SSRIs and brain neurosteroids, androgens

General Discussion
#1

Awor previously posted saying that our problem may be very similar to post-SSRI sexual dysfunction (PSSD). I found an interesting article that I thought I would share. Finatruth is funding a study that is looking at neurosteroids in PFS patients. Maybe in the future we can join with PSSD patients as that would gain the interest of many more scientists and institutions, as well as potentially attract more funding.

Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes

pnas.org/content/96/23/13512.full.pdf

The neurosteroid 3a-hydroxysteroid-5a-pregnan-20-one (allo- pregnanolone) acts as a positive allosteric modulator of a-ami- nobutyric acid at a-aminobutyric acid type A receptors and hence is a powerful anxiolytic, anticonvulsant, and anesthetic agent. Allopregnanolone is synthesized from progesterone by reduction to 5a-dihydroprogesterone, mediated by 5a-reductase, and by reduction to allopregnanolone, mediated by 3a-hydroxysteroid dehydrogenase (3a-HSD). Previous reports suggested that some selective serotonin reuptake inhibitors (SSRIs) could alter concen- trations of allopregnanolone in human cerebral spinal fluid and in rat brain sections. We determined whether SSRIs directly altered the activities of either 5a-reductase or 3a-HSD, using an in vitro system containing purified recombinant proteins. Although rats appear to express a single 3a-HSD isoform, the human brain contains several isoforms of this enzyme, including a new isoform we cloned from human fetal brains. Our results indicate that the SSRIs fluoxetine, sertraline, and paroxetine decrease the Km of the conversion of 5a-dihydroprogesterone to allopregnanolone by human 3a-HSD type III 10- to 30-fold. Only sertraline inhibited the reverse oxidative reaction. SSRIs also affected conversions of androgens to 3a- and 3a, 17a-reduced or -oxidized androgens mediated by 3a-HSD type IIBrain. Another antidepressant, imipra- mine, was without any effect on allopregnanolone or androstan- ediol production. The region-specific expression of 3a-HSD type IIBrain and 3a-HSD type III mRNAs suggest that SSRIs will affect neurosteroid production in a region-specific manner. Our results may thus help explain the rapid alleviation of the anxiety and dysphoria associated with late luteal phase dysphoria disorder and major unipolar depression by these SSRIs.

#2

A long time ago I came across a forum where a PSSD patient said he recovered via the use of licorice root extract (over 3 months). I had posted about it here but it doesn’t seem like anyone had any success. It could also be that no one used it long enough or it was not a high quality/concentration. The research is crucial as they will eventually be using a data base and animal models to determine which compounds could potentially reverse PFS (and/or PSSD). Finatruth’s study should reveal more about the neurological mechanism in PFS.

#3

Its an interesting link to PFS, just how similar is SSRI symptoms to ours? Do they have the dead mind-to-penis connection and pelvic floor/prostate issues as well?

Oscar mentioned this study in this thread…

viewtopic.php?f=27&t=1457&p=45644&hilit=Selective+serotonin+reuptake+inhibitors+directly+alter+activity+of+neurosteroidogenic+enzymes#p45644

And Anonn1 origonally posted it here in 2010
viewtopic.php?f=9&t=3747&hilit=Selective+serotonin+reuptake+inhibitors+directly+alter+activity+of+neurosteroidogenic+enzymes

#4

Their sexual dysfunction is very similar to ours, their most common complaint being genital anesthesia. In addition, there have been suicides due to SSRIs. On a side note, there was a former drug rep (can’t remember her name, but she was an attractive blonde woman) who’s niece committed suicide from an SSRI. She is a public speaker now against big pharma.

Since many women take SSRIs, you will read about many complaints of numb vaginas and lack of vaginal lubrication. I bet if a woman took finasteride, she’d develop similar, if not the same symptoms. PSSD has been around a long time and there are many many more sufferers of PSSD due to the widespread use of SSRIs. I don’t know if PSSD patients have the peripheral tissue alterations we have though. The Italian scientists think we have been affected neurologically and peripherally (i.e. skin).

Unfortunately, I don’t think we hear about it is because SSRIs are anti-depressants and when you have a “depressed” patient coming to you complaining of sexual dysfunction, the doctors attribute it to their “depression” and not to the brain chemically altering medication they prescribed to their patient. In our case, we were perfectly healthy young men until the use of finasteride. Thats why doctors cannot ignore our problem like they can PSSD, and thus must realize that it was the finasteride that caused our symptoms. I think PFS research will be of great benefit to PSSD as it will shine light on their problem and therefore possibly start PSSD research.

Also, there is this whole “ED is very common in young men” bullshit that is propagated by the media and doctors. I never had ED before PFS, in fact I had raging erections and a very sensitive penis and my concern was not problem getting an erection, but not to get an erection in an inappropriate setting (i.e. sitting next to a hot girl in class). I can’t help but think that this ED propaganda is a way for big pharma to cover up the sexual dysfunction caused by many medications and also to promote the use of ED drugs.

