Research review: Alterations to penile and prostatic tissue associated with finasteride and dutasteride treatment

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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.

Abstract

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.

Compare study results with reports of penile abnormalities linked to finasteride, as well as genital abnormalities in people with 5-alpha reductase deficiency.

Overview of studies

1. Human & pharmacovigilance studies
  • Schifano 2021 & 2022: Elevated probability of reports of penile curvature and Peyronie’s Disease linked to use of finasteride.
  • 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.

Study summaries

1. Human / pharmacovigilance studies

Schifano 2021

[Conference abstract] Schifano N, et al. SC36 – Is finasteride intake associated with penile curvature/Peyronie’s Disease? Assessment of both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pharmacovigilance databases. European Urology Open Science. 2021. DOI • PDF
[Paper] 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. 2022. DOI • PubMed

Note: This summary applies to Schifano, 2021. See also Schifano 2022 cited above, based on the same analysis. 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 linked to treatment with finasteride were found.
  • 84% of these cases were men who took finasteride for hair loss. 52% of reports were submitted by healthcare professionals.
  • 96 cases (45%) resulted in “levels of permanent disability” while 5 needed surgical management.
  • In the European Medicine Agency’s EudraVigilance database, 108 reports of penile curvature or Peyronie’s Disease were found in connection with treatment with finasteride.
  • The Proportional Risk Ratios (PRRs) of these adverse events linked to finasteride use were 6.6 in the FDA FAERS data and 11.8 in the EudraVigilance data, compared to nine other drugs. In plain language, this means the risk of these adverse events was several times more likely to be reported for finasteride than for the comparison drugs.

Khera 2020

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 2014

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.

Fig. 2C. Lower androgen receptor (AR) expression in prostate of men treated with finasteride (right) compared to non-treated men (left). (AR stained with 3,3′-diamonibenzidine [DAB])
[Likely epithelial tissue although the figure caption does not specify it. Stromal tissue did not show significantly lower AR expression.]

2. Animal studies

2.1. Studies including finasteride

Kilic 2019

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.

Intracavernosal pressure
Fig. 1. Time-dependent changes in mean ICP (blood pressure within the corpus cavernosum). The mean values were 50% lower in the finasteride and dutasteride groups. Although this difference was not statistically significant, the researchers attributed this to high variance and wrote that a larger sample size might have led to a finding of a difference.
Collagen density in corpus cavernosum
Fig. 2: Collagen density in penile cavernosal tissues. Blue-stained areas show higher collagen density (400x magnification). Purple represents smooth muscle.
Top-left: Control group. Top-right: Finasteride-treated group. Bottom-left: Dutasteride-treated group
Groups treated with finasteride or dutasteride have higher collagen density than control group.

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.

Fig. 1. Penile cross-section at x20 magnification. (b) Dutasteride and (c) Finasteride groups have reduced cross‐sectional penile area when compared to (a) Control group.
Fig. 2. Smooth muscle in corpus cavernosum at magnification x400. Smooth muscle was reduced in (b) Dutasteride group compared to (a) Control group. (c) Finasteride group did not show difference from (a) Control group.
Fig 3. Elastic fibers in corpus cavernosum at magnification x600. (b) Dutasteride and (c) Finasteride groups show increased amounts of elastic fibers compared to (a) controls.

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 2013

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
Fig. 2 (detail). Left (A): control group. Right (B): finasteride group
Purple stain indicates smooth muscle. Blue = connective tissue. Finasteride group has lower smooth muscle and higher connective tissue.
Fig. 2 (detail). Left (C): control; Right (D): finasteride group
Dark brown = endothelial nitric oxide synthase, an important factor in erectile function.1
Fig. 4. Cavernosal smooth muscle cells in rats with or without finasteride treatment.
Chart: Ratio of apoptotic (dead/inactive) cells to all cells is significantly higher in finasteride group (** p < .001).
Images: Black arrows indicate apoptotic (dead/inactive) cells with dark brown-stained nuclei in (A) control group and (B) finasteride-treated group.

Zhang 2012

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.

Fig. 2. Histological examination of the trabecular smooth muscle and connective tissue in the corpus cavernosum. Smooth muscle was stained in red and connective tissue was stained in blue. The arrows indicate the tunica albuginea tissues.
Left: Control group; Right: finasteride-treated group (Magnification x200)
Fig. 3. Prostate morphology.
A, top row: Control group at x40 and x200 magnification
D, bottom row: Finasteride-treated group with marked atrophic changes in the epithelial compartment of prostates.

