Safety Study for 300mg of Test a Week

Jda016

Member
I recently came across a study from 1990, where men were taking 25, 50, 100, and 300 mg of test a week for 6 months. The study concluded that "we found no evidence of major adverse health effects of T administered chronically even at the highest dosage." However, they did notice higher hematocrit in the men with 300 T, but did not consider that a "major adverse health effect."


I am curious how 300mg of test could be considered safe, when it clearly would bring the majority of men to supraphysiological levels. Is this evidence that 300mg is truly sustainable, or would major adverse health risks take years to appear? Did the study simply get "lucky" in terms of not having any men have adverse effects? Honestly, I find their conclusions confusing when I hear that 300mg of test a week is considered a "steroid cycle" by many people.

Any thoughts or insights on this?
 
I recently came across a study from 1990, where men were taking 25, 50, 100, and 300 mg of test a week for 6 months. The study concluded that "we found no evidence of major adverse health effects of T administered chronically even at the highest dosage." However, they did notice higher hematocrit in the men with 300 T, but did not consider that a "major adverse health effect."


I am curious how 300mg of test could be considered safe, when it clearly would bring the majority of men to supraphysiological levels. Is this evidence that 300mg is truly sustainable, or would major adverse health risks take years to appear? Did the study simply get "lucky" in terms of not having any men have adverse effects? Honestly, I find their conclusions confusing when I hear that 300mg of test a week is considered a "steroid cycle" by many people.

Any thoughts or insights on this?

The Matsumoto study from 1990.

It was a short-term study (6 months) and the treatment group using 300 mg T/week was n = 10!

10 men (mean age, 29 ± 1 yr)!

In the short-term considered safe as there was no significant adverse health effects or sides other than increased hematocrit, mild truncal acne and water retention as some of the weight gain would have been intra/extra cellular water.

Any negative impact on cardiovascular/brain health when abusing high doses of T/AAS would take much longer and there are many other factors involved here.

Age, genetics, lifestyle (diet, exercise, sleep, stress), and cardiovascular/overall health markers

A 5-10 year timeframe is the gold standard for a long-term study as it would allow researchers to observe cumulative damage and delayed risks.

With a large number of men to boot!

Even then 300 mg T/week is not therapeutic and well beyond what a man would need when on testosterone therapy.

Most men on therapy are injecting 100-200 mg T/week whether once weekly or split into more frequent injections.

Let me be very clear here the majority of men can easily achieve a healthy/high trough FT injecting 100-150 mg T/week especially when split into more frequent injections.

Yes there will always be those outliers who may need the higher-end dose 200 mg T/week but its far from common as in rare.

200 mg T/week would have the majority of men overmedicated!

Rare most would even need to go above 150 mg T/week.

Keep in mind there are also some men who can achieve stellar levels injecting <100 mg T/week especially when split into more frequent injections.

Most men abusing T for the sole purpose of muscle/strength gains are banging 300-600 mg T/week.

Many would consider 300 mg T/week as getting your feet wet!

300 mg T/week would be a sensible dose if you are going to dabble with doses well beyond therapeutic which would be used for the sole purpose of muscle/strength enhancement.

You know achieving that fake chemically enhanced build that one could never achieve natty or when using therapeutic doses of T!




 

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I recently came across a study from 1990, where men were taking 25, 50, 100, and 300 mg of test a week for 6 months. The study concluded that "we found no evidence of major adverse health effects of T administered chronically even at the highest dosage." However, they did notice higher hematocrit in the men with 300 T, but did not consider that a "major adverse health effect."


I am curious how 300mg of test could be considered safe, when it clearly would bring the majority of men to supraphysiological levels. Is this evidence that 300mg is truly sustainable, or would major adverse health risks take years to appear? Did the study simply get "lucky" in terms of not having any men have adverse effects? Honestly, I find their conclusions confusing when I hear that 300mg of test a week is considered a "steroid cycle" by many people.

Any thoughts or insights on this?
No, it doesn’t mean it’s truly sustainable, it only means what they showed… and even then they only showed it in a very small group as madman pointed out.


