Testosterone therapy for women and men: separating signal from noise

What did @alisa_frierson actually say?

The creator, a self-described functional medicine nurse practitioner, claims that applying testosterone cream anywhere on the skin except the vaginal area causes epithelial cells to convert "a lot of it to dehydrotestosterone" (DHT), driving side effects like acne, hair thinning, and chin hair growth. Her fixes: switch delivery forms, take 30 mg zinc daily, add saw palmetto, and use progesterone as a natural DHT blocker. For men specifically, she pitches low-dose progesterone as a sleep and mood aid that also curbs DHT conversion.

The framing is confident and clinical. That warrants a close look, because some of what she says is supported by real pharmacology, and some of it is shakier than she lets on.

Does the science back this up?

Partially, yes. The DHT-conversion concern with transdermal testosterone is real and documented, but the mechanistic explanation she gives is oversimplified and partly wrong.

Transdermal testosterone does produce disproportionately high DHT levels compared to injected forms. A 2003 study by Swerdloff et al. in the Journal of Clinical Endocrinology and Metabolism found that men using transdermal testosterone gel had significantly elevated DHT-to-testosterone ratios relative to those on injectable testosterone enanthate. The likely mechanism involves 5-alpha reductase activity in skin and subcutaneous tissue, not a unique failure of epithelial cells to "process" testosterone efficiently. The skin is rich in 5-alpha reductase, which is exactly why transdermal delivery amplifies DHT, not because the cells are inefficient but because they are very efficient at converting it.

Zinc has modest inhibitory effects on 5-alpha reductase in vitro (Stamatiadis et al., 1988, British Journal of Dermatology), but clinical evidence for 30 mg daily meaningfully reducing DHT in humans on exogenous testosterone is thin. Saw palmetto has similarly weak clinical data. A 2012 Cochrane-adjacent review by Tacklind et al. found saw palmetto no better than placebo for related androgen-driven outcomes.

What did they get wrong (or right)?

The claim that epithelial cells are "not very good" at processing testosterone and that this inefficiency drives DHT is the main factual stumble here. It inverts the biology. Skin keratinocytes and dermal fibroblasts express high levels of 5-alpha reductase type 1, which is precisely why they are very good at converting testosterone to DHT, too good, from a clinical standpoint. The elevated DHT with transdermal use is a feature of robust enzymatic activity, not a metabolic failure.

She gets the directional recommendation right: switching away from transdermal cream to injections or pellets does tend to lower DHT-to-testosterone ratios. That part is supported. Her progesterone recommendation is more interesting. Progesterone does have 5-alpha reductase inhibitory properties (Rittmaster, 1994, Journal of Clinical Endocrinology and Metabolism), and its use in men for sleep and anxiety has some biological plausibility via neurosteroid pathways. But dosing and safety in men is not well-established, and presenting it as a straightforward add-on understates the complexity.

Saying "you can even do low-dose progesterone" for men without flagging that this is off-label, understudied, and potentially affects estrogen feedback is the kind of casual framing that should come with more caveats.

What should you actually know?

If you are on testosterone therapy and experiencing DHT-related side effects, the form of delivery genuinely matters. Injection-based testosterone (cypionate or enanthate) and pellets generally produce lower DHT-to-testosterone ratios than skin-applied creams or gels. Scrotal application of testosterone cream, which the creator does not mention, paradoxically produces the highest DHT levels of any method due to the high 5-alpha reductase density in scrotal skin.

The standard clinical tool for blocking DHT conversion is a 5-alpha reductase inhibitor like finasteride or dutasteride, which have actual clinical trial data behind them. Zinc and saw palmetto are low-risk additions but should not be sold as reliable DHT blockers. Progesterone for women on testosterone therapy has reasonable support in the literature for mood and sleep benefits and some DHT-inhibitory effect. For men, the evidence base is thinner and the hormonal implications are more complex.

Anyone experiencing these side effects should talk to a licensed clinician about their specific protocol, including their testosterone dose, form, and injection frequency, before adding supplements or switching hormones based on a TikTok recommendation, even a well-intentioned one.