The mammary gland enlargement that worries Carlo

A well-known mechanism

Gynecomastia is the most common benign mammary pathology in males. Even though, up to day, there is not yet a universally acknowledged definition, it consists in an enlargement of the male mammary gland greater than 0.5 cm which is caused, from a physiopathological point of view, by an imbalance between estrogenic and androgenic hormones, with prevalence of the first ones.¹ From a etiopathogenetic point of view, 25% of gynecomastia causes do not acknowledge a known etiopathogenesis and are therefore classified among the idiopathic forms, whilst for the remaining part the causes range from age, obesity, hyperthyroidism, hepatic pathologies, familial aromatase excess syndrome, primitive or secondary gonadal insufficiency, testicular tumours and drugs.² Precisely drugs are the most common cause of secondary gynecomastia (10-25%); among these the most known are spironolactone, cimetidine, ketoconazole, growth hormone, gonadotropins, androgens, antiretrovirals, and 5-alpha reductase inhibitors (see also Focus Farmacovigilanza 2103,77:2-3).³ In the discussed case, the drug involved in the secondary gynecomastia onset is sertraline, an antidepressant belonging to the class of selective serotonin reuptake inhibitors (SSRI).
Antidepressant-induced gynecomastia is scarcely documented, in literature there are only few clinical cases associated to venlafaxine (a serotonin and noradrenaline reuptake inhibitors, SNRI), mirtazapine (a presynaptic alpha-2 antagonist), fluoxetine and sertraline (both SSRI).^4,5,6
The use of SNRI and SSRI antidepressants induces indirectly a decrease in the dopamine neurotransmission which has been reported as possible cause of gynecomastia and mammary neoplasia.⁶
In literature a case of sertraline-induced gynecomastia is described for a 67 years old patient, under polytherapy of duloxetine, alprazolam, rosuvastatin, metoprolol, amlodipine, metformin and sitagliptin, who, after taking sertraline, started presenting enlargement symptoms that worsened increasing the dose from 25 mg/day to 75 mg/day. Also in this case, after three months of drug discontinuation, the gynecomastia regressed quickly, therefore sertraline was ascribed of the adverse reaction. It can be noted how sertraline toxicity is dose dependant and how a rapid resolution followed in few months after the drug discontinuation.⁶
Gynecomastia is listed in the data-sheets of sertraline-based drug, but it is reported with unknown frequency. In fact the frequency of this drug adverse reaction is quite difficult to define, especially when associated to antidepressants, as the psychiatric patient is a complex patient who finds it hard to be seen by a doctor and struggles to describe the physical changes he is experiencing. In this cases it is essential that general practitioner, breast surgeon, psychiatrist, radiologist and pharmacist work well together in order to optimise the diagnostic-therapeutic profile, improve quality of life and avoid the onset of further discomfort in already fragile people.