Drug products: Propycil, Tiotil
ATC code: H03BA02
Thyreostatic drugs are associated with agranulocytosis which, according to some studies, is more common in women.
Propylthiouracil is recommended during pregnancy, however due to risk of liver toxicity for the mother the lowest dose should be used.
No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of propylthiouracil have been found. For both men and women, the lowest effective dose is recommended (see Adverse effects) . There is no evidence that the pharmacokinetics of propylthiouracil in pregnant and non-pregnant women differs .
Studies have shown that more men than women fail to enter long-term remission after thyreostatic therapy for Graves’ disease [1,2]. A clinical trial (92 men, 444 women) found that men had a markedly worse outcome after medical treatment with carbimazole (prodrug to methimazole) or propylthiouracil for 18 months. Men had with a remission rate of only 19.5% compared with 40% for females .Similarly, in a prospective cohort study of propylthiouracil treatment 300 mg/day for 18 months in Graves’ disease (4 men, 22 women), male sex was associated with failure to respond .
Antithyroid drug therapy is associated with agranulocytosis. Among reported cases of antithyroid-induced agranulocytosis, females are in majority [3-5]. Mean doses at onset of agranulocytosis are varying; for methimazole 25-44 mg/day and for propylthiouracil 217-383 mg/day. Although antithyroid-induced agranulocytosis is rare, it has been suggested that low-dose methimazole therapy may be safer than high-dose therapy or treatment with conventional doses of propylthiouracil . The reasons why women are affected more frequently than men are suggested to be due to pharmacokinetic differences between men and women, immunologic and hormonal factors as well as differences in co-medications .
Some epidemiologic studies suggest that methimazole exposure during the first trimester of pregnancy is associated with an increased risk of congenital malformations. Since propylthiouracil has not been associated with an increased risk of congenital malformations, this is the recommended drug during the first trimester during pregnancy . However, propylthiouracil is associated with hepatotoxicity (estimated incidence 0.1-0.2% of exposed adults), and therefore treatment with low-dose methimazole during the second and third trimesters have been suggested by American guidelines , but not in Sweden . Treatment of thyrotoxicosis during pregnancy should always be referred to a specialist. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Prescribing practices for methimazole and propylthiouracil in the U.S. between the years 1991-2008 were examined using data from pharmacy databases. Men were more likely to be on methimazole (82%) than women (74%), although 72% of methimazole prescriptions were to women .
Date of litterature search: 2019-08-23
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson