Acute intermittent porphyria, women and sex hormones. Screening for hepatocellular carcinoma in porphyria

• Main Author: Innala, Eva
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Obstetrik och gynekologi 2010
• Subjects: Obstetrics; Gynecology and Reproductive Medicine; Reproduktionsmedicin och gynekologi; Northern Sweden
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-36884

Background:  Porphyrias are inherited disorders with impaired heme biosynthesis. Acute intermittent porphyria (AIP) is the most common porphyria in Sweden. AIP attacks may be life-threatening. Female sex hormones are regarded as important precipitating factors. Hepatocellular carcinoma (HCC) is a severe complication in the older AIP population. The aim of the thesis was to describe the clinical expression of AIP in women, experience of hormonal contraception and hormonal replacement therapies (HRT) and of pregnancies. Secondly, we evaluated gonadotropin-releasing hormone (GnRH) agonist treatment for prevention of menstrual-cycle-related AIP attacks. Thirdly, we evaluated whether an altered sex-steroid metabolism was present in AIP women compared with controls. Finally, we evaluated the benefit of screening for HCC in AIP in a 15-year follow-up study. Methods and results: In a retrospective population-based study in northern Sweden, 166 female AIP gene carriers ≥18 years of age participated. Manifest AIP (MAIP) was reported in 55%; 82% had severe attacks and 39% had menstrual-cycle-related attacks. Hormonal contraceptives were used by 94, and 12 reported that this precipitated AIP attacks. HRT and local vaginal treatments in menopause did not precipitate AIP attacks. Only 10% reported impairment of AIP symptoms during pregnancy. In the retrospective follow-up study of GnRH-agonist treatment, 11 of 14 women improved during treatment. Porphyria attacks were triggered in two women after estradiol add-back and in 5 of 9 women after progesterone add-back. In the sex-steroid metabolism study, levels of s-progesterone, estradiol, allopregnanolone and pregnanolone during the menstrual cycle in 32 AIP gene carriers were compared with 20 healthy controls. Progesterone metabolism in the AIP group differed from controls. In the AIP group levels of allopregnanolone, but not pregnanolone, were significantly lower. In the prospective HCC screening study AIP gene carriers aged >55 years were included. On average 62 ...