Finasteride has been in the news recently, unfortunately not for the right reasons. It has been linked to sexual dysfunction, depression and suicidal tendencies in men. The recent controversy surrounds purchases made by men to treat male pattern baldness. However, while these new revelations have cast a shadow over this once revolutionary drug, we risk throwing the baby out with bathwater if we dismiss its many benefits. This is why we have decided to write a blog on the history of finasteride. As with most scientific breakthroughs, serendipity and a quick-witted scientist lay at the heart of its discovery.
-
Finasteride 0.05% Minoxidil 10% Topical Hair Loss Liquid£27.99 – £167.94 -
Finasteride 0.05% Minoxidil 5% Topical Hair Loss Liquid£27.99 – £167.94 -
Finasteride 0.1% Caffeine 0.2% Topical Hair Loss Liquid£20.99 – £125.94
Guevedoces or penis at twelve
Guevedoces is Spanish for penis at twelve. This term was used to describe a group of uniuqe children from a small Dominican Republic village of Las Salinas. What made the children of this community so special? Well, the girls tended to turn into boys at puberty.
The reports of girls transforming into boys caught the attention of Dr Julianne Imperato-McGinley, from Cornell Medical College, New York. In the 1970s she made her way to the Dominican republic to study this remarkable phenomena. Little did she know that her work would lead to the development of one the world’s blockbuster drugs.
Before we discover what Dr. Imperato-McGinley discovered, let’s go over some basic biology.
XX or XY
The combination of these two letters tell us a lot about a human being. They refer to the X and Y chromosomes and from them we can determine the biological sex of a person.
If during conception your mother’s s X chromosome gets paired up with another X chromosome from your father’s sperm, then you will be destined to become a biological female. But if on the other hand your father’s sperm delivers a Y chromosome then you will become a biological male.
Sexual differentiation in the womb
Sexual differentiation in the womb is driven by a complex interplay between chromosomes and hormones.
At conception, an embryo’s sex is determined by its chromosomes (XX for females, XY for males).
About eight weeks after conception, sex hormones take over the job started by the chromosomes.
If you’re genetically male, the SRY gene on the Y chromosome provides the instructions for making a protein called the sex-determining region Y protein. This protein is involved in male sex development.
The absence of the SRY gene means the default female genitalia are allowed to develop. Isn’t it interesting that the default mode for humans is female.
The development of male genitalia
If the embryo is genetically male (XY), the presence of the SRY gene on the Y chromosome triggers the undifferentiated gonads to develop into testicles at around eight weeks.
The testicles produce testosterone, which plays a critical role in the development of internal male reproductive structures, such as the vas deferens and seminal vesicles.
The role of testosterone and dihydrotestosterone (DHT)
For the external genitalia to develop into male structures, testosterone must be converted into a more potent hormone, dihydrotestosterone (DHT), by the enzyme 5-alpha reductase.
DHT is essential for forming male external genitalia, including the penis and scrotum, and it also influences the development of the prostate.
Without sufficient DHT, the male genitalia cannot fully masculinise, even if testosterone levels are normal.
Deficiency of 5-alpha reductase
Dr. Imperato-McGinley discovered the reason behind the lack of male genitalia at birth was because the Guevedoces were deficient in an enzyme called 5 -alpha reductase. This is the enzyme responsible for converting testosterone into the more potent dihydrotestosterone or DHT.
A deficiency in 5-alpha reductase, the enzyme responsible for converting testosterone to DHT, results in a condition known as 5-alpha reductase deficiency.
This is a rare genetic disorder that can lead to ambiguous or underdeveloped genitalia at birth. Affected individuals typically have XY chromosomes and functional testicles that produce testosterone, but due to the lack of DHT, their external genitalia may appear more typically female or ambiguous.
The village of Las Salinas
In the small, isolated village of Las Salinas where this rare genetic mutation was discovered, about 2% of babies born as males (with 46 XY chromosomes) appeared to have female genitalia at birth.[1]
These children were raised as girls, but at puberty, they experience a second surge of testosterone, and this time their bodies respond by developing muscles, testes, and a penis, similar to other boys.
Since at around the age of 12, the small phallus developed into a functional penis, the local term “Guevedoces” meaning “penis at 12” was coined.
Their testes descended into a scrotum, their bodies became more muscular, their voices deepened, and they typically developed a male gender identity.
After puberty, the Guevedoces live like other males in the community. However, there are a few differences: they have little facial hair, no acne, their hairline does not recede, and their prostate remains small throughout their lives.[1]
What caused the Guevedoces phenomena
The unique characteristics of the Guevedoces are due to the differing roles of testosterone and DHT (dihydrotestosterone) in the body. Testosterone levels in these individuals are normal, but DHT is significantly reduced.
Before birth, testosterone plays a key role in developing internal male reproductive structures like the seminal vesicles, vas deferens, epididymis, and ejaculatory ducts. After puberty, testosterone is responsible for typical male changes such as increased muscle mass, a deeper voice, sexual drive, growth of external genitalia, and sperm production.
