Evidence PFS is not (only) “in our heads”
Khera’s findings are particularly meaningful because many physicians frequently dismiss PFS patients’ sexual complaints as having a psychogenic cause.Dr John Santmann, PFS foundation
In a newly released publication entitled Penile vascular abnormalities in young men with persistent side effects after finasteride use for the treatment of androgenic alopecia, a clinical study at the Baylor College of Medicine reported important clinical findings in Post-Finasteride Syndrome patients. Chiefly, 17 of 24 patients who underwent Penile Duplex Doppler Ultrasound examination were found to have vascular abnormalities:
Eight […] patients had arterial insufficiency [defined as peak systolic velocity <25 cm/sec (17)], while 5 […] patients fell into the “gray zone” of possible ED, defined as a peak systolic velocity between 25–35 cm/sec (17). Four[…] patients had venous leak, defined as an end diastolic velocity >5 cm/sec (17).Khera et al., 2020
The International Prostate Symptom Score questionnaire was used to assess urinary symptoms. Post-Finasteride Syndrome patients scored significantly worse than controls (median 10 v 3), particularly in questions regarding weak stream, incomplete emptying, frequent urination and overall quality of life. PFS patients had high rates of anhedonia per the PHQ-9, and were found to be more likely to have signs and symptoms of hypogonadism per the Androgen Deficiency in the Ageing Male Questionnaire.
Importantly, over 75% of patients reported at least one musculoskeletal complaint:
45% of 5ARI subjects [reported] fatigue, and 25% [reported] muscle atrophy. 12% reported gynecomastia, weight loss, back pain, lower extremity pain and visual disturbance. 8% reported weight gain, ocular hyperhidrosis, throat tightness, constipation, polydipsia, and cold flashes. 4% mentioned tremors, xeroderma, xerophthalmia, hypothermia, palpitations, muscle spasms, rapid aging, swollen face, and facial flushing. Overall, 76% of the subjects reported at least one musculoskeletal complaint.Khera et al., 2020
These symptoms are historically self reported by PFS patients, and well accounted for in our Post-Drug Syndrome Survey. Attempted characterisations of the syndrome frequently fail to accurately denote the condition’s broad physiological endpoints, so it’s positive they are appropriately noted.
Regrettably, two PFS patients (8%) committed suicide during or after the study period.
Glimmers of progress towards an appropriate clinical appreciation of the Post-Finasteride Syndrome
The current paucity of clinical understanding presents a paramount challenge for us as patients and as a patient advocacy organisation. These findings challenge misconceptions about the Post-Finasteride Syndrome and form an important step towards widespread recognition of the condition and appropriate support for stigmatised patients.
The authors mention this to be the first PDDU investigation of PFS patients to their knowledge. However, it is interesting to note Rubin et al. had reported that 26 of 27 PFS patients (96%) demonstrated lack of homogeneity and hyperechoic/hypoechoic regions in erectile tissue upon PDDU examination (Rubin et al., 2018). This second clinical report confirms tissue abnormalities of the penile structure occur in PFS patients.
The PDDU findings and high amount of musculoskeletal problems cast further doubt on emergent theories in literature that do not appropriately acknowledge the multisystemic nature of the syndrome. Crucially, their conclusion appears to appreciate the post-withdrawal worsening common to most cases of PFS:
The present study supports the conclusion that 5ARI use may predispose to persistent sexual, genitourinary, psychocognitive, and anti-androgenic changes even after 5ARI therapy is discontinued.Khera et al., 2020
This can often occur after a resolution of on-drug side effects and onset suddenly and dramatically – colloquially known as the “crash”. This is a vital novelty of PFS.
A long road ahead (still)
The devastating consequences of taking finasteride for a subpopulation of young men have been reported to medical professionals for two decades. Over half a decade after the initiation of this clinical study, the glacial pace of clinical and scientific progress that is so urgently needed is apparent in parts of the discussion.
Unfortunately, the authors appear to hypothesise the significant urinary symptoms reported were present in the cohort prior to assumption of 5ari therapy:
5ARIs may not have had a treatment effect on lower urinary tract symptoms (LUTS) in our patient cohort as these are younger men and likely to have prostates significantly smaller than 40 cc.Khera et al., 2020
The propeciahelp team carefully considered over a decade of patient self reports, and gathered standardised data from over 200 post-finasteride patients describing their symptoms at time frames including before and after use of the drug.
As part of our comprehensive survey, we asked PFS patients if they were experiencing, or if they had experienced, lower urinary tract symptoms of frequent urination, pain in the prostate/perineal region or weak urinary flow. For those Post-Finasteride Syndrome patients who answered yes, we asked them to fill out a four-point likert scale for both the intensity and the frequency of each symptom. This was asked at 4 points in time, including before use of finasteride, and now. The median results, shown below, are remarkable:
Symptom Frequency assessment values: 0 Never, 1 Sometimes, 2 Often, 3 Always.
Symptom Intensity assessment values: 0 None, 1 A little, 2 A lot, 3 Extreme.
This data demonstrates that while negligible before use, a significant number of PFS patients develop LUTS after 5ari exposure, with a moderate severity on average. These symptoms are atypical for men in their mid thirties. We assert that LUTS are induced by 5ari exposure in the young men who develop PFS with these symptoms. LUTS constitute an important part of the heterogeneously distributed symptom profile of PFS.
It is also unfortunate that duration of finasteride use was not correlated to severity of clinical findings in this publication. It is important that clinical studies ascertain this, as many of the most severely affected patients took a low dose of finasteride for an extremely short time. Investigations in the past have used an arbitrary minimum use period in considering PFS patients, and this is not coherent with the clinical reality of the disease. PFS frequently progresses degeneratively in the absence of the drug after remarkably brief exposure, including the atrophy of androgen dependent tissue. Every study assessing trend of symptoms following withdrawal noted a worsening of symptoms in the majority of patients. Additionally, no study found a correlation between duration of use and symptom severity. This, and our own extensive standardised data set, support hypotheses that epigenetic alteration to the ordinary function of cells are occurring in predisposed consumers. As there is no way of telling who is at risk of PFS at the current time, this constitutes an urgent public health issue. A patient took his own life after just over a week of taking finasteride led to the post-withdrawal ‘crash’ and months of rapid physical and cognitive deterioration. He received a diagnosis of venous leak. This individual was noted in a recently published case series focusing on patients who took their lives after developing PFS (Irwig, 2020).
We thank the authors for their investigation. We endorse their concluding recommendation:
Given the significance of the observed and potential side effects, patients should be extensively counseled and monitored for possible side effects after initiation and discontinuation of this medication class.Khera et al., 2020.
Discussion as to the the disease, symptom profile and a mechanistic hypothesis were recently presented by the administrators of propeciahelp alongside a summary of existing research:
Click here to read Post-Finasteride Syndrome as an Epigenetic Post-Androgen Deprivation Syndrome: A potential pathological link between Drug-Induced Androgen Receptor Overexpression and Polyglutamine Toxicity
Researchers interested in the Post-Finasteride Syndrome may contact us at firstname.lastname@example.org.
- Irwig, M. S. (2020). Finasteride and Suicide: A Postmarketing Case Series. Dermatology, 1–6. https://doi.org/10.1159/000505151
- Rubin, R., Winter, A., & Goldstein, I. (2018). 311 Novel Penile Ultrasound Technique to Explain Mechanism of Erectile Dysfunction (ED) in Young Patients using Finasteride for Androgenic Alopecia. The Journal of Sexual Medicine, S81. https://doi.org/10.1016/j.jsxm.2017.11.194