Dihydrotestosterone

Importance of DHT

Index:
1. Functions of DHT
   1.1. Formation of the body and puberty
   1.2. Adulthood
      a. Maintenance of prostate health
      b. Libido and hormonal balance
2. Problems that Finasteride can cause to the hormonal balance of men
3. The importance of a high level of testosterone for general health
4. Secondary hypogonadism
5. Does Saw palmetto also inhibit DHT?
6. 5 Alpha Reductase enzyme

Finasteride inhibits the conversion of testosterone into DHT (dihydrotestosterone). This causes a decrease of 70% in the level of DHT in those taking finasteride.

1. Functions of DHT (dihydrotestosterone) in a man's body:
1.1. Development of the body and puberty:

- Formation of the male sex organs in the fetus. Boys who are born without the ability to convert testosterone into DHT are born with ambiguous genitalia, malformed penises. Pseudohermaphrodites. 
- Development of male characteristics at puberty. DHT is responsible for the emergence of body hair (including beard), penis growth, development of the libido and sexual function and prostate. In pseudohemaphrodites these functions do not develop fully at puberty, despite having a normal level of testosterone. They only develop male musculature, with little body hair and their sexual organ is between a micro penis and an overdeveloped clitoris. However, they never develop baldness. 

1.2. Adult stage : 
a) Maintaining the health of the prostate . 
The prostate is where it is found the greatest concentration of DHT in the male body. In  a simple analogy, DHT has to the prostate the same importance that oil and gasoline would have to an engine. It lubricates the prostate, maintains the size, stimulates and keeps the prostate functioning. And how important is the prostate? Well, without a prostate the penis does not work ... Men who undergo total prostatectomy (complete removal of the prostate), have impotence, decreased penis size, change in penile corpus cavernosum tissue (the tissue becomes cartilage, impairing the ability of erection), Peyronie's disease (scar in penile tissue, causes deformation and pain), among other problems. In a ripple effect, we can say that DHT is essential to maintain the structure and health of the penis. In the most severeous cases of men affected by finasteride (it has been called Post Finasteride Syndrome) they have exactly these problems ... change in penile tissue and Peyronie's disease (and impotence), which means that the inhibition of 5 alpha reductase in these men was so strong that their prostates were seriously affected (again, these patients are the most serious cases of SPF, not most cases). What's worse is that finasteride causes shrinkage of the prostate and this occurs by apoptosis (cell death), which means that depending on how this happens in the body (time of use, drug sensitivity, propensity, age, among other factors) the prostate can suffer serious consequences because of the use of Finasteride. 

b) Libido and hormonal balance : 
DHT is a hormone 5 times more erogenous and more potent than testosterone. The truth is that medicine is still crawling on the task of explaining the male libido and exactly how sexual hormones work together. What is known is there is a very subtle balance between testosterone, free testosterone, DHT, estrogen and prolactin (this one released in the brain). Furthermore, each of these hormones have by-products, each is transformed by enzymes into other hormones. It is like a large, interconnected network and one influences the other ... DHT also is subsequently transformed by the same 5 alpha reductase in 3 adiol G - 3 Alpha Androstenadiol Glucuronide (women with high levels of 3 Adiol G have excess hair and reproduction difficulties ... it is a masculinizing hormone. Unfortunately it is common to find an extremely low level of 3 Adiol G in men with persistent effects of finasteride. 



