is there a relationship between high-dose norethisterone therapy over 18 months

Clinical answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 15 October 2025Updated: 15 October 2025 Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

Relationship between high-dose norethisterone therapy over 18 months and cholesterol: There is no direct evidence in the NICE NG88 guidelines or BNF hormone safety protocols explicitly linking high-dose norethisterone therapy over 18 months to dangerously elevated cholesterol levels. However, norethisterone, a progestogen, is known to have potential metabolic effects, including possible impacts on glucose tolerance and cardiovascular risk factors such as dyslipidaemias, which require monitoring during treatment.

NICE NG88 guidelines on hormone therapy safety: NICE guidelines on menopause and hormone replacement therapy (HRT) emphasize using the lowest effective dose for the shortest duration necessary, with regular review of treatment benefits and risks, including cardiovascular risk factors. They do not specify cholesterol elevation as a direct risk of norethisterone but recommend caution and monitoring in patients with multiple cardiovascular risk factors, including dyslipidaemias.

BNF hormone safety protocols regarding norethisterone: The BNF notes that norethisterone can cause side effects such as hypertension and may worsen conditions related to fluid retention and cardiovascular disease risk factors, including dyslipidaemias. It advises caution and specialist advice when using norethisterone in patients with multiple cardiovascular risk factors. There is no explicit mention of dangerously elevated cholesterol as a common or known adverse effect, but monitoring lipid profiles is prudent in long-term or high-dose use.

Relevance: While high-dose norethisterone therapy over 18 months is not directly linked to dangerously elevated cholesterol in the cited UK guidelines, the presence of dyslipidaemia as a caution indicates that lipid monitoring is important. The NICE NG88 guideline's principle of individualized risk assessment and regular review supports careful monitoring of cardiovascular risk factors, including cholesterol, during prolonged progestogen therapy.

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