Serious complication of low-dose oral minoxidil for hair loss

To the Editor:

Dlova et al¹ are to be commended for their report of a serious complication of low-dose oral minoxidil in female androgenetic alopecia. Since the original introduction of low-dose oral minoxidil for this indication, reported adverse effects have been purported to be infrequent and of minor impact, with 15.1% hypertrichosis, 1.7% lightheadedness, 1.3% fluid retention, 0.9% tachycardia, 0.4% headache, 0.3% periorbital edema, and 0.2% insomnia reported in the largest retrospective multicenter study so far of 1404 patients, leading to drug discontinuation in 1.2% of patients.² Nevertheless, the package inserts of commercial oral minoxidil (Loniten) for the treatment of arterial hypertension report pericardial effusion to be a common adverse effect with a frequency of 3% to 5%.

We also witnessed a young and previously healthy female patient who developed, within weeks of treatment, a pericardial effusion at a dosage of oral minoxidil 1.25 mg for the treatment of female androgenetic alopecia. The patient complained of shortness of breath, discomfort while breathing in the supine position, chest pain, lightheadedness, and swelling in the legs. The patient assessment revealed pitting edema involving the lower limbs, and the ultrasound scans showed fluid collections in the pericardium.

Dlova et al¹ suggest that the relationship between minoxidil and pericardial effusion is an idiosyncratic drug reaction, where the risk is not dose-related or necessarily a known pharmacologic effect. And yet, despite the original assumption of Reichgott³ in 1981, today, this specific adverse effect may rather be understood to represent a property inherent to the mode of action of minoxidil. While the drug’s action as a vasodilating agent in the treatment of arterial hypertension has been best apprehended, more recently, the discovery of the mutation underlying hypertrichotic osteochondrodysplasia or Cantu syndrome has shed light on the molecular basis of the action of minoxidil. In Cantu syndrome, hypertrichosis leads to thick scalp hair extending onto the forehead and a general increase in body hair. It is caused by a mutation in the ABCC9 gene that codes for sulfonylurea receptor 2 involved in adenosine triphosphate–sensitive potassium channels,⁴ although minoxidil has been understood to be a potassium-channel opener, with evidence that this effect is mediated by the sulfonylurea receptor 2B.⁵ In Cantu syndrome, cardiac manifestations, including pericardial effusions, have been described as present in approximately 80% of patients.

Low-dose oral minoxidil has gained popularity as an off-label pharmacologic treatment for cosmetic conditions. However, as such, it should be prescribed with caution and monitored by physicians experienced and aware of the adverse effects of the drug and potential medicolegal issues. Nevertheless, the drug is currently available online, although the practice of unattended consumer use of the drug is discouraged for obvious reasons of consumer safety.

Conflicts of interest

None disclosed.