Pooled data do not prove the safety of finasteride for androgenic alopecia (AGA), with sexual side effects in particular not adequately evaluated, according to a new meta-analysis.

“The methods matter,” Dr. Steven M. Belknap told Reuters Health by email. “If you don’t take a temperature, you won’t find a fever. If investigators use flawed methods they may miss important adverse drug effects.”
In an April 1st online paper in JAMA Dermatology, Dr. Belknap of Northwestern University Feinberg School of Medicine, Chicago and colleagues noted that clinical use of finasteride “was prompted by the observation that male pseudohermaphrodites do not develop prostatic hyperplasia or AGA.”

Male pseudohermaphrodites have a mutation of the gene encoding 5-alpha reductase. Finasteride, a 5-alpha-reductase inhibitor, can induce a strikingly similar sex steroid profile.

Finasteride was approved in 1992 for treating benign prostatic hyperplasia and in 1997 for AGA. In an editorial, Dr. Thomas J. Moore says, “It was clear, or should have been, from the start that inhibition of a key metabolic pathway for the conversion of testosterone to other steroids was going to have many effects, not all of them necessarily desirable.”

For the current study, the researchers examined data from 34 controlled clinical trials. None, they say, had adequate safety reporting. In 19, safety reporting was partially adequate, in 12 it was inadequate, and three reported no adverse events.

No reports assessed adequacy of blinding, 18 (53%) disclosed conflicts of interest, and 19 (56%) received funding from the manufacturer. Duration of drug safety evaluation was one year or less for 26 of 34 trials (76%).
Overall, the investigators conclude, “Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.”

Moreover, they point out, funnel plots were asymmetric, with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic underdetection.

“The researchers that did these studies,” continued Dr. Belknap, “either knew or should have known that sexual dysfunction might occur in some men exposed to finasteride.” The trials “should have been designed to detect sexual dysfunction and the published reports of these RCTs should have included the results.”

Commenting by email, Dr. Moore, the editorialist, told Reuters Health, “There is clear evidence that finasteride can cause male sexual impairment, and that in some cases the effects are persistent.”

Dr. Moore, of the Institute for Safe Medication Practices in Alexandria, Virginia, added that the study “also illustrates that clinical trials do much better at measuring benefits than assessing harms.”