I just read the
full text of the rat study which provides the strongest suggestions for opposing roles of ER-alpha and ER-beta in hair. It's a fascinating read. Overall, I think this all provides some basis for about 50-70% of a good unified estrogen theory, which I will try to present to the best of my ability here.
I think we can conceptualize that estrogen works to affect hair growth in a few possible ways:
1) Systemic Castration Effect - Large doses of systemic estrogen in men leads to dramatic suppression of testosterone/androgen production. This is part of the intended purpose of taking estrogen in M>F transexual regimens. ie. Chemical castration. Shutting down androgens will always lead to an improvement in male pattern baldness. So any large amount of estrogen will likely be a "net positive" for male androgenic alopecia, regardless of what type is chosen, via this mechanism alone.
2) 5-alpha Reductase Inhibitor Effect - Estradiol has been shown to have an inhibitor effect on 5-alpha reductase (thus suppressing DHT production like finasteride/dutasteride). Probably it will work both locally and systemically for this effect. Interestingly enough, highlighting yet another difference between natural and synthetic estrogens (
@Georgie), ethinyl estradiol does not have the same 5-AR inhibiting properties as natural estradiol. (
ref)
3) Anti-Sebum Effect - Estrogen is known to downregulate sebum production in a disproportionate manner but it's not entirely known how. Sebum is known to increase hair inflammation and thus loss. Perhaps this is just a manifestation of the 5-ar inhibition effect, or maybe it is a separate behavior.
To summarize the principle:
Estrogens are also powerful suppressors of androgen-stimulated sebaceous activity in doses markedly lower than those required for anti-androgens (Ebling, 1974), the mechanism of action of estradiol in the sebaceous gland was concluded to be distinct from that of an anti-androgen (Ebling, 1974) suggesting that estrogens act via a non-androgen receptor (non-AR)-dependent pathway.
4) Androgen Receptor Downregulation Effect - ER-beta stimulation by soy isoflavones (phytoestrogens) has been shown to downregulate androgen receptors in the prostate. If they can do the same in the hair, this can make our hair more androgen resistant.
5) Direct Hair Cycle Manipulation Effect - Estrogen signalling pathways can directly manipulate the transition between telogen (shed) > catagen (rest) > anagen (growth). This is the newest and least well understood piece of the puzzle. Making this aspect more complex is that it seems there may be different mechanisms for different mammals, men vs. women, and different areas of the scalp. Science does not have all the answers here from what I can see, so we are stuck to speculate.
The rat study strongly seemed to suggest that in mice at least:
- ER-alpha promotes catagen and thus hair loss.
- ER-beta promotes an anti-oxidant and protective effect while also shutting off ER-alpha induced catagen signalling.
Here are a few pertinent excerpts from the study:
ERα expression is hair cycle dependent (with an expression maximum in telogen skin), whereas ERβ expression is more constant throughout the HF cycle (Fig. 2). Therefore, our results are consistent with the concept that stimulation of ERα, not ERβ, functions as a molecular hair cycle brake in mice.
Catagen progression is accelerated in mice lacking ERβ (Fig. 6). This supports the concept that, as in other organs, e.g. the uterus and mammary gland (43, 57), ERβ, (including ERβ ins), functions as a quencher of ERα-mediated effects.
ERβ stimulation by antiestrogens may mediate antioxidant actions on activator protein-1 sites by inducing quinone reductase (64), and the antioxidative stress enzymes glutathione S-transferase-π and γ-glutamylcysteine synthase are up-regulated by transcriptional activity of ERβ (65). Therefore, one role of ERβ may be to protect tissues from oxidative stress by inducing a battery of antioxidative enzymes (64, 65). Thus, the widespread and constant expression of ERβ within the pilosebaceous unit may also serve to protect the skin and its appendages, which are continuously more exposed to oxidative damage than most other organs.
Adding tangential support for ER-alpha = bad, ER-beta = good is some research I have just reviewed on prostate cancer. We know prostate problems are linked to androgenic alopecia, as those of us with hair loss are at higher risk of prostate cancer, and the same meds for enlarged prostates treat hair loss.
Here's a study summarizing some research on how ER-beta and ER-alpha connect to prostate cancer.
Here's another with the final punch line that suggests overall, just like with hair, ER-alpha = bad for prostate, and ER-beta = good for prostate:
Most evidence suggests that ERA mediates the harmful effects of estrogen in the prostate, whereas ERB is tumour suppressive.
My current biggest problem with the simplified ER-beta/ER-alpha theory is the fact that ER-alpha is not very much expressed in the human scalp as per
this study. If there are no significant ER-alpha receptors in the human scalp, then it may not be so simple. However, this was just one study and it focused on occipital nonbalding scalp. It makes me wonder if we would see more ER-alpha receptors in balding areas. It would be nice if that was the case as it would really tie all this together very neatly. We can't know for sure unless someone does a study to prove it.
Advantages of the ER-Alpha vs. ER-Beta Theory
To summarize, then, overall, I like this simplified theory of ER-beta being good for hair, and ER-alpha being bad as it fits with a number of things:
- Explains why pregnant women have a dramatic improvement in skin and hair after 12 weeks pregnancy, as estriol shoots up and they shift to a more ER-beta balance, and then hair sheds after pregnancy when estriol again drops.
- Explains why topical steroids in combination with estrogens help hair growth, as steroids increase ER-beta receptor expression.
- Explains why menopausal women tend to thin all over as menopause generally represents a shift towards estrone which is the most ER-alpha predominant natural estrogen.
- May explain why some women have hair shedding on birth control pills (ie. ethinyl estradiol which is weighted to ER-alpha activity).
- Fits with findings that ER-beta is likely generally good for prostates and ER-alpha is bad for them (knowing that the underlying processes of prostate pathology tend to mirror those of hair loss).
- Explains why S-Equol was chosen as a primary ingredient for the development of Brotzu (selective ER-beta agonist).
This is nowhere near a perfect theory. But I think this in total represents the most comprehensive theory of estrogen and hair that we can currently assemble. Current studies on estrogen and hair growth are poor in general. One of them from China I reviewed with
@bridgeburn a few months ago was riddled with errors that we easily picked up, so it goes to show that peer review is not perfect and we can't assume every study is perfect fact. When some studies contradict others, it may not be that estrogen is infinitely complex and beyond our potential for understanding. It may just be that some studies are crap.
Estrogen may in fact be simpler than it appears.
Final Outcomes
All this then provides more weight towards considering genistein as the cheapest, most freely available, and best suited topical estrogenic agent for hair growth, at least if growth cycle manipulation is your primary goal. Estriol would be the most ideal topical of the natural estrogens for hair.
For my own part, this is probably the absolute worst time for me to start experimenting with another agent, as I just had major scalp surgery last week. I will probably try to avoid starting genistein until at least 2-4 weeks from now to be sure my hair is stable first and not going Telogen Effluvium just from my surgery. I will continue estriol on my face and hairline unabated as I've been using that already for 2 months with good results.
I think that even if time shows there are more pieces to the estrogen puzzle, most of this general theory will be proven to be correct in time. I also think this concludes the useful extent of research that I can do on estrogen at this stage.
We'll see how the experiment goes in time.
