Norethisterone Other names: Norethindrone 19-nor-17α-ethynyltestosterone

Norethisterone has progestational actions similar to those of progesterone, but is a more potent inhibitor of ovulation and has weak oestrogenic and androgenic properties. It is used to treat a number of disorders of the menstrual cycle.

Norethisterone given at intermediate doses (5-10mg) suppresses ovulation via its effect on the pituitary. The endogenous production of oestrogens and progesterones are also suppressed, and the ectopic endometrium is converted to a decidua resembling that of pregnancy. In carcinoma norethisterone may act by pituitary inhibition or by direct action on tumour deposits.

Norethisterone is rapidly and completely absorbed after oral administration, peak plasma concentration occurring in the majority of subjects between 1 and 3 hours. Due to first-pass metabolism, blood levels after oral administration are 60% of those after i.v. administration. The half life of elimination varies from 5 to 12 hours, with a mean of 7.6 hours. Norethisterone is metabolised mainly in the liver. Approximately 60% of the administered dose is excreted as metabolites in urine and faeces.

The toxicity of norethisterone is very low.

Non-clinical data on norethisterone or its esters reveal no special risk for humans based on conventional studies of repeated dose toxicity, genotoxicity and carcinogenic potential which is not already included in other relevant sections. However, it should be kept in mind that sexual steroids might stimulate the growth of hormone-dependent tissues and tumours.

Reproduction toxicity studies showed the risk of masculinisation in female fetuses when administered at high doses at the time of the development of the external genitalia. Since epidemiological studies show that this effect is relevant in humans after high doses, it must be stated that norethisterone may provoke signs of virilisation in female fetuses if administered during the hormone-sensitive stage of somatic sexual differentiation (from day 45 of pregnancy onwards). Apart from this, no indications of teratogenic effects were obtained from the studies.