Alterations in Haem Biosynthesis during the Human Menstrual Cycle: Studies in Normal Subjects and Patients with Latent and Active Acute Intermittent Porphyria

1. The timing of onset of attacks of acute intermittent porphyria (AIP) in relation to the menstrual cycle has been studied in three patients experiencing frequent attacks. Nineteen of their 27 admissions in attack for which no exogenous precipitating causes could be identified were during the 7 days before the onset of menstruation. 2. Haem biosynthesis has been monitored throughout a complete menstrual cycle in six normal females and compared with that in male control subjects. In the females, there was marked fluctuation in the activity of the rate-controlling enzyme of haem biosynthesis, δ-aminolaevulinate (ALA) synthase, which was monitored in peripheral leucocytes. The fluctuation did not show any clear association with menstruation and no association was found between the enzyme activity and ovarian or adrenal steroid production as monitored by measurement of plasma concentrations of androstenedione, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone, oestradiol and progesterone. The activity of uroporphyrinogen I (URO) synthase, the enzyme which is deficient in AIP, was monitored in peripheral erythrocytes of four of the normal female subjects and was similar to that found in four male control subjects. The urinary excretion of ALA and porphobilinogen (PBG) was also similar in the male and female subjects and there was no association with the phase of the menstrual cycle or activity of the enzymes studied. 3. Studies of haem biosynthesis have been made throughout a complete menstrual cycle in a 26 year old female with latent AIP. The activity of leucocyte ALA synthase showed more marked fluctuation than in the normal female subjects and was highest at the time of menstruation. No association was apparent between the activity of ALA synthase and plasma concentrations of androstenedione, DHA and DHAS. The fluctuation in activity of erthrocyte URO synthase was similar to that of the normal subjects. The urinary excretion of ALA and PBG was normal throughout and showed no correlation with fluctuations in enzyme activity. 4. The human menstrual cycle modifies haem biosynthesis in normal subjects as well as in subjects with latent and manifested AIP. 5. The human female menstrual cycle modifies haem biosynthesis in peripheral blood cells as well as in the liver.