Can testosterone affect mast cell degranulation in patients with mast cell disorders or a history of allergic reactions?

Testosterone and Mast Cell Degranulation

Testosterone can directly induce mast cell degranulation through androgen receptor-mediated mechanisms in animal models, but human studies show conflicting results, with no demonstrated effect on IgE-mediated degranulation in human mast cells. 1, 2

Evidence from Animal Studies

The strongest evidence for testosterone-induced mast cell degranulation comes from animal research:

• Testosterone directly induces mast cell degranulation in Syrian hamsters through androgen receptor activation, as demonstrated by electron microscopy showing abundant degranulated mast cells after testosterone treatment 1
• This effect can be blocked by the antiandrogen cyproterone acetate, confirming receptor-mediated action 1
• In rats, testosterone increases mast cell degranulation in kidney tissue, with orchiectomy inhibiting this effect and testosterone replacement reversing the protective effect of orchiectomy 3
• Gender-dependent effects exist in rats, where mast cells from female rats are more susceptible to sex steroid effects than those from males, with testosterone showing dose-dependent modulation of histamine release 4

Evidence from Human Studies

The translation to human mast cells is less clear:

• Human skin mast cells express androgen receptors (confirmed by immunocytochemistry and PCR), as do human mast cell lines HMC-1 and LAD2 2
• However, testosterone treatment of human HMC-1 mast cells does not affect IgE-independent degranulation elicited by neuromuscular blocking agents, as measured by β-hexosaminidase release 2
• This suggests that despite receptor expression, testosterone may not directly trigger degranulation in human mast cells under experimental conditions 2

Clinical Implications for Mast Cell Disorders

For patients with mastocytosis or mast cell activation syndrome:

• The primary triggers remain non-immunologic stimuli including temperature extremes, stress, physical pressure, certain medications (NSAIDs, opioids, muscle relaxants), and alcohol 5, 6
• No clinical guidelines recommend avoiding testosterone or considering it a trigger in patients with mast cell disorders 5, 6
• The perioperative management guidelines for mastocytosis focus on avoiding known histamine-releasing drugs (certain muscle relaxants, morphine, meperidine, ketorolac) but do not mention sex hormones as triggers 5

Important Caveats

• Hormonal fluctuations are listed as potential triggers for mast cell activation in general, but this typically refers to endogenous hormonal changes rather than exogenous testosterone 6, 7
• The animal data showing testosterone-induced degranulation may not reflect human physiology, as in vitro human studies failed to demonstrate this effect 2
• Gender differences in anaphylactic reactions to neuromuscular blocking agents (with female predominance) suggest sex hormones may play a modulatory role, though the mechanism remains unclear 2