Progesterone

[AnnaCannibal]

Ok, so let me get this straight.  Whenever I read something like spiro and finasteride are so bad for you, I become a bit skeptical.  Sure there is the possibility of side effects, but isn't that the same for all long term medicine use?  I mean, a person taking a specific anti-psychotic would most definitely be prone to the side effects, but the benefits gained far outweigh the risk.  I think spiro and finasteride are well known enough to prove their usefullness in transition.  Whereas, progesterins are less well known and less studied so all the longterm risks still remain relatively unknown.  Please, PLEASE, correct me if I'm wrong.  A med or pharm student I am not, and I'm really just trying to understand.

The only experience I can offer is being on spiro and finasteride, no e yet.  So far I have noticed no serious side effects, but of course that doesn't mean something couldn't be happening internally I don't know about.  I guess if I'm taking this pills for the long haul, the goal should be to minimize side effects and maximize effectiveness. 

My trans specialized endo swears by these two and qualms my worries by reassuring me that's the whole purpose of monitoring blood.  He said of course there are side effects, but with proper monitoring I shouldn't worry so much.

[Hikari]

The problem isn't that there are side effects (spironolactone was very bad on me but I understand many tolerate it well) the problem is lots of endos prescribe them because that is what they have always done and there are medications that may have fewer side effects.

What I mean is, I switched off of spiro because it made me very dizzy and I was fainting upon standing too soon... This is on a really low dose. Had I not done a fair bit of research I wouldn't even know that there were alternatives much less got on one. Though I did take it one step further and relegated the doctors to monitoring, so I choose all of my medication now, and only consult rather than ask permission.

I drive an 80k lbs vehicle on a regular basis I can't afford anything that is going to make me dizzy, lives would be at risk. Especially when a doctor knows this and knows spiro reduces blood pressure which can make you dizzy or even faint.

If spiro is the choice with the least side effects for that specific person then great but, I take issue with endos who seem to think this is one size fits all.

[AnnaCannibal]

I drive as well!  The way you put it though makes sense.  Sometimes its easy to forget we're all different and one may react differently to the same exact thing.  It should be a requirement for all endos to know this these days.

[JessicaH]

Sometimes, information is pounded into our heads so hard that it's hard to accept that the established beliefs could be wrong. What if I told you there was no link between saturated fats and heart disease? Sounds, "crazy", huh?

[JessicaH]

June 13, 2014

New study finds no link between saturated fat and heart disease
http://medicalxpress.com/news/2014-06-link-saturated-fat-heart-disease.html#ajTabs

After reviewing nearly 80 studies involving more than half a million people, researchers at Cambridge University found that saturated fat doesn't cause heart disease.

The study, published in the journal Annals of Internal Medicine, also shows that 'good' fats do not lower the risk of heart attack.

So is it time to stop demonising fat?

"It's not saturated fat we should worry about," says Dr Rajiv Chowdhury, lead author of the study. "It's the high-carb or sugary diet that should be the focus of dietary guidelines."

Carbs and sugar contain more artery-clogging particles than saturated and non-saturated fat, and the researchers suggest these should be the focus of new dietary guidelines.

In October 2013, cardiologist Aseem Malhotra, who works at Croydon University Hospital in London, published a report in the British Medical Journal saying there's no link between saturated fat intake and cardiovascular risk. "Indeed, recent prospective cohort studies have not supported any significant association between saturated fat intake and cardiovascular risk. Instead, saturated fat has been found to be protective."

Malhotra believes that our 'fat obsession' comes from "The Seven Countries Study", which started in the late 1950s and was published in 1970. It was the first study to investigate the correlation between diet, lifestyle and heart disease in different countries, and it established that saturated and trans fats intake was associated with higher mortality rates. It was also the first one to high-light the many benefits of the Mediterranean diet.

The results of Chowdhury and Malhotra's studies, however, shouldn't be an excuse gorge butter and cake. "It would be unfortunate if these results were interpreted to suggest that people can go back to eating butter and cheese with abandon," said Alice H. Lichtestein, a nutritional biochemist at Tufts University, to The New York Times.

Over the past few years we've been advised to cut fat intake to 30% of total energy and saturated fat to less than 10%, and we should stick to those guidelines until new ones are published.

[JessicaH]

Ok, so let me get this straight.  Whenever I read something like spiro and finasteride are so bad for you, I become a bit skeptical.  Sure there is the possibility of side effects, but isn't that the same for all long term medicine use?  I mean, a person taking a specific anti-psychotic would most definitely be prone to the side effects, but the benefits gained far outweigh the risk.  I think spiro and finasteride are well known enough to prove their usefullness in transition.  Whereas, progesterins are less well known and less studied so all the longterm risks still remain relatively unknown.  Please, PLEASE, correct me if I'm wrong.  A med or pharm student I am not, and I'm really just trying to understand.

