Effects of tibolone or continuous combined oestradiol/norethisterone acetate on
glucose and insulin metabolism.
Author(s): Manassiev N, Godsland IF, Proudler AJ, Whitehead MI, Stevenson JC.
Affiliation(s): Goodrest Croft Surgery, Yardley Wood.
Publication date & source: 2013, Clin Endocrinol (Oxf). , 78(2):297-302
OBJECTIVE: To determine the effects of tibolone or oestradiol (E(2)
)/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 E(2) 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, S(i) , pancreatic insulin secretion
and hepatic and plasma insulin elimination.
RESULTS: Tibolone decreased S(i) 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 E(2) /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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