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Medscape

Third-Generation Progestins Linked to Lowest Melasma Risk

A study found that fourth-generation progestins in oral contraceptive pills (OCPs) were associated with more than double the risk for melasma than with no exposure, while third-generation progestins showed the lowest risk among all synthetic progestin types. METHODOLOGY: Researchers analyzed data from 51,101 women with melasma and 51,101 matched controls without melasma using the TriNetX research network on March 25, 2025. The mean age of participants was 45.1 years. About 54% of participants were White, about 14% were Black, about 8% were Asian, and nearly 15% were Hispanic/Latino. Those with melasma had a higher prevalence of exposure to estrogen/progestin combinations (21.58% vs 10.03%; P < .001) and to progestins alone (15.04% vs 7.75%; P < .001) than those without melasma. < .001) and to progestins alone (15.04% vs 7.75%; < .001) than those without melasma. The researchers examined the risk for melasma within 10 years after a progestin prescription. TAKEAWAY: All four generations of synthetic progestins were associated with a higher melasma risk than no exposure. The risk was highest for fourth-generation (hazard ratio [HR], 2.262; 95% CI, 1.797-2.846) and lowest for third-generation progestins (HR, 1.417; 95% CI, 1.317-1.524). Exposure to fourth-generation progestins was associated with a higher risk for melasma than exposure to first-generation (HR, 1.366; 95% CI, 1.148-1.627), second-generation (HR, 1.191; 95% CI, 1.000-1.419), and third-generation progestins (HR, 1.785; 95% CI, 1.464-2.176). Exposure to third-generation progestins was associated with a lower risk for melasma than exposure to second-generation (HR, 0.841; 95% CI, 0.754-0.937) and fourth-generation progestins (HR, 0.604; 95% CI, 0.503-0.726). IN PRACTICE: Based on these findings, 'choosing oral contraceptive pills containing third-generation progestins may mitigate melasma risk associated with hormonal contraceptives,' the study authors wrote. 'Further studies of the role of progestins in melasma pathophysiology may improve our understanding of this disorder,' they added. SOURCE: The study, led by Amit Singal, BA, Rutgers New Jersey Medical School, Newark, New Jersey, and Shari Lipner, MD, Department of Dermatology, Weill Cornell Medicine, New York City, was published online on May 21 in the Journal of the American Academy of Dermatology . LIMITATIONS: Information on dosing, route, duration of use, and adherence to hormone therapy was not available. The study lacked data on ultraviolet exposure, family history of melasma, and clinical reasons for hormone use. International Classification of Diseases, 10th Revision, coding limitations may have affected diagnostic accuracy. DISCLOSURES: This study did not receive any funding. The authors had no competing interests.