Clinical Outcomes of Adding Topical Cetirizine to Minoxidil Therapy in Patients with Androgenetic Alopeci

ABSTRACT

Objective:

The objective is to evaluate the efficacy and safety of adding 1% topical cetirizine to 5% topical minoxidil compared with topical minoxidil alone in patients with androgenetic alopecia (AGA).

Methods:

In this single-blind randomized clinical trial, 62 patients with AGA were allocated to receive either topical minoxidil 5% twice daily (monotherapy group, n = 31) or topical minoxidil 5% twice daily plus topical cetirizine 1% once daily (adjunctive therapy group, n = 31) for 16 weeks. Primary outcomes included changes in hair density and hair diameter scores. Secondary outcomes were global photography score, patient satisfaction, and treatment-related adverse events.

Findings:

Both groups demonstrated improvement from baseline in hair density and hair diameter scores after 16 weeks of treatment. However, no significant differences were observed between groups in hair density score (0.65 ± 0.61 vs. 0.68 ± 0.60, P = 0.987), hair diameter score (1.29 ± 0.59 vs. 1.39 ± 0.62, P = 0.628), or global photography score (1.00 ± 0.68 vs. 1.06 ± 0.57, P = 0.697). Patient satisfaction was significantly higher in the adjunctive therapy group than in the monotherapy group (1.82 ± 1.07 vs. 1.13 ± 0.85, P = 0.004). Two cases of local irritation were reported in the monotherapy group, whereas no adverse events were reported in the adjunctive therapy group.

Conclusion:

The addition of 1% topical cetirizine to topical minoxidil did not result in superior objective hair-growth outcomes compared with minoxidil alone. Although patient satisfaction was higher among patients receiving adjunctive cetirizine, this finding may be attributable to factors other than a direct pharmacologic effect. Further double-blind, vehicle-controlled studies with larger sample sizes are warranted to clarify the role of topical cetirizine in the management of AGA.

INTRODUCTION

Androgenetic alopecia (AGA) is an androgen-dependent polygenic disorder that primarily affects hair follicles in the vertex region of the scalp. It is caused by the vulnerability of hair follicles to androgens.[1] More than 50% of adult males over the age of 50 are affected by this condition.[2] Even moderate hair loss can significantly reduce a patient’s quality of life.[3] The underlying pathology of AGA is an increased concentration of dihydrotestosterone (DHT) due to higher activity of type II 5α-reductase in hair follicle cells. The affected hairs in this process become shorter, leading to balding in the scalp area.[4]

The primary goal of AGA treatment is to inhibit the miniaturization process of hair follicles, with treatment being more effective in the early stages of hair loss.[5] Topical minoxidil and oral finasteride are considered first-line treatments for managing alopecia. However, these treatments are not without side effects.[6] Oral finasteride, a systemic inhibitor of 5-alpha reductase, can cause various side effects, including decreased libido, sexual dysfunction, and mood disorders.[7,8] Similarly, topical minoxidil may cause localized side effects such as hypertrichosis, irritation, and contact dermatitis.[9,10] These side effects can lower patient compliance, and there is also a risk of hair loss upon discontinuation of the medication.[11] Therefore, alternative drug agents and therapeutic methods have been proposed to minimize these side effects.[10,12,13,14]

Although topical cetirizine has shown potential benefits in previous studies, the findings remain inconsistent, and most available trials have methodological limitations, including short follow-up durations and variable assessment techniques. Moreover, the additive value of cetirizine when combined with standard 5% topical minoxidil remains unclear.

The 1% concentration of topical cetirizine was selected based on previous clinical studies in patients with androgenetic alopecia. Earlier investigations using 1% topical cetirizine reported improvements in hair density, hair thickness, and patient satisfaction while demonstrating a favorable safety profile. Therefore, the same concentration was adopted in the present study to allow comparison with the existing clinical evidence.[15,16,17]

Therefore, this study aimed to evaluate whether adding 1% topical cetirizine to minoxidil provides superior clinical outcomes compared with minoxidil alone in patients with AGA.

METHODS

This single-blind, two-center, randomized clinical trial aimed to examine the efficacy of 1% cetirizine compared to 5% topical minoxidil with a 1:1 allocation ratio. The study was conducted at two dermatology clinics affiliated with a university medical center during 2022-2023.

