Aspirin With Castor Oil For Hair Loss

[Such_Saturation]

But why do normal people get away with normal levels of cortisol and PUFA with a full head of hair?

 

[eddiem991]

But why do normal people get away with normal levels of cortisol and PUFA with a full head of hair?

Good genetics probably

 

[Travis]

But why do normal people get away with normal levels of cortisol and PUFA with a full head of hair?

Well, perhaps hats effect the circulation in such a way as to increase cortisol deposition. But it is rare to see a person not eating linoleic acid these days. I think the case against prostaglandin D₂ is so strong that you'd think hair loss would be impossible without it. I had tried to find some good epidemiology on this, but everyone is so convinced that 'it is only androgens' that nobody seems to have examined this. I think you could crawl through the studies done by Ian Prior on the islanders who were eating essentially all saturated fat (with some fish, but still linoleic acid‐free)—the studies undertaken to examine the effects of saturated fat on cardiovascular disease.

As a sidenote, Ian Prior found essentially no cardiovascular disease in these populations; of these islander's total energy, between 30%–60% had come from saturated fat (depending on the island). I think I'll read them again and look for any observations on hair loss; I think there are only about three or four of them.

Prostaglandin D₂ formation is impossible without linoleic acid. All prostaglandins are ultimately derived from linoleic acid with the exception of the ones derived from eicosapentaenoic acid, which are designated by the subscript three. These are less active, and don't appear to bind the receptors as well. This study I had read today on prostaglandin E₃ showed about four times less activity than prostaglandin E₂. I would assume there is a cyclooxygenase product of eicosapentaenoic acid called prostaglandin D₃, but this hasn't been correlated with hair loss (not even sure if Garza had differentiated between the two).

Well they do have similar cardiovascular effects, making eicosapentaenoic acid also a risk factor for hair loss. This fatty acid is found in fish.

click to embiggen​

Garza states that it works through its G protein‐coupled receptor, but prostaglandin D₂ is unique in one other way. It can dehydrate to prostaglandin J₂ and irreversible bind to p53 through a covalent thioester. This has been experimentally proven, and this event leads to apoptosis.

If Garza is right than prostaglandin D₂ receptor antagonists should work for hair growth; there is one being tested for this right now.

 

[DaveFoster]

If it was that effective at regrowing hair, there’d be much more surrounding it.

Argumentum ad populum - Wikipedia

 

[Travis]

Argumentum ad populum - Wikipedia

Reminded me of the other comment, the one that was begging the question.

 

[ivy]

@Travis, has the literature you've been reading hinted at a distinction between the processes of loss and growth? Does such a distinction even make sense to you? From my empirical experience, I'd say I've been a lot more successful stimulating growth than stopping the loss. And I sure would like to know what might be at play at each step.

 

[DaveFoster]

Reminded me of the other comment, the one that was begging the question.

Are you referring to something in this thread, or something I posted elsewhere?

"Good genetics:" certainly good for employing barbers, although I do like my hair.

 

[Travis]

Are you referring to something in this thread, or something I posted elsewhere?

"Good genetics:" certainly good for employing barbers, although I do like my hair.

I wasn't talking about one of your comments, but a comment on this thread. I'm pretty sure you'd be able to tell which one I was referring to...

@Travis, has the literature you've been reading hinted at a distinction between the processes of loss and growth? Does such a distinction even make sense to you? From my empirical experience, I'd say I've been a lot more successful stimulating growth than stopping the loss. And I sure would like to know what might be at play at each step.

There's certainly some cycling going on with the transforming growth factors (i.e. TGF‐β) and the prostaglandins. The keratin genes have PPAR response elements, giving the impression that they are controlled through PPARs. There are other reasons to think this is so, since prostaglandin E₂ increases hair growth.

But prostaglandin J₂ is the best ligand for PPARγ, and prostaglandin J₂ is a spontaneous dehydration product of prostaglandin D₂. Whenever you have elevated prostaglandin D₂ you have elevated J₂. This would be a paradox, but prostaglandin J₂ can do something else in an entirely different part of the cell—concurrently. Prostaglandin J₂ can covalently bind with p53 causing cell apoptosis. The evidence behind this is very good, and I think anyone would agree that it had been sufficiently proven; no other prostaglandin does this.