#5

From my standpoint, the most relevant aspect of this paper is that 3a-HSD is also the enzyme that converts DHT into Androstanediol (en.wikipedia.org/wiki/3-alpha-HSD), and SSRIs are increasing the conversion.

Finasteride blocks DHT’s creation, and these drugs basically siphon off DHT. Both are temporary forms of androgen deprivation that lead to a persistent state.

In the full paper, they comment on the androgen changes.

1 Like
#6

Awor had told me in a message that SSRIs have anti androgenic effects in the brain. The interesting thing too is that PSSD people experience a crash as we do. I remember reading a post where a guy had almost identical 3 week crash after stopping Paxil that included brain fog and genital anesthesia. I am interested in what phytoestrogens do to brain chemistry and I wonder whether they can do anything to reverse what has happened to us.

#7

Effects of genistein and equol on human and rat testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 activities.

Hu GX, Zhao BH, Chu YH, Zhou HY, Akingbemi BT, Zheng ZQ, Ge RS.
Source
Population Council, New York, NY 10065, USA.
Abstract
The objective of the present study was to investigate the effects of genistein and equol on 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) in human and rat testis microsomes. These enzymes (3beta-HSD and 17beta-HSD3), along with two others (cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17alpha-hydroxylase/17-20 lyase), catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3beta-HSD activity (0.2 micromol L(-1) pregnenolone) with half-maximal inhibition or a half-maximal inhibitory concentration (IC(50)) of 87 +/- 15 (human) and 636 +/- 155 nmol L(-1) (rat). Genistein’s mode of action on 3beta-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD(+). There was no difference in genistein’s potency of 3beta-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3beta-HSD, genistein had lesser effects on human and rat 17beta-HSD3 (0.1 micromol L(-1) androstenedione), with an IC(50) >or= 100 micromol L(-1). On the other hand, equol only inhibited human 3beta-HSD by 42%, and had no effect on 3beta-HSD and 17beta-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3beta-HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.

So, phytoestrogens such as licorice root extract and genistein obviously have an effect, I just don’t know whether this is good or bad. At least one person recovered from PSSD via licorice root extract. I’m trying to find something more specific to 3a-HSD.

Whats also interesting is the improvements NYScientist feels with sulforaphane and the method by which he took a large dose and then experienced improvements over weeks, sort of like a reverse crash. Maybe sulforaphane reversed the peripheral effects of finasteride, now the researchers need to find a reversal of the neurological effects of finasteride.

#8

dgreene,

You did a 180. We can link the experiences through androgen deprivation, but that doesn’t necessarily mean a leap to estrogen.

I like to use this paper as a guide for what happens when you block androgens:

mcponline.org/content/5/11/2031.full

The profile they describe is not estrogenic.

Is there a forum for PSSD? I’d like to see where the community is in investigating their condition.

#9

I agree 100%. I know males who have married at the age of 80 years.
Also my issue for the last 20 years was how to keep my penis down. It was errect 24/7 hours. I never had good sleep because of getting up due to painful errections. I used many alkanizers and diuretic to keep my urine diluted because it used to be very thick. I took diuretics for almost fifteen years. My erections were so severe that in the office many times I had to visit toilet under the pretext of urination but to reseat my penis.

#10

There is a ‘forum’ for PSSD sufferers, if you can call it that, a yahoo group which I once subscribed to but don’t bother reading since practically no one posts apart from the same few people, so don’t expect anyone to be investigating anything.

This is my issue with associating our case with PSSD. The sexual side effects appear very similar in many cases, although even there I would argue that they don’t seem to have severe ED as much, but aside from that there doesn’t appear to be the wide range of symptoms we suffer. I’ve never read about gyno, muscle loss or extreme fatigue, and while anhedonia appears common, I also haven’t seen much if any mention of ‘brain fog’ cognitive problems which plague so many of us.

Plus, if the rate of permanent sides from SSRIs was even half as much as PFS, we would surely have far bigger groups of victims and message boards dwarfing this. Propecia is taken by about a million guys max, look how many are on or have been on Prozac alone guardian.co.uk/society/2008/ … alresearch

#11

Actually, brain fog, fatigue, and every possible sexual side effect IS common in PSSD. Just ask anyone at paxilprogress.org (which has millions of newvisitors every MONTH), pssd.forumotion.com, and others.

#12

Any updates on this?

#13

hi,

I took Finasteride for some years and added Paxil at some Point. Since adding Paxil 7 yeras ago I had permanent loss of Libido. I now at least two other guys who have permanent Problems after taking an SSRI and Finasteride. So I highly assume that there is a connection on the hormonal Level. Yes, would be nice when the PSSD sufferers could be involved in any way to the studies.

#14

The fact you took an SSRI in addition to Finasteride means you are not a clean case, unfortunately. There is no way to pinpoint which drug caused your issues.

#15

Yes, that’s right. :frowning: