Hydroquinone is described as a melanin synthesis inhibitor on the prescribing information for a fluocinolone acetonide, hydroquinone and tretinoin cream. Reviews describe it as inhibiting an enzyme called tyrosinase. That label also states that the mechanism of action of its active ingredients in melasma is unknown, so "how it might work" is the careful way to put it.
What hydroquinone is, according to labels
The label for the fluocinolone acetonide, hydroquinone and tretinoin cream says hydroquinone occurs as fine white needles that darken on exposure to air. That cream is Tri-Luma. An FDA drug safety communication states that Tri-Luma is currently the only FDA-approved drug containing hydroquinone. Its Drugs@FDA record lists fluocinolone acetonide, hydroquinone and tretinoin at 0.01%;4%;0.05%.
A separate prescription hydroquinone 4% cream label, listed on DailyMed as an unapproved drug, states that each gram of the cream contains 40 mg hydroquinone. These are two different products with two different labels.
What the labels say the creams are for
The Tri-Luma label states that the cream is indicated for the short-term treatment of moderate to severe melasma of the face, in the presence of measures for sun avoidance, including the use of sunscreens. The prescription hydroquinone 4% cream label states that the cream is indicated for the gradual bleaching of hyperpigmented skin conditions such as chloasma, melasma, freckles and senile lentigines. The two labels describe different uses for different products.
Mechanisms the sources describe or propose
The prescription hydroquinone 4% cream label above states that topical application of hydroquinone produces a reversible depigmentation of the skin by inhibition of the enzymatic oxidation of tyrosine to 3,4-dihydroxyphenylalanine (dopa). A review abstract states that hydroquinone has pharmacological uses in disorders of pigmentation because of its ability to competitively inhibit the enzyme tyrosinase. DailyMed shows that 4% cream listing with a disclaimer that the drug has not been found by FDA to be safe and effective and that its labeling has not been approved by FDA.
By contrast, the prescribing information for Tri-Luma (fluocinolone acetonide, hydroquinone and tretinoin) states that the mechanism of action of its active ingredients in the treatment of melasma is unknown.
A 2011 review of postinflammatory hyperpigmentation says depigmenting agents target different steps in the production of melanin, most commonly by inhibiting tyrosinase. It lists hydroquinone, azelaic acid, kojic acid, arbutin and certain licorice extracts among them.
Different agents, different proposed mechanisms
The same review states that other agents, including retinoids, mequinol, ascorbic acid (vitamin C) and niacinamide, depigment by different mechanisms. A 2006 review of retinoids says the basic mechanisms behind their effects on pigment are not completely identified, and that topical retinoids stimulate keratinocyte turn-over and promote a decrease in melanosome transfer.
For niacinamide, a 2002 laboratory study used a mushroom tyrosinase assay, cultured melanocytes and a coculture model. Niacinamide had no effect on the catalytic activity of mushroom tyrosinase or on melanogenesis in cultured melanocytes, but gave 35-68% inhibition of melanosome transfer in the coculture model. This was not a study in people. The paper's first author lists an affiliation with the Research & Development Department of Procter & Gamble Far East, Inc., Kobe Technical Center, Japan.
What this does not tell you
These mechanism statements are proposals from labels, reviews and one laboratory study. They do not show what any particular cream does in a particular person. Two of them are older, a 2006 review and a 2002 laboratory study. The sources used here report no trial of hydroquinone 8% or of a blend of hydroquinone, tretinoin, niacinamide and vitamin C, so nothing here shows how such a blend acts or how it compares with products at 4%. A list of agents with different mechanisms does not show that combining them adds up. The sources used here also do not say how vitamin C acts, only that it acts by a different mechanism. A licensed provider decides whether any product suits a person.