2. Problems that Finasteride can cause to the hormonal balance of men
To understand how Finasteride can affect the hormonal balance of a man, one must understand a bit how it works. Depending on the age, this balance occurs differently. In a very simplified explanation, this is glimpse of how it works: Men in andropause ("menopausal" in men) have a high level of DHT and estrogen and mean level of testosterone, as well as a higher level of prolactin. Young men have a "low" level of DHT and estrogen, high testosterone and low levels of prolactin. After ejaculation, at any age, prolactin level in the brain rapidly rises, causing lack of sexual interest at that time. The younger you are, the faster the prolactin level will fall back, and soon you will feel sexual interest again. Older men have a higher prolactin level and therefore are less interested in sex. This gradual increase in prolactin level, occurs naturally as the years go by. This is why older men have higher levels of prolactin then young men. The body, to maintain balance and sex drive, increases the level of DHT everytime the estrogen level increases. They are interconnected. The excess testosterone is converted into DHT and estradiol at similar levels. So, to make it clear: In men, DHT has the effect of enhancing libido and estrogen inhibits libido (because the last is linked to prolactin in the brain).
To maintain the balance of a man's body, DHT and estrogen are interconnected. When the level of one is low, the level of the other must be also low. When the level of one increases, the level of the other also increases. Never, in his natural state, a man has a high level of estrogen and a low DHT level, because estrogen is a highly feminizing hormone and DHT a highly masculinizing hormone. Only when a man takes Finasteride, he creates this imbalance in his body.

Below is a rough sketch to facilitate understanding. Note that the level of DHT in young men,  seems low compared to a mature man, but the balance between DHT and a low level of Estradiol gives him a higher libido. Remember, estrogen neutralizes libido in men:

Young Men (normal situation) 
Testosterone - high level 
DHT low - normal
Estrogen (estradiol) low level - normal

Prolactin low - normal 
Result: High Libido 


Mature men (normal)
Testosterone - median in range
DHT - elevated 
Estrogen (estradiol) - Higher than a young man  
Prolactin - median in range 
Result: average libido

Old men (normal situation) 
Testosterone: medium-low 
DHT - medium 
Estrogen (estradiol) - medium 
Prolactin -high
Result: Low Libido 

Young men taking Finasteride - the first month 
Testosterone - Elevated, anything between 15-20%
DHT - Very low (reduced by 70 %) 
Estrogen (estradiol)? 
Prolactin? 
Result:?


Young men taking Finasteride - after a few months
DHT very low (reduced by 70%) 
Estrogen (estradiol) - elevated (excess testosterone is converted into estrogen only, instead of E2 and DHT. Possibility of feminization of the body) 
Prolactin: elevated (increasing the level of estrogen causes increased prolactin)
Impact on libido: Lower libido due to high levels of Prolactin, Estradiol and low level of DHT.

The last two schemes are the only unbalanced ones. In the long run it is unsustainable for the man's body. This is because, as I said before, DHT and Estrogen are connected. DHT is the male body's natural protection against the increase of estrogen (estradiol). With finasteride, men artificially induce low levels of DHT, then the excess testosterone is converted into Estrogen only, instead of DHT and Estrogen. The body will try to find the balance every day, while you keep that state artificially. The problem is the body can find a balance in a way that is not good for the patient ... And that may cause some of the persistent effects in some men.

Risk 1: Risk of developing secondary hypogonadism

The body can interpret this increase in estrogen as an overproduction of testosterone (yes, you read that right). The pituitary "reads" estrogen and testosterone as a single hormone, the pituitary is the same in men and women, just suffered the action of different hormones during development. So if your body understands it is producing excess testosterone, the pituitary will signal to gradually decrease the testicles natural production of testosterone, which also causes a decrease in testicular size (irreversible in most cases). This is called secondary hypogonadism. So there are men who took finasteride and now show a low level of testosterone. The same thing can happen with someone who takes anabolic steroids. Result: low testosterone levels, infertility, impotence, lack of energy, depression, etc., etc.. Many doctors will roll the chair if you say that Finasteride can cause secondary hypogonadism in some men, but there are proven cases and published studies. The problem is that Merck hid the risk (or did not know it, it may never have appeared in the short-term studies). A few years ago, doctors around the world began calling for a thorough examination of sex hormones before the patient started treatment with finasteride. Thus, it is possible to prove that the fall in testosterone production was caused by the medicine. 
When secondary hypogonadism happens, the body can no longer return to the previous level of testosterone production alone in most cases. What you can do is try to reconnect the hypothalamic-testicles through drugs like Clomid and Nolvadex, which stimulate the production of FSH in the pituitary (more information in the "secondary hypogonadism", below).

