Gynecomastia induced by H1-antihistamine (ebastine) in a patient with idiopathic anaphylaxis
H1-antihistamine is generally a well-tolerated and safe drug. However, in resemblance with all other drugs, H1-antihistamines can also prompt adverse drug reactions (ADRs). We recently encountered the very unusual ADR of H1-antihistamine-induced gynecomastia. A 21-year-old man with idiopathic anaphylaxis was treated with ebastine (Ebastel), a second-generation H1-antihistamine, for the prevention of anaphylaxis. Three months later, the patient remained well without anaphylaxis, but had newly developed gynecomastia. Because anaphylaxis recurred after the cessation of H1-antihistamine, the preventive medication was changed to omalizumab. A few months later, his gynecomastia had entirely disappeared. Physicians should be aware of this exceptional ADR of H1-antihistamine.
........An endocrinologist recommended a hormonal study. The results were all within normal limits, although the prolactin level was high normal: prolactin, 18.74 ng/mL (normal reference, 1.61-18.77 ng/mL); testosterone, 5.78 ng/mL (normal reference, 2.41-8.27 ng/mL); estradiol, 37.44 pg/mL (normal reference, 5-4,300 pg/mL); thyroid-stimulating hormone, 1.45 µIU/mL (normal reference, 0.55-4.78 µIU/mL); luteinizing hormone, 2 (normal reference, 2-12). We concluded that the current medication (ebastine) was the probable culprit of the patient's gynecomastia.
.......At first, we changed the class of H1-antihistamine that was provided to the patient: ebastine (a class of piperidine) was stopped and cetirizine (a class of piperazine) was started. One month later, the gynecomastia had progressed further despite the new H1-antihistamine (cetirizine). We decided to stop the administration of H1-antihistamine because anaphylaxis had not occurred at any point during the preventive therapy with H1-antihistamine. A few weeks later, the patient's dyspnea, cough, wheezing, and urticarial/lip angioedema had relapsed and were worsening. His breasts had somewhat regressed. In the end, we started omalizumab (150 mg every 4 weeks) as a new preventive treatment for anaphylaxis. During the first few days after beginning omalizumab, the symptoms of anaphylaxis gradually subsided. His breasts also showed gradual regression. By approximately 6 months later, gynecomastia had completely disappeared. Further, the prolactin level had decreased to 8.91 ng/mL.
Gynecomastia induced by H1-antihistamine (ebastine) in a patient with idiopathic anaphylaxis
Famotidine
Histamine H2-receptor blockade is known to stimulate prolactin secretion.[4] Oral famotidine usually does not affect serum prolactin levels, but rare cases of hyperprolactinemia and galactorrhea have been reported.[5][6]
Famotidine - Drugs and Lactation Database (LactMed) - NCBI Bookshelf
H1- and H2-Histamine Receptor Antagonists and Induced Release of Prolactin in Male Rats
The effects of 3rd ventricle injection of metiamide, an H2-histamine receptor antagonist and pyrilamine, an H1-histamine receptor antagonist, on the increase of plasma prolactin induced by two doses of histamine in normal male rats were studied. Metiamide did prevent the stimulating action of histamine whereas pyrilamine was not effective. Histamine-induced prolactin release was also blocked by low doses of the 2 antihistamines given in combination. Metiamide per se has no effect but high doses of pyrilamine increased plasma prolactin levels and augmented the hormone response to histamine. The results suggest mediation of H2-receptors in the facilitatory action of histamine on prolactin release.
H1- and H2-Histamine Receptor Antagonists and Induced Release of Prolactin in Male Rats
I know cypro has been discussed in regards to the few studies suggesting it increases prolactin and the reason has been speculated to be dopamine antagonism. But none of the antihistamines in the above studies affect dopamine, as far as I can tell.
H1-antihistamine is generally a well-tolerated and safe drug. However, in resemblance with all other drugs, H1-antihistamines can also prompt adverse drug reactions (ADRs). We recently encountered the very unusual ADR of H1-antihistamine-induced gynecomastia. A 21-year-old man with idiopathic anaphylaxis was treated with ebastine (Ebastel), a second-generation H1-antihistamine, for the prevention of anaphylaxis. Three months later, the patient remained well without anaphylaxis, but had newly developed gynecomastia. Because anaphylaxis recurred after the cessation of H1-antihistamine, the preventive medication was changed to omalizumab. A few months later, his gynecomastia had entirely disappeared. Physicians should be aware of this exceptional ADR of H1-antihistamine.
........An endocrinologist recommended a hormonal study. The results were all within normal limits, although the prolactin level was high normal: prolactin, 18.74 ng/mL (normal reference, 1.61-18.77 ng/mL); testosterone, 5.78 ng/mL (normal reference, 2.41-8.27 ng/mL); estradiol, 37.44 pg/mL (normal reference, 5-4,300 pg/mL); thyroid-stimulating hormone, 1.45 µIU/mL (normal reference, 0.55-4.78 µIU/mL); luteinizing hormone, 2 (normal reference, 2-12). We concluded that the current medication (ebastine) was the probable culprit of the patient's gynecomastia.
.......At first, we changed the class of H1-antihistamine that was provided to the patient: ebastine (a class of piperidine) was stopped and cetirizine (a class of piperazine) was started. One month later, the gynecomastia had progressed further despite the new H1-antihistamine (cetirizine). We decided to stop the administration of H1-antihistamine because anaphylaxis had not occurred at any point during the preventive therapy with H1-antihistamine. A few weeks later, the patient's dyspnea, cough, wheezing, and urticarial/lip angioedema had relapsed and were worsening. His breasts had somewhat regressed. In the end, we started omalizumab (150 mg every 4 weeks) as a new preventive treatment for anaphylaxis. During the first few days after beginning omalizumab, the symptoms of anaphylaxis gradually subsided. His breasts also showed gradual regression. By approximately 6 months later, gynecomastia had completely disappeared. Further, the prolactin level had decreased to 8.91 ng/mL.
Gynecomastia induced by H1-antihistamine (ebastine) in a patient with idiopathic anaphylaxis
Famotidine
Histamine H2-receptor blockade is known to stimulate prolactin secretion.[4] Oral famotidine usually does not affect serum prolactin levels, but rare cases of hyperprolactinemia and galactorrhea have been reported.[5][6]
Famotidine - Drugs and Lactation Database (LactMed) - NCBI Bookshelf
H1- and H2-Histamine Receptor Antagonists and Induced Release of Prolactin in Male Rats
The effects of 3rd ventricle injection of metiamide, an H2-histamine receptor antagonist and pyrilamine, an H1-histamine receptor antagonist, on the increase of plasma prolactin induced by two doses of histamine in normal male rats were studied. Metiamide did prevent the stimulating action of histamine whereas pyrilamine was not effective. Histamine-induced prolactin release was also blocked by low doses of the 2 antihistamines given in combination. Metiamide per se has no effect but high doses of pyrilamine increased plasma prolactin levels and augmented the hormone response to histamine. The results suggest mediation of H2-receptors in the facilitatory action of histamine on prolactin release.
H1- and H2-Histamine Receptor Antagonists and Induced Release of Prolactin in Male Rats
I know cypro has been discussed in regards to the few studies suggesting it increases prolactin and the reason has been speculated to be dopamine antagonism. But none of the antihistamines in the above studies affect dopamine, as far as I can tell.