Kim, D. H. "15-Deoxy-Δ12, 14-prostaglandin J2 stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue." Oncogene (2010)
Kondo, Mitsuhiro. "15-Deoxy-Δ12, 14-prostaglandin J2: the endogenous electrophile that induces neuronal apoptosis." Proceedings of the National Academy of Sciences (2002)​

The p53 protein normally lies dormant in the nucleus, in its binding protein, until oxidative stress causes its disulfide bridges to separate. At that point, it is released and initiates apoptosis through a well‐studied cascade of events. Apparently by coincidence, prostaglandin J₂'s unique configuration allows it to bind and release p53; no other prostaglandin does this. You could argue that it's precursor—linoleic acid—is unnatural for humans to consume in such high amounts, and this p53–PGJ₂ interaction is a relatively new epihormonal accident.

So prostaglandin D₂'s spontaneous dehydration product—prostaglandin J₂—could stimulate hair growth through the PPARγ, while at the same moment another molecule of prostaglandin J₂ could be causing apoptosis through p53.

But Garza seems to think that the G protein‐coupled receptor for prostaglandin D₂ is involved (GPR44); this is on the cell membrane, and away from the nucleus. I think would be harder to explain since I don't think anyone really knows how this would work on a deeper level. But I think we will find out pretty soon, since prostaglandin D₂ receptor antagonists are being tested for this. Louis Garza's article had been published in 2012, so this is still a somewhat new finding. If these drugs specifically bind GPR44, and they grow hair, then Garza would be correct.

Both cortisol and aldosterone increases the enzyme prostaglandin D synthase through the mineralocorticoid receptor.

But the hair cycle is difficult to explain. The worlds leading expert, Ralf Paus, had basically admitted that he couldn't figure it out; he's got hundreds of articles on hair growth. What they are looking for is a sort‐of 'molecular clock'—or why doesn't hair just keep growing? or how does it even start growing at all? This is a difficult question, and I haven't seen a good explanation. In fact, I haven't seen anything even approaching an explanation—any explanation. People know which molecules cause growth and which ones inhibit it, but nobody can explain a week‐long cycle.

Paus, Ralf. "In search of the “hair cycle clock”: a guided tour." Differentiation (2004)​

 

[DaveFoster]

I wasn't talking about one of your comments, but a comment on this thread. I'm pretty sure you'd be able to tell which one I was referring to...

I don't usually read through threads.

I'm going to ask the audience and guess that it's the assumption that blocking all prostaglandins will result in hair growth, or rather that PGE2 results in hair growth; there's also the assumption that cortisol necessitates local inflammation.

I'm taking my $32,000 Regis, and I'm done with this quote mining, (which ironically has little to do with searching for quotes.)

 

[Such_Saturation]

Well, perhaps hats effect the circulation in such a way as to increase cortisol deposition. But it is rare to see a person not eating linoleic acid these days. I think the case against prostaglandin D₂ is so strong that you'd think hair loss would be impossible without it. I had tried to find some good epidemiology on this, but everyone is so convinced that 'it is only androgens' that nobody seems to have examined this. I think you could crawl through the studies done by Ian Prior on the islanders who were eating essentially all saturated fat (with some fish, but still linoleic acid‐free)—the studies undertaken to examine the effects of saturated fat on cardiovascular disease.

As a sidenote, Ian Prior found essentially no cardiovascular disease in these populations; of these islander's total energy, between 30%–60% had come from saturated fat (depending on the island). I think I'll read them again and look for any observations on hair loss; I think there are only about three or four of them.

Prostaglandin D₂ formation is impossible without linoleic acid. All prostaglandins are ultimately derived from linoleic acid with the exception of the ones derived from eicosapentaenoic acid, which are designated by the subscript three. These are less active, and don't appear to bind the receptors as well. This study I had read today on prostaglandin E₃ showed about four times less activity than prostaglandin E₂. I would assume there is a cyclooxygenase product of eicosapentaenoic acid called prostaglandin D₃, but this hasn't been correlated with hair loss (not even sure if Garza had differentiated between the two).

Well they do have similar cardiovascular effects, making eicosapentaenoic acid also a risk factor for hair loss. This fatty acid is found in fish.

