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Clinical Endocrinology

Effects of tibolone or continuous combined oestradiol/norethisterone acetate on glucose and insulin metabolism

Authors


Correspondence: John C. Stevenson, National Heart & Lung Institute, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. Tel.: +44 20 7351 8112; Fax: +44 20 7351 8771; E-mail: j.stevenson@imperial.ac.uk

Summary

Objective

To determine the effects of tibolone or oestradiol (E2)/norethisterone acetate (NETA) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women.

Design

Single-centre double-blind placebo-controlled randomized clinical trial.

Subjects/Methods

We randomized 105 healthy postmenopausal women to tibolone 2·5 mg daily, continuous combined oral E2 2 mg/NETA 1 mg daily or placebo over a 2-year study. We performed intravenous glucose tolerance tests (IVGTT) with measurements of plasma glucose, insulin and C-peptide concentrations and the IVGTT glucose elimination rate, k. Mathematical modelling was performed to determine measures of insulin sensitivity, Si, pancreatic insulin secretion and hepatic and plasma insulin elimination.

Results

Tibolone decreased Si to 53–63% and k to 72–79% of baseline values but increased IVGTT phase 2 C-peptide concentrations 1·6–1·8-fold and pancreatic insulin secretion 2·2–2·4-fold, so overall IVGTT glucose concentrations were unaffected. Similar, but for k, significantly smaller changes in insulin and C-peptide secretion were seen with E2/NETA, also with no effect on overall IVGTT glucose concentrations.

Conclusions

Tibolone reduces insulin sensitivity. Healthy postmenopausal women seem able to compensate for this and maintain normal postload glucose concentrations, but it may not be advisable to prescribe tibolone to women with, or at increased risk for, diabetes.

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