Maximus' Topical Dutasteride: Systemic Absorption and Side Effect Profile in Androgenetic Alopecia

Oral dutasteride is one of the most effective medications for lowering dihydrotestosterone (DHT), with studies showing up to a 95% reduction in serum levels.1 It has also demonstrated greater efficacy than finasteride in treating male androgenetic alopecia.2 This superior performance is attributed to its stronger and more comprehensive suppression of type I and type II 5-alpha reductase enzymes.

Although highly effective, oral dutasteride is generally well tolerated, especially when compared to other commonly used 5-alpha reductase inhibitors such as finasteride. A systematic review found that while both drugs can cause sexual side effects, the relative risk was higher with finasteride (1.66) compared to dutasteride (1.37), and the increase associated with dutasteride was not statistically significant.3

Finasteride is sometimes used topically rather than orally in an attempt to limit systemic DHT suppression, which may be linked to side effects in some patients. However, despite being applied to the skin, topical finasteride still reduces serum DHT to a significant degree. One study reported a 34.5% reduction in serum DHT compared to 55.6% with oral use, while another found topical and oral finasteride to be nearly equivalent in this respect, with reductions of 75 and 72%, respectively.4,5 This systemic absorption is likely due to finasteride’s relatively low molecular weight of 372.5 g/mol, which allows it to cross the skin barrier more easily.6

In contrast, dutasteride has a larger molecular weight of 528.5 g/mol, which places it above the commonly referenced 500 Dalton rule for transdermal drug absorption.7,8 This suggests that without the aid of permeation enhancers, dutasteride may not readily penetrate the skin. Our MaxAbsorb delivery system was developed to address this challenge by enhancing localized uptake through the scalp while limiting systemic exposure.

This study was designed to evaluate whether topical dutasteride, when delivered using MaxAbsorb, could achieve scalp-level effects while minimizing systemic absorption. The primary focus was to assess the extent of change in serum DHT levels and the incidence of side effects typically seen with oral 5-alpha reductase inhibitors, including alterations in libido, mood, and sexual function.

We conducted a single-arm, open-label study involving fifteen male participants between the ages of 27 and 66. Participants were on a variety of existing Maximus treatment protocols at the time of enrollment, including combinations of enclomiphene and topical testosterone, oral testosterone, injectable testosterone, or no testosterone-related therapies. Two participants were not using any testosterone products.

The trial required a minimum participation period of 30 days. Each participant was instructed to apply a compounded topical solution to the scalp once daily. The formulation contained 0.1% dutasteride, 0.01% tretinoin, 5% minoxidil, 0.1% fexofenadine, 0.0033% melatonin, and 0.2% caffeine in the MaxAbsorb permeation enhancer base.

Blood samples were collected at baseline and after the treatment period to measure serum DHT, total testosterone, estradiol, and SHBG. Participants also completed two validated self-assessment tools: the Quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire for quality-of-life evaluation, and the Patient Health Questionnaire-4 (PHQ-4) for screening depression and anxiety symptoms. In addition to these standardized measures, participants reported on lifestyle and health habits, including average sleep duration, physical activity levels, diet quality, attention and focus, and relationship satisfaction.

Paired t-tests were used to compare pre- and post-treatment values. A p-value of less than 0.05 was considered statistically significant.

Topical dutasteride reduced serum DHT by 20.40%, from 109.13 to 86.87 ng/dL, which was not statistically significant (p = 0.4577). This reduction was substantially lower than the 90 to 95% typically observed with oral administration. Total testosterone increased by 15.45% (p = 0.5503). Estradiol and SHBG remained stable, with p-values of 0.9997 and 0.8007, respectively.

Libido improved by 10.91%, and this change was statistically significant (p = 0.0280). Erection quality showed no meaningful change, with a 1.72% increase (p = 0.8544), indicating no adverse effect on sexual function.

Statistically significant improvements were seen in strength and endurance, which increased by 16.36% (p = 0.0016), and in enjoyment of life, which improved by 13.79% (p = 0.0462). Positive trends were observed in energy (10.53% increase, p = 0.1465), happiness (12.28% increase, p = 0.0849), and work performance (12.28% increase, p = 0.0849), although these did not reach statistical significance.

Note: All items were rated on a scale of 1–5, where a higher score indicates improvement, except for "How often do you fall asleep after dinner without intending to?" where a lower score indicates improvement.

All four PHQ-4 mental health items improved from baseline to the end of the treatment period. Nervousness and anxiety decreased by 24.81% (p = 0.1141), uncontrolled worrying decreased by 16.67% (p = 0.2097), depressed mood decreased by 24.81% (p = 0.1141), and anhedonia decreased by 19.05% (p = 0.1141). While none of these changes were statistically significant, all moved in a favorable direction.

Note: For PHQ-4 items, lower scores mean fewer days with symptoms, so a negative change reflects improvement.

Lifestyle and health habit measures showed modest improvements. Attention and focus improved by 9.26% (p = 0.149), relationship quality by 7.41% (p = 0.3673), and diet quality by 5.26% (p = 0.4087). Physical activity increased by 31.72%, from 4.83 to 6.37 hours per week (p = 0.3006). Average sleep duration remained unchanged at 7 hours (p = 1.0).

This study suggests that topical dutasteride, when delivered using the MaxAbsorb system, achieves successful scalp permeation while limiting systemic absorption. Serum DHT levels decreased by approximately 20%, supporting the hypothesis that dutasteride’s larger molecular structure, even with enhanced delivery, results in far less systemic exposure compared to oral administration.

In a recent randomized, double-blind, controlled trial, Panuganti and colleagues reported that a 0.05% dutasteride topical solution produced significant improvements in hair density and thickness compared with placebo and oral finasteride.9 Their solution contained only half the concentration of dutasteride used in our formulation, yet it still demonstrated clear efficacy. These findings strengthen the rationale for topical dutasteride and support the potential of our higher-strength MaxAbsorb system. As patient use expands, we plan to share outcomes that build on the safety and quality-of-life improvements already observed.

These findings highlight the potential of this approach for individuals seeking to minimize systemic DHT suppression that often occurs with oral dutasteride, oral finasteride, and even topical finasteride. This formulation may offer a favorable balance by maximizing the local therapeutic benefits of dutasteride while avoiding the broader hormonal impact seen with other 5-alpha reductase inhibitors.

Participants did not report the side effects typically associated with oral medications that exert a greater impact on systemic DHT levels. Instead, improvements were observed in libido, physical strength, and overall enjoyment of life, with erection quality remaining stable. Mood and anxiety scores on the PHQ-4 also moved in a favorable direction.

While not every outcome reached statistical significance, the consistent direction of change across multiple measures reinforces the goal of reducing systemic exposure without compromising quality of life. For individuals prioritizing safety, tolerability, and localized efficacy, these results support topical dutasteride with MaxAbsorb as a practical and powerful alternative to current oral and topical therapies.