Wooo's "Progesterone, The Master Hormone Myth"

[Ella]

why on earth this had to turn into a shitfight is beyond me.

Beyond me too I want to give you a big hug because I too was unaware of the immuno-suppressive mechanism of progesterone and is something I have been trying rack my brains over. This piece of the puzzle makes all the difference in how I now view my work with damaged corneas. Knowing this about progesterone changes the decision we make on treating certain conditions. I knew that immune-suppression was the genesis of the problem. The scarring in corneas was due to a particular pathogen. How on earth was this pathogen able gain entry in what should have been a robust tissue site with many mechanisms designed to keep pathogens gaining entry?

There was some suggestion presented to me that high progesterone and not high estrogen may somehow be responsible for the eye condition. I had only just stumbled onto Peat's work and was reading all the benefits of progesterone. The thought that progesterone had a role to play, just seemed preposterous to me and I dismissed it. I feel like a dill now because I should have been more open and looked deeper. I meant to explore it with Peat but never had the time available to pursue it further.

Please don't get me wrong and don't jump and attack me because I too am trying to make sense of it all. Everyone has an agenda and my agenda is to try and understand those variables that come together in destroying perfectly healthy corneas in some people and not others. I know it's not genes and I have fought hard against this notion.

Progesterone may be an innocent bystander and its elevation may be due to its protective role in the body. However, there is no trusting these organisms because they are extremely clever in taking advantage of a compromised system.

I don't know who the **** this scribble pad person is and if her only concern is fitting into flattering scrubs, then obviously she is completely oblivious to serious health conditions that many people are struggling with on a daily basis. Losing the ability to see is not something anyone wants to have to deal with. We need to remain open minded and discard biases and it is hard to discard foundational concepts such as genes, receptors, pumps and channels if we don't have a good alternative foundation to replace them and which to build upon.

 

[Ella]

Just to be clear, I am still adamant that cortisol and estrogen are the drivers, however, this is not the complete picture, otherwise, everyone with high cortisol and estrogen would be predisposed to this condition. There are other factors that come together to make it a perfect storm for this condition to manifest.

If progesterone opposes estrogen, then the immune-suppressive nature of progesterone will not be favourable in this condition.

 

[whodathunkit]

why on earth this had to turn into a shitfight is beyond me.

Beyond me too

Like Ella, I've found this thread to helpful, too, and hope that @Drareg's posts are posthumously moderated accordingly, @charlie or @tara. Really out of line here. AND he completely ignored tara's warning upthread. Uncool.

Anyway, thanks, @Hitoshi for bringing it up.

My own experience with bioidientical progesterone has been somewhat scattershot. Back in the day when I had uber-crappy lifestyle, really really high stress levels, and extreme symptoms of estrogen dominance, I couldn't tolerate it at all. Was as bad as taking synthetic progestins in birth control. Tried a few more times over the years because I felt like it would benefit me, but never with success.

Then last year after cleaning up my liver a bit and going Peaty I got some benefits from it. Couple benzo reactions (fun! :p) and just the benefits generally attributed to progesterone: higher temps, feeling of well-being, etc. Then after a month or so my uterine fibroids began to swell a little and things deteriorated a bit, not too bad, but enough that I wandered away from progesterone again. Then I tried again, same result...benefits then swelling. So it dropped off the regimen. But I want to get back to it because I did finally feel some benefits, confirming the fact that I probably need more progesterone that my body is making. So I started with it again about a month and a half ago. Felt pretty good for a couple of weeks then things started to go downhill again. I kept at it to see what would happen. I started menstruating lightly then stopped. Past few weeks I was really getting cortisol symptoms and some immune symptoms (which always appear when my cortisol goes high like with too much strenuous exercise), which didn't make sense. I was exercising but I haven't gotten cortisol symptoms from that level of exercise in a while. And of course fibroids swelled up pretty badly. Just started menstruating again and it's kind of bad, like a high-stress cycle.

The scribblepad post actually helped me realize why exogenous progesterone seems to work for a while and then not so much, especially given the potential HPA connection (I have had adrenal problems for a couple decades). It could explain why so very many women have trouble with progesterone...a lot of women, especially the mid-lifers most likely to try progesterone, are very stressed. I honestly have never met anyone in person or on a discussion board, that didn't have difficulty with it at least at first, as John Lee implies usually happens in his book about progesterone. Peat also doesn't adequately discuss the potential difficulties, no doubt because he hasn't experienced them and it's huge topic.

