Natesto: large shards UPDATE- batch is all bad.

[granger]

well I think I sorted out why I had variance in effectiveness for me....

took the label off and XLs of testosterone crystallized in both my natestos. all kept at room temp may of gotten up to 25C but thats it. not near AC or anything like that.

At any rate may have something to do with why they changed formula OR because of changed formula recently.

dang no wonder it lasted ALL day and 1 dose was MORE than enough and couldn't imagine more lol.. Jesus almost scary though if never noticed...

one time I even was like wow really strong taste thats weird, but guess they say its normal for a metallic taste. lol never happened after but was chatty that day... could taste in my nose/smell and mouth.

id warm it up to dissolve however cant shake so XL would still leave hot spots I would imagine....

would encourage others who use Natesto to peal label off and hold up to a window to see if have shards aswell or if this is truly a 1 off. (both bottles in my case)

 

[Willyt]

Thanks for the info, you may want to change title because "shards" makes it sound like there are pieces of glass in there.

 

[granger]

lol I think the 'crashed' should make folks realize its crystal shards. its called click bait so folks look super interested in if other folks have this aswell tried warm water briefly to see if a bit of warms was enough but it was not..

Natesto is having me send back and may or may not have no TRT for days in the interim which I said was not acceptable but nothing they can do as needs to go to higher ups and prob get the product and then determine what to do. hopefully not and pics are enough for them to get it shipped in for tom.

would need some folks who use other types of test to shed some light on how it grew large XLs at room temp OR perhaps they were never even dissolved. not sure how easy it is to XLs in oil at 4% as not at the bottom and just sort of wherever.

at any rate SUPER curious if other peoples look the same. exp JN2025 so presume was just made in June.

 

[Willyt]

I have used both Natesto and Empower nasal cream and never experienced what you describe

 

[granger]

but did u ever check? lol and with 3 doses obv less obvious.(or is not common at all) I had 176ng test level so pretty low and always sensitive to drug sides so prob notice more. OR was a bad batch OR was old stock exp2025 ie 2 years from when I got it exactly not sure if thats fresh or not. OR part of why had dosing issues in canada as maybe factory is colder or shipping etc. perhaps over saturated or never dissolved. never know.

at any rate waiting with baited breath for replacements to see if the same and for others to check theirs to see if its common or not.

pretty shitty formula if need it 3 times a day(keep on u) and crashes easily and live in canada. so assume likely poor mixing. suppose injections are 2.5% and have other solvents, this is at 4.5% with 11ml wi 330mg of test base with surfactants to keep in oil matrix perhaps instead of dissolved.

at any rate, something to keep an eye on for us pro HPTA nasal testers.

 

[granger]

 

[granger]

well my pharmacist called my dr to get a new refill for me and didn't want her too as wastes money/time of DR.. and should of been handled by ACerus and was told they would call the pharmacy and get it handled... they of course did not do as they said.... no reply (although when sent 1 pic they got back to me ASAP asking for more, cut to whole workday nothing after Qs about what to do)

anyway, went to pharmacist and we had a look at the newly ordered stuff that came in that afternoon... well it was same batch # and had testosterone crystals aswell.."Welp we cant sell u that now can we, I guess they owe now aswell so we will get it sorted out"...

I suggest if use Natesto to CHECK your stuff... esp if expires jun 2025.. also id stock up as likely a shortage coming from a recall. must be large batch as same as from 1 month ago so will be a MONTH at least of production gone and from largest pharma distributer.

UPDATE: also noted 1 bottle id have oil running down my nose and other was MUCH CLEANER... odd. the one that gave larger amount also didn't require priming and started to shoot oil on first compression. so I weighed a dose from one bottle and one from another and had 20% more in the one that I had oil running down my nose (one that stayed in nose nicely was .10 running down my nose was .12). weird it lined up that the one I figured was giving more was and of course 1 measurement so take with a grain of salt just weird it all lined up with my subjective experience. perhaps the reason it was pulled originally from canada for dosing reasons.

support your local compounder is perhaps the answer here lol

super surprised no one on here has a bottle of Natesto.

 

[granger]

another member who has used Natesto for some time also told me they get crystals in some bottles however just still uses it.... So not just 1 bad batch...

to me you should not use if have crystals as dosages would vary, likely wildly.
1. if crystallized in the bottle, you would get pure test crystal 1 time and then not another time, aswell as surrounding gel would be lower dosed as the crystal pulls test out of solution. ie may get huge dose one time and next to nothing the next.
2. if never was dissolved than forsure the dosages would be all over the place as never mixed properly.

so in either case its bad and its important not to take TOO much test, aswell as important to get consistent dosing. IMO

 

[granger]

Acerus told pharmacy to send in crystallized product for replacement...