It means that healthy men under 30 can probably run a 6 month cycle at 300 mg with only increased hematocrit being the primary concern. And they did list that as a significant adverse event, just not a major one:

“Except for mild truncal acne, weight gain, and increases in hematocrit, we detected no significant adverse health effects of chronic high dosage T administration”

Of course, that dose for that amount of time would significantly disrupt natural hormonal functions, and the amount of time it would take to bounce back and how close they could get back to baseline would vary from person to person.

That overview also doesn’t provide full details, so we’d need to see that to get more insight into exactly what it tells us. Fo example, did they administer questionnaires to determine impact on libido, emotional state, anxiety, etc.? If they didn’t, that’s a big piece not even being factored into their equation.


So again… no, the takeaway from that study isn’t “300 mg/week is a safe dose to run long term for most men”.
 
300 mg Test per week may or may not be healthy long term. The Matsumoto study only says it is safe for 6 months, and the power of that study to detect less frequent toxicity is limited by small numbers of subjects in the study.
It's likely the relevant issues for long term safety will be be cardiovascular in nature. Hematocrit/clotting, cardiac remodeling/LVH, lipid changes (eg. decreased HDL, variable but probably minimal effects on LDL/ApoB), elevated blood pressure (controllable), and general risk of premature atherosclerosis or arrythmia induction via mechanisms distinct from LVH.
With regard to Hematocrit, it is highly likely to be elevated and in a significant proportion elevated above 52-54%, which COULD lead to clotting issues and increase risk of LVH due to increased afterload. They didn't assess for LVH (eg. echocardiogram) and even if they did, it may take longer than 6 months to develop.
With regard to lipid changes, only HDL is likely to be significantly affected. But HDL may not have any effect on ASCVD risk since it is not causally related, only a marker. Thus artificially lowering HDL by administering testosterone may not be detrimental, we don't know.
The bottom line is that this study is somewhat reassuring for a prolonged modest "cycle" of testosterone alone at 300 mg for 6 months. However, it does not address the major risks associated with staying on supraphysiologic doses over a longer period, nor does it give us any dose-toxicity quantification of those risks.
It is not correct to say that 300 mg/wk Test long term is unsafe, nor is it correct to say it is safe. There are signals that raise concern but no real data to answer the question definitively.

BTW, thanks to madman for posting a link to the full text of the paper.
 
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... It is not correct to say that 300 mg/wk Test long term is unsafe, nor is it correct to say it is safe. ...

It may not be definitively unsafe for everyone, but it is statistically unsafe. If you are a susceptible individual doing this for many years then it will shorten your life for the exact reasons you mention. As with most hormones, there is a U-shaped mortality curve. This doesn't prove causality, but when you consider all of the specific mechanisms of harm I think you're most of the way there.

...
I am curious how 300mg of test could be considered safe, when it clearly would bring the majority of men to supraphysiological levels. ...

Not just "the majority". Every man on the planet by a wide margin. It's just a small fraction who even naturally produce more testosterone than what's in 100 mg TC/week.

Heavy smoking might appear fairly safe in the short-term, but that doesn't stop it from filling cemeteries over time.
 
It may not be definitively unsafe for everyone, but it is statistically unsafe. If you are a susceptible individual doing this for many years then it will shorten your life for the exact reasons you mention. As with most hormones, there is a U-shaped mortality curve. This doesn't prove causality, but when you consider all of the specific mechanisms of harm I think you're most of the way there.
I am not personally aware of data on long term Testosterone (only) at a dose of 300 mg weekly to prove that it is "statistically" unsafe. Certainly there are concerns. Cardiac remodeling and LVH are known effects, but we don't know at what dose or duration may cause this, or if it is independent of elevated blood pressure. Decrease in HDL-C is a known effect, but it is not known if this is detrimental or not. Other risks will be individually determined such as elevated blood pressure (not universal, and very treatable), elevated hematocrit (the degree of which is highly variable from person to person), etc.
So, to me at least, the answer is we just don't know. Reasons to be concerned, yes. Irrational to take unknown risks, perhaps. But I'm not aware of any convincing evidence for this specific dose. In fact, the Matsumoto study is probably the best data we have and it is inadequate to answer the long term question.

I do think it is clear that, directionally, supraphysiologic AAS are detrimental to cardiovascular health. We just don't know the details and quantification of the dose-response, or how it varies with the various compounds. Most of the data suggesting risk is based on bodybuilders, and to a lesser extent other athletes, who have utilized very high dosages, of multiple compounds, over long time frames, and with varied underlying confounding risk factors (smoking, multi-substance abuse, poor control of known risk factors like hematocrit, lipids, blood pressure, etc.).
 