View attachment 7736 click to embiggen​

Garza states that it works through its G protein‐coupled receptor, but prostaglandin D₂ is unique in one other way. It can dehydrate to prostaglandin J₂ and irreversible bind to p53 through a covalent thioester. This has been experimentally proven, and this event leads to apoptosis.

If Garza is right than prostaglandin D₂ receptor antagonists should work for hair growth; there is one being tested for this right now.

I never really wore hats and I always lost hair... but I daresay my friends with the best hair have the worst diet...

 

[Amazoniac]

I never really wore hats and I always lost hair... but I daresay my friends with the best hair have the worst diet...

Suchzord, your massive head makes you process 10x more information than them, so that's a tendency towards worry.

 

[Travis]

I never really wore hats and I always lost hair... but I daresay my friends with the best hair have the worst diet...

I'm under the impression that prostaglandin production has more to do with cytokines than with total linoleic acid intake. Interleukin‐6 induces cyclooxygenase‐2, and interferon‐γ upregulates phospholipase A₂. These enzymes are necessary for prostaglandin production. Cyclooxygenase‐1 always exists, and so does the extracellular phospholipase A₂, but a entire new—you could say redundant—set are induced by these cytokines. (Nitric oxide synthesase also has a cytokine‐induced variety.) The hair loss seen during leishmaniasis suggests this; the increased cytokines seen in alopecia areata suggest this; the ability of cyclosporine to cause hypertrichosis—as a side‐effect—in over 95% of transplant recipients suggest this: cytokines can increase prostaglandin production.

Even with a low linoleic acid diet—and milk does have about three percent—the influence of cytokines certainly appears to be a huge determinant in prostaglandin flux. Without these enzymes, much more linoleic acid would be metabolized or become less damaging lipoxygenase products (i.e. leukotrienes). So even a person eating less linoleic acid could theoretically—and I'd bet the farm—produce more prostaglandins.

Immunogenic proteins theoretically cause hair loss. This is because they induce the production of interferon‐γ and also sometimes interleukin‐6. These cytokines increase prostaglandin production throughout the body—perhaps initially as a defense measure because oxygenated lipids (especially the epoxide and endoperoxide groups) are highly reactive and antibacterial; these are like a slightly more stable hydrogen peroxides, on lipids, with affinity for the invading microbe's cell membrane. Plants make very similar molecules in response in invaders (lipoxins), and I'd think the hormonal effects of the prostaglandins came only later in evolution.

If someone loses hair on a low linoleic acid diet, than I would think cytokines would be increased (i.e. from grain consumption). Either that, or unusually high cortisol or aldosterone is involved.

 

[Such_Saturation]

I'm under the impression that prostaglandin production has more to do with cytokines than with total linoleic acid intake. Interleukin‐6 induces cyclooxygenase‐2, and interferon‐γ upregulates phospholipase A₂. These enzymes are necessary for prostaglandin production. Cyclooxygenase‐1 always exists, and so does the extracellular phospholipase A₂, but a entire new—you could say redundant—set are induced by these cytokines. (Nitric oxide synthesase also has a cytokine‐induced variety.) The hair loss seen during leishmaniasis suggests this; the increased cytokines seen in alopecia areata suggest this; the ability of cyclosporine to cause hypertrichosis—as a side‐effect—in over 95% of transplant recipients suggest this: cytokines can increase prostaglandin production.

Even with a low linoleic acid diet—and milk does have about three percent—the influence of cytokines certainly appears to be a huge determinant in prostaglandin flux. Without these enzymes, much more linoleic acid would be metabolized or become less damaging lipoxygenase products (i.e. leukotrienes). So even a person eating less linoleic acid could theoretically—and I'd bet the farm—produce more prostaglandins.

Immunogenic proteins theoretically cause hair loss. This is because they induce the production of interferon‐γ and also sometimes interleukin‐6. These cytokines increase prostaglandin production throughout the body—perhaps initially as a defense measure because oxygenated lipids (especially the epoxide and endoperoxide groups) are highly reactive and antibacterial; these are like a slightly more stable hydrogen peroxides, on lipids, with affinity for the invading microbe's cell membrane. Plants make very similar molecules in response in invaders (lipoxins), and I'd think the hormonal effects of the prostaglandins came only later in evolution.