The study protocol was approved by the Institutional Ethics Committee (Approval No: IR.MUI.MED.REC.1401.367). Written informed consent was obtained from all participants before enrollment.

The study included male and female patients with AGA who were admitted to the aforementioned clinics. Eligible participants were men and women aged 18–50 years with AGA classified according to the Norwood–Hamilton scale (men) or Ludwig scale (women).

Patients were excluded if they had a history of other types of alopecia, including alopecia areata, telogen effluvium, anagen effluvium, or scarring alopecias; serious medical illness; previous hair transplantation; allergy to minoxidil or cetirizine; systemic steroid use for more than 14 days within the two months before study initiation; or discontinuation of topical treatment or failure to complete follow-up.

In the initial steps, patients underwent a complete physical examination and medical history review, including past alopecia treatments. A thorough scalp examination was performed to rule out other causes of alopecia, and the severity of alopecia was assessed using the Norwood–Hamilton classification for male patients and the Ludwig classification for female patients.

Standardized photographs[18] were taken from four different views: vertex, mid-pattern, temporal, and frontal. For the vertex photo, the hair was combed out from the vertex (radially from the vertex); for the mid-pattern photo, the hair was parted in the center; and for the frontal and temporal views, the hairline was pulled back to reveal the hairline. Nonvellus hairs were also evaluated for count and diameter using dermatoscopy at a defined distance from the glabella, measured at three points: 12, 16, and 24 cm, with an area of 1 inch.[2]

All photographs were obtained under standardized conditions using the same camera setup, patient positioning, and scalp preparation procedures at baseline and week 16. Images from the vertex, mid-pattern, temporal, and frontal views were captured according to the standardized photographic technique described by Canfield. Care was taken to maintain consistent hair positioning and image acquisition conditions between visits to allow visual comparison over time.

Patients were randomized into two groups using a predefined allocation method based on the parity of their national identification number (odd = monotherapy; even = adjunctive therapy). Although this approach was not computer-generated, it ensured a reproducible allocation process. Assignment was concealed from the evaluating dermatologist, who remained blinded to treatment allocation throughout the study. Follow-up assessments were performed by an independent dermatologist not involved in the intervention process. The statistician was also blinded to group assignments during data analysis.

Eligible patients were randomized into two treatment groups. The monotherapy group received 1 cc of 5% topical minoxidil twice daily. The adjunctive therapy group received 5% topical minoxidil twice daily combined with 1 cc of 1% cetirizine daily.[19] The cetirizine solution was prepared by an expert pharmacologist using cetirizine powder manufactured by Amin Pharmed (Iran) and dissolved in 25% pharmaceutical-grade ethanol; full formulation details are provided in Supplementary Table 1. The 5% topical minoxidil used in this study was manufactured by Pakdarou (Iran). All patients continued their assigned treatment for a total duration of 16 weeks. A 16-week follow-up period was selected based on previous clinical studies evaluating topical cetirizine and minoxidil in AGA, which demonstrated that treatment-related changes in hair-growth parameters could be assessed within this timeframe.[15,16,19]

Supplementary Table 1.

Composition of cetirizine 1% topical solution

Component
Cetirizine: 1%
Ethanol: 25%
Propylene glycol: 20%
Aqua (purified water): 20%
EDTA: 0–0.4%
Isopropyl alcohol: q.s. to 100

The adjunctive-therapy group received an additional once-daily topical application (cetirizine 1%), resulting in a higher total number of daily applications compared with the monotherapy group. No vehicle or placebo solution was administered to match this additional application. This difference in application frequency was inherent to the study design and is addressed in the Limitations section.

Treatment adherence was monitored during scheduled follow-up visits. Participants were instructed regarding the correct use of study medications at enrollment and were encouraged to continue treatment throughout the 16-week study period. Discontinuation of topical treatment or failure to attend follow-up assessments was considered a protocol deviation and constituted a withdrawal criterion.

The primary outcomes were the changes in hair density score and hair diameter score. Hair diameter score represented the investigator’s semiquantitative assessment of changes in the apparent thickness of non-vellus hairs within the predefined scalp area. The score was derived from serial dermatoscopic evaluations of the predefined scalp area and reflected the investigator’s overall assessment of changes in non-vellus hair thickness between baseline and week 16. The score was assigned by comparing baseline and week-16 evaluations using the same 7-point scale ranging from −3 (greatly decreased) to +3 (greatly increased). Higher positive scores indicated greater perceived improvement in hair shaft thickness. Both outcomes were evaluated using a 7-point semiquantitative global assessment score ranging from–3 (greatly decreased) to +3 (greatly increased). The scoring system, originally developed for alopecia areata,[20] has been used in previous studies as a global estimation tool to assess hair changes in AGA. A dermatologist evaluated all patients at baseline and at week 16 using this semiquantitative scoring approach.

