What has been your experience with progesterone?

[Gianluca]

I have been watching closely for a couple years now and I would not say increased sex drive on progesterone is commonly reported. Occasionally perhaps. I think more commonly, if there is a report of impact on libido, it is reduced. It also has that reputation in women as being the least sexual of the three sex hormones they're dealing with.

None of this to detract from your experience, it's just that if progesterone had significant anecdotal support for improving sexual function in men, believe me I would have noticed.

When I hear about Progest decreasing libido, I think about either the Pro having an effect on E2, or possibly just too much of it. I think many try things without knowing their levels or if they really need it. There was a guy in the forum, stating that anytime he uses Prog his E2 will crash, we all different.


I really had no idea allopregnanolone was involved in sex drive, I would have thought the opposite actually

 

[M.J]

I have been watching closely for a couple years now and I would not say increased sex drive on progesterone is commonly reported. Occasionally perhaps. I think more commonly, if there is a report of impact on libido, it is reduced. It also has that reputation in women as being the least sexual of the three sex hormones they're dealing with.

None of this to detract from your experience, it's just that if progesterone had significant anecdotal support for improving sexual function in men, believe me I would have noticed.

Couldn’t agree more, but one thing I noticed is if I used hcg for 3 weeks and stopped it I get honey moon period. Without changing my testosterone or even stopping it.
This I am %100 sure of.

How can this be explained I am not sure there is something about hcg protocol change which increases libido. But hcg never did increase my libido by it self.

 

[FunkOdyssey]

Couldn’t agree more, but one thing I noticed is if I used hcg for 3 weeks and stopped it I get honey moon period. Without changing my testosterone or even stopping it.
This I am %100 sure of.

How can this be explained I am not sure there is something about hcg protocol change which increases libido. But hcg never did increase my libido by it self.

When you stop the hCG your T/E2 ratio increases. Maybe that causes a honeymoon period for you until you adapt to it?

@bixt noticed his protocol changes caused temporary honeymoon spikes of libido and so he just constantly rotates through a series of different protocols. Maybe you just keep starting and stopping hCG deliberately then. Whatever works!

 

[M.J]

When you stop the hCG your T/E2 ratio increases. Maybe that causes a honeymoon period for you until you adapt to it?

@bixt noticed his protocol changes caused temporary honeymoon spikes of libido and so he just constantly rotates through a series of different protocols. Maybe you just keep starting and stopping hCG deliberately then. Whatever works!

I agree, For now my secret recipe is 3 weeks on hcg 500. Then I completely stop it for a week or two. Only stopping hcg.

This is the only time I have good libido :~~(

 

[Bmac]

When I hear about Progest decreasing libido, I think about either the Pro having an effect on E2, or possibly just too much of it. I think many try things without knowing their levels or if they really need it. There was a guy in the forum, stating that anytime he uses Prog his E2 will crash, we all different.


I really had no idea allopregnanolone was involved in sex drive, I would have thought the opposite actually

When I hear about Progest decreasing libido, I think about either the Pro having an effect on E2, or possibly just too much of it. I think many try things without knowing their levels or if they really need it. There was a guy in the forum, stating that anytime he uses Prog his E2 will crash, we all different.


I really had no idea allopregnanolone was involved in sex drive, I would have thought the opposite actually

Progesterone, seemingly can be anti-androgenic, and competes for the 5ar with dht, but still am interested in your use of it if you choose to continue with it.

 

[Gianluca]

Progesterone, seemingly can be anti-androgenic, and competes for the 5ar with dht, but still am interested in your use of it if you choose to continue with it.

Progesterone is a hormone like other, it needs to be addressed if deficient.

 

[FunkOdyssey]

I really had no idea allopregnanolone was involved in sex drive, I would have thought the opposite actually

So this video was interesting, however I think he makes a mistake to attribute the hypersexual effects of various recreational drugs to their effects on allopregnanolone. All of those drugs increase dopamine signaling in the reward pathways and increase sexual desire directly with dopamine release. I also noticed a conspicuous absence of anyone confirming progesterone increased their sex drive in the 759 comments.