If someone loses hair on a low linoleic acid diet, than I would think cytokines would be increased (i.e. from grain consumption). Either that, or unusually high cortisol or aldosterone is involved.

So new age people who say gluten causes hair loss might be correct

 

[Such_Saturation]

Suchzord, your massive head makes you process 10x more information than them, so that's a tendency towards worry.

By Moore’s law I’ll be obsolete by 2025

 

[Amazoniac]

By Moore’s law I’ll be obsolete by 2025

That's one of the consequences: Eckhart Tolle deficiency.

 

[DuggaDugga]

I think that would certainly lower total prostaglandin synthesis is two ways: by inhibiting cyclooxygenase with aspirin, and also inhibiting the same with the castor oils. Any long unsaturated fatty acid appears to inhibit cyclooxygenase by competition (but they don't bind strongly like aspirin and indomethacin do).

But of course this does nothing about the prostaglandin D₂:E₂ ratio. For that, you need to inhibit cortisol. It is cortisol that increases the transcription of the enzyme which specifically makes prostaglandin D₂. Here is just one study that I've read, but I've read more:

Urbanet, Riccardo. "Adipocyte mineralocorticoid receptor activation leads to metabolic syndrome and induction of prostaglandin D₂ synthase." Hypertension (2015)​

And this is the long‐awaited link between cortisol and prostaglandin D₂.

The prostaglandin D₂ gradient which characterized the balding scalp is probably synonymous with the cortisol gradient. Cortisol is carried within the seven spongy α-helices of serum albumin. It has been experimentally determined, both with sex steroid binding proteins and serum albumin (using tryptophan), that steroids are concentrated in areas of microcirculation. This is indeed intuitive, as there is more surface are in said areas. Also: I think we could expect a slightly higher pressure in microcirculatory regions consequent of a progressively‐tapering artery, especially with a fluctuating blood pressure as small vessels are more sensitive to increasing pressure (greater relative increase in diameter per mmHg). You could only expect higher cortisol in microcirculatory regions, and higher prostaglandind D₂ synthase levels would be the result. This is exactly what is found:

Larson, Allison R. "A prostaglandin d‐synthase‐positive mast cell gradient characterizes scalp patterning." Journal of cutaneous pathology (2014)
Garza, Luis A. "Prostaglandin D₂ inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia." Science translational medicine (2012)​

Although cyclooxygenase inhibitors could work some, blockers of the mineralcorticoid receptor would work too. These are non‐conflicting pathways and the results would add—perhaps even synergize. You could also use cyclosporine to inhibit γ-interferon, a cytokine which invades the cells and transcribes the other main prostaglandin-forming enzyme: phospholipase A₂.

Wu, Tong. "Interferon-gamma induces the synthesis and activation of cytosolic phospholipase A₂." The Journal of clinical investigation (1994)​

This is a very consistent finding; you could bet the farm (or the house (or the apartment)) that interferon-γ will do this every time. This is also released by ingesting grains in some people, as the body thinks it's under attack whenever a large undigested peptide gets absorbed.

Hypertrichosis has been reported in over 95% of patients on cyclosporine therapy. Gamma-interferon is also released during leismaniasis infection, where it predictably causes bald spots in animals. Cyclosporine is the most effect hair drug but it's a large cyclic peptide, making transdermal absorption difficult. It is so notorious for low penetrance that covalent modifications of the structure have been made with specific intent of improving this (Rothbard, 2000).

So I personally vote a low linoleic acid diet, anti-mineralocorticoid (spironolactone), anti-γ-interferon (cyclosporine A), and anti-11β-HSD₁ (enoxolone)—the enzyme responsible for converting cortisone into cortisol on the skin. None of the aforementioned drugs compete with eachother and they all interfere with prostaglandin D₂ synthesis in some way—and they all have been shown to regrow hair.

But I must warn you: cyclooxygenase inhibitor indomethacin has been reported to cause hair loss (Tosti, 1994). I think if you near-completely inhibit prostaglandinds you can shut down the hair cycle. The hair keratin genes have PPAR reseponse elements, meaning that prostaglandins are needed to create keratin mRNA (and subsequent protein). I think cyclooxygenase inhibitors could be useful, but I think they could be a detriment if using an extremely strong one—such as indomethacin—in very high concentrations/dosages.

