What is the effect of progesterone on patients with Congestive Heart Failure (CHF) and reduced Ejection Fraction (EF)?

Effects of Progesterone on Patients with CHF and Reduced Ejection Fraction

Progesterone is not recommended for patients with congestive heart failure (CHF) and reduced ejection fraction as it is not part of guideline-directed medical therapy (GDMT) and may potentially worsen cardiovascular outcomes.

Current Guideline-Directed Medical Therapy for HFrEF

The cornerstone treatments for heart failure with reduced ejection fraction (HFrEF) are well-established in current guidelines and include:

1. Renin-Angiotensin System Inhibitors:

   • ACE inhibitors, ARBs, or preferably ARNI (sacubitril/valsartan) 1, 2

2. Beta-Blockers:

   • Carvedilol, metoprolol succinate, or bisoprolol 1, 2

3. Mineralocorticoid Receptor Antagonists (MRAs):

   • Spironolactone or eplerenone 1

4. SGLT2 Inhibitors:

   • Empagliflozin or dapagliflozin 2

The European Society of Cardiology (ESC) guidelines emphasize that these four medication classes form the foundation of HFrEF treatment, with each medication class demonstrating significant reductions in mortality and hospitalizations 1.

Progesterone and Cardiovascular Effects

Progesterone is not included in any heart failure treatment guidelines. The available evidence regarding progesterone in cardiovascular disease suggests potential concerns:

1. Vascular Effects: Progesterone receptors are present in arterial walls, and progestins can affect arterial function. While they may stabilize arteries in vasomotor instability, they can also induce vasoconstriction of estrogenized vessels 3.

2. Interaction with Other Hormones: When combined with estrogen therapy, certain progestins may attenuate some of estrogen's beneficial cardiovascular effects 3.

3. Absence from Guidelines: None of the major heart failure guidelines (ESC, ACC/AHA) include progesterone as part of recommended therapy for HFrEF 1, 2.

Potential Risks in HFrEF

For patients with HFrEF, several concerns arise regarding progesterone use:

1. Fluid Retention: Progesterone may cause fluid retention, which could exacerbate heart failure symptoms in already volume-overloaded patients.

2. Hemodynamic Effects: The potential vasoconstrictive effects could be particularly problematic in patients with reduced cardiac output.

3. Drug Interactions: Adding non-guideline medications increases the risk of interactions with established GDMT.

Optimization of Evidence-Based Therapy

Rather than considering progesterone, focus should be on optimizing the established GDMT:

1. Comprehensive Implementation: Less than 1% of HFrEF patients receive all life-prolonging treatments at trial-proven doses 1. Efforts should focus on implementing all four cornerstone medication classes.

2. Forced Titration Strategy: Guidelines recommend a forced titration strategy to achieve target doses of all medications, rather than maintaining patients on suboptimal doses 1.

3. Multidisciplinary Approach: The ESC Quality of Care Centre initiative emphasizes standardized, multidisciplinary heart failure care to improve GDMT implementation 1.

Special Considerations for Low Blood Pressure

If blood pressure is a concern when implementing GDMT:

1. Prioritize Essential Medications: Beta-blockers, ARNI/ACEi/ARB, MRAs, and SGLT2 inhibitors should be prioritized even in patients with lower blood pressure, as their benefits outweigh risks 1.

2. Careful Titration: Start with lower doses and titrate gradually while monitoring for symptoms of hypotension 1.

3. Address Reversible Causes: Identify and treat reversible causes of low blood pressure before adjusting heart failure medications 1.

Conclusion

Current evidence and guidelines do not support the use of progesterone in patients with CHF and reduced ejection fraction. Instead, clinicians should focus on optimizing the four cornerstone medication classes that have demonstrated mortality and morbidity benefits in clinical trials. Adding progesterone to the treatment regimen is not recommended and may potentially introduce additional risks without proven benefits.