Abstract Isotretinoin routinely causes mucocutaneous side-effects, such as cheilitis. Endocrine side-effects are not well documented, although reduced libido has been recognized recently. A 19-year-old male (weighing 60 kg and with a body mass index of 20.4 kg m−2) with no previous medical history developed unilateral left-sided gynaecomastia while taking oral isotretinoin for acne vulgaris (daily dose 20 mg for 1 month, 30 mg for 1 month, then 40 mg). He was taking no other medication or supplements, had never taken anabolic steroids and exercised daily. After 3 months of treatment, he noticed a firm, tender, left-sided subareolar mass, enlarging to 4.5-cm diameter, causing the areola to protrude approximately 5 mm above the level of the contralateral areola. Serum testosterone was 35.9 nmol L−1 (reference interval 8.7–29); a-fetoprotein and human chorionic gonadotropin were normal. Isotretinoin was discontinued, and the breast tissue returned to normal within 2 months, with no recurrence after 3 years of follow-up. Gynaecomastia in young adult males is uncommon, usually bilateral and is typically idiopathic in origin. Potential causes include hypogonadism and medications such as oestrogens, cimetidine, methyldopa, ketoconazole, spironolactone and tricyclic antidepressants. Obesity may lead to a similar appearance (pseudogynaecomastia). Isotretinoin has recently been linked to sexual dysfunction in both sexes, but a link is not proven: symptoms may have started after discontinuing isotretinoin and be long-lasting. Erectile dysfunction, loss of libido, anorgasmia and genital anaesthesia are reported; a minority of male patients have reduced testosterone. Gynaecomastia appears to be a very rare complication of isotretinoin use; only four previous cases have been reported in the literature. It is not listed as a potential side-effect in the Summary of Product Characteristics (SPC) leaflets for generic forms of isotretinoin, only being mentioned in the Roaccutane® SPC. The Medicines and Health products Regulatory Authority, in its updated online information leaflet (March 2022), lists gynaecomastia as a potential side-effect. The British National Formulary’s listing and the British Association of Dermatologists’ isotretinoin patient information leaflet do not mention gynaecomastia; however, reduced libido is stated. The European Medicines Agency and the National Health Service’s isotretinoin information webpage mention no endocrine side-effects. Cessation of isotretinoin was associated with resolution of the gynaecomastia; hence, we believe that it was responsible for it, although the mechanism of induction is unclear. An androgen–oestrogen imbalance has been suggested, leading to relative androgen deficiency. However, our patient had a high level of endogenous androgen, thought to be due to a high muscle mass, and entirely normal sexual function. Although uncommon, we would like to alert colleagues to the possibility of gynaecomastia resulting from isotretinoin treatment.
Read full abstract