-it was then rejected by acerus (ie pharmacy and me take a loss because of listening to them to send it in using the given fedex account to do so).. they then ghosted the pharmacist even though followed acerus instructions and said its fine and no investigation would be done...
-called by a higher up that they studied it and its ok... they said no problem would share results that within reasonable dosing limits, however a solution would be given...... 3 weeks later and multiple emails... saying next week next week next week... even though was told would send the variance in dosing with crystallized product they simply ghosting now(pharmacist aswell not just me being annoying).

while some crystallization may be ok there obv is a point where dosing would be radically effected ie like mine with 6mm long 2-3mm wide crystals and assume would just get worse over time... so who knows what was tested a bottle with 1-2 tiny crystals or something VERY crystallized... no way to know. would think they would have a limit to amount or size at very least for safety but appears they do not.

at any rate my pharmacist says they don't trust them by the way this was handled and pretty slimy folks as normally drug companies treat pharmacists with sooo much respect and wine and dine them so recommend there product. not tell them to take the time to send something in, then reject it, then ghost them lol...

so for anyone looking for nasal test its cheaper and better (no crystals) if go to compounding pharmacy. would not support this company and who knows what other types of shifty things they did during their studies as pretty clear they are shady AF.

funny part is then they said they will find none crystallized product to send to the pharmacy if fill out a form... HOWEVER who knows if actually get none crystallized product, and why do that if crystals are fine? very unlikely my pharmacy will want to order a bunch as either will come crystallized or will become crystallized anyway in coming weeks.

As it turns out my feeling was correct, got bloods and my test levels were the same(slightly lower) as pre use ie either product has bunk parts as I can feel OR im a hyper metabolizer of just testosterone and back to baseline in 1.5 hrs lol my guess is got bunk squirt. As again u can really taste/smell it when get a crystal and get the calming effects the strongest when that happens.

this is very unfortunate as was suppose to be a premium product. the compounders here haven't made it before just creams so seeing if will make it for me, im not sure if have to pay for the formula or comes with the PCCA subscription or have to invest in differing things and no one uses natesto never mind specially compounded stuff so may not want to.. anyhoo it is annoying AF and wasting DRs pharmacist and my time and not just minutes HOURS HOURS of time...

if you use natesto, check for crystals, even if you dont care you should contact regulatory bodies in your country and let them know ie FDA or Health Canada. That way it will force them to make a safer product.

them saying "oh we ran studies it ok" however cannot produce said studies(nor even answer a couple questions about them) for DR or pharmacists so who the hell knows if they are straight up lying raking in as much cash as possible and can either sell or get out easily as they hired third party manufacturing and have no physical office (everyone works remotely) and product itself as we know is a few bucks to make and lesser/cheap studies were done as it was just a reformulation and not a "new drug" so not heavily invested compared to other drug companies.

 

[trax123]

Surprised you're the ONLY poster who mentioned this. 100% new to TRT and after 3 days realized Natesto was completely ineffective, zero physical or psychological changes.

At first I thought maybe it was from poor absorption - used a cotton swab to better layer the gel in the nares, no effect. Then I thought perhaps it's because I have a history of nasal inflammation/allergies. But while that COULD reduce efficacy, it wouldn't go to ZERO. Testosterone is a powerful hormone and while skin transmission of course varies heavily between users, it's unlikely nothing would get through - clinical trials clearly showed significant serum spikes from the gel.

I also one time took a single pill - just one - of clomiphene - and had an almost instantaneous response. Different MoA but suggests I'm sensitive to increases in serum T in general.

SO I started looking for the next most likely issue - perhaps the drug is just misformulated or something is defective, and I FOUND YOUR POST here.

I checked the vial and indeed there are crystals identical to your photograph! Same expiry June 2025, and the vials I have are all the same lot number.

While it SHOCKS me that they could put out a product that is so obviously defective, and while I'm not 100% sure here (e.g. PERHAPS skin aborption really IS that bad, the dose it too low... etc.), your explanation DOES seem very plausible to me.

If the drug is precipitating out of the gel solution then basically the gel is inert castor oil and no hormone is being delivered, which explains why I have had zero effects after several applications; the actual hormone is all coagulated into crystals. Pumping/sucking out one of the crystals would result in a potentially massive overdose! That's QUITE dangerous sounding at worst, and at best leaves you with a completely nonfunctional therapy.