Tosti, Antonella. "Drug-induced hair loss and hair growth." Drug Safety (1994)​

Spironolactone isn't specifically/exclusively a mineralcorticoid antagonist. It's known to have anti-androgen properties. This isn't surprising. As much as the pharmaceutical company would have us believe their novel, patented drugs act exclusively on specific receptors, that's not how biochemistry works. You're ingesting a unnatural compound that is going to have some unpredictable consequences. They usually just package this up for off-label use to make more money rather than respect the fact they are taking a reductionist approach to the living organism. Anyways-- with regards to the anti-androgen properties of spironolactne, I think this is an especially dangerous recommendation to be making to men. Do you really think men should be taking anti-androgens, a drug prescribed to trans-gender patients?

Spironolactone has been used for 30 years as a potassium-sparing diuretic. Spironolactone is a synthetic steroid structurally related to aldosterone. Since the serendipitous discovery 20 years ago that spironolactone given to a woman for polycystic ovary syndrome (PCOS) and associated hypertension also improved hirsutism, it has been used as a primary medical treatment for hirsutism. Spironolactone both reduces adrenal androgen production and exerts competitive blockade on androgen receptors in target tissues. Spironolactone has been used off-label in FPHL for over 20 years

Spironolactone, an inhibitor of androgen synthesis, has been administered to castrated men with metastatic carcinoma of the prostate. Plasma levels of testosterone, androstenedione and dehydroepiandrosterone were significantly decreased. These data indicate that spironolactone suppresses adrenal androgen production and suggest that it may be of benefit in the treatment of orchiectomized patients with advanced carcinoma of the prostate.

There are no unanimous recommendations for the use of anti-androgens. Options are also listed in Table 2. Spironolactone is one of the most common medications used to suppress endogenous testosterone in trans female patients. The biggest risk associated with spironolactone is hyperkalemia, and this should be closely monitored. Other options include 5α-reductase inhibitors such as finasteride, but these can be associated with liver toxicity and may not be as effective as spironolactone (8). GnRH agonists can be very expensive, and are not always a good option for patients. Progestins are used by some providers, but should be used with caution as there is a theoretical risk of breast cancer associated with long-term exogenous progesterone use (15).

Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss. - PubMed - NCBI
Suppression of plasma androgens by spironolactone in castrated men with carcinoma of the prostate. - PubMed - NCBI
Spironolactone, a possible selective androgen receptor modulator, should be used with caution in patients with metastatic carcinoma of the prostate. - PubMed - NCBI
Comparative antiandrogenic potency of spironolactone and cimetidine: assessment by the chicken cockscomb topical bioassay. - PubMed - NCBI
Antiandrogenic effect of spirolactones: mechanism of action. - PubMed - NCBI

 

[Travis]

Spironolactone isn't specifically/exclusively a mineralcorticoid antagonist. It's known to have anti-androgen properties. This isn't surprising. As much as the pharmaceutical company would have us believe their novel, patented drugs act exclusively on specific receptors, that's not how biochemistry works. You're ingesting a unnatural compound that is going to have some unpredictable consequences. They usually just package this up for off-label use to make more money rather than respect the fact they are taking a reductionist approach to the living organism. Anyways-- with regards to the anti-androgen properties of spironolactne, I think this is an especially dangerous recommendation to be making to men. Do you really think men should be taking anti-androgens, a drug prescribed to trans-gender patients?

I had never said anyone should ingest it in significant quantity.

Spironolactone was developed in the 1970s as an antagonist for the mineralocorticoid receptor, and has a higher affinity for the mineralcorticoid receptor. I feel it's androgen inhibiting effects are exaggerated because it has been shown to regrow hair and the main paradigm naturally tends towards that explanation. But as a simple steroidal receptor antagonist it could be applied directly to the receptors on the skin. Steroids are absorbed topically, and spironolactone can be found in foreign hair products.

Gynecomastia with spironolactone is somewhat rare, and ingesting it would be silly—but convenient—because it absorbs transdermally just like any other steroid. Spironolactone in the blood after topical application is undetectable, and it's probably best done topically. But as a mineralocorticoid antagonist, it will lower blood pressure. True, it is synthetic; but humans have been ingesting natural molecules with mineralocorticoid activity—as in digoxin, solanine, and oubain—for thousands of years. As long as spironolactone is understood, there is little danger. It has been used topically for hair growth in the past.