Secondary outcomes included improvement in standardized global photography and patient satisfaction scores. Scalp photographs obtained before and after the intervention were compared and graded on a seven-level scale ranging from–3 (significantly deteriorated) to +3 (significantly improved). Global photographic assessment was performed by a dermatologist who was blinded to treatment allocation. Baseline and week-16 photographs were compared side-by-side, and an overall score was assigned based on the perceived change in scalp hair coverage, density, and cosmetic appearance within the predefined scalp regions. Negative scores indicated worsening, a score of zero indicated no visible change, and positive scores indicated improvement. Patient satisfaction was assessed using the same scale. Adverse effects were documented during follow-up using a structured checklist.

The sample size was calculated using the formula for comparing two proportions. Based on a 95% confidence level (α = 0.05) and 80% statistical power (β = 0.20), the required sample size was estimated according to the following formula:

Assuming Z₁₋α/₂ = 1.96, Z₁₋β = 0.84, P₁ = 0.43, P₂ = 0.13, and a precision (d) of 0.30 based on previous studies, the required sample size was estimated to be 31 participants per group.[21]

Data were analyzed using SPSS version 26 (Amin Pharmed, Kelishad, Isfahan Province, Iran 5% topical minoxidil: Pak Darou Pharmaceutical Co., 14^th Km of Karaj Special Road, Tehran, Iran). Continuous variables were summarized as mean ± standard deviation (SD), and categorical variables as frequencies and percentages. Between-group comparisons were performed using the Mann–Whitney U test due to the non-normal distribution of the semiquantitative outcome scores and the relatively small sample size. Within-group changes from baseline to week 16 were assessed using the Wilcoxon signed-rank test.

For all primary and secondary outcomes, effect sizes and 95% confidence intervals for between-group differences were calculated to provide additional information beyond P values. Age was approximately normally distributed but was still compared between groups using the Mann–Whitney U test for consistency across analyses. P < 0.05 was considered statistically significant. All analyses were performed on a per-protocol basis, as all participants completed the study. The flow of participants through the study is presented in Figure 1.

Figure 1.

CONSORT flow diagram of participant allocation, follow-up, and analysis

RESULTS

A total of 62 patients were included in the analysis, with 31 participants in each group. Baseline demographic characteristics were comparable between groups [Table 1]. The mean age was 29.0 ± 7.25 years in the monotherapy group and 30.16 ± 7.19 years in the adjunctive group (P = 0.521). The proportion of male participants was similar between groups (74% vs. 81%; P = 0.544). No significant differences were observed between groups in baseline hair density, hair diameter scores, or global photography assessments.

Table 1.

Baseline demographic characteristics of the study groups

Variable	Monotherapy	Adjunctive therapy	P
Age, years	29±7.25	30.16±7.19	0.521
Sex
Male	23 (74)	25 (81)	0.544
Female	8 (26)	6 (19)

Statistical analysis: Age was compared between groups using the Mann–Whitney U-test. Sex distribution was compared using the Chi-square test. Data are presented as mean±SD or n (%), as appropriate. A two-sided P<0.05 was considered statistically significant. SD=Standard deviation

Primary outcomes

Both groups demonstrated improvement from baseline in hair density and hair diameter scores at week 16 [Table 2]. The mean change in hair density score was 0.65 ± 0.61 in the monotherapy group and 0.68 ± 0.60 in the adjunctive-therapy group, with no significant between-group difference (P = 0.987). Similarly, the mean change in hair diameter score was 1.29 ± 0.59 in the monotherapy group and 1.39 ± 0.62 in the adjunctive group (P = 0.628). These findings indicate that adjunctive cetirizine did not produce additional improvement in objective hair-growth parameters compared with minoxidil alone. Representative dermatoscopic findings before treatment and after 16 weeks in both study groups are shown in Figures 2–5.

Table 2.

