Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology.

J Sex Med. 2013 Oct;10(10):2598-603. doi: 10.1111/jsm.12269. Epub 2013 Jul 24.
Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology.
Melcangi RC1, Caruso D, Abbiati F, Giatti S, Calabrese D, Piazza F, Cavaletti G.

INTRODUCTION:
Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation.
AIM:
A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology.
METHODS:
The levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in three postfinasteride patients and compared to those of five healthy controls.
MAIN OUTCOME MEASURES:
Neuroactive steroid levels in plasma and cerebrospinal fluid of postfinasteride patients and healthy controls.
RESULTS:
At the examination, the three postfinasteride patients reported muscular stiffness, cramps, tremors, and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Severity and frequency of the anxious/depressive symptoms were quite variable; overall, all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in patients showed some interindividual differences. However, the most important finding was the comparison of their neuroactive steroid levels with those of healthy controls. Indeed, decreased levels of tetrahydroprogesterone, isopregnanolone and dihydrotestosterone and increased levels of testosterone and 17β-estradiol were reported in cerebrospinal fluid of postfinasteride patients. Moreover, decreased levels of dihydroprogesterone and increased levels of 5α-androstane-3α,17β-diol and 17β-estradiol were observed in plasma.
CONCLUSION:
The present observations confirm that an impairment of neuroactive steroid levels, associated with depression symptoms, is still present in androgenic alopecia patients treated with finasteride despite the discontinuation of the treatment.

Hey CS,
My testosterone is in the lower limit range, but my dht is at highest limit and estradiol lower than range limits, so low that i have no libido. I was thinking finasteride, but is there something else should i try for balance dht to estradiol ratio?

TNT wrote:Hey CS,
My testosterone is in the lower limit range, but my dht is at highest limit and estradiol lower than range limits, so low that i have no libido. I was thinking finasteride, but is there something else should i try for balance dht to estradiol ratio?

is that serum or salivary DHT?

Have you used finasteride before?

It is blood test results. No, i haven't take finasteride before. I am 41 years old...

TNT wrote:It is blood test results. No, i haven't take finasteride before. I am 41 years old...

Low T usually equals low E..so that is probably the problem...But how to reverse it...there are many ways because of multiple or many potential causes. So there's rarely a single simple reason for it. Wouldn't go near the finasteride regardless.

My DHT levels must have been through the roof. Before finasteride I was growing as much facial hair in one day as most men in one week. Anyway I know the drug is bad, and as pathetic as this sounds, it -did- give me my life back...because for whatever reason I just, had no reason to leave my bed if I looked so different from my other 20-something counterparts.

CS...what can a guy like me do to try to make the best of the fact I'm taking this drug? What can I do during treatment, and after. Or is it just a dice roll and I need to hope I'm good by the time I finally give this hair charade up and go bald? My hair loss was so aggressive that I lost half my hair in a year, and the inflammation was downright painful so I just don't think I can survive off naturals.

I think the natural approach is more powerful. However, what is usually missing is hidden elements. These hidden elements are what can create significant problems, regardless of whatever natural things a person is using. So the bigger picture is more than just what they are using. Everyone is different and like any "autoimmune" condition. The cause(s) need to be identified. This is why it's not a "black and white" answer.

Finasteride is anti-health, and there's so much more than "DHT." Finasteride is an endocrine disruptor. How one persons body reacts is not always predicable. 

There are ways to help recover from finasteride poisoning. I usually recommend things like human chorionic gonadotropin (hCG) injections and certain combinations of liver and acetylcholine boosters to bring back the neurosteroid function.

My problem is that while some men have years to find their underlying issues and hidden elements I have months. My dad aggressively balded around the same time as myself. I know if I got off fin and began searching for an all natural regimen strong enough, I'd have one shot to get it right, and if I chose the wrong approach, my hair is done for. So basically, I can't ever wean off the drug unless I'm prepared to be bald. I have to make the best of it, or accept being a bald man.

I guess I'll have to look into recovering later down the road in a few years and hope the damage isn't too great. I'm not willing to throw away the quality of life I have right now, because where I was a year ago was not a good place.

Sonofodin, what did finasteride do for you exactly? It must of stopped the shedding...but did it regrow some hair back?

shaftless wrote:Sonofodin, what did finasteride do for you exactly? It must of stopped the shedding...but did it regrow some hair back?

Yes, a very cosmetically significant regrowth. When I got on the drug, I thought the fact my hair loss was aggressive would be a downfall, and that it wouldn't be strong enough. What happened was since I lost so much hair so recently, the follicles were not dormant for very long. I experienced much more regrowth than the average person because I caught it early, so to speak.

SonofOdin wrote:

shaftless wrote:Sonofodin, what did finasteride do for you exactly? It must of stopped the shedding...but did it regrow some hair back?

Yes, a very cosmetically significant regrowth. When I got on the drug, I thought the fact my hair loss was aggressive would be a downfall, and that it wouldn't be strong enough. What happened was since I lost so much hair so recently, the follicles were not dormant for very long. I experienced much more regrowth than the average person because I caught it early, so to speak.

