Reversal of an unfavorable effect of hydrochlorothiazide compared to angiotensin converting enzyme inhibitor on serum uric acid and oxypurine levels by estrogen–progestin therapy in hypertensive postmenopausal women

Abstract

Background: The aim was to assess the effect of estrogen–progestin therapy (EPT) on serum levels of uric acid (SUA) and its precursors xanthine (X) and hypoxanthine (HX), and on uric acid (UA) renal excretion in hypertensive postmenopausal women treated with an angiotensin-converting enzyme inhibitor (ACEI) or thiazide diuretic (HCTZ) (ClinicalTrials.gov identifier: NCT03921736, registered 19 April 2019).

Methods: Postmenopausal women with untreated essential hypertension were recruited to the study. The control group consisted of 40 postmenopausal women with normal blood pressure. Hypertensive women were randomized to two groups: hydrochlorothiazide (n = 50) or perindopril (n = 50) and to a group receiving or not receiving EPT (EPT+/EPT−) due to vasomotor symptoms. The follow-up period was one year. Blood pressure measurements as well as blood tests for SUA and its precursors X and HX were performed at baseline and after 12 months.

Results: In hypertensive women, baseline serum X and HX were significantly higher when compared to the group of normotensive women. Treatment with HCTZ led to a statistically significant increase in SUA in the subgroup of EPT- women. In this group concentrations of X and HX increased significantly after 12 months. UA/X significantly decreased after treatment with HCTZ. Lack of EPT resulted in a decrease of renal plasma flow in the HCTZ group. However, in the HCTZ and EPT + group, SUA decreased significantly when compared to baseline. None of these unfavorable effects was observed in the ACEI group regardless of EPT.

Conclusions: 1) EPT prevents the development of hyperuricemia during antihypertensive treatment with thiazide diuretics. 2) Arterial hypertension and menopause cause impairment of UA excretion and increase the levels of SUA and its precursors X and HX. 3) EPT reduces the risk of hyperuricemia in postmenopausal women.

Keywords:

• Hypertension
• uric acid
• xanthine
• hypoxanthine
• menopause
• estrogen–progestin therapy
• thiazide diuretic
• angiotensin-converting enzyme inhibitor

Notes

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Declaration of financial/other relationships

No potential conflict of interest was reported by the authors. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

None reported.

Notes

a Estracomb TTS is a registered trade mark of Novartis Pharma GmbH Nurnberg, Germany.

Additional information

Funding

None received.