I'm going to inquire with pharmacy as well as Acerus (though they almost went bankrupt and are now owned by a private equity company so while I think they did great scientific work, it's not the best situation in terms of a supplier).

Thank you for posting this as I have no familiarity with gels, etc., and I never would have considered it was precipitating like that.

 

[Deleted member 43589]

well I think I sorted out why I had variance in effectiveness for me....

took the label off and XLs of testosterone crystallized in both my natestos. all kept at room temp may of gotten up to 25C but thats it. not near AC or anything like that.

At any rate may have something to do with why they changed formula OR because of changed formula recently.

dang no wonder it lasted ALL day and 1 dose was MORE than enough and couldn't imagine more lol.. Jesus almost scary though if never noticed...

one time I even was like wow really strong taste thats weird, but guess they say its normal for a metallic taste. lol never happened after but was chatty that day... could taste in my nose/smell and mouth.

id warm it up to dissolve however cant shake so XL would still leave hot spots I would imagine....

would encourage others who use Natesto to peal label off and hold up to a window to see if have shards aswell or if this is truly a 1 off. (both bottles in my case)

Old trick.....if the product goes out of solution, place it in a pan of hot water until everything dissolves. If that doesn't do the trick, take the product back to where you bought it and get a refund.

 

[granger]

Old trick.....if the product goes out of solution, place it in a pan of hot water until everything dissolves. If that doesn't do the trick, take the product back to where you bought it and get a refund.

I have attempted to get a refund since july..... lol got run around, talked to higher up (who than left company while trying to sort out not crystalized product lol)... email them and they just say we will escalated and NOTHING HAPPENS.... try pull a karen to talk to a manager, nothing... try talk to teh one guy who does the customer service to talk to his manager... nothing... I think Health canada perhaps caught wind and why the sudden shut off of communication.

they said its fine to take large doses with the shards as they tested it... but when asked for the study/data they said yes... but then never sent it lol.. also was curious if getting those larger doses would negate the less HPTA effect its suppost to have and if LH etc was also studied with the crystal product.. I dont think they actually did test it, rather just original test results........

@trax123 yes see what pharamacy says they will likely say not to take as its not described in monograph to have crystals and logically of course dosage is random... that being said if used for a few weeks you likely got somewhat of a dosage. if had decent ie 350-400+ test levels you prob aren't going to feel as much (esp if didnt get 2 tests right at like 8 am that said you were sub 300 you may have decent test levels and your symptoms of low T may not be from low T if expereince any).. It is important though that you fill out a form and describe the issue to health canada so they get on them. I was told that q2 new product would be on the market that shouldn't be crystalized however it appears that they still are selling the old stock... anyway let us know what they say to you i think its unlikely will put anything in writing... maybe they just figured fuck that guy and you will have more luck? actually i dont know if i said this but the pharmacy even sent back product they had and apparently was a shit show for them as they sent it back to them after giving shipping instructions and fedex account # to charge etc.. but yes let FDA know aswell if live in USA, as they need enough complaints to see a "signal"... its pretty hard for DRs to say its product aswell because they make a note that half life can be as low as 15 min so if get a test done at an hour you may have little to no exogenous test or peak at 3000 when get a crystal but at an hour when get blood work your at 700... no way to really know.


ALSO because of the consistency of the product and i even asked them if i should just warm up, they said no....15-25C only.. ie you can't keep it in your pocket even technically as your body may warm it up or if outside and its cold or hot out lol. but because its thick even if crystals went into solution there still would be hot spots as you cannot shake it up as its made thick with methylcellulose or silica.. and if warm up it will likely screw with pump mechanism as it expands..

Id be interested what serum is like with troches? if they are just as fast acting and much lower dose seems like a win for liver and HPTA...

 

[trax123]

Update on this: two pharmacies and a physician noted they have never had any patients complain about crystallization with Natesto gel (they note its possible of course though). Acerus is basically unreachable/a shell company it seems they don't communicate with anyone (surprising the drug gets made at all!). They felt it would likely have been a temperature storage issue rather than a manufacturing one.

Physician also noted that the nasal form can be slow to take effect - even with good absorption - despite being bioidentical; apparently because the dose is very low and the spike - while significant - has a very short half-life (which is ofc a key operating 'feature' of Natesto). It can take several weeks in most patients to note any changes because of the very rapid dropoff in the level (this makes sense - clomiphene for instance has a much longer half-life effect because it doesn't merely add a hormone but manipulates the HPG feedback mechanism which doesn't pulse but acts continuously). All of Natesto's published studies were noted at 90 days I believe, though they did comment that within 30 days some patients reported various clinical responses.

In either case - these people all seem to believe that the crystallization, while real, may not have any actual clinical effect.

I've requested a new batch in either case, and I will close the loop on my experience with that.

 

[trax123]

tty hard for DRs to say its product aswell because they make a note that half life can be as low as 15 min so if get a test done at an hour you may have little to no exogenous test or peak at 3000 when

And yes, sorry didn't mean to be repeating what you said you mostly commented about this phenomenon already.

 

[madman]

Update on this: two pharmacies and a physician noted they have never had any patients complain about crystallization with Natesto gel (they note its possible of course though). Acerus is basically unreachable/a shell company it seems they don't communicate with anyone (surprising the drug gets made at all!). They felt it would likely have been a temperature storage issue rather than a manufacturing one.

Physician also noted that the nasal form can be slow to take effect - even with good absorption - despite being bioidentical; apparently because the dose is very low and the spike - while significant - has a very short half-life (which is ofc a key operating 'feature' of Natesto). It can take several weeks in most patients to note any changes because of the very rapid dropoff in the level (this makes sense - clomiphene for instance has a much longer half-life effect because it doesn't merely add a hormone but manipulates the HPG feedback mechanism which doesn't pulse but acts continuously). All of Natesto's published studies were noted at 90 days I believe, though they did comment that within 30 days some patients reported various clinical responses.

In either case - these people all seem to believe that the crystallization, while real, may not have any actual clinical effect.

I've requested a new batch in either case, and I will close the loop on my experience with that.

I would say more like 6 months to obtain peak benefits!




*Median testosterone levels at baseline and at 1, 3, and 6 mo after therapy with Natesto TID dosing. Note that changes at 1, 3, and 6 mo are significantly increased from baseline

Would I be making a mistake?

I've asked about clomid/Natesto... Again, I've heard from doctors who say they do a 3month run of clomid to try and kickstart the system to producing more T - is clomid a one and one type of thing? Same with Natesto? Are you basically on this for good if it drives T up? Also, need to keep in...

www.excelmale.com

Go nuts!

HELP: Indecisive - I think I need TRT but I want to have babies

Hi, 32 years old male here, I did 4 tests in the past 2 years and all of them go from 200 to 350, so in the lower end of the range. I have low fsh and low lh. Enclomiphene has not resolved my symptoms. I exercise 4 times a week on average: circuit training with weights, sometimes I run...

www.excelmale.com

 

[ZALEMAX]

I live here in USA been on Natesto since 5.2022 I started @ 2 dose per day and also was supersensitive receptor could feel effects then acclimated 6 months later @ 3 doses in 2023-2024. I do feel good on Natesto for about 2-3 hours with Vaga (100mg cafffine)sugar -free energy drink on workout days its hard for me to wait 6-8 hours till next dose sometimes I just bump the Natesto gel between doses. I could be undertreated on Natesto now. Also, my Dr. told me Natesto is out of your system by the AM upon waking up. I do not have shardes in my Natesto pump at all. I am going to give xyosted 50mg a try in April 2024.
Please feel free to ask any question.

 

[trax123]

Wanted to update on this. I obtained a second batch of Natesto (Dec 2025 expiry) and indeed the vials ALSO have inclusion crystals in them (thank you Zalemax for posting that photo above seemingly confirming that these inclusions are NOT present in all vials and do not seem to be a normal consequence of manufacturing).

This is definitely very disappointing and I'm shocked Acerus apparently has Inventorying/stocking AND manufacturing QC problems such as these.

Not really sure what to do yet - physician has offered the compounded "Empower" nasal gel version though this is also a bit of a letdown given all the studies were performed on Natesto AND there seems to be no reason they shouldn't be able to manufacture a simple gel without so much trouble.

I may try the new gel even though I see the crystals in there...

*I suspect this may not be widely reported because 1) the total number of Natesto users is not that high and 2) I think clinically after let's say 1 week of 3x daily use of COURSE the drug eventually goes in since the crystals are extruded. So of course the patient eventually responds to the drug. Given the effects are delayed, function differently in people based on their sensitivity and drug acclimation, etc. the patient reported effects probably are not being correlated with the simple fact that instead what is happening is the drug is being heavily underdosed and overdosed in that same time period.

