Aldosterone antagonists or mineralocorticoid receptor antagonists (MRAs) are used as therapeutic agents for the management of HF with reduced ejection fraction (HFrEF). Gender-related differences have been described in the regulation of the renin-angiotensin-aldosterone system (RAAS), which is at the core of the pathophysiology of HF. Regarding gender-related differences in the use of MRAs, less is known about the effects of androgens on the RAAS, even though studies have suggested that androgens may increase the RAAS pathway. There are conflicting results because many clinical trials were not specifically designed to investigate gender differences.

The RALES trial investigated the effect of spironolactone on symptomatic HF patients without any difference in treatment benefits between both genders. However, only 30 % of the patients enrolled were females. Another trial investigated the gender-based differences in the treatment of HFpEF patients with spironolactone. The results showed no significant sex differences in clinical endpoints, but a substantial reduction in all-cause mortality was associated with spironolactone use in females but not in males. The utilization of HF pharmacotherapy has been controversial, given recent discoveries presented by the PARAGON-HF trial.

Inclusion Criteria:

• All adult (≥ 18 years) ambulatory patients of both sexes with a diagnosis of HFrEF (LVEF≤ 40%) and NYHA class II-IV under optimized medical therapy who are presented to the outpatient clinic and started spironolactone at the time of enrollment.

Exclusion Criteria:

• Pregnancy or breastfeeding
• Serum creatinine > 2.5 mg/dL (221 µmol/L) in males and > 2 mg/dL (177 µmol/L) in women (or estimated glomerular filtration rate (eGFR) ≤ 30 mL/minute/1.73 m2)
• Hyperkalemia (serum potassium level > 5 mEq/L)
• Renal transplantation
• Concomitant administration of potent CYP3A inhibitors
• Concomitant administration of potassium supplements or potassium-sparing diuretics
• Disorders of the adrenal glands (such as Addison disease).
• Patients who used MRA in the last 2 weeks before enrollment.

adult (≥ 18 years) ambulatory patients of both sexes with a diagnosis of HFrEF (LVEF≤ 40%) and NYHA class II-IV under optimized medical therapy who are presented to the outpatient clinic and started spironolactone at the time of enrollment.