Risk 2: Raise the level of estrogen (E2) and affect the relationship E2 x DHT:

On this situation, the level of testosterone is not affected, but estrogen stabilizes at a high level. Consequences: Possibility of feminization of the body, gynecomastia or pseudo-gynecomastia, increased fat accumulation in the hips, reduced libido etc., etc.. If your body can balance the level of DHT with the Estrogen when you stop Finasteride, these effects will be mitigated. A possible treatment for this problem is the use of drugs such as Arimidex. It inhibits the conversion of testosterone into estrogen. But it is a very meticulous process, to balance precisely this way. If you overdo the dose and duration of treatment, estrogen level may plunge  (and this may worsen erection). So it may only be suitable for someone who is showing a very high level of estrogen and low DHT, and already has a reasonable time he stopped taking finasteride.

Risk 3 :

No known cause. Many men have normal levels of Testosterone, Estrogen and DHT after stopping Finasteride and still have lingering effects of the drug. Probably this group's problems are  related to the consequences of 5 alpha reductase inhibition, as it has other functions in the body.

3. The importance of a high testosterone level  for overall health

Testosterone is the locomotive of the male body. It runs several processes in the body, since the hormones interact in cycles (feedback loop). Having a higher testosterone level, a man  will feel more energy, better health, better fertility, increased sex drive, a faster metabolism, improved memory, more muscle tone, stronger bones, better mood, increased sense of satisfaction and peace. It is therefore extremely serious that finasteride decreases testosterone production in some men. Normal levels of testosterone range between 300 and 1000 ng/dl. However, this is a general range, doctors use this range for men from 13 to 80 years old. Obviously, the testosterone level in an adolescent is closest to the upper limit and in older men it will be closer to the lower limit. A normal level of testosterone for a young man is in the upper third of the scale. Then, on the range presented here, a normal level for a man from 20 to 30 years would be 650 to 1000 ng/dl. For an elderly person, the expected level would be approximately between 300 and 500 ng/dl. Men who have testosterone levels below the lower limit are considered to present hypogonadism. There are other ranges and the analysis must be done according to the range and the age of the patient.

Unfortunately Finasteride is bringing testosterone production down to these  levels in men 20 to 30 years old. But they still have a whole life ahead and already present hormone levels as 60 year old men. And in some young men, this decrease in production was more severe, and they have testosterone levels below 300 ng/dl (more about hypogonadism below).

From the age of 30, a man loses 1% of his testosterone production per year until the end of life. It's a very slow progress, and men only realize this situation when this process is close to 60 years old or later and he has already lost 30% of his testosterone level. It is a very different situation if you loose 30% in one year ... as it has happened to some users of Finasteride.

4. Secondary hypogonadism

Hypogonadism is a medical term that describes the decreased functional activity of the gonads (testes in men). Hypogonadism, as a result of defects in the hypothalamus or pituitary is called secondary hypogonadism. In secondary hypogonadism men show a decreased secretion of hormones (LH stimulates the testes to produce testosterone) and FSH (which stimulates the testes to produce sperm).  Men who suffer from hypogonadism have testosterone levels below the lower limit of the scale . In a range of 300 to 1000 ng / dL, it would be any level below 300. Problems that men can develop over the years, if they suffer from hypogonadism and do not seek treatment:

Low or complete lack of libido

Infertility

Depression

Anxiety

Irritability

Fatigue

Poor sleep

Cognitive problems such as difficulty concentrating and memory loss

Reduction in quality of life

Dry skin and weak nails

Decreased hair in the pubic area, underarms and legs

Decreased sense of smell

Bone loss (osteoporosis)

Increase in abdominal fat

Intolerance to glucose and diabetes

High Cholesterol

Muscle atrophy and loss

Decreased growth of facial hair and body hair.

Decrease in the size of the testicles, penis and prostate

Erectile Dysfunction

Frequent desire to urinate.

Gynecomastia and feminization of the body in general. 