Spironolactone is the classic antimineralocorticoid, but any one should be effective. If you have a better way—besides through 11β-HSD₁—to inhibit the transcription of prostaglandin D synthase I'd like to hear it.

 

[DuggaDugga]

I had never said anyone should ingest it in significant quantity.

Spironolactone was developed in the 1970s as an antagonist for the mineralocorticoid receptor, and has a higher affinity for the mineralcorticoid receptor. I feel it's androgen inhibiting effects are exaggerated because it has been shown to regrow hair and the main paradigm naturally tends towards that explanation. But as a simple steroidal receptor antagonist it could be applied directly to the receptors on the skin. Steroids are absorbed topically, and spironolactone can be found in foreign hair products.

Gynecomastia with spironolactone is somewhat rare, and ingesting it would be silly—but convenient—because it absorbs transdermally just like any other steroid. Spironolactone in the blood after topical application is undetectable, and it's probably best done topically. But as a mineralocorticoid antagonist, it will lower blood pressure. True, it is synthetic; but humans have been ingesting natural molecules with mineralocorticoid activity—as in digoxin, solanine, and oubain—for thousands of years. As long as spironolactone is understood, there is little danger. It has been used topically for hair growth in the past.

Spironolactone is the classic antimineralocorticoid, but any one should be effective. If you have a better way—besides through 11β-HSD₁—to inhibit the transcription of prostaglandin D synthase I'd like to hear it.

I think the better way would be to lower aldosterone production naturally by lowering serotonin, lowering ACTH, minimizing unnecessary liquid consumption, consuming sodium and other electrolytes to appetite. You say, "as long as spirolactone is understood", but how well do we really understand spironolactone? Everyone wants to believe these pharmaceutical interventions provide linear, isolated cause-and-effect, but I don't believe physiology is that simple. Unfortunately we need to correct our environment, our lifestyle. Anecdotally, I took finasteride for the better part of five years with no success. Two years of "Peating" a la Danny Roddy and no one can even tell I was ever losing my hair now.
Anyways, no offense to you, Travis. I think you're an incredibly well-read, intelligent person. I think recommending spironolactone is reckless however.

Interaction between serotonin and other regulators of aldosterone secretion in rat adrenal glomerulosa cells. - PubMed - NCBI
Stress-induced Aldosterone Hyper-Secretion in a Substantial Subset of Patients With Essential Hypertension. - PubMed - NCBI

 

[Travis]

I think recommending spironolactone is reckless however.

Interaction between serotonin and other regulators of aldosterone secretion in rat adrenal glomerulosa cells. - PubMed - NCBI

Reckless? But how could it possibly be reckless when blood levels are undetectable after topical application?

Exhibit 1: Rey, F. O. "Lack of endocrine systemic side effects after topical application of spironolactone in man." Journal of endocrinological investigation (1988)​

'No changes in any levels of these hormones have been detected and plasma canrenone levels were undetectable during the 72 hours of topical treatment. Topically administered, spironolactone appears to have only a local skin impregnation.' ―Rey​

Canrenone is the metabolite, the result of dethioacetylation. There is no systemic absorption of spironolactone, or its metabolite, after topical application.

And spironolactone is, first and foremost, an antimineralcorticoid:

Exhibit 2: Sica, Domenic A. "Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis." Heart failure reviews (2005)​

'Spironolacotone and eplerenone are mineralocorticoid-blocking agents used for their ability to block both the epithelial and non-epithelial actions of aldosterone. Spironolactone is a non-selective mineralocorticoid receptor antagonist with moderate affinity for both progesterone and androgen receptors.' ―Sica​

Spironolactone has about 6.5 higher affinity for the mineralocorticoid receptor than it has for the androgen receptor:

click to embiggen​

But eplerenone has a better ratio, making this drug more antihypertensive and less antiandrogenic. However, this drug is more expensive and harder to find. Topical spironolactone is not antiandrogenic anywhere besides the skin, but Valerie Randall has shown there to be essentially no androgen receptors on the follicle and few on the surrounding dermal papilla.⁽¹⁾ Topically, spironolactone should be better because it's more antiandrogenic; Valerie Randall also has shown DHT to promote hair growth on the scalp⁽²⁾—just like it promotes hair growth on the beard.

