TL;DR: Tadalafil is a great anti-aging drug (better erections, perfusion, rosy complexion, prostate health; penile health; potentially brain health) but it reliably triggers tinnitus even at microdoses. Anyone else?
So, a couple of years ago, I tried tadalafil at a fraction of a normal dose (1/8th of a 5mg tablet). 30 min later I developed a faint left-sided tinnitus. Stopped immediately.
Too bad, because tadalafil is not just great for penile health/erectile quality, it is also a reasonable longevity drug as it increases perfusion of many organs (e.g., brain, skin, prostate, etc.)
So, fast forward to a couple of weeks ago. I made my own microdosing capsules containing 0.05mg of tadalafil (yes, that is correct) and wanted to titrate up slowly to see whether the gradual accumulation from microdoses would give my cochlea and inner ear more time to accomodate to the increased NO signaling.
After 0.15mg, tinnitus started again. Initially, it was very faint. Every 4 days I continued to increase by 0.05mg, reaching 0.4mg. More on the left ear than the right ear. I was hoping that my inner ear would get used to it but it did not. After a couple of days, the tinnitus was so loud that it would bother me even while I was sleeping.
As an MD, I have easy access to ENT evaluations so I did an ENT evaluation on the same day. Perfect audiogram (at least up to 8kHz) but my otoacoustic emissions were weird and less than what they should be (a marker of outer hair cell health).
Anyway, I did some research, and on Reddit there are quite a few people for whom tadalafil causes tinnitus. For most people, the tinnitus went away again but for some it is reportedly permanent.
The tinnitus may represent cochlear stress.
SNHL (the tinnitus/hearing concern): there’s a real but small signal. The FDA added a sudden-hearing-loss warning to the class in 2007 after case reports. A large cohort study (Yafi et al.) found a small but statistically significant increased risk of sudden SNHL in PDE5i users. The proposed mechanism is the NO/cGMP pathway acting on cochlear vasculature/tissue.
Also, at least one small study found PDE5i users had poorer high-frequency thresholds than controls.
Furthermore, epidemiloogical data suggests that PDE5inhibitors have an odds ratio of 7 or more with new-onset tinnitus.
So, it seems that at least for some people, tadalafil damages the inner ear.
Interesting, for me, I had my otoacoustic emissions measured and they were much less than what they should be. In one study, otoacoustic emissions differ between the groups of high-dose sildenafil and the control group with long-term treatment. The authors stated that these results indicated a decrease in the number of outer hair cells of the organ of Corti and that the probable cause of this is the toxic effect due to excess nitric oxide in the auditory organs such as the cochlea and the auditory nerve. Based on these results, the authors demonstrated that the administration of large doses of sildenafil in the long term, may contribute to the development of sensorineural hearing loss ( Phosphodiesterase Type 5 Inhibitors and sudden sensorineural hearing loss - PMC )
The leading theory centers on the NO/cGMP pathway — NO is present in the cochlear vascular endothelium, PDE5 inhibitors raise cGMP, and downstream cGMP accumulation has been linked via NF-κB and MAP-kinase signaling to mechanisms postulated in sudden hearing loss. (Source: Phosphodiesterase type 5 inhibitors related hearing impairment: a real world study based on the FDA adverse event reporting system | Scientific Reports )
This is too bad because I really liked tadalafil, both on paper but also in . PDE5 inhibition increases cGMP signalling downstream of nitric oxide, which relaxes vascular smooth muscle and improves blood flow in certain vascular beds. There is also some research suggesting PDE5 inhibitors/tadalafil may improve endothelial function, cerebral vascular reactivity, and possibly cerebral perfusion/cognition in specific populations.
So in theory tadalafil looks like a very attractive long-term “vascular aging” drug: penis health, endothelial function, maybe brain perfusion, better skin perfusion/complexion, and generally better sexual function. But for some people, it may damage hearing subtly over the long run.
Edit: Interestingly, I also looked at Bryan Johnsons hearing and how shitty it is. Posted here by himself:
It also seems to get worse over time. Could this partially due to the daily dose of tadalafil he takes??
Also, Reuters has a report here that PDE5 inhibitors can double the risk of hearing loss over time. https://www.reuters.com/article/business/healthcare-pharmaceuticals/viagra-could-double-risk-of-hearing-loss-idUSTRE64I6YA/?utm_source=chatgpt.com
Given that hearing is so important for quality of life (and brain health), PDE5 inhibitors might be contributing to hearing loss over time. May be very underreported.