Low-dose estrogen and drospirenone combination: effects on glycoinsulinemic metabolism and other cardiovascular risk factors in healthy postmenopausal women

Villa, Paola; Suriano, Rosanna; Ricciardi, Luigi; Tagliaferri, Valeria; Cicco, Simona De; Franciscis, Pasquale De; Colacurci, Nicola; Lanzone, Antonio

doi:10.1016/j.fertnstert.2010.07.001

Cited by 21 publications

(9 citation statements)

References 32 publications

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“…In the present study, combined therapy with E2+DRSP in spontaneously hypertensive rats demonstrated a more pronounced vasodilatory response because it was significantly greater at the three highest concentrations evaluated compared with OVX rats, suggesting that this progestin improves E2 effects on coronary function. Human studies assessing flow-mediated dilation demonstrated that combined therapy can improve endothelium-dependent vascular function in young women and in healthy women in the post-menopausal period ( 30 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Borgo

Claudio

Silva

et al. 2016

Braz J Med Biol Res

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Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

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Section: Discussionmentioning

confidence: 99%

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Borgo

Claudio

Silva

et al. 2016

Braz J Med Biol Res

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“…In a prospective study [5], 0.3 mg/day decreased major coronary events in women compared to untreated controls, whereas 0.625 mg or more CEE combined with progestin increased the risk of stroke. Genant et al [59] and Villa et al [60 • ] showed that low-dose estrogen slightly increased plasma estradiol but improved endothelial function and lipid profile without endometrial hyperplasia, while higher doses increased plasma estradiol two-fold to three-fold and were associated with endometrial hyperplasia. Unfortunately, they did not examine the dose effect of estrogen on vascular calcification and risk of CVD.…”

Section: Hormonal Replacement Therapymentioning

confidence: 99%

Estrogen, hormonal replacement therapy and cardiovascular disease

Yang

Reckelhoff

2011

Current Opinion in Nephrology &Amp; Hypertension

234

150

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Purpose of review Premenopausal women have a lower risk and incidence of hypertension and cardiovascular disease (CVD) compared to age-matched men and this sex advantage for women gradually disappears after menopause, suggesting that sexual hormones play a cardioprotective role in women. However, randomized prospective primary or secondary prevention trials failed to confirm that hormone replacement therapy (HRT) affords cardioprotection. This review highlights the factors that may contribute to this divergent outcome and could reveal why young or premenopausal women are protected from CVD and yet postmenopausal women do not benefit from HRT. Recent findings In addition to the two classical estrogen receptors, ERα and ERβ, a third, G-protein-coupled estrogen receptor GPR30, has been identified. New intracellular signaling pathways and actions for the cardiovascular protective properties of estrogen have been proposed. In addition, recent Women’s Health Initiative (WHI) studies restricted to younger postmenopausal women showed that initiation of HRT closer to menopause reduced the risk of CVD. Moreover, dosage, duration, the type of estrogen and route of administration all merit consideration when determining the outcome of HRT. Summary HRT has become one of the most controversial topics related to women’s health. Future studies are necessary if we are to understand the divergent published findings regarding HRT and develop new therapeutic strategies to improve the quality of life for women.

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“…Sanada et al (Sanada et al 2003) confirmed that low-dose CEE (0.3 mg/day for 3 months) improved endothelial function and decreased LDL cholesterol nearly as well as the standard dose of 0.625 mg/day. More recently, Villa et al (Villa et al 2010) reported that low-dose estrogen (1 mg) in combination with drospirenone (a new progestin derived from 17α-spronolactone) had a favorable effect on lipid profile and endothelial function. In animal studies, wide range of estrogen dosages (from 0.17 to 83.3 μg/day) has been used.…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent toxic effects of high-dose estrogen on renal and cardiac injury in surgically postmenopausal mice

et al. 2011

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Aims-We previously found that in mice with experimental myocardial infarction (MI), 17β-estradiol (E2) increased mortality and worsened cardiac remodeling and these deleterious effects were associated with renal enlargement and hydronephrosis in a dose-dependent manner. In the present study we questioned whether E2-induced renal damage predisposes to rather than results from its adverse effectson the heart. Key findings-E2-L partially restored uterine weight and plasma estrogen levels without affecting heart, lung and liver weight, hemodynamic parameters, or heart and kidney morphology and function. E2-M restored normal uterine weight, but this was accompanied by a significant increase in kidney weight, albuminuria, glomerular matrix formation and markers for oxidative stress. E2-H increased uterine weight 4.5-fold and resulted in higher plasma creatinine levels, severe albuminuria, renal tubular dilatation, tubulointerstitial injury, hydronephrosis, glomerulosclerosis and oxidative stress. E2-H also caused ascites, hepatomegaly and fluid retention in the uterinehorns but had no significant effect on blood pressureor heart function.Significance-Our data demonstrated that an excessive dose of E2 that raises uterine weight beyond physiological levels adversely affects the kidney even before it damages the heart. We believe estrogen dosage should be taken into account when considering hormonal replacement therapy, sincei nappropriate doses of E2may damage not only the heart but also the kidney.

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Low-dose estrogen and drospirenone combination: effects on glycoinsulinemic metabolism and other cardiovascular risk factors in healthy postmenopausal women

Cited by 21 publications

References 32 publications

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Estrogen, hormonal replacement therapy and cardiovascular disease

Dose-dependent toxic effects of high-dose estrogen on renal and cardiac injury in surgically postmenopausal mice

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