Should you leave a legacy? Potential effects of delayed blood pressure lowering pharmacotherapy in individuals stratified by absolute cardiovascular disease risk

Background: Since aldosterone and cortisol levels vary during the menstrual cycle, and are utilized in the interpretation of adrenal venous sampling (AVS) to differentiate unilateral from bilateral primary aldosteronism, outcome of AVS could possibly be influenced by the time of sample collection. Aim: To assess the effect of phase of the menstrual cycle on adrenal and peripheral venous aldosterone and cortisol levels and on serum female sex steroid levels during AVS. Methods: In 23 pre-menopausal women with primary aldosteronism undergoing AVS, levels of aldosterone, cortisol, progesterone, estradiol, LH and FSH were compared, noting whether collection was during the follicular or luteal phase. Results were compared to those in age-matched males undergoing AVS. Results: Based on AVS results, 10 women (7 sampled during luteal phase) had unilateral over-production of aldosterone, and 13 (10 sampled during follicular phase) had bilateral over-production of aldosterone. The difference in proportions of luteal vs. follicular studies that showed unilateral disease was significant (P<0.05). Simultaneously collected peripheral levels of progesterone (P<0.0001), estradiol (P<0.05) and aldosterone (P<0.05) and bilateral adrenal venous levels of aldosterone (P<0.01) and cortisol (P<0.01) were higher in those sampled during the luteal phase. Importantly, luteal higher/lower side AV aldosterone/cortisol ratios were higher than follicular (P<0.05). Peripheral and adrenal venous aldosterone and cortisol levels and higher (but not lower) side AV aldosterone/cortisol ratios were significantly higher than male in the luteal group, but not the follicular. Conclusion: The phase of the menstrual cycle during which samples are collected significantly affected levels of aldosterone and cortisol used to interpret AVS. A risk of false lateralization appears to be present when AVS is performed during the luteal phase, but this requires confirmation with larger patient numbers, preferably with studies in each patient during both phases. Meanwhile, recording of the phase of the cycle during which AVS is performed should be encouraged.