說其實都不錯

約有68民眾能有效改善勃起狀態乃至成功完成性行為

 

由於是辦事前吃的

因此許多人認為這種藥只是應急用、而且「治標不治本」

但真的是如此嗎?

 

 

事實上

根據研究顯示

此類藥物能增加VEGF的產生,伴隨著更多cGMP的量,使內皮細胞增生

 

在動物實驗中

長期使用PDE-5抑制劑

改善內皮細胞功能減少血管發炎因子保護血管的內皮組織的功能

能顯著改善或預防因年齡、糖尿病或手術損傷引起的海綿體內結構改變

 

在男性性功能障礙治療中

臨床研究顯示

與需要時才用(as-needed)相比

每天持續使用PDE-5抑制劑顯著改善勃起功能陰莖海綿體動脈的血流速度 [peak systolic velocity (PSV) of penile cavernous arteries] 

 

接受低能量體外震波治療(Low-Intensity Shockwave Therapy)的男性

若能合併每天服用低劑量他達拉非(Tadalafil) 5 mg(商品名Cialis

治療效果會比單獨使用低能量體外震波治療更佳

 

而在接受攝護腺全切除手術後的男性性功能復健

長期使用PDE-5抑制劑

因其功效、易用性、良好的耐受性、出色的安全性和對生活品質的正面影響

已是治療不可或缺的一環

標準治療、也是第一線治療( first-line therapy)

 

 

 

另外除了治療性功能障礙

PDE-5抑制劑也被證實能有效治療男性攝護腺肥大下泌尿道症狀lower urinary tract symptoms, LUTS

除了有效降低逼尿肌、前列腺和尿道的平滑肌張力

也可能改善脊髓的反射通路和尿道、前列腺或膀胱的神經傳導

此外

PDE-5抑制劑的長期治療似乎可增加下泌尿道的血液灌注氧合

亦可以減少前列腺和膀胱的慢性炎症

 

 

雖然目前已有多種PDE-5抑制劑可供使用

且前述的研究結果亦非限定於某種特定藥物

然而若要以每日持續使用的方式治療男性性功能障礙、攝護腺肥大及下泌尿道症狀

目前只有低劑量他達拉非TadalafilCialis犀力士)5mg每日錠被歐洲藥品局(EMA)及台灣食藥署核准使用

 

 

最後整理一下重點

 

1.壯陽藥(PDE-5抑制劑)並不是只有辦事前才能吃,也不是只有短期治標

長期使用可以顯著改善性功能

搭配其他性功能障礙治療方式能達到更佳療效

亦為攝護腺手術後性功能復健的第一線標準治療

 

2.壯陽藥(PDE-5抑制劑)除了治療性功能障礙、亦可治療攝護腺肥大及下泌尿道症狀

低劑量他達拉非TadalafilCialis)5mg每日錠

是目前唯一通過衛生署核准、可持續每天服用的PDE-5抑制劑藥物

 

 

參考資料:

 

https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/management-of-erectile-dysfunction

 

https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts/chapter/disease-management

 

The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway

https://pubmed.ncbi.nlm.nih.gov/17226792/

Type 5 phosphodiesterase (PDE5) and the vascular tree: From embryogenesis to aging and disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333613/

in vitro treatment of dermal papillae with sildenafil induces VEGF and platelet derived growth factor A (PDGFA) secretion, increased dermal proliferation and neoangiogenesis 

https://pubmed.ncbi.nlm.nih.gov/30292404/

Behr-Roussel, D., et al. Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis. Eur Urol, 2005. 47: 87. https://pubmed.ncbi.nlm.nih.gov/15582254/

Ferrini, M.G., et al. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology, 2006. 68: 429. 

https://pubmed.ncbi.nlm.nih.gov/16904479/

Ferrini, M.G., et al. Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. Biol Reprod, 2007. 76: 915. https://pubmed.ncbi.nlm.nih.gov/17287493/

Kovanecz, I., et al. Chronic daily tadalafil prevents the corporal fibrosis and veno-occlusive dysfunction that occurs after cavernosal nerve resection. BJU Int, 2008. 101: 203. 

https://pubmed.ncbi.nlm.nih.gov/17888043/

Vignozzi, L., et al. Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. J Sex Med, 2006. 3: 419. 

https://pubmed.ncbi.nlm.nih.gov/16681467/

The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med, 2022. 19: 106. 

https://pubmed.ncbi.nlm.nih.gov/34866029/

Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year: a randomized trial

https://pubmed.ncbi.nlm.nih.gov/17187165/

Impact of Phosphodiesterase Type 5 Inhibitors on Endothelial Function

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2312340/