The only experience I can offer is being on spiro and finasteride, no e yet.  So far I have noticed no serious side effects, but of course that doesn't mean something couldn't be happening internally I don't know about.  I guess if I'm taking this pills for the long haul, the goal should be to minimize side effects and maximize effectiveness. 

My trans specialized endo swears by these two and qualms my worries by reassuring me that's the whole purpose of monitoring blood.  He said of course there are side effects, but with proper monitoring I shouldn't worry so much.

Ask your endo about this:
WHY PROGESTERONE ACTION in the BRAIN IS DAMAGED by FINASTERIDE (and Dutatsteride probably even more)

Here new research unsurprisingly reveals how males using even modest doses of finasteride for male pattern hair loss, in an article entitled,

Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma.

At the examination, post-finasteride patients referred muscular stiffness, cramps, tremors and CHRONIC FATIGUE in the ABSENCE OF CLINCIAL evidence of any muscular disorder or strength reduction.

Severity of the ANXIOUS/DEPRESSIVE SYMPTOMS were quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern.

Assessment of neuroactive steroid levels in CSF show a DECREASE of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated to an increase of its Precursor PREGNENOLONE (PREG)

If you've been following our various posts here on our page you know the following to be true"

(1) PREGNENOLONE is "the mother hormone" and within the brain this neurosteriod is converted to a great extent to Progesterone

(2)That FINASTERIDE and Dutasteride which are both alpha-reductase inhibitors NOT ONLY PREVENT TESTOSTERONE from being converted to DHT but ALSO PREVENT PROGESTERONE from being converted to ALLOPREGNANOLONE

(3) This conversion process of Progesterone to ALLOPREGNANOLONE within the brain is essentially to the REGULATION OF ANXIETY and depression and PREVENTION of those symptoms

(4) When the PROGESTERONE METABOLISM/CONVERSION IS BLOCKED YOU WOULD EXPECT SUCH SYMPTOMS and you would expect a BUILDUP of Pregnenolone as the conversion process is backed up by the inhibition of the enzymes processing Progesterone.

(5) What we haven't previously known is that EVEN AFTER DISCONTINUATION of the Finasteride there is a LINGERING IMBALANCE of altered levels of neurosteroid in cerebrospinal fluid and plasma. .

(6) The researchers state, "The present observations show that altered levels of neuroactive steroids, associated to depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment.

http://www.ncbi.nlm.nih.gov/pubmed/24717976

[teeg]

If Progesterone via injection requires injection once per day I think my needle phobia would want me to skip that idea...

Orally I've seen the pills are like liquid filled soft capsules? Are there any tablets of the same Prometrium (or comparable bio-identical progesterone) that can be taken sublingually like estradiol tablets can?

[Jill F]

If Progesterone via injection requires injection once per day I think my needle phobia would want me to skip that idea...

Orally I've seen the pills are like liquid filled soft capsules? Are there any tablets of the same Prometrium (or comparable bio-identical progesterone) that can be taken sublingually like estradiol tablets can?

I take a cycle of topical micronized progesterone gel.  Mah bewbs thank me.

[JessicaH]

ANXIETY/PANIC and ESTROGEN/PROGESTERONE BALANCE

The use of finasteride and dutasteride as part of androgen suppression in GG women and TG women and in men who seek cures for baldness is associated with interference in the action of the crucial alpha-reductase enzyme that not only controls DHT production but also conversion of Progesterone to Allopregnanolone.

It is not surprising that many men who try one of the two DHT blockers also report experiences of anxiety and panic attacks and nightmares, as well. See this article:

http://www.degruyter.com/view/j/hmbci.2010.1.issue-2/hmbci.2010.010/hmbci.2010.010.xml

In this recent study done with rats in whom the progesterone levels are measured suggests that emotionally volatililty and panic attacks during HRT in TG women as well as during phases of hormonal fluctuation in GG women are due to oscillations in the Estrogen/Progesterone balance....and to a kind of 'withdrawal" effect when the Progesterone gets too low in relation to Estrogen levels.



SEX DETERMINANTS OF EXPERIMENTAL PANIC ATTACKS

http://www.sciencedirect.com/science/article/pii/S0149763414000591

Here's what the researchers state:

"Panic disorder is twice a common in women than in men.

In women, susceptibility to PANIC INCREASES during the late luteal (premenstrual) phase of the menstrual cycle,WHEN PROGESTERONE SECRETION IS IN RAPID DECLINE.

This article considers the evidence for the midbrain periaqueductal grey (PAG) as a locus for panic and for the use of PAG stimulation as an animal model of panic in both sexes.

We show in females how a rapid FALL IN PROGESTERONE secretion, such as occurs during the late dioestrus phase of the ovarian cycle in rats (similar to the late luteal phase in women), triggers a NEURONAL WITHDRAWAL response during which the excitability of the midbrain panic circuitry increases as a result of upregulation of extrasynaptic GABAA receptors on inhibitory interneurones in the PAG.