So patients aren't noticing basically they're doing placebos for 2 days then a crystal of T then placebos etc. Not only that but Natesto's MOA actually involves a cyclical type of applique like this so even more reason for many to not notice it.

On the other hand this is obviously improper dosing (and totally unacceptable for an FDA approved drug) AND will likely NOT reproduce the drug's clinical findings given I assume they were performed with properly dispensed Natesto.

 

[granger]

I would say more like 6 months to obtain peak benefits!




*Median testosterone levels at baseline and at 1, 3, and 6 mo after therapy with Natesto TID dosing. Note that changes at 1, 3, and 6 mo are significantly increased from baseline
View attachment 41782

Would I be making a mistake?

I've asked about clomid/Natesto... Again, I've heard from doctors who say they do a 3month run of clomid to try and kickstart the system to producing more T - is clomid a one and one type of thing? Same with Natesto? Are you basically on this for good if it drives T up? Also, need to keep in...

www.excelmale.com

Go nuts!

HELP: Indecisive - I think I need TRT but I want to have babies

Hi, 32 years old male here, I did 4 tests in the past 2 years and all of them go from 200 to 350, so in the lower end of the range. I have low fsh and low lh. Enclomiphene has not resolved my symptoms. I exercise 4 times a week on average: circuit training with weights, sometimes I run...

www.excelmale.com

naa if look at actual results they seem pretty consistent. they fudged the data a wee bit as 10000% depends on WHEN they test.. perhaps start to metabolize slower as time goes on? the RANGE looks VERY similar accross those ranges.

testosterone is metabolized very quickly so some people are back to baseline 1 hr after application ie half life of 15 min.. saying median level is super inaccurate as its nothing to do with actual stabilization of free test. just 1 hr after application people range from 400-900 and fairly consistent is all that means. also should not equate that to benefits. ie compare month 1 range to month 6.. pretty much the same -/+ 70 or so....

BE VERY WARY of natesto data... be even more cautious about drawing conclusions from it.

new issue with natesto bottles is the shards get stuck so actuator does not depress all the way... "we will esculate this" yet no refund 7 months later, no answers, empty promises, was told they tested the crystalized product and would send results.... noda... people they had me speak to have left the company lol.. "restructured" have a feeling class action lawsuit is coming and no one wanted to be holding the bag they hired a shell company to manufacture so they dont have to be held accountable.

takes alot of complaints for FDA or health canada to actually do something particularly when no life or death risk as testosterone is pretty safe even if get 4x teh dosage your suppost to AND nearly impossible to gather data unless test 10 min after application AND hit a crystal that exact dose aswell (As 2 pumps 2-3 times a day) as by 1 hr + ur levels will be within range even if were 2500 for a small time. issue is of course causing damage to the HPTA axis having such high unintended spikes.

 

[granger]

I live here in USA been on Natesto since 5.2022 I started @ 2 dose per day and also was supersensitive receptor could feel effects then acclimated 6 months later @ 3 doses in 2023-2024. I do feel good on Natesto for about 2-3 hours with Vaga (100mg cafffine)sugar -free energy drink on workout days its hard for me to wait 6-8 hours till next dose sometimes I just bump the Natesto gel between doses. I could be undertreated on Natesto now. Also, my Dr. told me Natesto is out of your system by the AM upon waking up. I do not have shardes in my Natesto pump at all. I am going to give xyosted 50mg a try in April 2024.
Please feel free to ask any question.

i think i see a small shard near the bottom. take off the label and hold to the light

 

[madman]

naa if look at actual results they seem pretty consistent. they fudged the data a wee bit as 10000% depends on WHEN they test.. perhaps start to metabolize slower as time goes on? the RANGE looks VERY similar accross those ranges.

testosterone is metabolized very quickly so some people are back to baseline 1 hr after application ie half life of 15 min.. saying median level is super inaccurate as its nothing to do with actual stabilization of free test. just 1 hr after application people range from 400-900 and fairly consistent is all that means. also should not equate that to benefits. ie compare month 1 range to month 6.. pretty much the same -/+ 70 or so....

BE VERY WARY of natesto data... be even more cautious about drawing conclusions from it.

new issue with natesto bottles is the shards get stuck so actuator does not depress all the way... "we will esculate this" yet no refund 7 months later, no answers, empty promises, was told they tested the crystalized product and would send results.... noda... people they had me speak to have left the company lol.. "restructured" have a feeling class action lawsuit is coming and no one wanted to be holding the bag they hired a shell company to manufacture so they dont have to be held accountable.

takes alot of complaints for FDA or health canada to actually do something particularly when no life or death risk as testosterone is pretty safe even if get 4x teh dosage your suppost to AND nearly impossible to gather data unless test 10 min after application AND hit a crystal that exact dose aswell (As 2 pumps 2-3 times a day) as by 1 hr + ur levels will be within range even if were 2500 for a small time. issue is of course causing damage to the HPTA axis having such high unintended spikes.