[1] Randall, Valerie. "Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp." Journal of Endocrinology (1992)
[2] Randall, Valerie. "Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo." Journal of investigative dermatology (1992).​

In your post above (#36), we have this:

'Spironolactone, an inhibitor of androgen synthesis, has been administered to castrated men with metastatic carcinoma of the prostate.'―unattributed​

Which I think is worded in a confusing manner. I think the logical explanation for the lowered androgens seen upon spironolactone ingestion is that the body is compensating for additional pseudoandrogen (canrenone), and lowering androgen biosynthesis in a negative feedback manner in the spirit of maintaining homeostasis. The same thing has been seen with withaferin—also with a concomitant increase in facial hair growth (despite the very low testosterone, in a female).⁽³⁾ If you define an antiandrogen by its ability to lower androgens, withaferin is both an androgen and an antiandrogen. This is of course absurd, and even full‐blown androgens like DHT when taken orally would almost certainly lower de novo androgen biosynthesis.

What spironolactone does to dihydrotestosterone—the most active androgen—is nothing in comparison to what finasteride does. This drug inhibits DHT production directly by postitioning itself, rather rudely, inside of the enzyme 5α-reductase. The levels of DHT can drop from roughly thirty nanograms per deciliter down to four:⁽⁴⁾

​

Now this is dangerous. Androgens this low often cause impotence, as the nucleus of bulbocavernosus—a nervous offshoot from the spine found only in males which leads to the . . . — has androgen receptors and atrophies it their absence. Gynecomastia is also common.

Eplerenone is a better choice if taken orally since its less antiandrogenic, but topically I don't see much difference. Orally eplenerone would lower blood pressure just the same, but be nearly free of androgenic effects. But inhibiting androgens could be beneficial for those with prostatic hyperplasia, as the prostate has a relatively high density of androgen receptors which upon activation expresses the polyamine‐producing ornithine decarboxylase. Prostaglandin E₂ also upregulates this enzyme, an event that always leads to cell proliferation. Spironolactone and eplerenone both lower blood pressure, and lowering blood pressure can be considered beneficial in some people (but there are many other ways to accomplish this of course, and there are natural antimineralocorticoid agents found in certain plants).

Obviously, if anyone decides to ingest spironolactone it could be prudent to reduce the dose in the event of manboobs (unless of course, you're nursing an orphan squirrel or a lost kitten).

There is zero chance of manboobs—over that which would otherwise be expected to occur—upon the topical application of spironolactone, since doing so leads to undetectable circulating metabolite levels.

[3] Nguyen, Diep Dinh. "Effect of ashwagandha on adrenal hormones." Adrenal Insufficiency. Endocrine Society, 2013.
[4] Rittmaster, Roger. "Effect of finasteride on adrenal steroidogenesis in men." Journal of andrology (1994)​

 

[DuggaDugga]

'Spironolacotone and eplerenone are mineralocorticoid-blocking agents used for their ability to block both the epithelial and non-epithelial actions of aldosterone. Spironolactone is a non-selective mineralocorticoid receptor antagonist with moderate affinity for both progesterone and androgen receptors.' ―Sica

Spironolactone has about 6.5 higher affinity for the mineralocorticoid receptor than it has for the androgen receptor:

click to embiggen

"Moderate affinity" is not "zero affinity". Small effect does not equal zero effect. Anything that absorbs into your skin will, to some degree, enter the circulation, regardless of whether researchers decide it meets some level of statistical significance or not. The living state operates on a perfectly smooth continuum, not discrete thresholds (though the latter is convenient for research and justifying "safety" of pharmaceuticals). But never mind that for a moment;

Why would you not address the underlying deficiencies and toxicities causing the adjusted homeostasis that's leading to the pathology? Wouldn't a much more logical resolution include managing lifestyle rather than an eternity of rubbing sorta-kinda-maybe-specific chemicals into your scalp? If serotonin, parathyroid, prolactin, prostaglandins, etc. are at the heart of hair loss, wouldn't it stand to reason there is more to rectified in the individual than just the "superficial" state of hair loss? Why would we not seek to heal the individual in totality, rather than patch symptoms? Even a cursory review of the literature demonstrates age-adjusted hair loss is associated with countless other pathologies.