Sex and Gender Gaps in Dermatology Treatment

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“Although gender-specific medical approaches have notably found its way in certain fields like cardiology where ischemic heart disease serves as a prominent illustration of how gender and sex influence distinct disease trajectories, the exploration of gender differences within dermatological conditions, which represent the most prevalent diseases in mankind, has remained relatively understudied,” a recent review acknowledged while investigating gender differences in dermatologic treatment.^1-2

The review stated that for decades, it was believed that male and female cells exhibited identical characteristics, yet evidence-based medicine was largely delineated by clinical trials primarily in men. To this day, daily clinical patient care allows both men and women to receive identical medication at equivalent dosages, despite the inherent divergence in metabolic pathways.³ Beyond sex, referring to a person's physical characteristics at birth, gender, encompassing a person's identities, expressions and societal roles, affect all parts of a disease as well.² With this in mind, the review set forth to examine the current knowledge of sex and gender in treatment outcomes of skin diseases to identify gender-specific considerations that could lead to improved and tailored treatment approaches for both men and women.

Data Selection

Overall, 83 articles were included in the review after extensive searching and screening. The majority of the studies (67.5%) were conducted in Europe, followed by the US and Canada (16.7%), Asia (8.4%), and South America (4.8%). The review stated that most of the publications were retrospective, non-interventional, observational studies (65.1%), followed by prospective, observational studies (21.7%). In total, the review stated that 4 cross-sectional studies, 3 randomized controlled trials, 2 prospective, interventional studies, and 3 retrospective, cross-sectional studies were included.

Results

The review of 49 reports on psoriasis and psoriatic arthritis (PsA) brought to light notable gender differences in treatment and outcomes such as:

Treatment Choices

• Topical vs Systemic Therapies: Women tended to receive more topical treatments and fewer systemic therapies compared to men.⁴ Men were more likely to receive whole-body UV treatment and had higher chances of getting biologics like etanercept and adalimumab, while women were more often treated with ustekinumab.^5-6
• Use of Methotrexate: Women used methotrexate for shorter periods, resulting in lower cumulative doses.⁷

Time to Treatment Initiation

• Men generally started systemic therapy earlier and had higher psoriasis severity at the initiation of biological treatments compared to women. In younger patients (35-49 years), men were more likely to receive biologics, whereas, in older patients (>55 years), women were more likely to receive biological therapy.^6-7

Treatment Response

• Efficacy: Men showed better responses to TNF inhibitors and biologics compared to women. For example, men achieved higher improvements in PASI scores and had better outcomes with TNF inhibitors in PsA.^7-8
• Non-comorbid vs. Comorbid: Non-comorbid females achieved complete PASI 100 responses more easily than comorbid females.⁹

Adherence

• Topical Therapies: Women had better adherence to topical treatments.¹⁰
• Systemic Therapies: Anti-TNF treatments showed higher persistence compared to other systemic therapies, but female patients had lower continuation rates for biologics overall. Only 1study found that women had better adherence to specific therapies like adalimumab.¹¹

Adverse Events

• Women reported more side effects with various treatments, including higher incidences of contact dermatitis and infections when using biologics.¹²

Treatment Requests

• Women were found to place higher importance on treatment goals related to depression, sleep quality, and productivity compared to men.

Conclusion

The review noted significant gender and sex disparities in skin disease treatments, revealing that responses to drugs, adverse events, and treatment preferences vary between men and women. Researchers stated that current knowledge is particularly detailed for psoriasis but less so for other skin conditions. The review emphasizes the need for gender-specific research to better understand these differences and improve dermatological care for women.

Researchers suggested that future clinical studies should systematically consider sex and gender to address these disparities. While immediate new guidelines may not be necessary, the review stated that integrating sex and gender considerations into patient care is crucial. Ultimately, researchers believe gender-specific studies could lead to updated guidelines to enhance treatment outcomes.

References

1. Preis S, Ziehfreund S, Biedermann T, et al. A systematic review of sex and gender differences in treatment outcome of inflammatory skin diseases: Is it time for new guidelines? J EurAcad Dermatol Venereol. 2024; 00: 1–17. https://doi.org/10.1111/jdv.20256
2. Mehta LS, Beckie TM, DeVon HA, et al. Acute myocardial infarction in women: A scientific statement from the American Heart Association. Circulation. 2016;133(9):916-947. doi:10.1161/CIR.0000000000000351
3. Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, et al. Sex and gender: modifiers of health, disease, and medicine [published correction appears in Lancet. 2020 Sep 5;396(10252):668. doi: 10.1016/S0140-6736(20)31827-4]. Lancet. 2020;396(10250):565-582. doi:10.1016/S0140-6736(20)31561-0
4. Marques E, Paluch Z, Boháč P, et al. Epidemiology of moderate-to-severe psoriasis: a comparison between psoriasis patients treated with biological agents, conventional systemic drugs and topical agents. J Dermatolog Treat. 2022;33(3):1435-1448. doi:10.1080/09546634.2020.1826393
5. Nyberg F, Osika I, Evengård B. "The Laundry Bag Project"--unequal distribution of dermatological healthcare resources for male and female psoriatic patients in Sweden. Int J Dermatol. 2008;47(2):144-149. doi:10.1111/j.1365-4632.2008.03485.x
6. Kojanova M, Fialova J, Cetkovska P, et al. Demographic data, comorbidities, quality of life, and survival probability of biologic therapy associated with sex-specific differences in psoriasis in the Czech Republic. Dermatol Ther. 2021;34(2):e14849. doi:10.1111/dth.14849
7. Passia E, Vis M, Coates LC, et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22. Published 2022 Jan 11. doi:10.1186/s13075-021-02680-y
8. De Simone C, Caldarola G, Maiorino A, et al. Clinical predictors of nonresponse to anti-TNF-α agents in psoriatic patients: A retrospective study. Dermatol Ther. 2016;29(5):372-376. doi:10.1111/dth.12364
9. Gönülal M, Altunay İK, Doğan S, Türkmen M, Balcı DD, Öztürkcan S. Ixekizumab for the treatment of the patients with moderate to severe plaque psoriasis: Clinical data from a real-world experience. Dermatol Ther. 2022;35(12):e15955. doi:10.1111/dth.15955
10. Carroll CL, Feldman SR, Camacho FT, et al. Adherence to topical therapy decreases during the course of an 8-week psoriasis clinical trial: commonly used methods of measuring adherence to topical therapy overestimate actual use.J Am Acad Dermatol. 2004;51(2):212-216. doi:10.1016/j.jaad.2004.01.052
11. D'Angelo S, Cantini F, Ramonda R, et al. Effectiveness of adalimumab for the treatment of psoriatic arthritis: An Italian real-life retrospective study. Front Pharmacol. 2019;10:1497. Published 2019 Dec 13. doi:10.3389/fphar.2019.01497
12. Stein Gold L, Elewski B, Draelos Z, et al. Halobetasol 0.01%/Tazarotene 0.045% lotion for moderate-to-severe psoriasis: Pooled phase 3 analysis of males and females. J Drugs Dermatol. 2020;19(5):504-514.