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I am not personally aware of data on long term Testosterone (only) at a dose of 300 mg weekly to prove that it is "statistically" unsafe. Certainly there are concerns. Cardiac remodeling and LVH are known effects, but we don't know at what dose or duration may cause this, or if it is independent of elevated blood pressure. Decrease in HDL-C is a known effect, but it is not known if this is detrimental or not. Other risks will be individually determined such as elevated blood pressure (not universal, and very treatable), elevated hematocrit (the degree of which is highly variable from person to person), etc.
So, to me at least, the answer is we just don't know. Reasons to be concerned, yes. Irrational to take unknown risks, perhaps. But I'm not aware of any convincing evidence for this specific dose. In fact, the Matsumoto study is probably the best data we have and it is inadequate to answer the long term question.

I do think it is clear that, directionally, supraphysiologic AAS are detrimental to cardiovascular health. We just don't know the details and quantification of the dose-response, or how it varies with the various compounds. Most of the data suggesting risk is based on bodybuilders, and to a lesser extent other athletes, who have utilized very high dosages, of multiple compounds, over long time frames, and with varied underlying confounding risk factors (smoking, multi-substance abuse, poor control of known risk factors like hematocrit, lipids, blood pressure, etc.).
Without defining what constitutes safe vs. unsafe the discussion will likely just go round and round in circles.


We know there are risks. We know that the longer you live with increased risk the more of a gamble it is. Also, just because a person could take medication for elevated blood pressure, that doesn’t mean it shouldn’t be considered a risk. Same is true for lots of others like hematocrit and cholesterol. And this is without even getting into the aspects that are harder to quantify, like impact to HPT axis, anxiety, neurotransmitter changes, etc.

I’d say the bigger question is: are any of the added benefits of taking that much worth the added risks? You take triple the dose for double the blood levels. Why do you get for it? More muscle and probably some added bone density. What do you pay for it? That will vary from person to person, but even for someone lucky enough to respond with low risk to that dose, it still likely wouldn’t be worth it unless they just very heavily prioritize muscle mass.



There have been studies which compared various doses(including 300 and 600 mg per week) and they tend to find that the 100-125 dose is generally the best balance of benefits with minimal risks. And the study from this thread could be considered more evidence that 100 mg per week is a good dose.


the final month of the 6-month treatment period, blood was drawn daily for 7 days (between two consecutive weekly injections).


• The value reported (e.g., 24.9 ± 1.4 nmol/L for the 100 mg/week group and 51.8 ± 2.4 nmol/L for the 300 mg/week group) is the mean of those 7 daily measurements.


• The paper explicitly states: “mean T levels between injections gave a more accurate estimate of T exposure during treatment than those determined in monthly blood samples” because T enanthate levels fluctuate significantly after each IM injection.
 
Thank you for the replies.

The clinic I am with offers 300mg a week, which I am told is the largest legal limit the doctor can prescribe. At 150mg of test C a week, divided into three doses, my Total Test came back at 485; granted, this was at a trough level. My dosage has been upped to 200, and I will have blood work again in early June to see where I am at. I highly doubt I will need anything above 200, but my low T levels prompted me to do some research, and I stumbled across this study, which made me curious as to what other members thought.

Thanks again for the response.
 
Thank you for the replies.

The clinic I am with offers 300mg a week, which I am told is the largest legal limit the doctor can prescribe. At 150mg of test C a week, divided into three doses, my Total Test came back at 485; granted, this was at a trough level. My dosage has been upped to 200, and I will have blood work again in early June to see where I am at. I highly doubt I will need anything above 200, but my low T levels prompted me to do some research, and I stumbled across this study, which made me curious as to what other members thought.

Thanks again for the response.
Out of curiosity, what provider are you with?? I’d be amazed if they are giving you legit testosterone and you are only at a trough of 485 when doing 150 mg/week. This is especially true considering the fact you inject 3 times per week, which means your trough won’t be nearly as low as it would if you were only injecting once a week.


Have you ever gotten test from other providers? If so, were your levels similar?
 
I am not personally aware of data on long term Testosterone (only) at a dose of 300 mg weekly to prove that it is "statistically" unsafe. ...

