Does Tofacitinib Increase Prolactin Levels?
No, tofacitinib does not increase prolactin levels and is not associated with hyperprolactinemia.
Mechanism and Prolactin Pathway
Tofacitinib is a Janus kinase (JAK) inhibitor that preferentially blocks JAK1 and JAK3, interrupting the JAK/STAT signaling pathway used by inflammatory cytokines such as interferon-α/-β, interferon-γ, IL-2, IL-12, IL-20, IL-22, and IL-23 1, 2. This mechanism does not involve dopamine receptor antagonism or disruption of the hypothalamic-pituitary axis—the primary pathways through which medications cause hyperprolactinemia 3, 4.
Medications That Do Cause Hyperprolactinemia
Prolactin elevation is caused by drugs that block dopamine D2 receptors or increase serotonin activity, not by JAK inhibitors 3, 5:
- Antipsychotics – Typical antipsychotics and risperidone are the most common culprits, with prolactin levels rising 10-fold or more above baseline in approximately 60% of women and 40% of men 4, 6
- Antidepressants – Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAO-I), and some tricyclics can elevate prolactin through serotoninergic mechanisms 3, 6
- Prokinetic agents – Metoclopramide and domperidone block dopamine receptors in the pituitary 5, 6
- Antihypertensives – Methyldopa, reserpine, and verapamil have been implicated 3, 5
- H2-receptor antagonists – Cimetidine and ranitidine may cause modest prolactin elevation 3, 6
- Opiates, estrogens, and anti-androgens – These agents can also raise prolactin through various mechanisms 3, 5
Tofacitinib Safety Profile
The extensive safety monitoring required for tofacitinib focuses on hematologic, hepatic, lipid, infectious, and thrombotic risks—not endocrine or prolactin-related adverse effects 7, 8:
- Mandatory baseline and ongoing laboratory monitoring includes CBC with differential, comprehensive metabolic panel, and lipid profile 7, 8
- Absolute contraindications include lymphocyte count < 500 cells/mm³, absolute neutrophil count < 1000 cells/mm³, hemoglobin < 9 g/dL, and active serious infection 7, 8
- Black-box warnings cover serious infections, increased mortality, venous thromboembolism, and malignancies—not hyperprolactinemia 2
No guideline or drug label mentions prolactin monitoring, prolactin-related adverse effects, or hyperprolactinemia as a concern with tofacitinib 1, 7, 8, 2.
Clinical Implications
- If a patient on tofacitinib develops symptoms suggestive of hyperprolactinemia (galactorrhea, menstrual irregularities, erectile dysfunction, gynecomastia), investigate other causes such as concomitant medications (especially antipsychotics or antidepressants), pituitary adenoma, or hypothyroidism 4, 5, 6
- Do not attribute prolactin elevation to tofacitinib; the drug does not interact with dopaminergic pathways 3, 4
- Perform MRI or CT of the hypothalamic-pituitary region if hyperprolactinemia is confirmed and no medication cause is identified 5, 6