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Science & Humans
5α-reductase, the enzyme responsible for converting testosterone to dihydrotestosterone, exists in 2 forms: Type 1 and Type 2. Finasteride selectively inhibits Type 2 whereas dutasteride inhibits both forms. Dutasteride curbs 20 to 24 percent more 5a enzyme; consequently, prevents more DHT conversion (94%) than finasteride(70%) in the scalp. DHT in the scalp causes hereditary hair loss in men, and male pattern baldness(MPB) is the most prevalent cause of hair loss.
Different Factors that Cause Androgenetic Alopecia or MPB
The medical term Androgenetic Alopecia (AGA) points to the role of androgens and genetic factors causing progressive hair loss in men. DHT is a potent form of testosterone, the androgenic hormone that defines male characteristics and plays an important role right from fetal stage to old age in men. But DHT in the scalp causes hair loss to those who have the gene that makes them susceptible.
Here is a caveat. Although a gene is responsible for hair loss, and is inherited, the trigger that releases the gene can be unhealthy lifestyles - Late nights, junk food, sedentary habits. So if baldness does not run in the family and just the one case this may be the reason.
How are Type-1 and Type-2 5a Reductase Enzymes Different?
Type 1 5AR enzyme is mostly found in the liver and skin, and a bit in the prostate as well. It is also the dominant isoform or protein variant in sebaceous glands. The face and scalp have the highest amount of sebaceous glands, and they are found around hair follicles.
Dutasteride is three times more effective than finasteride in inhibiting TYPE-1 and one hundred times more effective against Type-2. Another reason why dutasteride prevents more DHT conversion than finasteride.
Type 2 5AR enzyme is the dominant isoenzyme in the prostate, and is minimally present in the liver and skin.
The primary function of both type 1 and type 2 5a reductase enzyme is to convert testosterone to DHT.
Half-Life
Dutasteride also has a longer half-life of 5 weeks compared to the half-life of 5-6 hours for finasteride. This can also factor in the higher efficacy of dutasteride to mop up DHT.
Drug Development and FDA Approval
Dutasteride is the new kid on the block, extremely enthusiastic and too good at the job, while Finasteride is the mature adult who does what is required. Finasteride has been well researched, studied since it was patented in the 70s and FDA approved for hair loss in 1998.
Dutasteride is a new drug approved to treat Benign Prostate Hyperplasia(BPH) in 2001, and is not yet FDA approved for hair loss. It is prescribed off label to treat hair loss from male pattern baldness for now. It will be approved as more trial data is assimilated and long-term effects, adverse side effects are well established.
Forms of Drug Delivery and Dosage
Oral (1mg/day pill) and topical finasteride(.5 mg with minoxidil) is a well established treatment for alopecia (hair loss) The treatment can be only topical as well depending on when treatment started. If treatment started early in 20s as a preventive measure the need to take both forms might not be necessary. If treatment starts later it benefits to use both forms of medication. Some topical finasteride solutions can be a bit higher than .5 mg.
Due to the high potency of dutasteride, .5 mg is prescribed for hair loss and the 5 mg tablet for treating Benign Prostate Hyperplasia(BPH).
Liposomal drug delivery of topical dutasteride and finasteride is another form which is coming into vogue. It has not become mainstream yet. Results from a few studies demonstrate that the skin permeability or rate of absorption in the skin is much higher using this drug delivery method. This was established by growing hair on excised abdominal mice cells. The liposomal formulation showed a seven fold higher deposition of drug in skin as compared to hydro-alcoholic solution and conventional gels. Overall the study proved improved and localized drug action in the skin and thus could be formulated as a better option to cure androgenetic alopecia.
What is Liposomal Drug Delivery?
Liposomal drug delivery is a process where fatty (lipids) medium is used to form a multi-layered envelope or bubble to target drug delivery to specific parts of the body, to prevent adverse side effects or damage other parts of the body.
Nano-Particle Drug Delivery
Several studies have suggested that nanoparticles are able to deeply penetrate into hair follicles after topical application to human and animal skin, with some researchers suggesting that follicular delivery is more efficient with nanoparticles with diameters under 300 nm compared to larger nanoparticles. Mostly in the experimental stage these are the future in hair loss treatments.
Side Effects
Both medications work similarly, and have similar side effects. Dutasteride with its higher rate of efficiency might increase estrogen, with higher chances of gynecomastia, breast tenderness. But with right dosage, and active monitoring of the doctor, side effects are manageable.
In long term studies of finasteride and dutasteride treating BPH, feeling dizzy while sitting up was noted as a side effect.
Most noted side effects are loss of libido which can be reversed by stopping usage, watery sperm, and watery ejaculation.
Side effects do go away after the body adjusts to the medication, or can be safely managed.
Important point to note: while those suffering from MPB hair loss, and those who do not have comparable levels of DHT, it is the scalp concentration of DHT that really matters.
While topical solutions stay on the scalp itchiness from the Poly propylene glycol, and ethanol, dryness can be a bother for sensitive skin. Water based formulations should be used to avoid itchiness.
If pregnant women come into contact with finasteride or dutasteride, they should immediately wash the area with soap and water. It might affect the development of a male fetus.
Considering dutasteride is highly potent, and DHT is an essential hormone for the male body to function effectively, prescribing dutasteride will be under doctor's discretion depending on medical necessity weighing pros and cons of both medications.
FAQs
What is the role of 5α-reductase enzymes in hair loss, and how do finasteride and dutasteride work?
5α-reductase enzymes are responsible for converting testosterone into dihydrotestosterone (DHT), a potent androgen that, in genetically predisposed individuals, leads to hair follicle miniaturization and male pattern baldness (MPB). There are two types of 5α-reductase: Type 1, mainly found in the liver, skin, and sebaceous glands, and Type 2, predominantly located in the prostate. Finasteride selectively inhibits Type 2, reducing DHT by about 70% in the scalp, whereas dutasteride inhibits both types, achieving a more comprehensive DHT reduction of around 94%. This makes dutasteride significantly more effective at preventing DHT-driven hair loss.
How do genetics and lifestyle factors contribute to androgenetic alopecia (AGA)?
Androgenetic alopecia is primarily influenced by both genetic inheritance and androgen activity, particularly DHT. If someone carries the gene that sensitizes hair follicles to DHT, they are more likely to experience progressive hair loss. However, lifestyle factors such as poor diet, lack of exercise, stress, and irregular sleep patterns can also trigger or accelerate hair loss, even in individuals without a strong family history of baldness. Thus, maintaining a healthy lifestyle might help delay or mitigate the expression of AGA.
How are Type 1 and Type 2 5α-reductase enzymes different in function and distribution?
Type 1 5α-reductase is found largely in the liver, skin, and sebaceous glands, which are highly concentrated around hair follicles, especially on the scalp and face. Type 2 is primarily located in the prostate and present in smaller amounts in the skin and liver. Although both enzymes convert testosterone to DHT, their distribution affects how treatments like finasteride and dutasteride perform. Dutasteride’s superior ability to inhibit both types, especially being 100 times more potent against Type 2, explains its higher efficacy compared to finasteride.
Why does dutasteride have a longer-lasting effect compared to finasteride?
Dutasteride has a notably longer half-life of about five weeks compared to finasteride’s short half-life of 5-6 hours. This means dutasteride remains active in the body much longer, allowing for a more sustained suppression of DHT levels. This extended half-life contributes to its increased effectiveness in treating conditions like MPB, but also requires careful monitoring to manage potential side effects due to its longer presence in the system.
Why does dutasteride have a longer-lasting effect compared to finasteride?
Currently, dutasteride is FDA-approved only for treating benign prostatic hyperplasia (BPH), not hair loss. However, many doctors prescribe it off-label to treat male pattern baldness due to its higher DHT suppression rates. Finasteride, on the other hand, has been FDA-approved for hair loss since 1998 after extensive research. As more clinical trials and long-term studies on dutasteride accumulate, it is likely that formal approval for hair loss treatment could follow in the future.
What forms of drug delivery are available for finasteride and dutasteride?
Finasteride is available both as an oral pill (1 mg/day) and in topical forms (typically 0.5 mg mixed with minoxidil). Topical formulations are becoming more popular, especially when treatment is started early, to minimize systemic side effects. Dutasteride is primarily prescribed orally at 0.5 mg/day for hair loss, though topical forms are emerging, often using advanced delivery systems like liposomal formulations. Liposomal drug delivery increases absorption directly into the skin and hair follicles, offering a more targeted, effective treatment while reducing systemic exposure.
What is liposomal drug delivery, and why is it being used for hair loss treatments?/h3>
Liposomal drug delivery involves encapsulating the active drug in lipid-based vesicles, which improve penetration and targeted release of the drug at the intended site—in this case, the scalp. This method helps maximize the drug’s effectiveness while minimizing systemic absorption and potential side effects. Recent studies have shown that liposomal delivery of finasteride and dutasteride significantly increases drug deposition in the skin compared to traditional alcohol-based solutions, making it a promising innovation for treating androgenetic alopecia.
