# PDE5 Inhibitors: Not just for Erectile Dysfunction



## Arnold (Aug 15, 2019)

*PDE5 Inhibitors: Not just for Erectile Dysfunction*

Sildenafil (Viagra) is one of the most poplar popular drugs ever released. Most people remember it as the original medication used to combat erectile dysfunction. It?s not. Way before the days of the little blue pill there was Caverject; so named because it was administered via intracavernous injection.

What?s an intracavernous injection? It?s a penis injection. Needless to say, Caverject never really gained a ton of popularity. Most people are at least slightly squeemish about needles, but just about everyone is squeemish when the needle is going anywhere near their genitals. And in logistical terms, it needs to be injected between five and twenty minutes prior to intercourse, and lasts about an hour.

If you?re new to injecting, the best practice is wash your hands, then swab the injection site and the top of the multi-use vial with alcohol?you get the idea. It requires a bit of time and isn?t exactly discreet As you could imagine, while this was technically a viable option to treat ED, it wasn?t very practical at all. So like I said, Caverject didn?t exactly set the world on fire as a remedy for erectile dysfunction.

*Viagra, on the other hand?*
Viagra is a pill that needs to be taken 30-60 minutes prior to intercourse, and lasts four hours. It didn?t require access to needles and alcohol swabs, and could be consumed discreetly with a lengthy window of effect. It became an overnight success, producing billions of dollars in revenue for Pfizer. It also produced numerous competing products, all of which are Phosphodiesterase-5-inhibitors, and all of which increase intracavernosal cyclic guanosine monophosphate levels, which results in corporal smooth muscle relaxation (in other words, they all help guys get boners).

In simplest terms, the major difference between the different PDE5 inhibitors is how long they last and how long they require before taking effect:

? Cialis (tadalafil) is the most popular of Viagra?s competition, likely because it lasts the longest, between 24 and 36 hours with a single dose ? although the manufacturer also produces a lower-dosed version meant to be taken daily

? Levitra (vardenafil) lasts a bit longer than Viagra but nowhere near as long as Cialis

? Stendra (avanafil) lasts roughly as long as Levitra but is absorbed more quickly than all of the other medications and takes effect within 15 minutes, reaching maximum concentration in about 30?45 minutes

But that?s not all they do. In various trials and experiments, as well as throughout off-label prescribing, PDE5 inhibitors were shown to have a host of potential nonerectogenic (non-boner-producing) effects. They?re certainly not going to be the primary form of treatment for anything except erectile dysfunction?but they were a useful adjunct in the management of pulmonary hypertension. Additional uses were extended to different utilities: essential hypertension, benign prostatic hyperplasia, gastrointestinal disorders, endothelial dysfunction, female sexual dysfunction, genital blood flow, exercise capacity, Raynaud?s phenomenon, sperm motility, etc.

*Viagra Boosts Testosterone*
Viagra has been shown to have a direct effect on the testes and to increase testosterone. One study administered sildenafil for three to seven weeks to 140 men with erectile dysfunction, aged 40-70 years, who also had low testosterone levels (right on the cusp of being hypogonadal, in the low 300ng/dl neighborhood). Sildenafil was associated with mean increases of about 100 points, bringing the men to what I?d generally call a log-medium testosterone level. Because steroid hormones also rose, the researchers concluded that the boost in testosterone was likely due to a direct effect on the testis.

*Cialis helps with Benign Prostate Hypertrophy*
Men with erectile dysfunction often suffer from other maladies such as benign prostate hypertrophy and frequent urination (which all frequently co-occur). But men taking tadalafil for their erectile dysfunction started noticing that they were urinating less frequently. So a group of researchers got together and studied 1,500 men with trouble the kinds of urinary tract issues that often accompany BHP. The tadalafil not only appeared to lessen the frequency with which the men were urinating, but also appeared to improve prostate health (as measured by the International Prostate Symptom Score)

*Viagra and Cialis help manage Cardiovascular Problems*
Numerous preclinical studies have shown that PDE5 inhibitors can protect against pulmonary hypertension, endothelial dysfunction, myocardial ischemia/reperfusion injury, doxorubicin and post-myocardial infarction, heart failure, cardiac hypertrophy, heart transplantation, Duchenne muscular dystrophy and preconditioning of stem cells. The mechanism of action is thought to be related to nitric oxide generated from endothelial and/or inducible nitric oxide synthases and opening of mitochondrial ATP-sensitive potassium channels.

There are a few more but you get the idea. I?m not saying that PDE5 inhibitors are first-line therapy or the primary modality of treatment for any of these issues, but they showing promise as adjunct therapy and protectants. And just like the old advice to take a children?s aspirin every day to protect against heart attacks, judging by the laundry list of benefits we?re starting to see from PDE5 inhibitors, I wouldn?t be surprised if daily use for general health purposes wasn?t on the horizon.


*References:*
?	Andrology. 2013 Nov;1(6):913-8. doi: 10.1111/j.2047-2927.2013.00131.x. Epub 2013 Sep 18. Sildenafil increases serum testosterone levels by a direct action on the testes. Spitzer M1, Bhasin S, Travison TG, Davda MN, Stroh H, Basaria S.
?	Sex Med Rev. 2016 Jul;4(3):270-284. doi: 10.1016/j.sxmr.2015.12.005. Epub 2016 Mar 19. Useful Implications of Low-dose Long-term Use of PDE-5 Inhibitors. Mostafa T.
?	J Sex Med. 2008 Nov;5(11):2502-18. doi: 10.1111/j.1743-6109.2008.00983.x. Epub 2008 Aug 26. Oral phosphodiesterase type 5 inhibitors: nonerectogenic beneficial uses. Mostafa T.
?	Ann Intern Med. 2009 Nov 3;151(9):650-61. doi: 10.7326/0003-4819-151-9-200911030-00150. Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis. Tsertsvadze A, Fink HA, Yazdi F, MacDonald R, Bella AJ, Ansari MT, Garritty C, Soares-Weiser K, Daniel R, Sampson M, Fox S, Moher D, Wilt TJ.
?	Patient Prefer Adherence. 2016 Jul 12;10:1205-15. doi: 10.2147/PPA.S105241. ECollection 2016. Treatment satisfaction among men with concurrent benign prostatic hyperplasia and erectile dysfunction treated with tadalafil or other phosphodiesterase type-5 inhibitor combinations. Lee LK, Goren A, Boytsov NN, Donatucci CF, McVary KT.
?	J Urol. 2014 Apr;191(4):1045-50. doi: 10.1016/j.juro.2013.10.074. Epub 2013 Oct 25. Effects of tadalafil once daily on maximum urinary flow rate in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Roehrborn CG, Chapple C, Oelke M, Cox D, Esler A, Viktrup L.
?	Arch Cardiol Mex. 2015 Jul-Sep;85(3):215-24. doi: 10.1016/j.acmx.2015.03.001. Epub 2015 Jun 2. [Phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension].
[Article in Spanish] Beltr?n-G?mez ME1, Sandoval-Z?rate J, Pulido T.
?	Pharmacol Ther. 2015 Mar;147:12-21. doi: 10.1016/j.pharmthera.2014.10.003. Epub 2014 Oct 31. PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer. Das A, Durrant D, Salloum FN, Xi L, Kukreja RC.
?	Curr Pharm Des. 2013;19(39):6842-7. Sildenafil and cardioprotection. Kukreja RC.


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