We don't have RCTs for cigarette smoking either, yet we're pretty comfortable declaring it to be unsafe. To me the evidence is sufficient to label the protocol unsafe for long-term use, even to the point that I would bet large sums that there would be statistically worse outcomes versus healthy controls after say 15 years, maybe sooner. You acknowledge reasons for concern, but then seem to give equal weight to the likelihood that all of them would turn out to be groundless. There are enough independent factors to render this scenario improbable.
 
Out of curiosity, what provider are you with?? I’d be amazed if they are giving you legit testosterone and you are only at a trough of 485 when doing 150 mg/week. This is especially true considering the fact you inject 3 times per week, which means your trough won’t be nearly as low as it would if you were only injecting once a week.


Have you ever gotten test from other providers? If so, were your levels similar?
I am with a men's clinic in West Palm Beach, Florida. I receive Gonaderlin and nandrolone from them. However, I still get my Test C from my family doctor as I always have, and I pick it up at Walgreens. I have thought about switching my Test C from my family doctor to the men's clinic, but I have not made that decision yet.

My family doctor always uses LabCorp, which is where I got the 485 Total T result. However, I have used Quest once, and it had a higher T number. From what I understand, both Labcorp and Quest are reputable. In my 18-month journey, my Total and Free Test have fluctuated quite a bit. I do have extremely low SHBG (6L range: 10-50nmol/L), and it has always been below the reference range since I started TRT. I am not sure if this causes me to metabolize the Test very quickly, which might be why I get such crazy fluctuations.
 
I am curious why the FDA would even allow 300mg to be the legal limit for "TRT." Did they cap it at 300 for the 0.001 of men who barely respond at all to 200+, or was it some type of oversight? Are T clinics just cashing in on the 300mg limit without any concern for the safety of the individual, or were there more research studies done regarding the efficacy and safety of 300mg? From what I am seeing, it seems like the allowance for 300mg is a critical oversight.
 
I am curious why the FDA would even allow 300mg to be the legal limit for "TRT." Did they cap it at 300 for the 0.001 of men who barely respond at all to 200+, or was it some type of oversight? Are T clinics just cashing in on the 300mg limit without any concern for the safety of the individual, or were there more research studies done regarding the efficacy and safety of 300mg? From what I am seeing, it seems like the allowance for 300mg is a critical oversight.

CATER TO!

It's not 300 mg/week.

FDA approves drugs/abeling and the official range is broad TC/TE (50–400 mg every 2–4 weeks) to cover numerous scenarios.

Based on outdated dosing practices.

Wide open for titration.

Look at any of the package inserts for TC/TE.

The FDA does not regulate how doctors prescribe within practice.

Doctors are not required to follow this exactly (off-label prescribing is legal).

A doctor can legally prescribe within a broad range especially off-label even if it’s not considered ideal by the mainstream and if anything it would be some of the T-mills or even some doctors in the know who cater to men looking for that anabolic advantage.

When prescribing off-label it would be based on clinical judgment, benefits outweigh the risks and informed consent.

Take insurance out of the mix and pay out of pocket clinics will have your FT sky-high off the hop or on therapy!

Rare anyone would need to go above 150 mg T/week as the majority of men can easily hit a healthy/high trough FT injecting 100-150 mg T/week especially when split into more frequent injections.

Yes there is always outliers who would need the higher-end therapeutic dose but its far from common as in rare.
 
I am with a men's clinic in West Palm Beach, Florida. I receive Gonaderlin and nandrolone from them. However, I still get my Test C from my family doctor as I always have, and I pick it up at Walgreens. I have thought about switching my Test C from my family doctor to the men's clinic, but I have not made that decision yet.

My family doctor always uses LabCorp, which is where I got the 485 Total T result. However, I have used Quest once, and it had a higher T number. From what I understand, both Labcorp and Quest are reputable. In my 18-month journey, my Total and Free Test have fluctuated quite a bit. I do have extremely low SHBG (6L range: 10-50nmol/L), and it has always been below the reference range since I started TRT. I am not sure if this causes me to metabolize the Test very quickly, which might be why I get such crazy fluctuations.