5. Does Saw palmetto also inhibit DHT?

Some men begin treatment with the supplement known as saw palmetto, in an attempt to escape from the side effects of finasteride. Unfortunately, saw palmetto is also an inhibitor of 5 alpha reductase. It reduces DHT levels and may cause the same side effects than finasteride. There are men enrolled in Propecia Help who never used finasteride, but were treated with saw palmetto and present the same Post-Finasteride Syndrome symptoms. Unfortunately, the way it affects men also is similar to finasteride. Some do not have any side effects, others develop temporary effects that go away when they stop the drug and a third group has permanent and irreversible effects that do not resolve even years after stopping treatment with saw palmetto.


6. 5 Alpha Reductase enzyme

The enzyme 5 alpha reductase is responsible for converting part of the testosterone in men into the most potent and active masculine hormone DHT (dihydrotestosterone). Finasteride acts in the body by inhibiting the action of 5 alpha reductase enzyme. There are two types of this enzyme: type I and type II (recent studies indicate the possible existence of type III as well). While Finasteride inhibits the activity of 5 alpha reductase type II, dutasteride inhibits both types. 5 alpha reductase enzymes are present throughout the body at the cellular level. They perform various functions. There is a very common misunderstanding regarding the activity of finasteride in the body. Most men have the impression that finasteride will act only on the scalp, inhibiting DHT convertion on site, preventing follicle miniaturization. However, being an oral drug, blood will take finasteride throughout your body, inhibiting the activity of the enzyme 5 alpha reductase in the brain, skin, prostate, endocrine glands, etc.. To make matters worse, Finasteride is considered an irreversible  5 alpha reductase inhibitor. For irreversible, it is understood that after taking the drug, even after stopping, these enzymes which have been blocked do not return to activity anymore. Does the body replace them or does the body adapt? 

Perhaps in these questions lie the answers to why some men suffer with persistent effects and others do not ... It may be the body's ability to replace the activities of 5 alpha or produce new enzymes. Perhaps in some individuals, this process is not fully reversed, causing persistent effects.

And what is the importance of the activities of the 5 Alpha Reductase for the proper functioning of the body?
This enzyme acts in the conversion of hormones into other hormones. So, without the activity (or other mechanism to replace that activity), the body stops producing essential substances. Functions of the enzyme 5 alpha reductase: 

1. Conversion of testosterone into DHT 
DHT or dihydrotestosterone is the most potent and erogenous form of testosterone. Exerts major role in male sexuality. Read about the importance of DHT on the previous page. 

2. Conversion of progesterone to allopregnanolone . 
Men also secrete progesterone, only in much smaller quantities than women. Part of progesterone is converted by 5 alpha reductase into allopregnanolone. This substance (allopregnanolone) acts on the brain, modulating (stimulating) the neurotransmitter known as GABA-A. GABA-A brings feeling of safety, calmness, relaxation (including muscle relaxation) to the individual. When a person takes a tranquilizer for example (as benzodiazepines) the goal is to increase the amount of GABA-A in the brain, and take the person out of a panic attack or treat chronic anxiety. Finasteride triggers the opposite effect in some men ... it decreases the production of allopregnanolone, and consequently the level of GABA-A in brain. It is the action of allopregnanolone, which allows relaxation when a person ingests an alcoholic beverage. This effect disappeared in patients who developed Post-Finasteride Syndrome. Not coincidentally, finasteride is being tested in the U.S. in alcoholics. See studies on the following page. 

3. Intense activity in the skin. 
The highest concentration of 5 alpha reductase in the body is the skin. And in the whole skin, the largest concentration of 5 alpha reductase is the head of the penis. The glans has a huge amount of activity of 5 alpha reductase ... I remember I read an interesting analogy some time ago, that an area the size of a pinhead on the skin of the penis has more activity of 5 alpha reductase than the rest of the body skin combined. Remember that this enzyme converts testosterone into DHT, a hormone that is five times more erogenous than testosterone. It is obvious that this organization of the body is not for nothing. Probably the glans needs all this 5ar activity (the conversion of testosterone into DHT) to promote pleasure in the sexual act. And coincidentally, one of the biggest complaints of men who suffer from Post-Finasreride Syndrome is the loss of sensation in the glans. There are also complaints about reduced sensitivity in the skin in general and very dry skin. 