The withdrawal effect is due not to the native hormone but to its neuroactive metabolite allopregnanolone.

Differences in the kinetics of ALLOPREGNANOLONE metabolism may contribute to individual differences in susceptibility to PANIC iIN WOMEN."

And we at the Gender Research Group must add that those differences in Allopregnanolone also make all the different in the world in Transgender Transitioning and Emotional Balance.

[JessicaH]

I take a cycle of topical micronized progesterone gel.  Mah bewbs thank me.

Wiley Protocol?

[teeg]

I take a cycle of topical micronized progesterone gel.  Mah bewbs thank me.

Cycling progesterone is uncertain to me. I'm unsure if it's the progesterone by itself, or the cycling of the progesterone that creates the positive effects people report.

But also, I'm wondering about the actual FORM of the micronized progesterone. I'd prefer to take it sublingually, not orally, but I'm pretty sure it's not possible to take liquid filled soft capsules suglingually like you can estradiol tablets?

[Paige]

(6) The researchers state, "The present observations show that altered levels of neuroactive steroids, associated to depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment.

Hi Jessica,
Thanks for posting this.  So just to be clear, I took finasteride for a couple years about 10 years ago, so I may still be suffering these effects?  How would you know if this problem lingers or even if I have the problem?  Would taking micronized progesterone help solve this if I did have the problem or would it not be metabolized properly anyway?
Thanks,
Paige 

[JessicaH]

It's hard to say how long the effect lasts but  "the results demonstrate is that the diminiution of progesterone by the finasteride (and also by dutasteride) will lead to a lowering of allopregnanolone which controls anxiety (in a characteristic U shaped curve...so that either too much or too little allopregnanolone will cause you to suffer). It has come to my attention that various members of other non research oriented groups have advised to keep pumping in progesterone when you are taking finasteride. This may not be the smartest thing in the world to do, if you don't have a clear idea of the enzymatic balance. It may well result in an excess of progesterone which remains unprocessed to finasteride...and could, in part be responsible for some of the bad responses to progesterone i.e., when the balance between progesterone and its alpha-reductase enzymes is out of whack...simply putting in larger quantities of progesterone and finasteride is likely to not be too smart." Rachel Francon- Gender Research for All Genders

[JessicaH]

Cycling progesterone is uncertain to me. I'm unsure if it's the progesterone by itself, or the cycling of the progesterone that creates the positive effects people report.

But also, I'm wondering about the actual FORM of the micronized progesterone. I'd prefer to take it sublingually, not orally, but I'm pretty sure it's not possible to take liquid filled soft capsules suglingually like you can estradiol tablets?

It's not suggested to take sublingually and made to swallow. A good alternative would be to have doc prescribe it in a cream from a compounding pharmacy or find a Wiley Protocol provider. Their stuff is good but a little on the expensive side. Wiley highly advocates cycling.

[Hikari]

I am a bit skeptical because I have been taking dutasteride for a while now and I seem to have no ill effect at all. In fact I am a pretty chill person without much panic or stress compared to lots of other transwomen (after all transitsion is a stressful thing).

From what those posts seem to say the action of blocking the 5ar itself causes these massive changes but it can't be all that simple because I felt no change while I once had a friend describe finasteride as suicide in pill form due to how depressed it made her... But upon stopping it she got better too.

I am quite self aware and if anything my general mood has increased since dutasteride.

[KayXo]

Injection is always preferable. You will maintain higher and more stable level.

As stated earlier, the problem with injectable progesterone is its short half-life so you would have to inject daily, a pain in the ass LITERALLY!

[Ashey]

I think that all this stuff really does vary from person to person. I heard great things about bicalutamide, but when I tried it for three months, it did nothing to suppress my testosterone and I got bad anxiety attacks. And since switching back to spiro, I'm getting even less of the side-effects than before. I think it might be because I changed my pill schedule. I also got off the provera because of all the negative comments about it, and because I felt like it wasn't doing anything (didn't even have any negative effects). But now I realize it had a positive impact on my sex-drive and cycle, which I had mistakenly attributed to the estradiol and low T-levels. I was getting regular periods on it, and while some may not see that as a good thing, it made me feel 'normal'. So I might actually go back on that if I can't get on the prometrium again. 

[KayXo]

Spiro works to suppress Testosterone differently than Estradiol does. Spiro intercepts the brain's signalling hormone LH which triggers the testes to produce testosterone by disabling aldosterone production in the testicles.

Just to clarify...

I think you mean to say that Spiro reduces LH (luteinizing hormone) production by the pituitary gland but so does Estradiol, with the end result being that testicles produce much less androgens, not aldosterone which is a mineralocorticoid produced by the adrenal glands and which increases sodium retention and blood pressure which Spiro inhibits as well. However,  a study found that Spiro use actually increased LH production and perhaps, that action changes according to the dose used. Regardless, despite the increase in LH, testosterone and DHT (dihydrotestosterone, the strongest androgen) reduced after Spiro administration. Here is the study.

J Urol (Paris). 1981;87(9):635-8.
[The influence of spironolactone on the concentration of gonadotrophins and gonadal hormones in prostatic hypertrophy (author's transl)].

"The authors examined the influence of spironolactone on the concentration of testosterone, 5 alpha - dihydrotestosterone (DHT), progesterone, oestradiol (E2), LH, and FSH in 47 patients with prostatic hypertrophy, aged from 60 to 80 years. The control group consisted of 58 men of the same age. Spironolactone was prescribed (...) for three months. There was a considerable fall in the concentration of testosterone and of DHT and, at the same time, an increase in the concentration of progesterone, E2 and LH. After treatment with spironolactone there was a decrease in the size of the prostate gland. Results obtained show that spironolactone is an effective drug in the treatment of prostatic hypertrophy, since it inhibits androgen metabolism."

Any wild and crazy excessive spiro long term use will lead to the pituiatry being 'fooled' and producing more and more LH....which doesn't prove effective....so your LH scores will be very high.

Whether LH is high or not, androgens are reduced, estradiol is increased on Spiro so in terms of hormonal effects, it's exactly what we are looking for. Estrogen will reduce LH anyways.

The elevated LH also acts on your adrenals and this unnatural excess could cause adrenal overproduction of steroids, among the many other bad effects of Spiro.

Like I said, with the use of estrogen in combination with Spiro, LH will be low. As far as I know, LH does NOT affect the adrenals, only ACTH does and is also produced by the pituitary gland in response to mostly corticosteroids. Spiro actually interferes with the action of one corticosteroid (or mineralocorticoid), aldosterone, as explained above and this is why it reduces blood pressure, reduces water/salt retention, etc.

A NOTE: As we expected: There may be the kind of exaggerated adrenal production of estrone (from DHEA in this case) via adrenal activation by the high LH levels produced by high Spiro Intake

DHEA converts to androgens (testosterone, androstenedione, DHT) and estrogens (estradiol, estrone) in the body so increased DHEA will result in increased androgens and estrogens. How much of either will be produced is anyone's guess and will vary from one individual to another.

The adrenal gland may be a target of LH action in postmenopausal women.

http://www.ncbi.nlm.nih.gov/pubmed/16728548

Interesting but this is still far from conclusive. A correlation between two variables does not imply a cause and effect relationship. We would have to investigate this further and control one variable to see if it affects the other and how so. Perhaps, in the case of post-menopausal women, the low estradiol levels not only cause increased LH production but also increased ACTH production which impacts directly the production of the adrenal gland. 

Also, Spiro being an anti-mineracorticoid agent would actually block the effect of aldosterone at the pituitary gland and reduce negative feedback, increasing ACTH production and thus adrenal production. So, it could well be be that Spiro has an effect on the adrenal gland but this should also be checked further in studies showing a clear cause and effect relationship between the use of Spiro and impairment in either the pituitary gland or adrenal gland. One must be VERY careful before jumping to conclusions.

And, yes, what likely happens to the DHEA along the hormonal flow chart pathways that we have posted regularly is that much of the DHEA can get converted to Estrone.

Why not to testosterone or androstenedione or estradiol, etc? I don't think this can be predicted in advance. This probably varies from one person to another. Even if estrone would end up being the predominant hormone produced from DHEA, several transwomen take oral estrogen with levels of estrone being quite high, much higher than estradiol. So why not also condemn the use of oral estrogen?

[KayXo]

I was just quoting what my endo said.  I swore he gave me the literature back in January, but I lost it.  I could possibly ask for it again in July.  As for oral, no clue.  I take pellets which last 3-4 mo. 1 pellet and testis' production dropped to almost zero in three days.

In the case of pellets (non-oral), progesterone is more likely to cause some effect at the pituitary gland, reducing LH production just as estrogen does since progesterone bioavailability is much higher and thus levels would be higher making it more potent. Less LH, less androgen from testicles.

[KayXo]

Orally I've seen the pills are like liquid filled soft capsules? Are there any tablets of the same Prometrium (or comparable bio-identical progesterone) that can be taken sublingually like estradiol tablets can?

These pills can be taken sublingually but would take quite a long time to dissolve so very inconvenient. Or you could just squeeze out the content of the pill onto the area under your tongue for quicker effect. But this could end up being messy and there would be highs and lows which can have negative effects neurologically speaking. Some compounding pharmacies prepare subligual troches containing progesterone but like I said, I'm not too sure constant highs and lows are good for us mentally.