I agree, and you have been extremely lucky in that respect. It seems to me that follicles which have been in telogen for too long, stop producing the stem cells required for terminal growth. That Swiss guy said he'd been taking fin for six years, but it did jack shit for his temples. I also read cases of transsexuals who experienced MPB from taking testosterone, and even when they stopped T therapy, their hair did not grow back. So who knows? Perhaps follicles become conditioned into remaining permanently in the telogen phase if they remain in that state too long.

I suppose it can be comparable to alopecia areata sufferers in that respect -- some remain permanently bald for life, whereas others experience regrowth even after decades of being bald. Who knows what this mysterious regrowth trigger could be? It could be that reducing stress + anti-inflammatory diet reduces inflammation to the point where progenitor cells / matrix cells can effectively proliferate.

I think you're on the right track with inflammation. We've discussed this before in another thread but perhaps a big reason why Fin works is DHT is inflammatory. Anyway up there with diet and reducing stress, I'd put sleep. I'm real big on sleep theory right now. I'm convinced that hair is the first thing to deteriorate when the body is not given proper time to recuperate. I'm not sure where you're from but a big problem here in American culture is that it is cool to be a workaholic. There are so many 'motivational' quotes suggesting complete disregard for ones physiology, and I often hear people bragging about how they only got 4 hours of sleep, etc. Sleep reduces inflammation, and I hope it receives the honor it deserves in slowing mpb...I say slowing because I doubt going bear-mode and hibernating will regrow any hair and too much of anything tends to be bad.

Yeh, Odin, I've had first hand experience of the inflammatory effects caused by sleep deprivation. According to a book I was reading: Dreaming as Delirium: How the Brain Goes Out of Its Mind it states the following: "When animals are sleep deprived muramyl peptides (MP's) accumulates in spinal fluid, thus suggesting that sleep deprivation may enable bacterial growth, whereas sufficient sleep impedes it. When illness causing bacteria invade the body, white blood cells counter-attack, killing many bacteria resulting in a massive increase of MP's. The MP's influence the production of IL-1, which in turn influences the production of PGD2 which induces sleep."

Apparently, PGD2 induces sleep so that our bodies can fight off infections better, whereas sleep deprivation gives rise to slowed immune response and thus increased infection. Yet, why these problems seem to be localized to hair follicles of the scalp (initially) is something of a mystery. This is why I wondered if hair follicles act as an early warning system to prevent worse shit happening down the line. I could be way off the mark, of course, but it is still strange how these follicles so readily inflame when stressors are present.

Edited: some additional info:

"Notably, human and animal males, in general, are more susceptible to protozoan, fungal, bacterial, and viral infections than females [7]. This susceptibility could be due to the lower immune responses presented in males than in females,
since innate responses, antibody-mediated, and cellular responses are typically lower in males than in female [if correct, then I take it that increased androgens are the catalyst].

The scalp, like skin anywhere on the body, is prone to infections from many different types of infectious agents. Fungal and bacterial infections are by far the most common. The scalp is in fact more at risk of an infection at times. A combination of factors like unwashed hair, overactive oil glands, harsh hair treatments, perspiration and so on may increase the risk of infections as compared to the skin elsewhere on the body.

However, many infections are caused by microbes that naturally occur on the skin. These microbes are not usually a problem for healthy skin but once there is a disturbance in the skin or immune system it can quickly cause an infection."

Hi CS, would you be kind enough to elaborate on the words you said about Propecia and liver and acetylcholine, I have had anxiety since that's lessened somewhat but the sleep quality / general day to day still isn't what it was. I've recently been taking bacopa monieri which genuinely seems to help my mood but it's definately gaba / neurotransnitter related. Thanks

Xenon that's some real interesting stuff. Is the book overall, worth a read? I may have to pick it up at some point. PM me if you come across anything else worth a look. Right now I've been hitting 8-9 hours of sleep a night and in only a few weeks I'm noticing my quality of life improving.

What I need to work on now is releasing anxiety. I notice it always seems like...lets take lions for an example. The alpha always seems to be lounging, and doesn't seem anxious or, scurrying around. The key to vitality may just be that. Live as stress free as possible, and focus on giving yourself consistent time to recover from each day. For now I'm going to try some guided meditation tracks to deal with the anxiety.

I think my regrowth from fin has tapered off, so anything now may be purely due to my lifestyle changes and natural methods.

RKERR9 wrote:Hi CS, would you be kind enough to elaborate on the words you said about Propecia and liver and acetylcholine, I have had anxiety since that's lessened somewhat but the sleep quality / general day to day still isn't what it was.  I've recently been taking bacopa monieri which genuinely seems to help my mood but it's definately gaba / neurotransnitter related.   Thanks

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524603/

Hi CS, wow that's a very good study, thank you, explains the way I feel on a daily basis, very buzzy etc and then a sudden crash, overly emotional and difficult to calm down, also I possibly raised glutamate. I do underhand it but do you have any thoughts to mitigate effects, in terms of sexual functioning luckily I am mostly recovered but being able to be more calm / balanced would make a lot of difference to me. Bacopa seems to be really helping which is interesting as it upregulates receotors but I can feel a bit too euphoric from it at times.
It's a complicated issue....any advice appreciates but very informative study!

It's a bit more difficult to mitigate the effects of finasteride while still being on it. To me it's a bit like Russian roulette. Each person is hit with different levels of endocrine impairment. Also since finasteride does perpetuate levels of anxiety and depression it could be masking other underlying issues.