Changes in clinical and patient-reported outcomes after 16 weeks of treatment

Variable	Monotherapy	Adjunctive therapy	P
Hair density score	0.65±0.61	0.68±0.6	0.987
Hair diameter score	1.29±0.59	1.39±0.62	0.628
Standard photography score	1±0.68	1.06±0.57	0.697
Patient satisfaction score	1.13±0.85	1.82±1.07	0.004

Statistical analysis: Between-group comparisons were performed using the Mann–Whitney U-test. Data are presented as mean±SD. A two-sided P<0.05 was considered statistically significant. SD=Standard deviation

Figure 2.

Dermatoscopic assessment before intervention (minoxidil group). Baseline dermatoscopic view of the affected scalp area in the minoxidil group

Figure 5.

Dermatoscopic assessment after 16 weeks (minoxidil + cetirizine group). Follow-up dermatoscopic findings after 16 weeks of combination therapy

Figure 3.

Dermatoscopic assessment after 16 weeks of treatment (minoxidil group). Follow-up dermatoscopic evaluation showing changes in hair density and diameter after 16 weeks

Figure 4.

Dermatoscopic assessment before intervention (minoxidil + cetirizine group). Baseline dermatoscopic view in the combination-therapy group

Secondary outcomes

Standardized global photography scores improved in both groups compared with baseline [Table 2]. The mean change was 1.00 ± 0.68 in the monotherapy group and 1.06 ± 0.57 in the adjunctive group, with no significant between-group difference (P = 0.697).

Patient satisfaction scores were significantly higher in the adjunctive-therapy group compared with monotherapy (1.82 ± 1.07 vs. 1.13 ± 0.85; P = 0.004); however, this difference could be influenced by the additional daily application rather than a pharmacologic effect.

Regarding safety outcomes, two patients in the monotherapy group experienced localized scalp irritation, while no adverse events were reported in the adjunctive-therapy group.

Standardized global photograph obtained according to Canfield guidelines, demonstrating the scalp appearance after 16 weeks of treatment. Representative standardized global photographs obtained according to Canfield guidelines before treatment and after 16 weeks are shown in Figures 6 and 7.

Figure 6.

Standardized global photography before intervention (combination group)

Figure 7.

Standardized global photography after 16 weeks (combination group). Standardized global photograph obtained according to Canfield guidelines, demonstrating the scalp appearance after 16 weeks of treatment

DISCUSSION

This randomized clinical trial evaluated the efficacy and safety of adding topical 1% cetirizine to 5% topical minoxidil in patients with AGA. Both treatment groups showed improvement in hair density and hair diameter after 16 weeks of treatment; however, no significant differences were observed between the groups in any objective efficacy outcome. Patient satisfaction was significantly higher in the adjunctive-therapy group, while adverse events were infrequent in both groups. Overall, the addition of topical cetirizine did not provide measurable improvement in hair-growth outcomes compared with minoxidil monotherapy.

AGA is a condition affecting hair follicles, leading to hair loss in both males and females. Various therapeutic strategies have been developed to manage androgenetic alopecia.[12,13,14] However, topical minoxidil and oral finasteride are commonly considered first-line treatments, though they can cause side effects such as decreased libido, mood disorders, and localized symptoms like dermatitis. Therefore, new therapeutic approaches are being explored for managing androgenetic alopecia.[12,13] Cetirizine, an antihistaminic agent, has been proposed as a potential treatment option, and its clinical efficacy has been examined by researchers with varying results.

Findings from previous studies vary substantially due to differences in treatment duration, patient populations, and assessment methods. A recent clinical trial by Bassiouny et al.[19] examined the efficacy of topical cetirizine as an adjunctive therapy to topical minoxidil. In this study, patients received 1 ml of 1% topical cetirizine daily. Outcome measurements using trichoscopy showed significant improvement in vellus and terminal hair density in both the vertex and frontal views; however, there was no significant difference between the groups. Patients in the adjunctive therapy group did show significant improvements compared to baseline in terms of average hair thickness and hair count. Moreover, patient satisfaction regarding hair growth, new hairs, and bald areas increased at 24 weeks post-intervention.

Another study by Hosein Mostafa[15] compared the clinical efficacy of topical 5% minoxidil with topical 1% cetirizine, showing significant improvements in both total and vellus hair density in both groups. However, minoxidil demonstrated higher efficacy when the results were compared between groups. Similarly, a study by Zaky et al.[16] showed the efficacy of topical minoxidil compared to placebo. Rossi[17] also confirmed the efficacy of topical cetirizine over placebo. These studies suggest that while cetirizine may improve hair loss, its efficacy compared to minoxidil remains uncertain.