On the other hand, DHT is crucial before birth for forming male external genitalia. However, after puberty, DHT is often considered a “troublemaker” hormone because it causes facial hair, acne, male-pattern baldness, and prostate growth. In the case of the Guevedoces, the lack of DHT explains their distinctive development patterns.[1], [2]
So, what was it about the Guevedoces that made the researchers at Merck so excited? It was Dr. Imperato-McGinley’s observation that the Guevedoces tended to have small prostates.
DHT and the prostate
Testosterone, the main male hormone, isn’t the primary driver for prostate growth—that role belongs to DHT (dihydrotestosterone).[3]
DHT is made inside prostate cells when the enzyme 5-alpha reductase (5AR) converts testosterone into DHT.
While testosterone is more abundant in the bloodstream (about 10 times higher than DHT), within the prostate, DHT levels are much higher because it binds more strongly to androgen receptors and doesn’t decrease with age like testosterone does.[4]
This consistent presence of DHT in the prostate is thought to play a key role in developing conditions like benign prostatic hyperplasia (BPH).[5]
The types of 5-alpha reductase enzymes
There are two types of 5AR enzymes [6] that convert testosterone into DHT:
- Type 1 is mainly found in the liver and skin, contributing DHT to the prostate through the bloodstream.[5]
- Type 2 is the dominant form in the prostate and directly creates DHT within the gland.[5]
In certain rare conditions, like those seen in individuals from the Dominican Republic with 5AR deficiency, the Type 2 enzyme doesn’t function properly. This leads to significantly lower DHT levels in the prostate and alters development.[1]
The development of finasteride
Scientists realised that if they could block the enzyme 5-alpha reductase (5AR) after the male genitalia had fully developed, they could create a safe medication to shrink the prostate, relieve urinary symptoms associated with benign prostatic hyperplasia, and even treat male pattern baldness.
This idea led to the development of drugs like finasteride, which the FDA approved in 1992 for treating enlarged prostates (BPH) at a 5mg dose. Later, finasteride was also approved to treat male pattern hair loss using a reduced dose of 1mg. [7]
Summary
Over 30 years ago, no one could have predicted the huge breakthrough in prostate treatments that came from studying a group of people in the small Dominican Republic village of Las Salinas.
Those individuals, known as “Guevedoces” (which means “penis at 12” in Spanish), had the rare genetic condition called 5 -alpha reductase deficiency which prevented the normal development of male genitalia and characteristics until they reached around 12 years old.
This discovery helped shift the focus of urology from just surgery to treatments involving medication and less invasive procedures.
The biggest impact of the Guevedoces was the development of a group of drugs called 5?-reductase inhibitors (5ARIs), which became the first “prostate pills” and later were also used to treat male pattern baldness.
-
Finasteride 0.1% Caffeine 0.2% Topical Hair Loss Liquid£20.99 – £125.94
-
Finasteride 0.1% Minoxidil 5% Topical Hair Loss Solution£27.99 – £159.99 -
Finasteride 0.1% Minoxidil 10% Topical Hair Loss Solution£29.99 – £170.99
Safety of finasteride
The Medicines and Healthcare products Regulatory Agency (MHRA) is introducing a patient alert card for men taking finasteride to raise awareness about possible psychiatric and sexual side effects, including depression, suicidal thoughts, and sexual dysfunction.
Patients are advised to read the medicine leaflet and seek medical advice immediately if they notice mood changes or sexual health issues.
If you are concerned about the safety of using finasteride for male pattern baldness please contact us and one our prescribers will go over the risks and benefits.
At Medical Mojo we can reduce the risks associated with finasteride by compounding it as a topical solution. This means there is less systemic absorption and hence fewer side effects.
To learn more, read our blog: How to reduce the side effects of finasteride
Disclaimer: This information is for educational purposes only and is not a replacement for professional medical advice.
References:
- Imperato-McGinley, J., Guerrero, L., Gautier, T. and Peterson, R.E., 1974. Steroid 5?-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science, 186(4170), pp.1213-1215.
- Bartsch, G., Rittmaster, R. and Klocker, H., 2002. Dihydrotestosterone and the concept of 5?-reductase inhibition in human benign prostatic hyperplasia. World journal of urology, 19, pp.413-425.
- McConnell, J.D., 1995. Prostatic growth: new insights into hormonal regulation. British journal of urology, 76, pp.5-10.
- Wilson, J.D. and Walker, J.D., 1969. The conversion of testosterone to 5?-androstan-17?-ol-3-one (dihydrotestosterone) by skin slices of man. The Journal of clinical investigation, 48(2), pp.371-379.
- Marks LS. 5alpha-reductase: history and clinical importance. Rev Urol. 2004;6 Suppl 9(Suppl 9):S11-21.
- Carson III, C. and Rittmaster, R., 2003. The role of dihydrotestosterone in benign prostatic hyperplasia. Urology, 61(4), pp.2-7.
- U.S. Food and Drug Administration. (1997). Propecia (finasteride) tablets, 1 mg: Medical review (NDA 20-788). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20788_PROPECIA%20TABLETS,%201MG_MEDR_P1.PDF
Are weight loss treatments making you tired, or have they led to a sudden increase in hair loss? Do you struggle with sleep?
Get a free month’s supply of one of our compounded treatments for energy, hair loss or sleep, with your first purchase of Mounjaro or Wegovy from Medical Mojo.
Claim your FREE offer