4. Bile acid biosynthesis. 
Bile acid is composed of acidic steroids. It is synthesized by oxidation of cholesterol. 5 alpha reductase operates in the production of bile acid, which is essential in the digestion of fats. It is noteworthy that many patients with Post-Finasteride Syndrome complain of digestive problems and increased cholesterol levels after the use of Finasteride. See study on cholesterol increase and Finasteride on the next page 

5. Metabolism of estrogen in women.  5 alpha reductase is directly involved in the metabolism of estrogen in women. This is another reason why women should not use Finasteride.

Sources:

•  5-Alpha-Reductase Deficiency | WebMD
•  Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML (March 2011). "Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients". The Journal of Sexual Medicine 8 (3): 872–84.doi:10.1111/j.1743-6109.2010.02157.x.PMID 21176115.
• Irwig, Michael S. (2012). "Depressive Symptoms and Suicidal Thoughts Among Former Users of Finasteride With Persistent Sexual Side Effects". The Journal of Clinical Psychiatry 73 (09): 1220-1223.doi:10.4088/JCP.12m07887. ISSN 0160-6689.PMID 22939118.
• Irwig MS and Kolukula S "Persistent Sexual Side Effects of Finasteride for Male Pattern Hair Loss"      J Sex Med 2011;8:1747–1753.http://onlinelibrary.wiley.com/doi/10.1111/j.1743-6109.2011.02255.x/abstract
•  Finn DA, Beadles-Bohling AS, Beckley EH, et al.(2006). "A new look at the 5alpha-reductase inhibitor finasteride". CNS Drug Reviews 12 (1): 53–76.doi:10.1111/j.1527-3458.2006.00053.x.PMID 16834758.
• Gina Kolata (June 15, 2008). "New Take on a Prostate Drug, and a New Debate". NY Times. Retrieved 2008-06-15.
• Altomare G, Capella GL (October 2002). "Depression circumstantially related to the administration of finasteride for androgenetic alopecia". The Journal of Dermatology 29(10): 665–9. PMID 12433001.
• Rossi, A.; Cantisani, C.; SCARNò, M.; Trucchia, A.; Fortuna, M. C.; Calvieri, S. (2011). "Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up". Dermatologic Therapy 24(4): 455-461. doi:10.1111/j.1529-8019.2011.01441.x.ISSN 13960296. PMID 21910805.
• Römer B, Gass P (December 2010). "Finasteride-induced depression: new insights into possible pathomechanisms". Journal of Cosmetic Dermatology 9 (4): 331–2. doi:10.1111/j.1473-2165.2010.00533.x.PMID 21122055.
• Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A (2006). "Finasteride induced depression: a prospective study". BMC Clinical Pharmacology 6: 7.doi:10.1186/1472-6904-6-7. PMC 1622749.PMID 17026771.
• Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
• Morrow, David J. (March 19, 1999). "New Profits in Old Bottles; Companies Find Bonus in Drugs That Cure Several Ills". The New York Times. Retrieved June 6, 2010.
• Drugs.com | Propecia Side Effects
• 5α-reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer | U.S. Department of Health & Human Services ^ Walsh, PC (2010 Apr 1). "Chemoprevention of prostate cancer.". The New England Journal of Medicine 362 (13): 1237–8. doi:10.1056/NEJMe1001045. PMID 20357287.
• Package Leaflet Information for the User, Swedish package insert for Propecia 1mg.
• MHRA PUBLIC ASSESSMENT REPORT | The risk of male breast cancer with finasteride
•  PROPECIA® (finasteride) | Merck & Co., Inc.
• <http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm299754.htm?utm_source=fdaSearch&utm_medium=website&utm_term=finasteride&utm_content=2>
• <http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/020180s039ltr.pdf>
•  <http://www.businessweek.com/ap/2012-04/D9U3HR3G0.htm>
•  Gunn BG, Brown AR, Lambert JJ, Belelli D (2011)."Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress". Frontiers in Neuroscience 5: 131.doi:10.3389/fnins.2011.00131. PMC 3230140.PMID 22164129.