Although patient satisfaction was higher in the adjunctive-therapy group, this finding should be interpreted cautiously. Because this group received an additional daily application, the increased satisfaction may reflect perceived treatment intensity, improved adherence, or a nonspecific placebo response rather than a true pharmacologic benefit of cetirizine. Therefore, the higher satisfaction scores should not be considered evidence of enhanced efficacy.

Regarding adverse effects, patients in the adjunctive therapy group showed a lower rate of adverse reactions, which may be partly related to cetirizine’s antihistaminic properties.[14] Several studies have demonstrated cetirizine’s efficacy in relieving allergic reactions.[17] Therefore, cetirizine may be considered as an adjunct to minoxidil, not for enhancing hair growth but for reducing minoxidil’s side effects. Minoxidil can still be used as a single therapy for moderate and early stages of alopecia, though its efficacy as monotherapy in more severe cases remains unproven.[10]

Although the exact mechanism of cetirizine is unclear, researchers suggest its role in regulating prostaglandins may be significant. The regulation of hair growth involves several key prostaglandins. Prostaglandins in the F category promote the extension of the anagen phase, aiding hair growth, while prostaglandin D2, in particular, pushes hair follicles into the catagen phase, which precedes the telogen phase and eventually leads to hair loss. Prostaglandin D2’s connection to the GPR44 receptor triggers hair shedding. Studies have found a relationship between AGA and increased prostaglandin D2 levels. Reducing prostaglandin D2 levels by inhibiting prostaglandin D2 synthase, the enzyme responsible for converting prostaglandin H2 to D2, is one potential approach.[22] Cetirizine has been shown to inhibit the release of prostaglandin D2 while promoting the secretion of prostaglandin E2.[23]

The present study adds to the limited body of clinical evidence regarding the use of topical cetirizine as an adjunctive treatment for AGA. While previous studies have reported inconsistent findings, our results suggest that adding 1% topical cetirizine to topical minoxidil does not provide a significant advantage in objective hair-growth outcomes over minoxidil alone. These findings contribute to clarifying the clinical role of topical cetirizine and may help guide future controlled studies evaluating adjunctive therapies for AGA.

This study had several limitations. First, a placebo/vehicle-controlled arm was not included, and the number of daily applications differed between groups, which may have introduced adherence bias or enhanced placebo effects, particularly for patient-reported outcomes. Second, the sample size was relatively small and the 16-week follow-up period may not have been long enough to capture the full therapeutic potential of adjunctive treatments in AGA. Third, semiquantitative scoring methods were used instead of objective digital hair-counting tools, which may limit measurement precision. Future trials should use a double-blind, vehicle-controlled design with equal application schedules and more robust quantitative assessment tools to better isolate the pharmacologic effect of cetirizine.

CONCLUSION

Adding 1% topical cetirizine to 5% topical minoxidil did not improve objective hair-growth outcomes over 16 weeks. Although patient satisfaction was higher in the adjunctive-therapy group, this finding could be related to the additional application frequency rather than a pharmacologic effect of cetirizine. The lower rate of reported local adverse effects in the adjunct group may similarly reflect differences in usage patterns rather than a true therapeutic benefit. Overall, our results do not provide evidence of a clear clinical advantage for cetirizine as an adjunct to minoxidil. Double-blind, vehicle-controlled trials with equal application schedules are needed to more definitively assess the contribution of cetirizine in the management of AGA.

Ethics approval and trial registration

This study was conducted in accordance with the Declaration of Helsinki and was approved by an institutional ethics committee (Approval ID: IR.MUI.MED.REC.1401.367). Written informed consent was obtained from all participants prior to enrollment. The trial was prospectively registered in a national clinical trials registry (IRCT20230308057655N1).

AUTHOR CONTRIBUTIONS

F.M. contributed to data collection, patient recruitment, and project administration. G.F. contributed to study design, methodology, and supervision. S.M. (corresponding author) contributed to conceptualization, data analysis, and writing – Original draft. S.M.H. contributed to statistical analysis and writing – Review and editing. P.S. contributed to clinical assessment, data interpretation, and validation. All authors reviewed and approved the final version of the manuscript.

Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.