*I would say more like 6 months to obtain peak benefits!


Peak benefits meaning overall relief/improvement of low-T symptoms including any beneficial effects when it comes to body composition.

If anything I would say 3-6 months without any deviation from the protocol (dosed 2-3 times daily).

We are not just talking about the median here!

Look over any of the Natesto stuides, sure the mean (SD)/median Cavg is nothing to brag about.

Peaks are stellar for most and even though they are short-lived far from common you are crashing back to baseline immediately.

*A maximal peak of testosterone appears at about 1 hour, followed by a return to endogenous, pre-dose levels 4 to 6 hours later (half-life ∼1 hour)

*The pharmacokinetic (PK) profile of TNG of different concentrations has been studied in a series of single and multidose PK studies, including in women, healthy volunteers with allergic rhinitis, and men with TDS [15]. The 24-hour PK profile of testosterone for patients receiving TNG treatment has two or three discrete peaks (“pulses”) of testosterone provoked by LH secretions that occur, on average, every 2 hours. A maximal peak of testosterone appears at about 1 hour, followed by a return to endogenous, predose levels 4 to 6 hours later (half-life ∼1 hour) [4]. The nadir (trough) between doses correlates well with pretreatment endogenous levels at diagnosis.


*In fact, the observed PK profile after a TNG dose is a sum of all sources of testosterone [20, 21]; exogenous and endogenous sources were not independently quantifiable in this study. When exogenous testosterone was administered, there was a suppression of LH and testosterone production. Endogenous testosterone levels decreased as a result of ongoing elimination and reduced or halted production. Later (>1 hour after administration), as the exogenous testosterone absorption rate was reduced and elimination predominated, resulting in a drop in exogenous testosterone, the HPG recovered, reinitiating endogenous testosterone production (Fig. 6a). The degree of HPG suppression appeared to be proportional to the initial baseline TT. For patients with less severe hypogonadism with a supposedly more active HPG and higher baseline TT level, there was more endogenous testosterone suppression during each dose than for a patient with more severe hypogonadism with less HPG axis potential (Fig. 6b). This model is supported by the larger decreases in LH in patients with higher baseline TT concentration seen in this study. It should be noted that in the Rogol et al. study [15], administration of TNG to healthy men with a predose TT baseline of 534 ng/dL (18.4 nmol/L) also showed Cmax peak levels in the same range as seen in this study and again a return to predose baseline nearly 6 hours after a dose.







In the case of testosterone nasal gel, 90% of hypogonadal subjects in the fixed-dose arm and 68% of subjects in the titration arm (ITT) were in the eugonadal range (300–1050 ng/dL) after 90 days of treatment with testosterone nasal gel. Subject's mean total testosterone Cavg level after 90 days was 415 ng/dL when taking the b.i.d. dose and 428 ng/dL when receiving the t.i.d. dose. These levels are consistent with the mean Cavg (418 ng/dL) reported for a large, population-based epidemiological survey of healthy adult males aged 30–79 years (Litman et al., 2006). After considering the protocol violations, the PP percentage of subjects achieving normal serum testosterone is 91% in the fixed-dose arm and 71% in the titration arm. Protocol violations included failure to up-titrate subjects upon direction of physician or at patient request (b.i.d. being adequate for symptoms) despite estimated Cavg values <300 ng/dL. Notably, the percentage of PP subjects in the normal range on the b.i.d. dose of the titration arm was 75% (95% CI, 66–83%).

Each individual dose of nasal gel provides a reproducible short-acting peak that returns near to baseline by the time of the next dose. While there are up to three peaks per profile, Cmax values were consistently below 1500 mg/d and only 3.3% of subjects had values of 1800–2500 ng/dL. While one subject showed a Cmax >2500 ng/dL (3570 ng/dL); this subject would appear to have violated the protocol by continuing finasteride treatment. No safety concerns were identified for this subject.

The peaks-and-troughs PK profile did not appear to have a negative impact on symptomatology. There were statistically significant improvements because of treatment in mean values for the erectile function and mood, and positive trends in improvement for body composition and BMD when compared to pre-treatment baseline values.