Your reply from post # 8

The clinic I am with offers 300mg a week, which I am told is the largest legal limit the doctor can prescribe. At 150mg of test C a week, divided into three doses, my Total Test came back at 485; granted, this was at a trough level. My dosage has been upped to 200, and I will have blood work again in early June to see where I am at. I highly doubt I will need anything above 200, but my low T levels prompted me to do some research, and I stumbled across this study, which made me curious as to what other members thought.


Not sure why you are caught up on TT as FT is the critical fraction that truly matters here!

Hope you understand that with a absurdly low SHBG 6 nmol/L and what would seem to most a far from stellar trough TT 486 ng/dL your trough FT would be healthy.

If we calculate your FT using the go to linear law-of-mass action Vermeulen (cFTV) with a trough TT 486 ng/dL, low SHBG 6 nmol/L and Albumin 4.3 g/dL (default) your trough cFTV 17.9 ng/dL would be very healthy and. higher than where a healthy young natty male cFTV 13-15 ng/dL would sit and that is a daily short-lived peak to boot.

Your peak TT/FT and estradiol will be higher.

Again the majority of men will easily do well hitting a trough FT 15-25 ng/dL!


1774833292052.webp



Yes you would have room to bring up your trough FT if need be especially if you are aiming for a high-end/high trough.

Keep in mind that with an absurdly low SHBG 6 nmol/L you would only need a trough TT 675 ng/dL to hit a high trough cFTV 25.4 ng/dL!.

1774833512359.webp


Bad news here is if you are truly only hitting a trough TT 486 ng/dL on 150 mg T split 3x/week then jumping up to 200 mg T/week split would be overkill as a 50 mg jump will most likely push your FT too high.

If anything I would go from 150--->175 before diving in head first here!
 
It's not 300 mg/week.

FDA approves drugs/abeling and the official range is broad TC/TE (50–400 mg every 2–4 weeks) to cover numerous scenarios.

Based on outdated dosing practices.

Wide open for titration.

Look at any of the package inserts for TC/TE.

The FDA does not regulate how doctors prescribe within practice.

Doctors are not required to follow this exactly (off-label prescribing is legal).

A doctor can legally prescribe within a broad range especially off-label even if it’s not considered ideal by the mainstream and if anything it would be some of the T-mills or even some doctors in the know who cater to men looking for that anabolic advantage.

When prescribing off-label it would be based on clinical judgment, benefits outweigh the risks and informed consent.

Take insurance out of the mix and pay out of pocket clinics will have your FT sky-high off the hop or on therapy!

Rare anyone would need to go above 150 mg T/week as the majority of men can easily hit a healthy/high trough FT injecting 100-150 mg T/week especially when split into more frequent injections.

Yes there is always outliers who would need the higher-end therapeutic dose but its far from common as in rare.

I appreciate the response. That makes sense as to how and why doctors can prescribe what they do. When I originally started 18 months ago, my urologist put me on 400mg once every three weeks. It was atrocious!
 
Your reply from post # 8

The clinic I am with offers 300mg a week, which I am told is the largest legal limit the doctor can prescribe. At 150mg of test C a week, divided into three doses, my Total Test came back at 485; granted, this was at a trough level. My dosage has been upped to 200, and I will have blood work again in early June to see where I am at. I highly doubt I will need anything above 200, but my low T levels prompted me to do some research, and I stumbled across this study, which made me curious as to what other members thought.


Not sure why you are caught up on TT as FT is the critical fraction that truly matters here!

Hope you understand that with a absurdly low SHBG 6 nmol/L and what would seem to most a far from stellar trough TT 486 ng/dL your trough FT would be healthy.

If we calculate your FT using the go to linear law-of-mass action Vermeulen (cFTV) with a trough TT 486 ng/dL, low SHBG 6 nmol/L and Albumin 4.3 g/dL (default) your trough cFTV 17.9 ng/dL would be very healthy and. higher than where a healthy young natty male cFTV 13-15 ng/dL would sit and that is a daily short-lived peak to boot.

Your peak TT/FT and estradiol will be higher.

Again the majority of men will easily do well hitting a trough FT 15-25 ng/dL!


View attachment 56310


Yes you would have room to bring up your trough FT if need be especially if you are aiming for a high-end/high trough.

Keep in mind that with an absurdly low SHBG 6 nmol/L you would only need a trough TT 700 ng/dL to hit a high trough cFTV 25.4 ng/dL!.

