The first clinical experience on efficacy of topical flutamide on melasma compared with topical hydroquinone: a randomized clinical trial

Figures & data

Table 1 Past medical history of the participants in two groups of the clinical trial comparing effect of flutamide and hydroquinone on melasma

Clinical history	Trial group	Current suffering frequency (%)	Previous history frequency (%)	Not suffered frequency (%)
Menstrual irregularities	Flutamide	13 (37.1)	3 (8.6)	19 (54.3)
	Hydroquinone	9 (24.3)	4 (10.8)	24 (64.9)
	Total	22 (30.6)	7 (9.7)	19 (54.3)
Ovarian cysts	Flutamide	2 (6.1)	8 (24.3)	23 (69.7)
	Hydroquinone	3 (8.3)	8 (22.2)	25 (69.4)
	Total	5 (7.25)	16 (23.2)	48 (69.6)
Infertility	Flutamide	1 (3.45)	1 (3.45)	27 (93.1)
	Hydroquinone	3 (12)	0 (0)	22 (88)
	Total	4 (7.4)	1 (1.85)	49 (90.7)
Hair loss	Flutamide	14 (41.2)	1 (2.9)	19 (55.9)
	Hydroquinone	11 (31.4)	0 (0)	24 (68.6)
	Total	25 (36.2)	1 (1.45)	43 (62.3)
History of Addison’s disease, Cushing’s syndrome, or hyperthyroidism	Only one patient in the flutamide group had history of hyperthyroidism
Drug history
History of OCP usage	Flutamide		Yes: 20 (55.6)	No: 16 (44.4)
	Hydroquinone		Yes: 12 (32.4)	No: 25 (67.6)
	Total		Yes: 32 (43.8)	No: 41 (56.2)
History of spironolactone usage	Flutamide		Yes: 1 (2.8)	No: 35 (97.2)
	Hydroquinone		Yes: 0 (0)	No: 37 (100)
	Total		Yes: 1 (1.4)	No: 72 (98.6)
History of phenytoin usage	No one reported use of phenytoin among participants
Family history
Hirsutism in mother	Flutamide		Yes: 0 (0)	No: 35 (100)
	Hydroquinone		Yes: 3 (8.1)	No: 34 (91.9)
	Total		Yes: 3 (4.2)	No: 69 (95.8)
Melasma in mother	Flutamide		Yes: 4 (11.1)	No: 32 (88.9)
	Hydroquinone		Yes: 8 (21.6)	No: 29 (78.4)
	Total		Yes: 12 (16.4)	No: 61 (83.6)
Hirsutism in sister	Flutamide		Yes: 9 (25.7)	No: 26 (74.3)
	Hydroquinone		Yes: 6 (16.2)	No: 31 (83.8)
	Total		Yes: 15 (20.8)	No: 57 (79.2)
Melasma in sister	Flutamide		Yes: 20 (55.6)	No: 16 (44.4)
	Hydroquinone		Yes: 26 (70.3)	No: 11 (29.7)
	Total		Yes: 46 (63)	No: 27 (37)
Hirsutism in either one of mother, sister, or aunts	Flutamide		Yes: 11 (31.4)	No: 24 (68.6)
	Hydroquinone		Yes: 9 (24.3)	No: 28 (75.7)
	Total		Yes: 20 (27.8)	No: 52 (68.6)
Melasma in either one of mother, sister, or aunts	Flutamide		Yes: 24 (66.7)	No: 12 (33.3)
	Hydroquinone		Yes: 31 (83.8)	No: 6 (16.2)
	Total		Yes: 55 (75.3)	No: 18 (24.7)

Abbreviation: OCP, oral contraceptive pill.

Table 2 Mexameter melanin repeated measurements on various face spots compared for topical flutamide and hydroquinone over the treatment course

Trial group	Location	Measurement time points and mexameter measurement score
		Baseline	Month 1	Month 2	Month 3	Month 4
Hydroquinone	Forehead	22.6	20.7	19.7	17.7	15.8
	Right malar	20.7	18.2	18.1	16.2	16.3
	Left malar	20.1	18.2	17	18.5	15.5
	Lip	30.7	23.9	23.8	23	20.4
	Nose	26.5	25.5	26.6	24.7	21.7
Topical flutamide	Forehead	25.8	19.1	18.5	17.1	15.4
	Right malar	24.2	18.2	16.2	16.7	15.7
	Left malar	23.2	17.9	15.4	14.9	15.3
	Lip	27.4	20.8	21	20.2	19
	Nose	27.5	23.4	21.6	20.1	21.5

Figure 1 The trend of change in skin darkness and homogeneity scores compared for flutamide and hydroquinone randomized clinical trial groups.

Notes: (A) Skin darkness and (B) skin homogeneity trend. Measurement time points from baseline (1) to final measurement (5), 4 months after treatment. Skin darkness and homogeneity scores assessed by the physician (possible range: 0–4).

Figure 2 Box plot presenting the changes in MASI score over the time among patients treated either by topical flutamide or hydroquinone. *Indicates an outlier.

Abbreviation: MASI, Melasma Area and Severity Index.

Table 3 Randomized clinical trials conducted to compare hydroquinone as the standard treatment with other topical alternative treatments

Comparison groups	Outcome(s)	Author conclusions	References
1 – Hydroquinone 4% cream 2 – 1% flutamide cream	1 – Patient satisfaction 2 – MASI 3 – Mexameter melanin assay	Comparable efficacy in objective assessments but higher patient satisfaction for 1% flutamide cream	Present study
1 – Hydroquinone 4% cream 2 – 3% Rubus occidentalis cream	Patient satisfaction	Occidentalis 3% cream is a safe and effective skin-lightening agent for melasma and is comparable in efficacy with 4% hydroquinone cream	^Citation25
1 – Hydroquinone 4% cream 2 – Kojic acid cream (0.75% kojic acid and 2.5% vitamin C)	MASI	Kojic acid cream found to be less effective than hydroquinone 4% cream	^Citation26
1 – Hydroquinone 4% cream 2 – Zinc sulfate 10% solution	MASI	Zinc sulfate 10% solution found to be less effective than hydroquinone 4% cream	^Citation27
1 – Hydroquinone 4% cream 2 – Azelaic acid cream	MASI	20% Azelaic acid cream applied twice daily may be more effective than hydroquinone 4% in reducing mild melasma	^Citation28
1 – Hydroquinone 4% on one side of the face 2 – Niacinamide cream on other side of the face	1 – Colorimetric measures 2 – Histological sections	Generally, similar efficacy but proportion of good to excellent improvement higher for hydroquinone	^Citation29
1 – Hydroquinone 2% cream as priming agent 2 weeks before peeling with glycolic acid 2 – Tretinoin and 0.025% cream as priming agent 2 weeks before peeling with glycolic acid	MASI	Results are better with hydroquinone as priming agent compared to tretinoin in enhancing the results with glycolic acid peels in melasma and in decreasing postpeel postinflammatory hyperpigmentation	^Citation30
1 – Hydroquinone 4% cream 2 – A triple combination (TC) cream	Static global severity assessment of melasma	Was more effective than the hydroquinone cream for the treatment of moderate-to-severe facial melasma	^Citation31
1 – Hydroquinone 5% cream on one side of the face 2 – Ascorbic acid cream on other side of the face	1 – Colorimetry 2 – Digital photography and regular color slides	Hydroquinone showed a better response than ascorbic acid	^Citation32

Abbreviation: MASI, Melasma Area and Severity Index.

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