Estrogen Therapy and Hair Growth

For the male readers of this blog, estrogen (also known as oestrogen) is not something that one would consider to be of interest. For one, estrogen is largely a female sex hormone. What male would want to start taking it and develop female secondary sexual characteristics such as breast enlargement?

Having said that, estrogen does have some properties that benefit overall health. Among these include heart protection (less atherosclerosis); strengthening of immunity; and reduction of inflammation. High levels of estrogen are though to be one of the reasons behind why females outlive males. The main negative of high estrogen is a greater chance of developing breast cancer.

Update: Recently, I discovered the below advice on Realself from Dr. Stephen Mulholland. He gives estrogen injections to his hair loss patients. I do not know of any other hair transplant surgeon who publicly advertises such a unique treatment strategy.

Estrogen Hair Loss
A doctor recommends estrogen injections as a hair loss treatment.

Update: December 24, 2021

Estrogen Monotherapy for Hair Growth

Since I originally wrote this post, I have become increasingly fascinated by estrogen’s hair growth properties. In my 2021 updated post on Male-to-Female (MTF) transgender persons, some of the before and after transformations are astounding.

Most transgender females take estrogen (typically in the form of estradiol, aka “E2”) as well as Finasteride or Dutasteride. Many also add anti-androgens such as spironolactone or cyproterone acetate into the mix. This is known as hormone replacement therapy (HRT).

What I am most curious about is non-transgender men who only use topical estrogen (cream, lotion, patch or spray) to regrow their hair. I would have never though that this would be a very effective solo hair loss treatment. Moreover, some amount of topical medication always gets absorbed into the bloodstream. So the feminizing side effects are likely to be significant, even if perhaps less so than with injected or oral estrogen supplementation.

Diane-35 and Alfatradiol

Some women take Diane-35 (which is a combination of ethinylestradiol estrogen and cyproterone acetate) to tackle androgen-dependent conditions. These include acne, seborrhea, hirsutism and scalp hair loss.

Yet others take alfatradiol, also known as 17α-estradiol. It is a weak estrogen and 5α-reductase inhibitor that is used topically in the treatment of pattern hair loss. One famous study found that topical alfatradiol resulted in deceleration or stabilization of hair loss in women, but did not increase hair thickness and density like topical minoxidil.

Reddit to the Rescue

What encouraged me to re-examine subject matter is Reddit. In recent months, I have seen a number of threads by people focused on using estrogen monotherapy to treat hair loss. In many cases, the “monotherapy” is ultimately supplemented with Minoxidil or Finasteride, but this is still okay by me.

I do not frequent Reddit more than twice a week, and rarely go to the transgender related subreddits. So I likely missed dozens of other threads in 2021. Thankfully, I bookmarked the below ones. I hope to ultimately find more such testimonials from males who are definitely not transgender. In the comments, feel free to post links to any that you find interesting. And they need not just be limited to Reddit.

  • Yesterday, someone posted a question titled “Can estradiol mono-therapy help grow back your hairline”? Several of the responses are quite encouraging.
  • Three days ago, someone posted this amazing transformation from using just Finasteride and Oestrogel for two years. She claims that this is all her real hair.
  • One month ago, someone posted a very interestingly titled thread with six before and after photos (make sure to swipe right of each image). According to this person’s theory, an artificial selective estrogen receptor modulator (SERM) would be almost as good as a hair loss cure. Provided it is combined with an oral Minoxidil and an anti-androgen. Note that most people prefer an anti-androgen and DHT blocker combination. But oral Minoxidil is becoming a lot more popular too.
  • Earlier in 2021, someone posted phenomenal before and after results from using just estrogen plus Minoxidil as a hair loss treatment. I would guess that the vast majority of this transformation is due to the estrogen.

