Post-Finasteride Syndrome: Myth or Fact?
One explosive topic that is currently causing a great deal of uncertainty in the broad media and professional circles is the so-called post-finasteride syndrome (PFS). This term refers to a complex of symptoms consisting of changes in sexual, physical, mental and neurological aspects that occur after taking finas terid or even after the end of therapy. Since finasteride is widely used in urology for the treatment of benign hyperplasia of the prostate (BPH), we would like to use this article to shed some light on this exciting disease. Finasteride is, as is generally known, a member of the group of 5a-reductase inhibitors and belongs, biochemically speaking, to the group of synthetic ste- roids. Due to its chemical similarity to testosterone, an irreversible inhibition of 5a-reductase can be achieved, which is mainly responsible for the conversion of testosterone to dihydrotestosterone (DHT). More precisely, there are 3 isoenzymes of 5a-reductase (type I-III), which are expressed to different degrees in different organs. Type 1 is mainly found in the brain, epididymis and skin and is involved in the production of allopregnonolone, which, by modulating the GABA receptors, contributes to euphoric and anxiety-relieving mood changes similar to the effect of benzodiazepines. Type 2 can be found in the muscles, liver, kidneys and prostate. In patients with BPH, increased expression of this isoenzyme has been shown to increase the risk of a drug attack. Type 3 is produced in the mammary glands, uterus, brain, liver, ovaries, skin, kidneys, pancreas, spleen, heart and prostate and seems to represent the most important subtype. By converting polyprenol to dilichol, type 3 increases - additionally influencing the process of glycosylation. Although finasteride was designed as a selective inhibitor of types 2 and 3, it can be assumed that inhibition of 5a-reductase will trigger more far-reaching changes in the metabolism. In this respect, it has been shown that finasteride not only leads to a reduction in DHT and an increase in testosterone levels, but also has an effect on luteinizing (LH) and follicle stimulating hormone (FSH) levels and influences the biosynthesis of neurosteroids such as allopregnanolone (ALLO) and tetrahydrodeoxycorticosterone (THDOC). Likewise, the conversion of progesterone to dihydro-progesterone is inhibited and the cerebral GABA-receptor activity is influenced by neurosteroids, which can persist beyond the period of use [1]. Since various play - gel changes have been demonstrated in patients with PFS, these interactions are currently the most plausible biochemical explanation for the occurrence of the various symptoms [2]. Since the approval, reduced libido, erectile dysfunction, impotence or even depression are known side effects of finasteride [3]. Essentially, however, the larger studies, such as PROSPECT, have shown high rates of side effects in the placebo group, as in the treatment group. Likewise, the group of âwell informedâ patients showed significantly higher rates of side effects in relation to erectile dysfunction. After discontinuation of therapy, however, a normalisation of the DHT level was shown within two weeks and a disappearance of symptoms was observed [4]. In contrast, post-finasteride syndrome is defined as the occurrence of symptoms from a wide variety of areas (see Table 1) that began while taking finasteride or only after discontinuation of finasteride and persist beyond discontinuation of therapy. Interestingly, this seems to be independent of whether a dose of 5 mg daily was applied to treat BHP or 1 mg to treat androgenetic alopecia. Patients describe these symptoms up to years after discontinuation or even persistence of the symptoms. In addition, the occurrence seems to be independent of the duration of intake, as cases have also been documented from an intake of about 10 days. So far, there is still a great deal of uncertainty about the exact background of the development of PFS, but thousands of cases with similar symptom constellations have been registered worldwide and a massively higher number of unreported cases is expected. Patient associations have founded their own support groups and registries, so that there are already a large number of online platforms that use PFS. Websites such as www.post-finasterid-syndrom.de , www.pfsfoundation.org or similar have helped to achieve a high media presence and create broad awareness of the PFS [5]. An incidence or risk factors for the development of a PFS cannot be stated at present, as the data so far are mostly from case-specific and uncontrolled studies. In addition, it has not yet been clearly shown whether the PFS is a nocebo effect or a permanent drug side effect. Persistent sexual impairment has so far only been shown in studies with limited evidence [7]. There is currently an intensive, interdisciplinary discussion in the literature about the validity of PFS. Similar complaints with regard to persistent sexual dysfunction are also described after the use of selective serotonin reuptake inhibitors (SSRIs) to treat depression, which experts refer to as âpost-SSRI sexual dysfunctionâ [8]. As a result, the hypothesis regarding the influence on neurosteroids as a conceivable cause of the symptoms is confirmed, but not confirmed [9]. Since PFS is a symptom that is known to be mutually potentiating, such as erectile dysfunction and depression, an objective assessment is significantly more difficult. Finally, the results of larger, randomised and blinded studies must be awaited in order to provide clarity. Regardless of whether a disease - picture in the sense of PFS is actually present or not, the focus should remain on what we can offer our patients suffering from the above-mentioned symptoms in good conscience. In this case, as is often the case, it seems advisable to provide the patient with detailed information and multi-faceted advice on the various therapy options. Through an open discussion, it may be possible to establish a medical prescription with regard to mental illnesses and, if necessary, finasteride therapy can be dispensed with in patients at risk. In addition, the status quo with regard to sexuality should be ascertained in advance in order to identify changes at an early stage or to counteract them with additional drug therapy. Openness between doctor and patient must be a top priority here, as the occurrence of unpleasant side effects often leads to contact being broken off rather than the problem being addressed. Furthermore, the existence of two different subtypes of patients depending on the dominant brain half (left vs. right) with increased sensitivity to DHT or dihydro-progesterone is discussed in the literature. Against this background, a possible therapy of PFS with appropriate hormonal substitution is also being considered, even though there is currently still a lack of sufficient data [1]. In principle, it is better to refrain from drug therapy of depressio within the framework of PFS with antidepressants, as this subclass of dance can also lead to similar side effects, as already mentioned. In conclusion, despite the new findings on drug safety, finasteride should not be disregarded as a potent drug with good results in many respects. Rather, it should not be used by the general public and its targeted use in suitable patients should be considered. This should make it possible to limit the rate of side effects to a large extent and still provide suitable patients with a good and simple therapy.
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Korrespondezadresse:
Dr. Mona Kafka
Priv. Doz. Dr. Jasmin Bektic
(Vorsitzender des AK Prostata der ĂGU)
Medizinische UniversitÀt Innsbruck
Abteilung fĂŒr Urologie
AnichstraĂe 35
6020 Innsbruck
mona.kafka@tirol-kliniken.at
jasmin.bektic@tirol-kliniken.at
https://www.uro.at/images/uro/downloads/noegu/NOEGU_59-2019.pdf (pages 40-41)
