THE IMPACT OF ENDOGENOUS AND EXOGENOUS SEX HORMONES ON THE COURSE OF PORPHYRIA IN WOMEN: A NARRATIVE REVIEW

Abstract

Porphyrias are a group of metabolic diseases caused by an impairment of the heme synthesis pathway, resulting in the accumulation of heme precursors. First symptoms usually occur during puberty and can be triggered by a range of factors such as drugs, alcohol, fasting, infection, and, most importantly for this study, hormonal changes. Women in the reproductive age are known to be the main group presenting with porphyria symptoms (1.5–2.5 times more frequent in women than in men) mainly due to higher concentrations of steroid hormones, particularly progesterone. Hormonal fluctuations associated with the menstrual cycle are the most commonly identified trigger causing an AIP attack in female patients. Pregnancy and exogenous hormone administration may also precipitate attacks in susceptible individuals, although there is considerable interindividual variability, and the underlying mechanisms remain incompletely understood. This review summarizes existing knowledge on hormonal changes induced by the menstrual cycle, pregnancy, hormonal contraception, and GnRH agonists in women diagnosed with porphyria. It compares it with the conclusions reached by the IPNET panelists in the newly published guidelines, released in May 2026. The available evidence, derived mainly from retrospective studies, small cohorts, and case reports, indicates that endogenous and exogenous hormones can have a major impact on susceptible women with porphyria. Most data confirmed that the use of oral contraceptives appears to carry the highest risk of precipitating attacks, whereas levonorgestrel-releasing IUDs seem to be better tolerated. GnRH agonist therapy proved highly effective and significantly safer than hormonal contraception in the treatment of recurrent cycle-related porphyria, although it requires add-back therapy, posing a threat itself. Despite recent advances and the publication of IPNET recommendations, high-quality evidence remains limited. Further prospective studies are required to establish evidence-based recommendations for hormonal management and contraception in women with acute hepatic porphyrias.