Kaya 2005

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.

Fig. 1 (detail). Reduced microvessel counts in prostates of finasteride group
Fig. 2. Microvessels in ventral prostate of control rats (higher density)
Fig. 4. Microvessels in ventral prostate of finasteride-treated rats (lower density)

Shen 2005

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).

Figure 2. Immunohistochemical staining of corpus cavernosum of rats at 10 weeks (×400). Arrows indicate CGRP-positive nerve fibers (CGRP-PNF).
The nerve fibers of controls (left) contain significantly higher proportion of CGRP-PNF than those of the Finasteride group (right).

Liu 2004

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.

Figs. 1 & 3. Protein expression of VEGF in prostatic tissue of rat in (left) control group and (right) rat fed finasteride for 14 days.
Figs. 4 & 6. Protein expression of eNOS in prostatic tissue of rat in (left) control group and (right) rat fed finasteride for 14 days.

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 2003

Shen ZJ, et al. Effect of androgen deprivation on penile ultrastructure. Asian J Androl. 2003. Abstract • Full text • 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.

Tunica albuginea

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.”

Fig. 1. Tunica albuginea from control group (x300)
Fig. 3. Tunica albuginea from finasteride group (x300)
Corpus cavernosum

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:

Figs. 4 & 6: Ultrastructure of corpus cavernosum
Left column: Control rats
Right column: Finasteride-treated rats
Top images x300; bottom images x900.

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 2020

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).

Fig. 1. Corpus cavernosum tissue. Muscle = red, collagen = blue. Markedly decreased smooth muscle content and increased collagen were observed in dutasteride group (right) compared to control group (left) (p < .001).

Sung 2019

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 2017

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
Fig. 2A. Histological stains indicating tissue fibrosis in the prostate and penis.
Group A (left) = controls; Group B (right) = dutasteride-treated rats
In the prostate (top row), areas of collagen stained blue are considered fibrotic changes in the prostate.
In the penis (bottom row), arrows indicate corpus cavernosum, fascia, and skin stained in blue. Areas of fibrin stained red are considered fibrotic changes in the penis.
Fig. 2B. Collagen/cytoplasm ratio in the prostate. *P < 0.05
Fig. 2D. Fibrin/collagen ratio in the penis. *P < 0.05
Altered androgen receptor and estrogen receptor expression
Fig. 3A. Androgen receptor and estrogen receptor in the rat prostate (top row) and penis (bottom row). Androgen receptor was stained in red and estrogen receptor was stained in green. Overlaps of androgen and estrogen receptors are indicated in orange.
Top row: Group B (Dutasteride group at right) shows higher estrogen receptor expression and lower androgen receptor expression in prostate.
Bottom row: Group B (right) shows lower androgen receptor expression in penis.
Fig. 3B. The average area of androgen and estrogen receptors within the entire tissue area.
In prostate (chart at left), androgen receptor expression is lower and estrogen receptor is higher in prostate.
In penis (chart at right), androgen receptor expression is lower in penis.
*P < 0.05, significantly different from group A.

Pinsky 2011

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).

Fig. 1. Ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was significantly lower (p < .001) in dutasteride-treated rats.
Intracavernosal pressure refers to blood pressure in corpus cavernosum.
Fig. 5 – detail. Immunuhistochemical stain of nNOS and iNOS in nerves of corpus cavernosum smooth muscle
Left: Control group. Right: Dutasteride group
Top row: Reduced expression of nNOS (dark brown) in dutasteride group
Bottom row: Increased expression of iNOS (dark brown) in dutasteride group
Fig. 5 – detail. Red represents smooth muscle; blue represents collagen.
Ratio of smooth muscle to collagen is lower in dutasteride group (right) compared to control (left).

References

1. Bivalacqua TJ, Musicki B, Usta MF, et al. Endothelial nitric oxide synthase gene therapy for erectile dysfunction. Curr Pharm Des. 2005. doi:10.2174/138161205774913345 • PubMed

2. Zhang XH, Hu LQ, Zheng XM, Li SW. Apoptosis in rat erectile tissue induced by castration. Asian J Androl. 1999 Dec. PubMed

Note

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.

Image credits

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.