This might have been due to additional ethinylestradiol generated by higher doses of norethisterone. Overdose
There have been no reports of serious side effects with overdose of norethisterone, even in small children. As such, overdose usually does not require treatment. High dosages of as much as 60 mg/day norethisterone have been studied for extended treatment durations without serious adverse effects described. Interactions
5α-Reductase plays an important role in the metabolism of norethisterone, and 5α-reductase inhibitors such as finasteride and dutasteride can inhibit its metabolism. Norethisterone is partially metabolized via hydroxylation by CYP3A4, and inhibitors and inducers of CYP3A4 can significantly alter circulating levels of norethisterone. For instance, the CYP3A4 inducers rifampicin and bosentan have been found to decrease norethisterone exposure by 42% and 23%, respectively, and the CYP3A4 inducers carbamazepine and St. Johns wort have also been found to accelerate norethisterone clearance. Pharmacology
Pharmacodynamics
Norethisterone is a potent progestogen and a weak androgen and estrogen. That is, it is a potent agonist of the progesterone receptor (PR) and a weak agonist of the androgen receptor (AR) and the estrogen receptor (ER). Norethisterone itself has insignificant affinity for the ER; its estrogenic activity is from an active metabolite that is formed in very small amounts, ethinylestradiol (EE), which is a very potent estrogen. Norethisterone and its metabolites have negligible affinity for the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) and hence have no glucocorticoid, antiglucocorticoid, mineralocorticoid, or antimineralocorticoid activity. Progestogenic activity
Norethisterone is a potent progestogen and binds to the PR with approximately 150% of the affinity of progesterone.
A common channel longer than 3 cm in length usually has poor sphincter muscles and a poor sacrum, suggesting a prognostic outcome for bowel control and urinary function to be less likely. Common channels longer than 3 cm are generally considered more complex and more technically challenging in surgical repair. See also
Cloaca (embryology)
Cloaca

References


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