Sertraline's Effect on Prolactin Levels
Sertraline can cause hyperprolactinemia as evidenced by the FDA drug label which explicitly lists galactorrhea and hyperprolactinemia among its adverse effects. 1
Mechanism and Evidence
Sertraline, like other SSRIs, can increase prolactin levels through both serotonin-dependent and independent mechanisms:
Serotonergic pathway: SSRIs increase serotonin levels, which inhibit tuberoinfundibular dopamine (TIDA) neurons in the hypothalamus 2
- These neurons normally suppress prolactin secretion
- When inhibited by serotonin, prolactin secretion increases
Direct inhibitory effect: Sertraline can directly suppress TIDA neuron activity independent of serotonin transmission 2
- This involves decreased intrinsic excitability and slowing of TIDA network rhythms
Clinical Evidence
The FDA drug label for sertraline explicitly lists hyperprolactinemia and galactorrhea (milk production due to elevated prolactin) as adverse effects 1. This represents the strongest regulatory evidence of this association.
Research studies show mixed but generally supportive evidence:
A 2017 prospective study found that 34.8% of patients receiving SSRI monotherapy (including sertraline) for 3 months developed hyperprolactinemia 3
A 2013 cross-sectional study of patients on SSRI monotherapy found a 10.9% prevalence of hyperprolactinemia 4
A 2021 randomized controlled trial in women with PCOS found no significant difference in prolactin levels between sertraline and placebo groups after 6 weeks of treatment 5
A 2011 pharmacovigilance database analysis found that while most SSRIs were associated with increased reporting of hyperprolactinemia, sertraline specifically did not show this association 6
Clinical Implications
Clinicians should be aware of the potential for sertraline to cause hyperprolactinemia, which may manifest as:
- Galactorrhea (inappropriate milk production)
- Menstrual disorders in women
- Sexual dysfunction in both men and women
- Reduced fertility
Monitoring Recommendations
While routine monitoring of prolactin levels is not required for all patients on sertraline, clinicians should:
- Consider measuring prolactin levels in patients who develop symptoms suggestive of hyperprolactinemia
- Be particularly vigilant in patients with pre-existing prolactin disorders or those at risk for complications from hyperprolactinemia
- Remember that hyperprolactinemia can occur even with sertraline monotherapy, though the risk appears lower than with some other SSRIs 6
Conclusion
The evidence indicates that sertraline can alter prolactin levels, with the FDA drug label explicitly listing hyperprolactinemia as an adverse effect. While not all patients will experience this side effect, clinicians should be aware of this potential and monitor for clinical manifestations of elevated prolactin in patients taking sertraline.