View attachment 56312

Bad news here is if you are truly only hitting a trough TT 486 ng/dL on 150 mg T split 3x/week then jumping up to 200 mg T/week split would be overkill as a 50 mg jump will most likely push your FT too high.

If anything I would go from 150--->175 before diving in head first here!
Thanks! Good points!

Looking back at my blood work, my Free T was 179.8 (range: 30-183 pg/ml), and my estrodial was 24 (range 8-35 pg/ml). So, considering this, I think you are right, and I don't truly need 200mg a week.

From what I understand, if SHBG is super low, then FT is going to be high, as a low SHBG allows the test to be free within my body. I still don't understand why my SHBG has always been low in all of the bloodwork I have ever gotten on TRT. When I see other men's SHBG, it is usually in range. I need to look further into why my SHBG is so low.
 
... I do have extremely low SHBG (6L range: 10-50nmol/L), and it has always been below the reference range since I started TRT. I am not sure if this causes me to metabolize the Test very quickly, which might be why I get such crazy fluctuations.
...
From what I understand, if SHBG is super low, then FT is going to be high, as a low SHBG allows the test to be free within my body. I still don't understand why my SHBG has always been low in all of the bloodwork I have ever gotten on TRT. When I see other men's SHBG, it is usually in range. I need to look further into why my SHBG is so low.

Do you have a measurement of SHBG from before TRT? If not it's harder to say what's going on. Androgens, e.g. testosterone, tend to drive down SHBG. Therefore with higher TRT doses it is possible to crush levels. However, some men seem to have low levels regardless, probably influenced by genetics.

SHBG has little influence on the metabolism of testosterone. Its level affects total testosterone, but not free testosterone. Under TRT free testosterone is determined directly and proportionally by the dose.

 
Do you have a measurement of SHBG from before TRT? If not it's harder to say what's going on. Androgens, e.g. testosterone, tend to drive down SHBG. Therefore with higher TRT doses it is possible to crush levels. However, some men seem to have low levels regardless, probably influenced by genetics.

SHBG has little influence on the metabolism of testosterone. Its level affects total testosterone, but not free testosterone. Under TRT free testosterone is determined directly and proportionally by the dose.


Thank you for the response.

Looking back, I found a HRT panel from three years ago when I was 39 (started TRT at 40, am now 42). Strangely enough, it does not include SHBG, though the newer blood panels do for some reason. My total T was 567ng/dl. Free T was 6.7 (range: 8.7-25.1 pg/ml). Estradiol was 8.6 (range: 7.6-42). Though I know that is not what you were looking for.

After looking back at previous bloodwork when I started TRT, I do notice my Total T was higher when I was on 100mg a week and has since gotten lower now that I am on 150. Of course, the higher the dosage, the more Free T I have as well.
 
...
Looking back, I found a HRT panel from three years ago when I was 39 (started TRT at 40, am now 42). Strangely enough, it does not include SHBG, though the newer blood panels do for some reason. My total T was 567ng/dl. Free T was 6.7 (range: 8.7-25.1 pg/ml). Estradiol was 8.6 (range: 7.6-42). Though I know that is not what you were looking for.

After looking back at previous bloodwork when I started TRT, I do notice my Total T was higher when I was on 100mg a week and has since gotten lower now that I am on 150. Of course, the higher the dosage, the more Free T I have as well.

That free testosterone test is Labcorp's direct version, which unfortunately cannot be trusted. It does hint at the possibility that your SHBG was originally somewhat above average, which would give credence to the idea that excessive TRT dosing has crashed it. Similarly, the drop in total testosterone seen at a higher dose points strongly towards falling SHBG. If you wanted to resolve this then you would need to adjust your dosing to achieve levels that are physiological for your body. Average production for healthy young men centers around 6-7 mg per day, equivalent to 60-70 mg of testosterone cypionate per week. However, cypionate does not provide a normal diurnal variation in levels, so simply matching your healthy natural production rate wouldn't necessarily yield optimal results.
 
I appreciate the response. That makes sense as to how and why doctors can prescribe what they do. When I originally started 18 months ago, my urologist put me on 400mg once every three weeks. It was atrocious!

Sad state of affairs that doctors are still dishing out those stone-aged ridiculous protocols!

What a horrible experience it would be for. any man!
 

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