Not relevant to the topic but you may find it interesting how Leo met his end: YouTube’s ‘Penis Enlargement’ Grifter Suffers Bloody Death in Thailand

I did a little digging on progesterone today and found some interesting studies. One followed men on TRT (Nebido, 1000mg E12W) for 12 years and charted a reduction in serum progesterone that was still within the normal range:

Their conclusions:

Progesterone is a precursor to T and very low levels of the hormone affect spermatogenesis in men, and its metabolites have functions in the central nervous system, specifically regulating sleep and gonadotropin secretion [44,45]. In healthy adult men, the reference levels of progesterone have been reported to be in the range of 0.13–0.97ng/mL which encompasses the levels observed in this study [46]. Moreover, even though we observe a decrease in progesterone levels over the time course of the study, the magnitude of the effect is small and any biological consequences of this decrease are unlikely.

Another one that just came out used the latest and greatest test methods to quantify the levels of sex steroids in the CNS of men. This one is very interesting and may be worth its own thread. They found no detectable progesterone in male cerebrospinal fluid.

Sex steroid levels in corresponding cerebrospinal fluid and serum samples quantified by mass spectrometry in men

Sex steroids exert important biological functions within the CNS, but the underlying mechanisms are poorly understood. The contribution of circulating sex steroids to the levels in CNS tissue and cerebrospinal fluid (CSF) has been sparsely investigated ...

www.ncbi.nlm.nih.gov

Analyses of CSF revealed that DHEA was the major sex steroid (73.5 ± 31.7 pg/mL) followed by 4D (61.4 ± 29.6 pg/mL) and testosterone (49.5 ± 18.9 pg/mL). The CSF levels of DHT, E2, and E1 were substantially lower, and P was in general not detectable in CSF. For all sex steroids except E2, strong associations between corresponding CSF and serum levels were observed. We propose that testosterone in CSF is derived from circulating testosterone, DHT in CSF is from local conversion from testosterone, while E2 in CSF is from local conversion from 4D in CNS.

This paper finds that dietary progesterone can contribute significantly to serum progesterone levels in male mice and propose that the same may be true in humans. Dairy products, eggs, and some meats are rich sources of dietary progesterone. It would be interesting to look at vegan men to see what their serum progesterone looks like without any dietary contributions. This raises the question for me: how much of your serum progesterone was supposed to be there and how much was just something you ate?

Dietary Progesterone Contributes to Intratissue Levels of Progesterone in Male Mice

Progesterone serum levels have been identified as a potential predictor for treatment effect in men with advanced prostate cancer, which is an androgen-driven disease. Although progesterone is the most abundant sex steroid in orchiectomized (ORX) male ...

www.ncbi.nlm.nih.gov

In conclusion, although adrenal-derived progesterone contributes to intratissue progesterone levels in males, nonadrenal progesterone sources also contribute. We propose that dietary progesterone is absorbed and contributes to intratissue progesterone levels in male mice. We speculate that food with high progesterone content could be a significant source of progesterone in males, possibly with consequences for men undergoing androgen deprivation therapy for prostate cancer.

This study finds higher progesterone levels associated with metabolic syndrome in men, and cite prior research finding higher progesterone associated with prediabetes and T2DM in men.

Gender-Specific Independent and Combined Effects of the Progesterone and 17-Hydroxyprogesterone on Metabolic Syndrome: From the Henan Rural Cohort Study

Although the concentrations of progesterone (P4) and 17-hydroxyprogesterone (17-OHP) have been correlated with some characteristics of metabolic syndrome (MetS), the relationships with MetS are inconclusive. Therefore, we investigated the relationship ...

www.ncbi.nlm.nih.gov

They speculate on some potential mechanisms:

