Introduction: Blood glucose regulation of women with type 1 and type 2 diabetes changes around menopause, which may be partly caused by estrogen deficiency. There is conflicting evidence about the impact of hormone replacement therapy (HRT) on blood glucose regulation. Therefore, we conducted a systematic review and meta-analysis to investigate the effect of HRT on glucose regulation in postmenopausal women with type 1 or type 2 diabetes.

Methods: Medline, Embase, Scopus, the Cochrane Library and the clinicaltrials.gov registry were searched to identify randomized-controlled trials (RCTs). We selected RCTs investigating the effect of HRT with at least estrogen monotherapy in postmenopausal women (final menstrual period > 6 months) with type 1 or type 2 diabetes. Outcomes were HbA1c (mmol/mol), fasting glucose (mmol/l), postprandial glucose (mmol/l), and differences in use of glucose lowering drugs. The protocol was registered as PROSPERO-ID CRD42021258615.

Results: 2,592 records were identified. Nineteen RCTs were included (12 parallel-group trials and 7 crossover trials), with a total of 1,412 participants, of which 4.0% had type 1 diabetes. HRT reduced HbA1c (mean difference -6.08 mmol/mol [95% CI -8.80, -3.36]) and fasting glucose (mean difference -1.15 mmol/l [95% CI -1.78, -0.51]), with substantial heterogeneity. Subgroup analyses of the effect of transdermal HRT (4 studies) showed no differences in HbA1c or fasting glucose.

Conclusion: HRT reduces HbA1c and fasting glucose concentration in postmenopausal women with type 2 diabetes. The effect might be limited to oral HRT. Evidence for postmenopausal women with type 1 diabetes is scarce.