Journal September 27, 2026 6 min read

How Hyperpigmentation Changes With Age

Hyperpigmentation is not one condition but a family of acquired melanin disorders whose presentation shifts with age. This page reviews what clinical research has examined in melasma, post-inflammatory hyperpigmentation,

peptides-pro Editorial

Hyperpigmentation is the umbrella term for acquired, localized excess of melanin in the skin. It is not a single diagnosis: the literature separates melasma (also written chloasma, an acquired symmetric facial hyperpigmentation), post-inflammatory hyperpigmentation (PIH, hypermelanosis following cutaneous inflammation or injury), and solar lentigines or age spots, which are cumulative ultraviolet-associated lesions. These are clinical descriptors rather than molecular entities, and the evidence base does not assign them a sequence, formula, or molecular weight.

The mechanistic work in this area centres on the melanocyte and its pigment-production machinery — tyrosinase activity, MITF transcription, and melanosome transfer — together with the inflammatory and hormonal signalling that drives melanocyte stimulation after injury or ultraviolet exposure [5][12].

Research Studies

Curcuma xanthorriza Roxb. and tyrosinase inhibition in melasma

A registered trial has examined a 10% cream of Curcuma xanthorriza Roxb., a plant native to Indonesia, in melasma. The stated rationale is that the extract inhibits the tyrosinase enzyme and reduces MITF transcription, and the study frames hydroquinone as the first-line depigmenting agent whose adverse-effect profile motivates alternatives [5]. Melasma itself is described in that record as an acquired hyperpigmentation disorder with multifactorial etiology and a high recurrence rate [5].

Bakuchiol and post-inflammatory hyperpigmentation

A separate registered study evaluates bakuchiol, a plant-derived compound reported to inhibit melanin synthesis, in PIH. The investigators use a previously validated model and compare bakuchiol against acne-induced PIH [8]. PIH is characterized in that record as an acquired hypermelanosis arising after cutaneous inflammation or injury, and as disproportionately affecting darker-skinned individuals [8].

Retinal and azelaic acid in blemish-prone skin with post-inflammatory hyperpigmentation

An eight-week randomized, prospective, split-face, vehicle-controlled study examined an anhydrous concentrate of 0.1% retinal and 10% azelaic acid in blemish-prone skin. The background given is that blemish-prone skin is driven by follicular hyperkeratinization, excess sebum, microbial dysbiosis, and inflammation, and is often accompanied by post-inflammatory erythema and hyperpigmentation. Retinal and azelaic acid are described as established topical actives with complementary mechanisms [11].

Kojic acid and melanosome production

A review of kojic acid as a hypopigmenting agent describes hyperpigmentation as overproduction and uneven distribution of melanin, and notes that it is among the most common complaints in dermatology clinics. The review states that treatment focuses mainly on reducing melanocytes and stopping melanosome production, and that delivery challenges have prompted nanotechnology-based strategies [12].

Glycolic, lactic, kojic acid, vitamin C and emblica in a peel regimen for skin of color

A single-centre, prospective, non-blinded, non-randomized 12-week study evaluated a comprehensive skincare regimen for reducing PIH in skin-of-color patients. The regimen centres on a pigment-balancing peel combining glycolic acid, lactic acid, kojic acid, vitamin C, and emblica, supplemented with a hydrating gel, a discoloration product, a cleansing gel, and a brightening sunscreen [4].

Oral tranexamic acid combined with 1064-nm Q-switched fractional laser in melasma

A clinical observation study examined 1064-nm Q-switched fractional laser combined with oral tranexamic acid for melasma. The record describes melasma as a common acquired symmetric facial hyperpigmentation with higher prevalence in females and in darker skin types, and lists topical, oral, procedural, and combination approaches among its treatments. The 1064-nm wavelength is described as effectively absorbed by pigment, leading to damage of pigment and melanocyte [7].

Sun protection and hyperpigmentation in post-surgical scars

A randomized split-wound study assessed whether sun protection influences the aesthetic outcome of scars after linear repair of Mohs micrographic surgery defects. Half of each wound received a zinc-containing sunscreen and half did not; at three months the scar was scored with the patient observer scar assessment scale and a colorimeter measured vascularity and hyperpigmentation in treated versus untreated areas relative to surrounding skin [6].

Effervescent glutathione-containing tablets and facial dark spots

A randomized, double-blinded, single-centre, two-arm, placebo-controlled, prospective study evaluated the clinical safety, efficacy, and in-use tolerability of effervescent tablets in subjects with facial hyperpigmentation and dark spots, including pimple marks, sunspots, and age spots, and uneven skin tone [3].

Setmelanotide and melanocortin 4 receptor signalling in monogenic obesity

Setmelanotide is a melanocortin 4 receptor (MC4R) agonist studied in rare monogenic obesity conditions affecting the leptin-melanocortin signalling pathway. A case report described a 40-year-old female with a heterozygous PCSK1 N221D (c.661 A>G) variant and severe early-onset treatment-resistant obesity, who achieved a total weight loss of 11.8% on setmelanotide after a suboptimal response to bariatric surgery and conventional obesity medications [2]. A second report followed two pediatric kidney transplant recipients with genetically confirmed Bardet-Biedl syndrome, a ciliopathy associated with hyperphagic obesity and kidney disease. In Patient 1, a 17-year-old boy with a homozygous pathogenic SDCCAG8 exon deletion, measures improved over 12 months: weight 55.6 to 48.0 kg, BMI 26.6 to 23.0 kg/m², BMI-for-age z-score +1.60 to +0.43, maximal-hunger score 8/10 to 5/10, and HbA1c 6.5% to 5.1% [1]. These findings concern metabolic and appetite endpoints in defined genetic populations and do not address cutaneous pigmentation.

Study population	Intervention examined	Reported outcome measure
Melasma	Curcuma xanthorriza Roxb. 10% cream	Tyrosinase inhibition, MITF reduction [5]
PIH	Bakuchiol	Melanin synthesis inhibition [8]
Blemish-prone skin with post-inflammatory hyperpigmentation	0.1% retinal + 10% azelaic acid concentrate	Split-face, vehicle-controlled, 8 weeks [11]
Skin of color with PIH	Peel (glycolic, lactic, kojic acid, vitamin C, emblica) plus regimen	12-week non-randomized study [4]
Melasma	1064-nm Q-switched fractional laser + oral tranexamic acid	Pigment and melanocyte damage [7]
Post-Mohs linear repair scars	Zinc-containing sunscreen vs no sunscreen	POSAS and colorimeter at 3 months [6]
Facial hyperpigmentation and dark spots	Effervescent tablets	Randomized, double-blinded, placebo-controlled [3]

Adrenal and thyroid case reports

Two case reports describe endocrine presentations in adolescents. One documents cytotoxic lesions of the corpus callosum secondary to Addison's disease in a 13-year-old girl, an association not previously reported [9]. The other describes persistent elevation of thyroid-stimulating hormone despite levothyroxine therapy, revealing autoimmune adrenal insufficiency in an adolescent with autoimmune thyroiditis, and notes that routine screening for autoimmune adrenal insufficiency is not recommended in that population [10]. Neither report concerns pigmentation.

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