P4 exhibits its function through binding to its related receptors. Accumulating researches have indicated that P4 is involved in several pathogeneses of obesity, INS resistance, HTN, and dyslipidemia. P4 receptors are expressed in food-related areas outside the hypothalamus, including the caudate,27 amygdala, hippocampus, and frontal cortex.28 They are also widely distributed in many regions which can mediate pleasure, motivation, and cognition especially in the control of abnormal eating. On the other hand, P4 receptor membrane-associated component 1 contributes to the development of obesity via lipid accumulation in adipocytes to regulate adipohenesis.29 Previous studies also shed light on the expression of glucose transporter 4 could be inhibited by P4,30 resulting in increased INS resistance,31 especially in skeletal muscle and adipose tissue. The different steps of the PI 3-kinase pathway may be inhibited by P4, resulting in increased INS resistance as well as decreased glucose intake.32 Another study further validated the association and suggested that obesity and adiponectin may mediate the relationship between P4 and INS resistance.33

Finally, the following study is a recent review of the effects of progesterone and ways in which it might be useful. They have a section on Progesterone in Men which is enlightening. The only function they list that would be relevant to men on TRT, unconcerned with fertility, are "interactions with the GABA-A receptor complex in the CNS, including sedative and anesthetic actions". We know the sedation well and it can be helpful in some cases.

Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine

Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, ...

www.ncbi.nlm.nih.gov

6.7. Progesterone in Men​

Defined in the majority of the literature as a female hormone, the importance of PROG in the male endocrine system has remained largely neglected. Testicular and adrenal PROG has been regarded as a physiologically unimportant by-product of steroidogenesis. However, in several conditions, including aging, the serum PROG/androgen ratio increases. The average reference range for serum PROG in healthy men is generally considered under 1 ng/mL, which is similar to in postmenopausal women [210].

The male-specific actions of PROG are predominately membrane-dependent, including a rapid increase in Ca2+ resulting in a sperm capacitation/acrosome reaction, LH receptor suppression and the subsequent influence of testosterone biosynthesis in Leydig cells, increased classical PR expressions in the prostate (benign prostatic hyperplasia as well as prostate cancer), interactions with the GABAA receptor complex in the CNS, including sedative and anesthetic actions, and interactions in adipose tissue and the kidneys. PROG-binding membrane proteins have been identified in the liver, sperm and lens epithelial cells [210]. PROG is also one of the steroid hormones that affect spermatogenesis. It has been found that the co-administration of progestins in androgen-based contraceptive pills for men augments the induction of gonadotropin-induced spermatogenic suppression [211]. One study found that the inhibition of sperm production is not caused indirectly by affecting the hypothalamus, but rather the effect of PROG was confirmed directly in the testes [212]. Adding PROG to androgens reduces circulatory concentrations of inhibin and alters the expression of some germ cell-specific genes in human testes [213]. Clinical studies have shown that sperm obtained from oligospermic men had reduced responses to PROG stimulation, suggesting that this membrane effect of PROG can be crucial for the development and fertilizing capacity of sperm [214,215]. It was also reported that PRs may play a role in the regulation of spermatogenesis in humans and that a lack of PR expression in germ cells may be linked to impaired spermatogenesis and could be one possible cause of male infertility [216,217]. PROG is therefore considered to directly act on the testes to regulate spermatogenesis.

"Testicular and adrenal PROG has been regarded as a physiologically unimportant by-product of steroidogenesis." I think that sums up my current position. I remain open to new information though.

 

[Cataceous]

...
"Testicular and adrenal PROG has been regarded as a physiologically unimportant by-product of steroidogenesis." I think that sums up my current position. I remain open to new information though.
...

I was envisioning an experiment in which men would be given something like lilopristone, a PR antagonist, to see if anything bad happens. But you really need something that irreversibly binds to progesterone itself and effectively deactivates it. Then one would also be testing whether progesterone's opposition to estradiol is important.

I wouldn't be so quick to dismiss the importance of allopregnanolone. Wiki cites this reference in saying that it is "prosexual". There is some discussion of human studies also.

Our research has demonstrated that 3α,5α-THP facilitates social and sexual behavior of rodents, which evokes further increases in 3α,5α-THP in midbrain and hippocampus, brain areas involved in [social, cognitive, emotional and physical processes].​

The drop in progesterone under TRT may be small in absolute terms, but losing half of the total seems significant. How is that unlikely to have biological consequences? Try losing half of your testosterone or estradiol. I also see that the lead author of the study received some perks from Bayer, which could be an incentive to downplay the issue.

 

[FunkOdyssey]

The "Dual-Control Model" regards progesterone as an anti-sexual hormone, at least in women:

An Overview of Hypoactive Sexual Desire Disorder: Physiology, Assessment, Diagnosis, and Treatment

Nearly half of women in the United States report problems with sexual function. Many healthcare providers do not ask about sexual concerns during routine clinical encounters because of personal discomfort, lack of familiarity with treatment, or the belief ...

www.ncbi.nlm.nih.gov

 

[Gianluca]

So this video was interesting, however I think he makes a mistake to attribute the hypersexual effects of various recreational drugs to their effects on allopregnanolone. All of those drugs increase dopamine signaling in the reward pathways and increase sexual desire directly with dopamine release. I also noticed a conspicuous absence of anyone confirming progesterone increased their sex drive in the 759 comments.

Not relevant to the topic but you may find it interesting how Leo met his end: YouTube’s ‘Penis Enlargement’ Grifter Suffers Bloody Death in Thailand

I did a little digging on progesterone today and found some interesting studies. One followed men on TRT (Nebido, 1000mg E12W) for 12 years and charted a reduction in serum progesterone that was still within the normal range:

View attachment 40626

Their conclusions:


Another one that just came out used the latest and greatest test methods to quantify the levels of sex steroids in the CNS of men. This one is very interesting and may be worth its own thread. They found no detectable progesterone in male cerebrospinal fluid.

Sex steroid levels in corresponding cerebrospinal fluid and serum samples quantified by mass spectrometry in men

Sex steroids exert important biological functions within the CNS, but the underlying mechanisms are poorly understood. The contribution of circulating sex steroids to the levels in CNS tissue and cerebrospinal fluid (CSF) has been sparsely investigated ...

www.ncbi.nlm.nih.gov

This paper finds that dietary progesterone can contribute significantly to serum progesterone levels in male mice and propose that the same may be true in humans. Dairy products, eggs, and some meats are rich sources of dietary progesterone. It would be interesting to look at vegan men to see what their serum progesterone looks like without any dietary contributions. This raises the question for me: how much of your serum progesterone was supposed to be there and how much was just something you ate?

Dietary Progesterone Contributes to Intratissue Levels of Progesterone in Male Mice

Progesterone serum levels have been identified as a potential predictor for treatment effect in men with advanced prostate cancer, which is an androgen-driven disease. Although progesterone is the most abundant sex steroid in orchiectomized (ORX) male ...

www.ncbi.nlm.nih.gov

This study finds higher progesterone levels associated with metabolic syndrome in men, and cite prior research finding higher progesterone associated with prediabetes and T2DM in men.

Gender-Specific Independent and Combined Effects of the Progesterone and 17-Hydroxyprogesterone on Metabolic Syndrome: From the Henan Rural Cohort Study

Although the concentrations of progesterone (P4) and 17-hydroxyprogesterone (17-OHP) have been correlated with some characteristics of metabolic syndrome (MetS), the relationships with MetS are inconclusive. Therefore, we investigated the relationship ...

www.ncbi.nlm.nih.gov

They speculate on some potential mechanisms:



Finally, the following study is a recent review of the effects of progesterone and ways in which it might be useful. They have a section on Progesterone in Men which is enlightening. The only function they list that would be relevant to men on TRT, unconcerned with fertility, are "interactions with the GABA-A receptor complex in the CNS, including sedative and anesthetic actions". We know the sedation well and it can be helpful in some cases.

Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine

Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, ...

www.ncbi.nlm.nih.gov

"Testicular and adrenal PROG has been regarded as a physiologically unimportant by-product of steroidogenesis." I think that sums up my current position. I remain open to new information though.

View attachment 40628

I can tell the 2.5mg got me really wild, sex drive and sexual thoughts were too much, like in an unnatural way, fun but just too much. I’m down to 1.5mg again, I’m going to test level at peak now.

In this video at 24:27 is also reported the effect of TRT on Progesteorne level. However, levels and symptoms are what we need to look at. If progesterone is whithin the normal range while on TRT, and there are no symtoms, I would probably leave it alone.

Progesterone improved my anxiety but it is just a piece of the puzzle here, I’m sure it is allopregnenolone related. You probably saw them already, but If you search the forum you will find few study on allopregnenolone and mental health

 

[Gman86]

I can tell the 2.5mg got me really wild, sex drive and sexual thoughts were too much, like in an unnatural way, fun but just too much. I’m down to 1.5mg again, I’m going to test level at peak now.

In this video at 24:27 is also reported the effect of TRT on Progesteorne level. However, levels and symptoms are what we need to look at. If progesterone is whithin the normal range while on TRT, and there are no symtoms, I would probably leave it alone.

Progesterone improved my anxiety but it is just a piece of the puzzle here, I’m sure it is allopregnenolone related. You probably saw them already, but If you search the forum you will find few study on allopregnenolone and mental health

Wow so injectable prog has helped u in a lot of ways it sounds like. Do u inject it subQ right before bed?

have u had any labs done while on the 2.5mg or 1.5mg dosages?

 

[Gianluca]

Wow so injectable prog has helped u in a lot of ways it sounds like. Do u inject it subQ right before bed?

have u had any labs done while on the 2.5mg or 1.5mg dosages?

I started injecting 1.5mg subQ at bed time, and 12 hrs after my Pro level came back at .2, (starting level was .1) My doc guessed the peak at .4/5. I have never measured the 2.5mg

Because some insomnia I was having, which turned out to be Thyroid related, doc suggested to do the Pro in the am. I'm basically back at the 1.5mg, and I want to test it at peak now.

My doc mentioned that because the Progesterone in oil it is not attached to an ester, after injection it will peak in about 1 to 2 hrs. I think it would make more sense then to test it at peak for better assessment, maybe 2/3 hrs post injection, just like you would measure a DHEA-S or Thyroid. Since Pro endogenously peaks in the am, it would also make more sense to take it then. However, I have to say it is more practical for me to do the injection at night

 

[Gianluca]

The "Dual-Control Model" regards progesterone as an anti-sexual hormone, at least in women:

An Overview of Hypoactive Sexual Desire Disorder: Physiology, Assessment, Diagnosis, and Treatment

Nearly half of women in the United States report problems with sexual function. Many healthcare providers do not ask about sexual concerns during routine clinical encounters because of personal discomfort, lack of familiarity with treatment, or the belief ...

www.ncbi.nlm.nih.gov

View attachment 40656

we want to put this in context, or I should probably say with a better word in balance.

I like the pic you attached because it really shows both sides. Too much Progesterone can certainly inhibit the "excitation of desire" side, but we don't want to be too much in that side either, that may come with an elevated blood pressure and too much Ca influx into the cells "excitation". That is the state that may cause the anxiety/palpitations or increased HR some people complain after starting TRT, possibly caused by a lack of Progesterone.

someone correct me here if I'm wrong.
to my knowledge Testosterones is stimulant of the CNS, when for sure Progesterone is a depressant of the CNS, yin and yang (balance)

 

[Gman86]

I started injecting 1.5mg subQ at bed time, and 12 hrs after my Pro level came back at .2, (starting level was .1) My doc guessed the peak at .4/5. I have never measured the 2.5mg

Because some insomnia I was having, which turned out to be Thyroid related, doc suggested to do the Pro in the am. I'm basically back at the 1.5mg, and I want to test it at peak now.