Perhaps the best thing many of us can do, esp. us more mature types with falling estrogen levels, is do the Katharina Dalton dietary recs @PakPik posted about in this thread, and just leave it at that.
At least try that for a couple of months before using supplemental. Then low supplemental at most. Stress and cortisol are also discussed in PakPik's thread but the scribblepad post added some dimension to the complex topic.

Worth noting is that I still get the same immune symptoms from high cortisol so it's not entirely clear to me that the progesterone is the driver of the immune modulation. But in the presence of already elevated cortisol levels IME exogenous progesterone makes it worse.

I have been simultaneously been experimenting with other things that can drive estrogen levels down like high-dose K2 and glycine. So I probably got out of balance from all that. However, given that my difficulties with progesterone have been occurring for a couple of decades but my experiments with other stuff is relatively recent, I'm going to say that the points made in this thread and in scribblepad are valid.

I'm still a fan of progesterone, but as has been noted everywhere in this thread, even in the notorious scribblepad post, there are a lot of variables at play and it's just not going to work the same way for everyone. To argumentatively assume that it should is...unhelpful.

 

[PakPik]

Dear @whodathunkit

Worth noting is that I still get the same immune symptoms from high cortisol so it's not entirely clear to me that the progesterone is the driver of the immune modulation.

Progesterone indeed has a fairly immunosuppressive profile (I've shared a paper with good info earlier on this thread). That's why many people, me included, have found it so useful for acute inflammatory situations. It has some caveats to it, I personally regard it as safer than corsticosteroids, but of course there are people, like those who deal with chronic infections and/or who deal with immunosuppression (both are more common than we'd think) would want to make sure that any supplement, incl. progesterone, is not going to act to their detriment.

I have been simultaneously been experimenting with other things that can drive estrogen levels down like high-dose K2 and glycine.

I've been aware for a long time now that glycine has very powerful immunosuppressive effects. Again, like with any other agent with such immunosuppressive power, good judgement is required when and if used to avoid worsening of the condition. I personally restrict glycine to no more than once a week in very small doses because my personal situation so has required it (glycine worsened my infections if I did it more frequently, and lead to further shut down of my already low immunity).

In this study they compare glycine to betamethasone (Note: betamethasone is considered one of the most powerful corticosteroids in existence).

Modification of immune response by glycine in animals. - PubMed - NCBI

"Glycine (50, 100 and 300 mg/kg), administered daily for 10 days in rabbits challenged with typhoid 'H' antigen and sheep erythrocyte antigen, caused dose- dependent reduction of antibody titre. Inhibition of antibody titre observed with 300 mg/kg was comparable to immunosuppression observed with 1 mg/kg betamethasone."​

In this study, they suggest that glycine can be used as an immunosuppressant in the setting of organ transplantation! That tells a lot about the immunosuppressive power of glycine.

Glycine Inhibits Growth of T Lymphocytes by an IL-2-Independent Mechanism | The Journal of Immunology

"Data presented here demonstrate that glycine has immunosuppressive effects and suggest that it could be used in combination with reduced doses of cyclosporin A to maintain effective immunosuppression and prevent rejection of transplanted organs."​

As for the mechanisms, there are several, but one important one is the powerful induction of the immunosuppressive cytokine Interleukin-10 (Il-10). If so desired, anyone can research the science databases on that subject to learn about that.

 

[Braveheart]

"Progesterone indeed has a fairly immunosuppressive profile (I've shared a paper with good info earlier on this thread). That's why many people, me included, have found it so useful for acute inflammatory situations."

I don't understand this....inflammatory situations are bad?...then why suppress immune system? sorry if this is a totally stupid question....I am very interested in my immune system being strong, and I .take a small amt of progesterone

 

[whodathunkit]

Wow, @PakPik, thanks for the great info! As per usual. :) I think I do tend towards perhaps a higher level of inflammation and perhaps autoimmunity problems...episodic eczema has been a lifelong problem, for example. It's mostly absent these days, but interestingly, seems to flare in certain spots when I go very low fat with diet. Which I did a couple of weeks ago, leading to me being out of sorts and then starting this fairly severe bout of menstruation.

Progesterone doesn't seem to have any effect on my eczema, though. Neither does glycine. And no eczema this time from very low fat. Although I didn't do it for that long.

A lot to ponder, for sure.

 

[Such_Saturation]

This thread is confusing. Is it a good idea or not to supplement progesterone? ¯\_(ツ)_/¯

It's happening, lol

 

[Hitoshi]

"Progesterone indeed has a fairly immunosuppressive profile (I've shared a paper with good info earlier on this thread). That's why many people, me included, have found it so useful for acute inflammatory situations."

I don't understand this....inflammatory situations are bad?...then why suppress immune system? sorry if this is a totally stupid question....I am very interested in my immune system being strong, and I .take a small amt of progesterone

our preferences prefer comfort over inflammatory/uncomfortable states, but we must realise that the inflammation is part of the healing process. simply suppressing it for our preferences only serves to drive the aggravating pathogen (toxic material/organism/irritant) to higher centers.
it has been said that suppression of acute inflammation only leads to chronic illness, and that chronic ilness can only clear via the re-expression of acute again.
this is why using blunt objects to back laboratory values back into place, be they pharmaceutical, nutriceutical, hormones etc, is generally unwise without a guiding knowledgable practitioner or at least a vast knowledge of the ins and outf of signalling molecules and so on.
the lab values are like people on a boat. we want the boat sitting flat on the water, but if one were to drop a tonne of bricks in one end, the people must scurry to the other end to balance the situation, lest the boat sink. this goes for inflammatory markers. do not simply suppress NFKb without looking for why NFKb is elevated, etc.

 

[Mito]

inflammation is part of the healing process

It's my understanding that Peat does not share this view?

 

[ken]

Maybe this simple post about "inflammation " will help you out. Diet and Inflammation

 

[Hitoshi]

Maybe this simple post about "inflammation " will help you out. Diet and Inflammation

generally speaking, this article is correct

this quote, however:

"To take a simple example, say you sprain your ankle. It gets all swollen and painful and immobilized from what process? Inflammation. In fact, everyone knows that the immediate treatment of choice is to put ice on it. To do what? To suppress inflammation!


Why? Because the inflammation prevents healing from taking place."

is false.

the body is choosing heat, and increased metabolic rate at the iste of injury. why on earth does the conceptual mind want to choose otherwise? the innate intelligence of the body is doing the right thing for self correction.

moreover: this guy subscribes to the self/not self view of inflammation and immune action. Cunliffe's work is to the contrary and seems more appropriate.

 

[Hitoshi]

It's my understanding that Peat does not share this view?

i think context is in order here, as it is in so many threads on this forum.

Inflammation is an essential immune response that enables survival during infection or injury and maintains tissue homeostasis under a variety of noxious conditions. Inflammation comes at the cost of a transient decline in tissue function, which can in turn contribute to the pathogenesis of diseases of altered homeostasis.

 

[haidut]

First, I think we need to clarify that supplemental doses of pregnenolone or progesterone are not "shunt to glucocoticoids". The synthesis of glucocorticoid happens entirely in the adrenal cortex -- ie: you put cholesterol in there, and get out glucocorticoids under certain conditions. You do not put progesterone into the adrenal cortex and suddenly get stuff like cortisol.

Any serum bio-identical progesterone from supplements will mostly be metabolised in the liver, and form a whole host of products which have lots of side effects.

NOTE: there are documented cases of formation of mineralocorticoids from progesterone, but I do not view this as a major progesterone metabolic pathway -- FORMATION OF DEOXYCORTICOSTERONE FROM PROGESTERONE IN EXTRAADRENAL TISSUES:DEMONSTRATION OF STEROID 21-HYDROXYLASE ACTIVITY IN HUMAN AORTA | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic​

And of course, progestogens and bio-identical progesterone are not the same. IMO, bio-identical Progesterone's metabolic products are what is responsible for the bulk of the "good effects" that are seen (the reader can go look up all the effects themselves). How these conversion pathways are modulated in people with different conditions is unknown (but liver metabolism is definitely a bottleneck when taking supplemental progesterone)

There will be different agonistic effects on the Glucocorticoid receptors (GR) and Mineralocorticoid receptors (MR) by the various progestogens. Progesterone itself definitely has strong crosstalk with MRs, and is also pretty agonistic for GRs (cross-talk between MRs and GRs is significant).

Whether or not we believe in receptors, there is definitely a functional overlap of progesterone to the MRs and GRs (ie: having progesterone around gives you "MR activation side effects").

- Glucocorticoid and Mineralocorticoid Cross-Talk with Progesterone Receptor to Induce Focal Adhesion and Growth Inhibition in Breast Cancer Cells | Endocrinology | Oxford Academic
- Progesterone Acts via the Nuclear Glucocorticoid Receptor to Suppress IL-1β-Induced COX-2 Expression in Human Term Myometrial Cells
- http://cancerres.aacrjournals.org/content/canres/36/12/4602.full.pdf
- http://www.eje-online.org/content/146/6/789.full.pdf

This indirect stimulation of GRs and MRs could be described as a "glucocorticoid-like effect", but it isn't from actual glucocorticoid production from supplemental progesterone.

----

Progesterone is definitely a significant immune-suppressant. Whether or not the above receptor cross-talk plays a role is irrelevant to the fact that immune system compromise is consistently seen during natural periods of high progesterone, and/or bio-identical progesterone supplementation.

This mechanism is useful under certain contexts, and harmful under other contexts.

....

I disagree on progesterone being GR agonist. The evidence for it is that while it has affinity for the GR it is very weak compared to the glucocorticoid and the synthetic progestins (which behave as full agonists at GR) and it also had additional effects such as increasing the dissociation of cortisol from the GR as well preventing the translocation of the bound steroid-receptor GR complex into the nucleus. So the overall effects of progesterone are systemically quite anti-glucocorticoid.
Glucocorticoid antagonists - ScienceDirect
"...It also overcame the inhibition of prostacyclin and thromboxane A2 after the administration of progesterone which is known to be a glucocorticoid antagonist [1-5], possibly due to its antiprogestin activity."
The Anti-cortisol Mechanism Of Progesterone

Finally, progesterone has about 40%-50% of the anabolic effects of testosterone. Measured by dry muscle weight increase, it was actually equal to testosterone. I will post that study tomorrow when I have more time. So, the combination of these things make it quite unlikely that progesterone is a glucocorticoid - quite the opposite actually.
The idea of progesterone being a significant immunosupressant is also quite foreign to me, especially considering recent news of progesterone's protection against the lethal effects of the flu virus. But I am open to discussion in the appropriate context. I do agree that progesterone protects from excessive immune activation and the septic shock it can develop as a result of this so in that respect it can be called "immunosupressant".
Oh, and more thing. Progesterone is also a functional antagonist on MR even though it's binding profile can be agonist or antagonist depending on the situation/tissue. The sodium-excretion effect of progesterone is undisputed, so it's hard to argue that progesterone has significant MR agonist activity.
Antimineralocorticoid - Wikipedia
"...Some drugs also have antimineralocorticoid effects secondary to their main mechanism of actions. Examples include progesterone, drospirenone, gestodene, and benidipine.[3"

 

[Such_Saturation]

i think context is in order here, as it is in so many threads on this forum.

Inflammation is an essential immune response that enables survival during infection or injury and maintains tissue homeostasis under a variety of noxious conditions. Inflammation comes at the cost of a transient decline in tissue function, which can in turn contribute to the pathogenesis of diseases of altered homeostasis.

Actually, Ray Peat says inflammation is the failure to contain stress in the tissue. So effectively inflammation is an additional thing to heal other than the initial insult.

 

[tyw]

@haidut Firstly, I am of the opinion that "receptors" as cell-surface proteins are not a good model. Regardless, what I am interested is the observable behavioural patterns that occur when certain compound are introduced to cells.

The word "agonist" gets confusing here. I shall change my terminology, and instead use phrases like "induces Mineralocorticoid Receptor expression side effects".

That is because I separate:

(a) The protein activity of the claimed receptor (which is what most tests are referring to when they talk about "agonism" and "antagonism")

(b) The side effects that occur concurrent with said protein activity (we do not know if "receptor activity" directly drives the observed side effects, but can at least can have some confidence that "receptor activity" occurs at the same time as the observed associated behaviour)

My point was that there is functional overlap in the side effects of different receptors. This is why we will need to pay more attention to the side effects, rather than just straight up receptor activity.

In that light, we see overlap in the side effects between MR and GR activation, and as mentioned above, clear overlaps between Progesterone Receptor and MR activity:
- Specificity in mineralocorticoid versus glucocorticoid action. - PubMed - NCBI
- Glucocorticoid and mineralocorticoid cross-talk with progesterone receptor to induce focal adhesion and growth inhibition in breast cancer cells. - PubMed - NCBI

If say, we were to draw a Venn Diagram of all the side effects of Aldosterone (a mineralocorticoid) and Cortisol (a glucocorticoid), there would be a section of overlap between the two circles. eg: cellular water retention and swelling.

This is why I say we can get "cortisol-like" effects from MR activation, though obviously not all of cortisol's effects, since cortisol is a separate molecule.

SIDENOTE: I very much agree with Harold Hillman, that the effects of a particular compound must be mediated by the cell itself reacting to the compound.

Cortisol and Aldosterone, while activating some of the same protein activity within a cell, also do other things that make them unique from each other.

The same logic applies to natural Progesterone vs Progestins. The latter obviously activate the "Progesterone Receptor" and its associated downstream protein activity, but there is obviously other things that happen, and each progestin must be treated uniquely.​

----

With this view, I encourage the readers to look at the following two articles:
- Hormone Research Review: Sad state of progesterone research on bone
- Hormone Research Review: Hormone overdose: How can you tell?

Back to Progesterone vs synthetic Progestins for a bit, it is clear that Progestins can induce further cortisol activity, while natural Progesterone does not. If both activate the "Progesterone Receptor", why the different effects? It is likely that both the unique reaction to Progesterone, as well as the natural progesterone downstream metabolites.

Regarding progesterone metabolites (which is only achievable through natural progesterone use), these probably "balance out" the side effects of "Progesterone Receptor activation". eg: all the "calming" benefits on GABA activity come from downstream progesterone metabolites, and not progesterone itself. Whether or not synthetic progestins and natural progesterone would behave exactly the same if these natural progesterone metabolites were not permitted to exist, is unknown. But in practical terms, natural progesterone should always be used anyway.

The author also claims natural Progesterone can enhance Estrogen activity in certain tissues (not the uterus though, where progesterone opposes estrogen pretty strongly), and that can in turn enhance Cortisol activity. If true, we have yet another indirect link between progesterone and cortisol, which is clearly heavily context dependent.

In any case, too much Progesterone is not good, and it has to play in the hormonal soup of a particular person's context. That is why I focus on all the potential crosstalk and side effects of receptor activation, rather than just receptor activation.

The first article also linked to a study, which found significant increases in deoxy-corticosterone (a mineralocorticoid) after 100mg or oral progesterone supplementation (natural form) -- Oral progesterone and estrogen/progestogen therapy. Effects of natural and synthetic hormones on subfractions of HDL cholesterol and liver proteins. - PubMed - NCBI

This is where dosage and mode of application becomes important, and I agree with the article author's (Etsuko Ueda) take on using transdermal natural progesterone at low doses, and if using supplements, to balance out both Estrogen and Progesterone (both non-synthetic). Her second article above touches on some practical measures.

....

 

[sladerunner69]

Progesterone has been killing my sex drive. Too much coffee also kills my sex drive. I have post finasteride syndrome and my sex drive is best when I only take fat soluble vitamins and a little dht or dhea. Too much and I get brain fogged and cant concentrate. I thought progesterone woud help increase allpregneenlone which is supposed to be very low in post finasterid epeople, but it makes me feel sleepy and weak like it is strongly opposing my androgens.

 

[Mito]

I've been aware for a long time now that glycine has very powerful immunosuppressive effects. Again, like with any other agent with such immunosuppressive power, good judgement is required when and if used to avoid worsening of the condition. I personally restrict glycine to no more than once a week in very small doses because my personal situation so has required it (glycine worsened my infections if I did it more frequently, and lead to further shut down of my already low immunity)

Do you get the same immunosuppressive effects from glycine containing foods such as gelatin? Or just from ingesting free-form glycine?

 

[PakPik]

Hello @haidut

The idea of progesterone being a significant immunosupressant is also quite foreign to me

Regarding progesterone immunosuppressive effects, that's not a new thing nor speculation (unless those findings are wrong). Progesterone does lower/dampen certain parts of the immune system. One important immunosuppressive effect being the suppression of Natural Killer (NK) cells and Macrophage activity. Another key, well studied one is progesterone's dampening of Th1 immunity (which is crucial in order to fight most intracellular pathogens), whilst increasing the Th2 immunity -specifically the anti-inflammatory cytokines- (the cytokines of this branch can aggravate many of the intracellular pathogen infections). An important mediator of progesterone suppressive functions
-at least in the setting of pregnancy- is the protein Progesterone Induced Blocking Factor (PIBF). Progesterone has some caveats that make it different and more benign in my opinion than corticosteroids, but this doesn't negate the immunosuppressive effects. Also, doses/concentrations and pregnancy status are important determinants of the specific effects that are exerted.

... considering recent news of progesterone's protection against the lethal effects of the flu virus.

I checked out the study you referred to here: Progesterone Protects Against The Flu And Helps Recovery. What this study proves is that progesterone **deficiency** makes (mice) lungs more prone to damage induced by a strong infection with the flu. The study does NOT show that an **excess** of progesterone (i.e supra-physiological levels) is protective against the flu -in fact too much progesterone may be detrimental if it gets to suppress antiviral immunity-. These are two different things.

This study was done on "progesterone-depleted adult female mice". Moreover, the supplemented progesterone amount was "at concentrations that mimic the luteal phase". Therefore, this is technically a Hormone Replacement Therapy study. So what this study proves, as I mentioned, is that being progesterone depleted may make your lungs fare worse if facing a heavy influenza infection due to the lack of a protective physiological amount of progesterone

(Note: this is of course something expected since progesterone, as cortisol, is one of the antiinflammatory agents that the body produces and/or uses for protection when tissues are under strong inflammatory reactions. So, similarly to the case of progesterone, being cortisol depleted/deficient would be a problem as well, as Hans Selye showed, and normalization of cortisol would be protective.)​

Regarding direct effects on virus, in this study they showed that progesterone "had no effects on viral load". It is not that progesterone helped fight the virus or clear it: "lack of an effect of P4 treatment on virus titers, clearance of infectious virus, numbers of Th1 cells, and CD8+ T cell activity in lungs".

(Link to the full study: Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females)

Do you get the same immunosuppressive effects from glycine containing foods such as gelatin? Or just from ingesting free-form glycine?

Hi @Mito, I don't remember getting noticeable effects with gelatin (during the period when I consumed 12-24 grams almost daily). I'd suspect that with free glycine the body achieves a greater blood/tissue concentration.

 

[ken]

All this stuff is very interesting. Dr.Peat is interested in inflammation to. If you search his articles you get 9 pages of links. Probably every article mentions it. Here's a typical quote.
Fifty years ago, inflammation was seen as a necessary part of the healing process, but now it is recognized as a cause of heart disease, diabetes, cancer, and aging itself. During the development of the organism, the nature of healing changes, as the nature of inflammation changes. Early in life, healing is regenerative or restorative, and there is little inflammation. In adulthood as the amount of inflammation increases, healing fails to completely restore lost structures and functions, resulting in scarring, the replacement of functional tissue with fibrous tissue. Identifiable changes in the nature of inflammation under different conditions can explain some of these losses of healing capacity. Factors that limit inflammation and fibrosis, while permitting tissue remodeling, could facilitate regeneration and retard aging

 

[Drareg]

@Hitoshi Can we the see the emails exchanges form Peat on progesterone/immunity?
Would be interesting to get his view on excess progesterone in an environment where you might get Aids or herpes.
Ask him how all this applies to natural progesterone production.
Thanks.

@whodathunkit you will be delighted to know I served a ban,funny how in the thread on Trump and Peat you went on a rant against Peat which was an obvious strawman however nobody called for mods or editing of your post,people addressed your points. Here you are attempting the high road on me.
https://raypeatforum.com/community/threads/ray-peat-on-donald-trump.15743/

Interesting in all of this the scribble pad lady speaks about meaning,she prefers the meaning from what she feels is high estrogen,for me I see this as an example of rigidity in meaning,she can't take substances that may shift her paradigm away from the rigid meaning she has set in stone.
Progesterone probably scared her as it gave feelings of "love",the studies haidut posted on childhood rejection would be relevant here imo, the rejection doesn't always come directly from parents,teenage rejection is a potent force as is sex rejection,unaware parents don't help.
An oversimplification to assign all this to one hormone but it's relevant to scribble pad lady's "point" and it was her discussing psychology and meanining just to be clear.(the thread is also about scribble pad lady and progesterone)