The number that matters isn't just how much DHEA is applied. It's how much reaches the tissue that needs it — and what happens to the rest.

What the published science says about DHEA safety

DHEA has been studied extensively across a wide dose range. A 52-week randomized double-blind study found that oral DHEA at 50mg daily was not associated with any effects on blood lipids, insulin resistance, or the endometrium in postmenopausal women.[1] A separate study examined 100mg oral DHEA daily for six months in age-advanced women and found no significant adverse effects.[2]  DHEA has been studied at dosages of 25–200mg per day, with 50–100mg being the most frequently examined range. 

These are oral doses — meaning DHEA entering full systemic circulation daily. Restore delivers 30mg three times weekly to vulvar skin. The comparison isn't even close.

The intravaginal reference point

The FDA-approved prescription product for local DHEA use — Intrarosa — is dosed at 6.5mg daily intravaginally. Independent published research has tested intravaginal DHEA at doses up to 23.4mg daily and found that serum estradiol and testosterone remained within normal postmenopausal values at all doses tested.[3]  The concern about local DHEA doses has never been about the number — it has been about systemic sex steroid exposure. At every dose tested locally, that exposure remained within normal range.

Why vulvar application is different from intravaginal

Vaginal mucosa has no functional skin barrier. Absorption is rapid and moves freely between local tissue and systemic circulation. That's why even 6.5mg intravaginally daily produces measurable — though still within normal range — systemic estradiol changes in some studies. [4]

Vulvar skin is different. It retains a thin but functional skin barrier. Combined with liposomal delivery — which deposits DHEA directly into skin cells rather than allowing it to diffuse freely — this means the dose concentrates in local vulvar tissue rather than escaping into systemic circulation. More goes where it's needed. Less goes where it isn't.

This is why Restore can deliver 23mg and still show no systemic sex steroid increase. We tested up to 60mg per day and saw no rises in systemic sex steroids. The delivery mechanism is doing the work of keeping it local.

How liposomal delivery works

Liposomes are microscopic carriers made from the same lipid material as your own cell membranes. Because they share that structure, they don't sit on the skin surface waiting to diffuse — they fuse directly with skin cell membranes and deposit their payload inside the cell. In Restore's case, that payload is DHEA — delivered directly into the vulvar tissue cells where your body converts it locally.

So why does Restore use 23mg?

Because vaginal mucosa and vulvar skin absorb differently — and the dose has to match the route.

Vaginal mucosa has no skin barrier. Almost everything applied absorbs immediately. 6.5mg works intravaginally because that route is maximally efficient.

Vulvar skin has a barrier layer. Not all of the applied dose reaches the tissue cells where it's converted. 23mg is calibrated for this — enough to deliver a meaningful amount to vulvar tissue.  Liposomal delivery concentrates DHEA inside skin cells specifically — which keeps more of it local and less of it systemic.

The result: a higher number on the label, a comparable amount working in the tissue, and less systemic exposure than intravaginal delivery produces.

23mg vulvar is not a higher dose than 6.5mg intravaginal. It's a different dose for a different route. 

Most other topical DHEA products use micronized powder suspended in a cream base. The powder absorbs through the skin surface via passive diffusion — non-selectively, meaning it disperses between local tissue and systemic circulation without preferential cellular targeting. At lower doses this produces modest local and modest systemic effects. At higher doses systemic exposure increases proportionally.

Liposomal delivery works differently. More reaches the tissue. Less escapes systemically. This is why a higher applied dose can produce more local tissue effect with less systemic exposure than a lower powder-based dose.

The weekly exposure picture

Restore is applied at minimum three times weekly. If used daily, total weekly DHEA exposure is 161mg. Published safety literature considers 50mg daily — 350mg weekly — to be the reference threshold for oral DHEA. Restore's weekly exposure is less than half of that threshold, delivered locally rather than systemically.

 

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References

1. Panjari M, et al. The safety of 52 weeks of oral DHEA therapy for postmenopausal women. Maturitas. 2009. PubMed

2. Morales AJ, et al. The effect of six months treatment with 100mg daily dose of DHEA on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clinical Endocrinology. 1998. PubMed

3. Labrie F, et al. A low dose of intravaginal DHEA permits a strictly local action while maintaining all serum estrogens or androgens within normal values. Hormone and Molecular Biology and Clinical Investigation. 2017. PubMed

4. Martel C, Labrie F, et al. Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5mg intravaginal prasterone for 12 weeks. Journal of Steroid Biochemistry and Molecular Biology. 2016. PubMed