Does Spironolactone Affect Prolactin Levels?
Yes, spironolactone causes a modest but statistically significant reduction in serum prolactin levels, not an increase, even at doses ≥100 mg daily.
Evidence from Clinical Studies
The most robust evidence comes from multiple clinical trials demonstrating that spironolactone actually decreases prolactin concentrations:
In women with hyperandrogenism treated with low-dose spironolactone (50-75 mg daily), prolactin values showed statistically significant reduction at the end of treatment. 1
In anovulatory women receiving 100-150 mg daily of spironolactone, serum prolactin levels significantly decreased during six consecutive treatment cycles. 2
In transgender women treated with estradiol plus spironolactone, no statistically significant rise in prolactin occurred, and prolactin levels remained stable across up to 6 years of follow-up data. 3
Comparative Effects: Spironolactone vs. Cyproterone Acetate
The differential effects between antiandrogens are clinically important:
Cyproterone acetate (CPA) increases prolactin by +11.8 μg/L on average, while spironolactone causes only a minimal change of +3.10 μg/L (P < 0.001). 4
This 4-fold difference in prolactin elevation between CPA and spironolactone remained significant after adjusting for baseline prolactin levels. 4
Clinical Implications for Monitoring
Routine prolactin monitoring is unnecessary in patients taking spironolactone alone or with estrogen. 3
When Prolactin Monitoring IS Indicated:
- Patients switching from or combining spironolactone with other antiandrogens (particularly cyproterone acetate) 4
- Patients on medications known to cause hyperprolactinemia (typical antipsychotics, risperidone, SSRIs, MAO inhibitors, prokinetics, opiates, H2-receptor antagonists) 5
- Patients developing symptoms of hyperprolactinemia (galactorrhea, amenorrhea, sexual dysfunction) regardless of medication regimen
Common Pitfall to Avoid:
Do not confuse spironolactone's prolactin-lowering effect with the hyperprolactinemia caused by other antiandrogens or antipsychotic medications. The evidence clearly shows spironolactone reduces, rather than elevates, prolactin levels. 1, 2
Mechanism of Prolactin Reduction
While the exact mechanism is not fully elucidated in the provided evidence, the consistent finding across multiple studies of prolactin reduction with spironolactone treatment at doses ranging from 50-150 mg daily suggests this is a reproducible pharmacological effect. 1, 2