Mind the gaps: remarks on the evidence base

This post makes a few not-so-obvious points about the sprawling literature on finasteride and 5-alpha syndrome. If you are new to this literature, consider starting with a brief history of the research and a guide for researchers. Those pages describe what is in the literature, but it is also important to discern what is not in the literature. Two points below describe hidden forces which limit the scope of the literature, while the other two add context to research on 5-alpha syndrome.

1. Penile alterations are a feature of 5-alpha syndrome (post-finasteride syndrome)

In numerous animal studies, treatment with 5-alpha reductase inhibitors (5-ARIs) was associated with alterations to penile tissue including smooth muscle loss, increased connective tissue, and reduced size and weight of the penis. Two studies of human males reported similar findings. The significance of this work is that penile alterations cannot be explained in psychological terms.

2. The literature is shaped by political and economic interests

Many authors seem to read the literature as a faithful representation of reality, so that anything not in the literature cannot be true. They fail to appreciate that this literature is controlled and produced by physicians, sometimes in partnership with industry. As such, the literature overweights benefits of treatments while downplaying their risks and harms. The specter of permanent harm due to a treatment poses a threat to medicine, so this topic is likely to be excluded or minimized in the literature.

A critical reader should not only look at what is in the literature, but ask: What are the studies that were not done for lack of interest or funding? The streetlight effect bears mentioning. The drunkard who lost his wallet looks under the streetlight, because the light is better there. Some researchers do the same: they search the literature without considering that the answer may lie outside of the existing body of research.

On a related note, almost all published clinical trial data about finasteride was produced by Merck. Later, other researchers went on to write reviews and meta-analyses incorporating trial results, without noting that most results were produced by the drug’s sponsor. Merck’s results are thus laundered to seem more authoritative.

The limited amount of high-quality research on post-finasteride syndrome is not a signal that the syndrome is illegitimate; rather, it reflects the fact that physicians and industry control medical knowledge.

3. Social taboos suppress harms

Physicians tend to overlook the influence of taboos surrounding sexual and psychological problems. These strong forces prevent patients from reporting problems or perhaps even facing up to them internally. The physician may likewise hesitate to ask about such problems. As a result, these experiences may never be expressed in studies or pharmacovigilance data. On a related note, dermatologists lack expertise in sexuality and psychiatry, so they are less attuned to concerns in these areas.

Physicians should not assume studies and pharmacovigilance data are veridical, but instead ask what external factors might have dampened signals of trouble before they could be recorded.

4. Is the Milan animal model valid?

This item merits a separate post, so it will be only briefly mentioned here. The research group led by Dr. Roberto Melcangi has produced by far the most research on post-finasteride syndrome, starting over a decade ago. Their productivity and technical prowess are impressive. Much of the work relies on an animal model of post-finasteride syndrome. In evaluating their work, a fundamental question must be answered: do the experiments with rats provide a model of post-finasteride syndrome in human males? This question will be taken up in a future post.