1. In hypertensive women, both the results of the screening for hyperaldosteronism and of the evaluation of insulin resistance depend on the timing of assessment in relation to the ovarian cycle

We have reported that in low-renin hypertensive women the increment of plasma aldosterone that occurs in the luteal compared to the follicular phase of the ovarian cycle markedly increases the positivity for suspected primary hyperaldosteronism; it has also been reported that aldosteronism is associated with insulin resistance (IR) (Garg J.Clin.Endocrinol.Metab, 2010) and that IR slightly but significantly increases in the luteal phase in normotensive women (Yeung J.Clin.Endocrinol.Metab, 2010). We here report the results of a study on 31 women in the fertile age evaluated because of arterial hypertension in whom both aldosterone and HOMA-IR index (glucose*insulin/405) levels were investigated during the ovarian cycle. All measures (plasma aldosterone, PRA, insulin, glucose and progesterone levels) were done at the 5-7th (follicular phase) and 21-25th (luteal phase) day of the menstrual cycle, without hypotensive therapy or with doxazosin 4mg per day. All women reported a regular cycle, age: 41.7±8.4 [mean±SD] (range:19-53) years, BMI 25.1±4.6 (19.3-35.8) kg/m2. Compared to the follicular phase, in the luteal phase plasma progesterone (P), aldosterone (ALDO), renin activity (PRA), insulin (I) and HOMA-IR all increased significantly: P from 0.6±0.3 to 8.7±4.1 ng/mL (p<.0001, t-paired); ALDO from 13.6±83 to 21.1±83 ng/dL (p<.0001); PRA from 0.42±0.40 to 0.69±0.87 ng/mL/hr (p<.02); I from 6.23±2.96 to 8.67±4.11 mU/L (p<.0001); HOMA-IR from 1.39±0.8 to 2.01±1.21 (p<.0001). For example, the proportion of ALDO>15 ng/dL with ALDO/PRA>40 increased from 7/31 (23%) to 16/31 (52%); the proportion of HOMA-IR>2.5 increased from 3/22 (14%) to 6/22 (27%). Multiple regression analysis demonstrated that P - but not ALDO - and BMI were strong positive independent predictors of plasma insulin and HOMA-IR: univariate analysis 1.) I vs P p=0.016; vs BMI p<0.0001; 2.) HOMA-IR vs P p=0.065; vs BMI p<0.0001; multivariate analysis 1.) I vs P (p=<0.002) + BMI (p<0.0001); 2.) HOMA-IR vs P (p<0.02) + BMI (p<0.0001). These results in hypertensive women confirm that plasma aldosterone may greatly increase during the luteal phase of the ovarian cycle and suggest that also insulin resistance may increase to a greater extent than in normotensive women. The ovarian cycle is thus a source of variability of plasma aldosterone and of insulin resistance in hypertensive women in fertile age, with potential relevance in the diagnostic workup and pathophysiology of hypertension.