My doc mentioned that because the Progesterone in oil it is not attached to an ester, after injection it will peak in about 1 to 2 hrs. I think it would make more sense then to test it at peak for better assessment, maybe 2/3 hrs post injection, just like you would measure a DHEA-S or Thyroid. Since Pro endogenously peaks in the am, it would also make more sense to take it then. However, I have to say it is more practical for me to do the injection at night

So ur still taking it first thing upon waking atm?

progesterone peaks in the am huh? Didn’t know that. good to know. If I ever trial inj prog again I’ll give it a go in the am

 

[Gianluca]

So ur still taking it first thing upon waking atm?

progesterone peaks in the am huh? Didn’t know that. good to know. If I ever trial inj prog again I’ll give it a go in the am

Still taking it first thing in the am.

Most hormones really peak in the am, including testosterone, thyroid, DHEA, cortisol, aldosterone, progesterone and I’m pretty sure Pregnenolone as well, melatonin and I believe GH are mostly secreted at night.

 

[Gman86]

Still taking it first thing in the am.

Most hormones really peak in the am, including testosterone, thyroid, DHEA, cortisol, aldosterone, progesterone and I’m pretty sure Pregnenolone as well, melatonin and I believe GH are mostly secreted at night.

Guess I assumed it peaked at night since prog can be associated with improved sleep

 

[Gianluca]

Guess I assumed it peaked at night since prog can be associated with improved sleep

I think the most used form of Pro is really the capsules, we know that because the first pass in the liver the capsule will be heavily converted into allopregnenolone and maybe other metabolites, this can make people feeling drowsy, that’s why it is generally taken at night I would think

 

[Gianluca]

I pulled my 1.5mg Progesterone injection at peak, it came back at .7 ng/ml vs .2 ng/ml after 12 hours. However, I'm out of the country now, so I used a different laboratory, I'm not really sure if it is even comparable, ref range here in Italy for Pro in male is .05 - .15 ng/ml it seems very low

 

[Gman86]

I pulled my 1.5mg Progesterone injection at peak, it came back at .7 ng/ml vs .2 ng/ml after 12 hours. However, I'm out of the country now, so I used a different laboratory, I'm not really sure if it is even comparable, ref range here in Italy for Pro in male is .05 - .15 ng/ml it seems very low

I mean, at least it’s still measured in ng/ml. And 0.7ng/ml is around what I would think someone could expect their prog level to be on 1.5mg of injectable prog. Might be pretty accurate

how u feeling? Still getting all the benefits u’ve mentioned previously? Any negatives that I’ve noticed?

 

[Gianluca]

I mean, at least it’s still measured in ng/ml. And 0.7ng/ml is around what I would think someone could expect their prog level to be on 1.5mg of injectable prog. Might be pretty accurate

how u feeling? Still getting all the benefits u’ve mentioned previously? Any negatives that I’ve noticed?

You are right, the .7ng/ml must be just about right. To consider also is my low SHBG, I think Pro also binds to it.

no really sides, just the 2.5mg I thought it was a bit too much, I could maybe take 2mg max. I tried it for two weeks in the am instead of pre bed, but I switched again to pre bed beginning this week, and I think taking it in the am may make me a bit sleepy during the first part of the day, but I cut back on Armour thyroid a month ago also.

I noticed more deep sleep for the past two days I took it at night. I need a full week or so to confirm all of this.

I lost a bit of sex drive libido/erection benefit, but I think this happened because I lowered my Thyroid, not the Pro.

However, I'm not sure you have ever heard of this, but in the Ray Peat community, is "believed" that Progesterone initially will detoxify and pull estrogen out of the cell into circulation, possibly creating all kind of sides. My hyper sexuality on the 2.5mg also came here and there, with a sense of melancholia and just being more emotional. I thought I have experienced a little bit of this in the beginning with the 1.5mg. I'm fine with these side effects now. I do not think there is any science behind this at all.