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.
Pharmacokinetics and dosing
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 .
Reproductive health issues
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
- Allahabadia A, Daykin J, Holder RL, Sheppard MC, Gough SC, Franklyn JA. Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab. 2000;85:1038-42. PubMed
- Cinemre H, Bilir C, Gokosmanoglu F, Akdemir N, Erdogmus B, Buyukkaya R. Predictors of time to remission and treatment failure in patients with Graves' disease treated with propylthiouracil. Clin Invest Med. 2009;32:E199-205. PubMed
- Cooper DS, Goldminz D, Levin AA, Ladenson PW, Daniels GH, Molitch ME et al. Agranulocytosis associated with antithyroid drugs Effects of patient age and drug dose. Ann Intern Med. 1983;98:26-9. PubMed
- Tajiri J, Noguchi S, Murakami T, Murakami N. Antithyroid drug-induced agranulocytosis The usefulness of routine white blood cell count monitoring. Arch Intern Med. 1990;150:621-4. PubMed
- Nakamura H, Miyauchi A, Miyawaki N, Imagawa J. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. J Clin Endocrinol Metab. 2013;98:4776-83. PubMed
- Vera Regitz-Zagrosek. Sex and Gender Differences in Pharmacology. Springer-Verlag Berlin Heidelberg; 2012.
- Tiamazol Kloka Listan 2018. Kloka Listan 2018. Expertråd Endokrinologiska och metabola sjukdomar [updated 2018-12-12, cited 2019-08-23]. länk
- Cassina M, Donà M, Di Gianantonio E, Clementi M. Pharmacologic treatment of hyperthyroidism during pregnancy. Birth Defects Res A Clin Mol Teratol. 2012;94:612-9. PubMed
- Emiliano AB, Governale L, Parks M, Cooper DS. Shifts in propylthiouracil and methimazole prescribing practices: antithyroid drug use in the United States from 1991 to 2008. J Clin Endocrinol Metab. 2010;95:2227-33. PubMed
- Clark SM, Saade GR, Snodgrass WR, Hankins GD. Pharmacokinetics and pharmacotherapy of thionamides in pregnancy. Ther Drug Monit. 2006;28:477-83. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-08-19.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson