Simple summary: Numerous studies have shown that treatment with finasteride and dutasteride can change the size, tissue composition and function of the penis and prostate. Changes in the penis linked to finasteride or dutasteride treatment include: reduced size and weight; reduced erectile response; decreased smooth muscle; increased collagen density; fibrosis (scarring); smaller cavities for blood to support erections; and decreases in substances that support erectile function and androgen signaling. In the prostate, treatment with finasteride or dutasteride is linked to: reduced size and weight; tissue atrophy; fewer blood microvessels; and decreases in substances which maintain blood vessels.
Aim and scope: This review summarizes studies of the effect of treatment with finasteride and dutasteride on penile and prostatic tissue in humans and animals.
Reporting of results: The results reported below are limited to effects on penile tissue, the prostate, erectile function, and expression of related enzymes, proteins and neurotransmitters. Findings on changes to testosterone and dihydrotestosterone levels, which were consistent with expected effects of 5-alpha reductase inhibitors, are not reported below. In animal studies, results for castrated groups receiving no treatment are not reported below. Figures and tables have been adapted to only show drug treatment and control groups. For complete results, figures and methods, see the original studies which are cited below.
Conclusions. Collectively, the included studies indicated the following effects of finasteride and dutasteride treatment:
- Effects on penis and erectile function: Reduced size and weight of penis; reduced erectile response; decreased smooth muscle density and increased collagen density in corpus cavernosum; fibrosis / presence of thick, irregularly-arranged collagenous fibers; reduced size of sinusoidal spaces in corpus cavernosum; reduced expression of eNOS, LC3-II protein, and erectile neurotransmitter CGRP; and in a dutasteride study, reduced expression of androgen receptor.
- Effects on prostate: Reduced size and weight; reduced microvessel density indicating suppression of angiogenesis; reduced expression of eNOS and VEGF; tissue atrophy; reduced expression of androgen receptor, correlated with luminal epithelial atrophy in a human study; and increased expression of estrogen receptor.
Animal and human studies have different strengths and limitations.A Generally, animals receive high doses for days or weeks, while humans take lower doses for months or years. Despite different patterns of drug exposure across these populations, there are notable similarities in effects on reproductive anatomy and function—specifically fibrosis, tissue alterations and erectile dysfunction. While evidence from animal studies is reasonably consistent and detailed, more research is needed to characterize penile tissue changes in humans.
Overview of studies
1. Human & pharmacovigilance studies
- Schifano 2023: Disproportionate reports of penile curvature and Peyronie’s Disease associated with finasteride in pharmacovigilance databases.
- Khera 2020: Penile vascular abnormalities in post-finasteride patients as measured by ultrasound technique.
- Bauman 2014: In prostate, lower expression of epithelial androgen receptor, correlated with increased atrophy of luminal epithelium. Basal cell hyperplasia.
2.1. Animal studies including finasteride
- Kilic 2019 (incl. finasteride & dutasteride groups): Increased collagen density in corpus cavernosum and atrophic changes in prostatic epithelial tissue.
- Da Silva 2018 (incl. finasteride & dutasteride groups): Lower cross-sectional penile area and lower area of corpus cavernosum. Within corpus cavernosum, lower area of sinusoidal space and higher density of elastic fibers. In dutasteride group, reduced smooth muscle in corpus cavernosum.
- Zhang 2013: In corpus cavernosum: reduced erectile response; decreased smooth muscle; increased collagen deposition; and decreased eNOS and LC3-II protein expression.
- Zhang 2012: Reduced weights of prostate and corpus cavernosum; significant atrophy of prostate.
- Kaya 2005: Significantly lower number of microvessels in ventral prostate, indicating finasteride suppressed angiogenesis.
- Shen 2005: Significantly lower expression of erectile neurotransmitter CGRP in corpus cavernosum.
- Liu 2004: In ventral prostate, lower microvessel density and reduced expression of VEGF and eNOS, with larger effects in the group receiving longer treatment.
- Shen 2003: In electron microscopy images, tunica albuginea lacked elastic fibers and were replaced by thick, irregular collagenous fibers. Corpus cavernosum had thick and irregularly-arranged collagenous fibers; sinusoids were partially depressed.
2.2. Animal studies with dutasteride treatment only
- Da Silva 2023: Reduced sinusoidal space, smooth muscle density and cross-sectional penile area. Increased density of connective tissue and elastic fiber.
- Gul 2020: Significantly lower intensity of nNOS and eNOS in penile tissue; higher intensity of iNOS. Smooth muscle to collagen ratio significantly lower.
- Sung 2019: Significantly decreased erectile parameters associated with dutasteride treatment. After 8 weeks of dutasteride followed by 2 weeks off treatment: decreased erectile parameters, increased levels of fibrosis-related factors, loss of smooth muscle and increased collagen.
- Enatsu 2017: Reduced size of prostate and seminal vesicles; fibrotic changes in prostate and penis; reduced androgen receptor expression in prostate and penis; and increased estrogen receptor expression in prostate.
- Pinsky 2011: Significantly decreased erectile response; increased collagen in corpus cavernosum; altered expression of nNOS and iNOS.
1. Human / pharmacovigilance studies
Schifano N, et al. Are finasteride-related penile curvature/Peyronie’s disease adverse event reports worthy of further clinical investigation? Disproportionality analysis based on both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pharmacovigilance databases. Int J Impot Res. 2023. DOI • PubMed
An analysis of adverse event (AE) reports found a disproportionate association of finasteride use with penile curvature and Peyronie’s disease compared to AE reports for nine other drugs. The data came from US FDA’s Federal Adverse Event Reporting System (FAERS) and the European Medicines Agency’s EudraVigilance database.
- In the FDA FAERS database, 214 reports of penile curvature or Peyronie’s Disease were associated with finasteride. 57% of these were submitted by a healthcare professional. 84% were associated with male pattern hair loss.
- The outcome of most events was “serious”. 96 cases (45%) resulted in levels of permanent disability.
- Proportional reporting ratios (PRRs) for these adverse events were 6.6 (95% CI: 5.6–7.8) in the FAERS database and 11.8 (95% CI: 9.08–15.33) in the EudraVigilance database.
Khera M, et al. Penile vascular abnormalities in young men with persistent side effects after finasteride use for the treatment of androgenic alopecia. Transl Androl Urol. 2020. DOI • PubMed • PMC full text
This study used an ultrasound technique to assess the vascular status of penile tissue of men who reported persistent symptoms after discontinuing finasteride or dutasteride. 24 of 25 patients were assessed using penile duplex Doppler ultrasound (PDDU).
17 patients (68%) had some vascular abnormality on penile Doppler ultrasound. Of these:
- 8 patients (32%) had arterial insufficiency.
- 5 patients (20%) fell into the “gray zone” of possible ED.
- 4 patients (16%) had venous leak.
Bauman TM, et al. Finasteride treatment alters tissue specific androgen receptor expression in prostate tissues. Prostate. 2014. DOI • PubMed
Background. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens.
Methods. The study used prostate specimens from patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride. Prostate specimens were stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed and results were compared between groups of finasteride treated and non-treated patients.
Results. Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride-treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy.
Conclusions. Finasteride decreased the expression of epithelial androgen receptor in a tissue-specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment.
2. Animal studies
2.1. Studies including finasteride
Kilic S, et al. The effects of oral 5-alpha reductase inhibitors on penile intracavernosal pressures and penile morphology in rat model. Urology J. 2019. DOI • PubMed
This study measured the effects of finasteride and dutasteride on penile intracavernosal pressures (ICP, associated with erectile function) and penile morphology in rats, compared to a control group.
Results: Approximately 50% decrease was seen in mean intracavernosal pressure (ICP) in the finasteride and dutasteride groups compared to the control group. However, this difference was not statistically significant (P > .05). A statistically significant increase in cavernosal tissue collagen density, and marked atrophic changes in prostatic epithelial tissues were observed in the treatment groups.
Conclusion: Although 5-ARIs cause marked atrophic changes in prostatic epithelial tissues, and prominent collagen deposition in penile cavernosal tissues, no significant effect on penile ICPs was seen in this study. The failure to show a statistically significant difference was attributed to higher standard deviations of ICP values. If sample size and duration of the treatment are increased, statistically significant results in ICPs may be reached. The penile morphology evaluation results point to a negative effect of 5-ARIs on erectile function.
Collagen density in corpus cavernosum
Da Silva 2018
Da Silva MHA, et al. The corpus cavernosum after treatment with dutasteride or finasteride: a histomorphometric study in a benign prostatic hyperplasia rodent model. Asian J Androl. 2018. DOI • PubMed • PMC full text
This summary focuses on 3 of 6 groups included in this study: untreated control rats, control rats receiving finasteride, and control rats receiving dutasteride. (All three are called control groups because they were compared to animals with a model of benign prostatic hyperplasia, not included here.)
As shown in Figures 1–3 below, this study found smaller cross-sectional penile area and increased elastic fibers in rats receiving finasteride and dutasteride. They wrote in the Discussion:
The probable mechanism involved in the observed morphological modifications is DHT depletion in penile tissues. The penis is an androgen-dependent organ, and a decrease in masculine hormones leads to morphological and functional penile prejudice [ed.: the word ‘prejudice’ is unclear here]. Further, DHT is a potent activator of the enzyme nitric oxide synthase and this enzyme is involved in one of the main mechanisms of smooth muscle relaxation, which ultimately results in penile erection. Thus, the reduction of DHT, caused by the 5AR inhibitor treatment, decreases the nitric oxide relaxation response, impairing normal penile erections…
How the corpus cavernosum reacts after discontinuing treatment with dutasteride or finasteride is unknown. It is also not clear if a completely normal penile architecture can be achieved after the washout period. In addition, it is not known how long it takes to restore normal morphology.
Selected results from Table 2:
- Groups of rats treated with finasteride or dutasteride had the following differences from untreated control rats:
- significantly lower area of penis
- lower area of corpus cavernosum (including and without tunica albuginea)
- lower area of tunica albuginea
- lower area of connective tissue
- lower area of sinusoidal space (“Swiss cheese” cavities in tissue where blood pressure is maintained for erectile function)
- higher surface density of elastic fibers
- lower area of elastic fibers
- The dutasteride-treated group had lower smooth muscle surface density and lower smooth muscle area in the penis.
Zhang MG, et al. Long-term oral administration of 5α-reductase inhibitor attenuates erectile function by inhibiting autophagy and promoting apoptosis of smooth muscle cells in corpus cavernosum of aged rats. Urology. 2013. DOI • PubMed
This study examined the effects of finasteride treatment on penile tissue. The study had two groups of aged rats, one treated with finasteride for 16 weeks and the other group with no treatment (controls). The following differences in the corpus cavernosum of the finasteride-treated group were reported
- Reduced erectile response
- Decreased smooth muscle
- Increased collagen deposition
- Decreased endothelial nitric oxide synthase and LC3-II protein expression in the corpus cavernosum of the finasteride-treated group
Zhang MG, et al. Effects of oral finasteride on erectile function in a rat model. J Sex Med. 2012 May. DOI • PubMed
Results (selected): The tissue weights of the corpus cavernosum and prostate were reduced by 25.9% and 92.3% in the finasteride-treated group compared with Control group (both P < 0.001). Histopathology revealed a significant atrophy of the prostate in the finasteride-treated group. There was not a significant decrease in the smooth muscle content of the finasteride-treated group.
Kaya C, et al. Comparison of microvessel densities in rat prostate tissues treated with finasteride, bicalutamide and surgical castration: a preliminary study. Int J Urol. 2005 Feb. DOI • PubMed
To assess approaches to treating benign prostatic hyperplasia, the study compared the effects of finasteride, bicalutamide and surgical castration in suppressing microvessel formation in the prostate.
Selected results: The mean number of microvessels in the finasteride group was 24.5 (+/-8.44 SE) vs. 40.3 (+/-5.03 SE) in the control group. The number of microvessels in rat prostate tissues of the control group was significantly higher than the treatment groups.
Selected conclusions: The effect of finasteride was equal to that of bicalutamide in terms of suppressing the angiogenesis in prostatic tissue.