February 25, 2015

Estrogen Hormone Therapy and Hair Growth

The reason I decided to write a post on estrogen is because I recently read an extremely interesting 2012 interview with Dr. George Cotsarelis. While the main part of the interview is devoted to the oft discussed PGD2, there are several other interesting subjects discussed. The second page of the interview is what really surprised me in a good way.

In the first part of this interview, Dr. Cotsarelis discusses the old and well known Dr. James Hamilton study from the 1950s. In this research, it was found that men who were castrated before puberty (eunuchs) never went bald. However, upon being given testosterone, those with a family history of baldness still started to loose hair.

The second part of the interview is more interesting. It covers the fact that even after someone has lost much of his hair due to androgenic alopecia, he can regrow a lot of it when given estrogen (after castration)!

This point is supposedly verified by many studies on Male-to-Female (MTF) transitioning transgender persons. Such patients show hair regrowth after their being castrated and getting on estrogen hormone replacement therapy (HRT). Usually with the addition of an anti-androgen such as Spironolactone.

While I do not think any of us men want to get castrated or take estrogen (estradiol), this is still an incredible finding. One of the best examples is in the before and after image below from this study.

Estrogen Hair Growth
Estrogen (Estradiol) treatment for hair growth. Source: Journal of the American Academy of Dermatology.

Note that both estrogen and progesterone extend the anagen growth phase cycle of hair follicles. In contrast, testosterone and dihydrotestosterone (DHT) do the opposite and shorter the hair growth phase. Make sure to also read my post on how finasteride impacts testosterone and estrogen levels.

Hair Regrowth Difficulties

Over the years, I have read a number of articles in which doctors and professionals seem to suggest that once hair is gone (turns vellus), it can never return. This is also why Finasteride and Minoxidil virtually never bring back any significant amount of hair for someone who is mostly or entirely bald. However, it seems like hair can regrow in fully bald areas of the scalp in some instances.

There have been anecdotal reviews on Dutasteride actually regrowing long dormant hair. But these have been few and far between. Over a decade ago, Dr. Marty Sawaya caused an insane level of excitement on hair loss forums when she reported that one of her older patients gained back most of his lost hair when on Dutasteride. But that whole episode was controversial and not replicated.

More recent research suggests that a balding scalp still has all the follicle stem cells intact. But certain progenitor cells have become depleted. Basically, the cells are there, but the activity is not there. Dr. Cotsarelis has suggested that perhaps blocking PGD2 will allow the stem cells to make progenitor cells again. However, this is not a certainty, and neither is hair regrowth guaranteed once PGD2 is inhibited.

I suspect that this powerful impact of estrogen on hair regrowth is still not strong enough to grow back all of one’s lost hair. This is because many older balding MTF transsexuals seem to get hair transplants even after getting castrated and beginning estrogen therapy.

Finally, for men who take Finasteride (Propecia, Proscar), one potential side effect is increased estrogen levels. This sometimes results in the dreaded gynecomastia (male breast enlargement), along with fat gain in other parts of the body. Their are numerous complaints on hair loss forums about this side effect. Most studies indicate that the chances of developing gyno from taking 5-alpha-reductase inhibitors is extremely low.

Replenology: Arbor Life’s Branded ALRV5XR

A few months ago, I heard about a relatively new company named Replenology. It is headquartered in Canada, and produces a natural hair growth product with 21 key hair growth pathway targets.

Replenology Hair Growth
Replenology supplement, serum, shampoo and conditioner.

This week, someone on our chat mentioned Arbor Life Labs and its ALRV5XR hair growth product.

Upon further research, I discovered that Replenology® is Arbor Life Labs’ branded version of its ALRV5XR hair regeneration product.

Replenology: 21 Hair Growth Pathways

I am very skeptical about natural and botanical products for hair growth being able to reverse baldness. However, countless studies have proven that natural products are able to make existing hair thicker and stronger. In some cases, even reverse recent hair loss (at least temporarily).

In recent years, things such as propolis, sandalwood and seaweed have all been in the news for their hair growth properties. The most famous natural product to benefit scalp hair is saw palmetto via its modest dihydrotestosterone (DHT) blocking activity.

While their Instagram is not updated regularly, I found Replenology’s website content to be of high quality. In particular, their amazing “21 to Grow” brochure (the product targets 21 factors or pathways that contribute to hair loss). The active natural ingredients (expand below image) target different molecular pathways that promote hair growth. Although I am still skeptical, kudos to this company for making such a great effort. Make sure to also read my past post on natural DHT blockers for hair growth.

Over 200 Ingredients

The number of ingredients in Replenology’s product portfolio (capsule supplement, follicle serum, shampoo and conditioner) easily exceeds 200. The below screenshot only lists the active ingredients. See a more complete list here.

Replenology ALRV5XR Active Ingredients
Replenology ALRV5XR active ingredients for hair growth.

Hair Follicle Health

The Replenology formulation targets seven key area of hair follicle health:

  1. Growth factors.
  2. Circulation.
  3. Anti-androgens.
  4. Follicle protection.
  5. Hair stem cell stimulation.
  6. Immune regulation.
  7. Nutrition.

Among the natural ingredients include ones that reduce DHT; inhibit PGD2; inhibit the COX enzyme; inhibit the interferon (IFN) class of cytokine proteins; increase good (when it comes to hair growth) interleukins (IL-10) and decrease bad ones (IL-1 and IL-6); and block the negative effects of TNF-α and TGF-ß on hair cells;.

The formulation also further activates the Wnt/ß-catenin pathway to increase cell proliferation; influences the SHH (Sonic Hedgehog) pathway and induces the anagen (growth phase) of resting hair follicles; inhibits the bone morphogenic protein (BMP-4); stimulates the noggin protein; activates mTORC1 (target of rapamycin); activates FGF-7; inhibits FGF-18; activates hepatocyte growth factor (HGF); activates insulin-like growth factors (in particular, IGF-1); activates vascular endothelial growth factor (VEGF).

It is hard for me to believe that one oral supplement (even if combined with topical shampoo, conditioner and serum) can do all the above. Especially beyond a modest efficacy level. At present, you cannot find Replenology products on Amazon, so no reviews and ratings on that site.

In any event, I am glad that someone has finally tried to come up with an all-encompassing hair loss product. Something that I implied in my 2019 post on “creating the ultimate hair loss drug cocktail“.

ALRV5XR from Arbor Life Labs

Arbor Life Labs completed separate safety and efficacy clinical trials for male and female androgenetic alopecia patients in 2020. Both trials entailed 46 subjects each. The treatment entailed a dietary oral supplement of ALRV5XR, a hair follicle serum, a shampoo and a conditioner.

The company’s current pipeline indicates that ALRV5XR trials are complete. This is probably because you do not need three trials for natural products.

Arbor Life ALRV5XR Pipeline
Arbor Life Labs’ ALRV5XR hair growth product clinical trials and pipeline.

The Phase 1 trial results were discussed (separately, for men and women) in the prestigious Lancet journal in 2021. However, note that the lead author Mr. Peter Feldman is also the co-founder and CEO of Arbor Life as well as CEO of Replenology.

  • September 11, 2021: Safety and efficacy of ALRV5XR in men with androgenetic alopecia: A randomized, double-blinded, placebo-controlled clinical trial. Also in ScienceDirect in October 2021.
  • June 23, 2021: Safety and efficacy of ALRV5XR in women with androgenetic alopecia or telogen effluvium: A randomized, double-blinded, placebo-controlled clinical trial. See the PR News article from October 19, 2021 (included a before and after photo).

The findings indicate that ALRV5XR caused new terminal hair growth in both men and women. Arbor Life’s patent for ALRV5XR is pending, and is titled as:

“Botanicals as Wnt/β-Catenin Activators, Molecular Pathway Regulators, Tissue Regenerators and Health Biomarker Regulators.”