What is the lowest effective dose of topical testosterone (currently 100 mg twice daily on three days and 100 mg once daily on four days) to reduce acne while maintaining therapeutic benefit?

Topical Testosterone Dose Reduction for Acne Management

Direct Recommendation

You should discontinue topical testosterone entirely and transition to standard acne-specific hormonal therapy, as testosterone directly worsens acne through increased sebaceous gland stimulation and dihydrotestosterone (DHT) formation in the skin. 1

Why Dose Reduction Won't Solve the Problem

The acne is not a dose-dependent side effect that will resolve with minor adjustments—it's a direct pharmacological consequence of testosterone therapy:

• Testosterone is converted to DHT in sebaceous glands via 5α-reductase, which is the most potent androgen stimulating sebum production and acne formation 1
• Even physiological testosterone levels (which your current regimen aims to achieve) maintain sebaceous gland activity at levels that promote acne 2, 3, 4
• The research on testosterone gel demonstrates that doses maintaining serum testosterone in the normal adult male range (which is the therapeutic goal) consistently produce DHT levels at or above normal ranges 4, 5

The Fundamental Problem

Your patient is experiencing the expected androgenic effect of testosterone replacement therapy. The evidence shows:

• Androgens produced in the skin itself stimulate sebaceous glands, and DHT formed locally in sebaceous glands is the primary driver of acne 1
• Transdermal testosterone gel at therapeutic doses (50-100 mg daily) produces steady-state serum testosterone levels 4-5 fold above hypogonadal baseline and maintains DHT at or above normal adult male ranges 4, 5
• There is no "sweet spot" dose of testosterone that maintains therapeutic benefit for hypogonadism while avoiding acne—the two are mechanistically linked 1

Evidence-Based Acne Management Instead

Rather than continuing to adjust testosterone doses, implement guideline-directed acne therapy:

First-Line Topical Therapy

• Combine a topical retinoid with benzoyl peroxide as multimodal therapy targeting multiple acne mechanisms 6
• Consider adding clascoterone (topical antiandrogen) specifically to counteract the androgenic effects of testosterone therapy 6

Systemic Therapy for Moderate-Severe Acne

• Oral isotretinoin should be considered for patients with treatment-resistant acne or those with psychosocial burden/scarring 6
• Isotretinoin at 0.5-1.0 mg/kg/day is the most effective treatment for severe acne and addresses the underlying sebaceous gland hyperactivity 6
• Daily dosing is recommended over intermittent dosing, with a goal cumulative dose of 120-150 mg/kg 6

If Patient is Female (Not Specified in Question)

• Spironolactone 50-100 mg daily is first-line for hormonal acne, directly antagonizing androgen receptors 6, 7
• Combined oral contraceptives containing drospirenone provide anti-androgenic effects and are FDA-approved for acne 6, 8, 7

Critical Clinical Decision Point

You must weigh the indication for testosterone therapy against the quality of life impact of persistent acne. If testosterone is medically necessary for hypogonadism:

1. Continue testosterone at the dose needed to maintain therapeutic serum levels (typically 50-100 mg daily for topical formulations) 2, 3, 4
2. Treat the acne aggressively with guideline-directed therapy rather than compromising testosterone replacement 6
3. Consider oral isotretinoin as definitive acne treatment if topical therapy fails, as it directly reduces sebaceous gland size and secretion 6, 7

Common Pitfall to Avoid

Do not continue making incremental dose adjustments to testosterone hoping the acne will resolve—this approach fails to address the fundamental mechanism and leaves both conditions inadequately treated. The patient needs either full testosterone replacement with aggressive acne management, or discontinuation of testosterone if it's not medically essential. 1