Hemodynamic and metabolic effects of estrogen plus progestin therapy in hypertensive postmenopausal women treated with an ACE-inhibitor or a diuretic

Abstract

Objectives: The aim of the study was to assess the hemodynamic and metabolic actions of estrogen plus progestin therapy (EPT) in hypertensive, postmenopausal women treated with perindopril (ACEI) or hydrochlorothiazide (HCTZ). A group of normotensive postmenopausal women was also studied.

Methods: 100 hypertensive and 40 normotensive postmenopausal women were recruited for the study. The hypertensive females were randomly assigned to receive ACEI or HCTZ for 12 months. The patients of the ACEI group and the patients of the HCTZ group, as well as normotensives, were further subdivided into two subgroups each. One subgroup received estrogen plus progestin therapy (EPT+), the other subgroup received no hormone replacement (EPT-). Combined hormone replacement with transdermal patches releasing 17β-estradiol and norethisterone was used. Office and 24-hour ambulatory blood pressure was measured at baseline and during follow-up. Renal plasma flow (RPF) was measured using the clearance of [125I]-iodohippuran. Pulse wave velocity (PWV) was determined with an automatic device.

Results: In normotensive postmenopausal women, transdermal estrogen plus progestin therapy increases RPF and insulin sensitivity, decreases PWV, decreases total and LDL cholesterol, and decreases uric acid serum levels. Perindopril (4 mg/day) and hydrochlorothiazide (25 mg/day) were equally effective in reducing blood pressure in postmenopausal, hypertensive subjects. In these females, perindopril increased RPF and decreased PWV and plasma insulin levels. These effects of the ACEI were not altered by estrogen plus progestin therapy. Hydrochlorothiazide decreased RPF and increased plasma insulin and uric acid concentrations in hypertensive subjects whom were not receiving estrogen plus progestin therapy.

Conclusions: The unfavorable metabolic and hemodynamic actions of the diuretic were counteracted by estrogen plus progestin therapy. Concomitant estrogen plus progestin therapy may be a method to avoid unfavorable hemodynamic and metabolic effects of thiazide diuretics in hypertensive, postmenopausal women.

Fig. 1

The interaction between the type of hypotensive treatment and EPT on insulin change (unfilled triangles) shows its reduction by an average of 4.87 µI/L in women with EPT added to HCTZ (β the regression coefficient and its error of estimation, EPT estrogen plus progestin therapy, ACEI angiotensin converting enzyme inhibitor, HCTZ hydrochlorothiazide)

Fig. 2

The interaction between the type of hypotensive treatment and EPT on uric acid plasma level shows its reduction by an average of 1.56 mg/dL in patients with EPT added to HCTZ (β the regression coefficient and its error of estimation, EPT estrogen plus progestin therapy, ACEI angiotensin converting enzyme inhibitor, HCTZ hydrochlorothiazide)

Fig. 3

The interaction between the type of hypotensive treatment and EPT on PWV shows its reduction by an average of 1.97 m/s in patients with EPT added to HCTZ (β the regression coefficient and its error of estimation, PWV pulse wave velocity, EPT estrogen plus progestin therapy, ACEI angiotensin converting enzyme inhibitor, HCTZ hydrochlorothiazide)

Fig. 4

The interaction between the type of hypotensive treatment and EPT on RPF shows its increase by an average of 107.5 mL/min in patients with EPT added to HCTZ (β the regression coefficient and its error of estimation, RPF renal plasma flow, EPT estrogen plus progestin therapy, ACEI angiotensin converting enzyme inhibitor, HCTZ hydrochlorothiazide

Fig. 5

The comparison of plasma levels of insulin, total cholesterol, LDL cholesterol, uric acid between women treated with (n = 60) or without EPT (n = 60) (EPT estrogen plus progestin therapy)