Hypogonadism and Gynecomastia with Duloxetine

We present the case of a 23-year-old male patient with a 3-year history of bulimia nervosa and major depressive disorder who developed hypogonadism and gynecomastia under treatment with duloxetine. With regard to the course of the disease we hypothesize that duloxetine might have contributed to the development of hypogonadism and gynecomastia through a prolactin-independent mechanism.

Gynecomastia and hypogonadism occur with many anti-dopaminergic drugs, presumably as a consequence of drug-induced serum prolactin rises. There is, however, limited evidence linking antidepressant drugs to hypogonadism or gynecomastia. Here we report the case of a 23-year-old man with a 3-year history of bulimia nervosa and major depressive disorder who had been treated with duloxetine 30 mg B.I.D. for 6 months, and developed significant bilateral gynecomastia. Since serum prolactin and testosterone concentrations were normal and an etiological role of duloxetine was not considered possible, duloxetine was continued and bilateral mastectomy was performed. 4 months later, the patient again complained of swelling and tenderness in the breasts. Endocrinological work-up was repeated and now revealed reduced serum testosterone concentration, reduced testicular volume, and otherwise normal results. Body weight was 63 kg at a height of 179 cm. Neurological status, including olfactory function, was normal. Cranial MRI including the hypophysis and olfactory bulbs was unremarkable. A diagnosis of hypogonadotropic hypogonadism was made. Since no alternative etiology could be identified, duloxetine was stopped. Following removal of duloxetine, swellings and tenderness subsided within 3 weeks.

Prolactin rises are common with antipsychotic drugs, especially with amisulpride and other dopamine-D2 antagonist drugs. Hypogonadism, mostly polycystic ovary syndrome, is generally thought to arise from suppression of the gonadotropic axis by elevated prolactin levels. We know of very few single cases of gynecomastia with fluoxetine and venlafaxine, all linked to elevated prolactin levels. In the present case, the close temporal relationship between breast growth and onset of duloxetine treatment, recidivism under continued treatment, and rapid improvement with treatment cessation suggest a possible causal role of duloxetine. At first view, perfectly normal prolactin levels in the presented case suggest a prolactin-independent mechanism. However, the phenomenon of absent serum prolactin increase in the context of prolactin-related clinical symptoms induced by antipsychotics is well known. Apart from questions regarding the particular underlying mechanism, one could say that in the present case unnecessary bilateral mastectomy could have been prevented if duloxetine had been earlier taken into consideration as a possible causal agent.

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