Category Archives: Acne

Novan, Acne, Nitric Oxide

Novan, Nitric Oxide, Acne and MPB

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Recently, reader “John Doe” brought to our attention a US-based biotechnology company named Novan. Their work in developing a topical nitric oxide based product for male pattern baldness (MPB) seems quite unique and is worth a post.

Update: April 2024 — Ligand Pharmaceuticals acquired the rights to some of the technologies of Novan in September 2023. Now they have launched Pelthos Therapeutics to accelerate the launch of ZELSUVMI.

Novan, SB204, Acne and Hair Loss

Novan (sometimes also called Novan Therapeutics) is developing a number of dermatological products. Per its pipeline, their acne vulgaris product SB204 is already in stage 3 clinical trials. This is the same product that can also be used for hair loss.

However, unlike Cassiopea (Breezula for MPB and Winlevi for acne), Novan is not undertaking separate trials for its hair loss product. The company does list androgenetic alopecia as a potential therapeutic application of nitric oxide at the bottom of its pipeline page.

Perhaps the assumption is that if Novan’s topical nitric oxide (NO) based SB204 product for facial acne is proven safe, it can also be used on heads? And this can be done without necessitating FDA approval for such off-label use? In any event, who can prevent someone for getting a prescription for SB204 for acne, but then using it on their head instead?

Initially, I thought that Novan was a new company. However, it seems like they have been working on NO based drug candidate products since 2010.

Novan Pipeline Acne and Hair Loss
Novan’s nitric oxide based dermatological products pipeline.

Nitric Oxide and Hair Loss

Over the years, I have read about Sildenafil (Viagra) impacting nitric oxide pathways and temporarily curing erectile dysfunction. The vasodilatory effect from Sildenafil relaxes and widens blood vessels. I have also heard about nitric oxide’s important cardiovascular impact. In 1992, NO was voted as the molecule of the year.

However, I have not paid much attention to nitric oxide levels on the scalp and their impact on hair loss. One clinical trial in China that ended in 2013 compared the safety and efficacy of nitric oxide gel in promoting hair growth in men. No results were posted.

According to an excellent paper from Novan’s Dr. William Kelce, nitric oxide on the scalp or skin can inhibit skin steroidogenesis. This results in reduced levels of key androgens testosterone and dihydrotestosterone (DHT). Nitric oxide also reduces sebum levels.

Even more interesting than its anti-androgenic effects, nitric oxide levels can inhibit prostaglandin D2 (PGD2) synthesis. See my past posts on the connection between PGD2 and balding.

It has been postulated that one of the ways in which laser hair growth devices benefit scalp hair growth is via stimulating increased nitric oxide levels. Moreover, it is thought that Minoxidil has the chemical structure of nitric oxide and may be a nitric oxide agonist.

Spironolactone, Acne, Aldactone, Anti-Androgen, Hirsutism, PCOS, Seborrheic Dermatitis

Spironolactone for Hair Loss

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Spironolactone and Hair Loss
Spironolactone for hair loss.

On this blog, I have often discussed the only two (Finasteride and Minoxidil) FDA approved drugs to treat hair loss. Finasteride is an oral drug that inhibits the enzyme 5α-reductase, which in effect then reduces the harmful-to-hair dihydrotestosterone (DHT).

Minoxidil is an antihypertensive medication that also happens to benefit scalp hair when used topically. This post covers a hair growth medication called Spironolactone (brand names Aldactone or Carospir).

Update: March 9, 2023 — A systemic review of the efficacy and safety of oral and topical Spironolactone in the treatment of androgenetic alopecia.

Anti-Androgens

When it comes to hair loss medications, one area that I have neglected is anti-androgens such as Spironolactone, which have many favorable reviews. I did discuss RU-58841 in one post at the start of this year. However, there are numerous other anti-androgens out there, such as Fluridil and Flutamide.

In general, the potential side effects from anti-androgens are more severe than from Finasteride and Minoxidil. Moreover, scalp hair regrowth is typically more significant with Finasteride and Dutasteride.

Note that while some strict definitions consider Finasteride to also be an anti-androgen due to its inhibition of DHT, I only consider drugs that inhibit the binding of testosterone to androgen receptors as being anti-androgens. Finasteride, while reducing DHT, actually raises testosterone levels by around 10 percent. Also worth noting is that the popular Nizoral shampoo might have some anti-androgenic properties per several recent studies.

In this post I will discuss the most popular “true” anti-androgen in the world: Spironolactone.

Spironolactone for Hair Loss

Spironolactone (generally sold under the brand name Aldactone) is also referred to as “Spiro” and is a synthetic drug available via prescription. It belongs to a class of drugs known as potassium-sparing diuretics, and is used primarily as a diuretic and antihypertensive in the treatment of heart failure and hypertension.

However, secondary anti-androgenic applications have become more prevalent in recent decades. Spironolactone can stop hair loss, reduce body hair (hirsutism), reduce acne, help women with polycystic ovary syndrome (PCOS) and improve seborrheic dermatitis.

In 2020, a study found topical Spironolactone 1% gel and Minoxidil 5% gel to be an effective combination treatment for hair loss. An older study from 1998 concluded that topical Spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands

Spironolactone Side Effects

While this drug may seem like a miracle product that can kill many birds with one stone, potential side effects are significant and plentiful. For men, feminization is a real danger when taking Spironolatone, meaning that you can developed gynecomastia (larger breasts) and see your testicles shrink. Men can also develop premature ejaculation and become infertile (although in most cases it seems like this side effect is not permanent) when taking this drug.

Less traumatic side effects include drowsiness, dry skin, excess urination, headache, nausea and vomiting. Spiro can potentially even lead to death from severe allergic reactions, hyperkalemia, kidney failure and more, although I have not read about this happening to any hair loss forum members. In general, the doses that hair loss patients take tend to be on the lower side.

You can learn a lot more about Spiro and its use to treat hair loss by tracking patients that take this product and post about it in the various online hair loss forums. I have never tried to take Spironolactone since I am very cautious when it comes to taking any kind of drug.

Mechanism of Action

Aldactone (Spironolactone) is a specific pharmacologic antagonist of aldosterone. It primarily acts through competitive binding of receptors at the aldosterone dependent sodium-potassium exchange site. Aldactone causes an increase in sodium and water excretion rates, while potassium is retained. The drug therefore acts as both a diuretic as well as an antihypertensive via this dual mechanism.

Spironolatone for Male-To-Female Transsexuals

I first learnt about Spironolactone when I read testimonials and forum posts from numerous male-to-female (MTF) transsexuals out of my own curiosity many year ago. It seems like estrogen and Spiro are the two main drugs that MTF transsexuals are almost always given.

Moreover, transsexuals often have to take a much higher dosage (100-200 mg per day to start, and considerably higher doses if ineffective) of Spiro compared to men or women who are only tackling balding. It is therefore important for you to visit transsexual/transgender forums on the internet and ask questions if you ever intend to take Spiro.