Shen ZJ, et al. Preliminary study on androgen dependence of calcitonin gene-related peptide in rat penis. Asian J Androl. 2005 Mar. DOI • PubMed
Background: Calcitonin gene-related peptide (CGRP) is one of the important erectile neurotransmitters… The purpose of this study was to investigate the androgen dependence of CGRP-immunoreactive nerves in rat penis.
Results (selected): After 10 weeks of treatment, the proportion of CGRP-PNF in rats receiving finasteride was significantly less than that of controls (P < 0.01).
Liu XD, et al. [Effects of finasteride on capillary in the ventral prostate of rat] [article in Chinese]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2004. PubMed
Objective: To investigate the effects of finasteride on capillary in the ventral prostate of rats, and the mechanisms involved.
Methods: Male rats were given finasteride for 7 days (group B) and for 14 days (group C).
Results (selected): In comparison with the control group, the microvessel density values in ventral prostate tissue of group B and group C decreased by 35.2% and 56% respectively. The protein expression of VEGF [a growth factor for vascular tissue] in group B and group C decreased by 31.7% and 62.6% respectively. The protein expression of eNOS [endothelial nitric oxide synthase, an enzyme that produces NO which is involved in erectile function] in group B and group C decreased by 15.7% and 52.5% respectively.
Conclusion: Finasteride can inhibit the protein expression of VEGF and eNOS and thereby can suppress angiogenesis of capillary in the ventral prostate of rat.
Shen ZJ, et al. Effect of androgen deprivation on penile ultrastructure. Asian J Androl. 2003. Abstract • Full text (archive.org) • PubMed
This study compared penile tissue in three groups of rats: controls, castrated rats and those treated with finasteride (results of castrated group not included here). Penile tissue was assessed using scanning electron microscopy.
The Discussion section noted: “The tunica albuginea of penis plays a major role in the erection mechanism. It compresses the subalbugineal venules, thus decreasing the venous outflow during erection and provides an inextensible fibrous frame for the erectile tissue of the penis.”
In the tunica albuginea of control rats, “the elastic fibers in tunica albuginea were very rich and arranged regularly and undulatedly.” In finasteride-treated rats, “the regularly-arranged elastic fibers were not seen and replaced by thick and irregularly-arranged collagenous fibers.”
In the corpus cavernosum of control rats, “the smooth muscle fibers in the trabeculae were rich and contained a few elastic and collagenous fibers. Structure of the sinusoids was perfect and clear.” In finasteride-treated rats, “the corpus cavernosum…contained a considerable amount of thick and irregularly-arranged collagenous fibers, but the degree of fibrosis was not so marked as in [the castrated group – not shown] and the types of fibrosis were different between these two groups. The sinusoids were partially depressed, but the structure of the sinusoids was still retained.” Sinusoids are “Swiss-cheese”-like areas where blood pressure is maintained to support erectile function. Images of the control group corpus cavernosum are in the left column while those of finasteride-treated rats are in the right column:
The discussion points to a potential mechanism for the observed tissue changes: “Results suggest that androgen is essential for the maintenance of normal ultrastructure of corpus cavernosum. Zhang et al2 demonstrated that in mature rats, castration induced apoptosis in corpus cavernosum with the replacement of the apoptotic tissues by fibrous tissue. This may be one of the pathways through which androgen deprivation acts on corpus cavernosum.” Results indicate that “androgen is also essential for the maintenance of the normal structures of tunica albuginea.”
2.2 Studies with dutasteride treatment only
Da Silva 2023
da Silva MHA, et al. Effects of dutasteride and tamsulosin on penile morphology in a rodent model. Int Braz J Urol. 2023. Full text (PDF) • PubMed
This paper was published after original publication of this post. A Twitter thread provides highlights.
Gul A, et al. Effect of tadalafil on penile nitric oxide synthase and corporal smooth muscle in rats under dutasteride treatment. Aging Male. 2020 Jun. DOI • PubMed
While tadalafil treatment is not of interest for this summary, this study analyzed levels of the enzyme nitric oxide synthase (NOS) in rat penis and tissue composition of corpus cavernosum. The study included a third group (dutasteride + tadalafil) whose results are not included in this summary. Certain statistical tests included all three groups. See the paper for full results.
Results: Staining intensities of neuronal NOS and endothelial NOS were significantly lower in the dutasteride group compared to controls (p < .05). Inducible NOS was observed higher in the dutasteride group than controls (p = .01).
The mean smooth muscle to collagen ratio was the lowest in the dutasteride group (p < .001) (Controls: 0.31 ± 0.03; Dutasteride: 0.15 ± 0.04).
The dutasteride group had the lowest cGMP and NO levels (p < .05); and significantly decreased dihydrotestosterone and increased testosterone compared to controls (p < .001).
Sung HH, et al. Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment. World J Mens Health. 2019. DOI • PubMed • PMC full text
Results: Dutasteride administration for 4 and 8 weeks significantly decreased erectile parameters compared with the control group. Reduced erectile responses were recovered during 2 weeks of drug-free time in the 4-week treatment group, but were not in the 8-week group. Protein levels of fibrosis-related factors transforming growth factor (TGF)-β1, TGF-β2, and p-Smad/ Smad (Smad 2/3) in the corpus cavernosum showed no significant change after 4 weeks of dutasteride oral administration, but were enhanced after 8 weeks. Dutasteride markedly decreased smooth muscle content and increased collagen after 4 and 8 weeks of use, but no nuclear size changes; however, neither group showed significant improvement in the smooth muscle to collagen ratio after the rest period.
Enatsu N, et al. Dutasteride-mediated morphological changes in the genitourinary tract associated with altered expression patterns of the androgen and estrogen receptors in male rats. Andrology. 2017. DOI • PubMed
Aim: Assess the effects of dutasteride on the genitourinary tract.
Method: Evaluated tissue fibrosis and hormonal receptor expression in three groups: Group A, a control group; Group B treated with finasteride from 8 weeks to 16 weeks of age; and Group C which were castrated at 8 weeks.
Results: At 16 weeks, the mean size of the prostate and seminal vesicles was smaller in the Group B (which received dutasteride) compared to controls (Group A). Group B showed fibrotic changes in the prostate and penis compared with the Group A. In Group A, androgen receptor was more strongly expressed than the estrogen receptor beta in Group A. In Group B, weak expression of the androgen receptor and strong expression of the estrogen receptor beta was noted in the prostate and penis.
Conclusions: These findings suggest that dutasteride cause morphological changes not only in prostate but also in penis. These changes are associated with altered expression patterns of androgen receptor and estrogen receptor.
Tissue fibrosis in prostate and penis
Altered androgen receptor and estrogen receptor expression
Pinsky MR, et al. The effects of chronic 5-alpha-reductase inhibitor (dutasteride) treatment on rat erectile function. J Sex Med. 2011. DOI • PubMed
Aim: To further investigate the mechanisms of erectile dysfunction (ED) related to dutasteride therapy using a rat model.
Results (selected): Erectile response in the dutasteride-treated group decreased significantly compared with control (P < 0.001). Dutasteride group had increased collagen deposition in corpus cavernosum smooth muscle as well as altered expression of neuronal NOS (nNOS) and inducible NOS (iNOS).
2. Zhang XH, Hu LQ, Zheng XM, Li SW. Apoptosis in rat erectile tissue induced by castration. Asian J Androl. 1999 Dec. PubMed
A. In animal studies, animals are typically administered high doses of a drug for a period of weeks or months. After sacrifice, histological techniques can be used to analyze any part of penile tissue or the prostate. Of course, a limitation is that animal models do not give a comprehensive picture of how a human would respond to a drug. In human studies, patients take a lower dose over months or years. Opportunities for analysis of tissues are limited because of the requirement of a biopsy or surgical removal. Moreover, some human studies may be retrospective, with no baseline measurements prior to drug treatment or onset of a disease. In such studies, conclusions are limited by potential confounding factors other than the drug treatment.
Figures from Zhang et al., 2013 are reproduced with permission of the publisher. Figures from Da Silva et al., 2018 and Sung et al., 2019 are used under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License.