Viagra, Cialis, ... & PCT

[Michael Scally MD]

IMO, this is worthy of an addition to PCT/AIH. It will not hurt and just might help with the return of testes function. And, timing would be easy! There is none.

Spitzer M, Bhasin S, Travison TG, Davda MN, Stroh H, Basaria S. Sildenafil increases serum testosterone levels by a direct action on the testes. Andrology. Sildenafil increases serum testosterone levels by a direct action on the testes - Spitzer - 2013 - Andrology - Wiley Online Library

Phosphodiesterase-5-inhibitors, such as sildenafil, increase intracavernosal cyclic guanosine monophosphate levels, which results in corporal smooth muscle relaxation and penile erection. Here, we determined the effects of sildenafil administration on the hypothalamic-pituitary-gonadal axis in men with erectile dysfunction and low testosterone levels.

The Testosterone and Erectile Dysfunction trial (ClinicalTrials.gov # NCT00512707) initially administered an optimized dose of sildenafil to 140 men, aged 40–70 years with erectile dysfunction, low serum total testosterone (<11.4 nmol/L; 330 ng/dL) and/or free testosterone (<173 pmol/L; 50 pg/mL) over 3–7 weeks. Sex steroids and gonadotropins were measured at baseline and after sildenafil optimization in a longitudinal study without a separate control group. Serum testosterone, dihydrotestosterone (DHT) and oestrogens were measured using liquid chromatography-tandem mass spectrometry.

Administration of an optimized dose of sildenafil was associated with mean increases of 3.6 nmol/L (103 ng/dL; p < 0.001) and 110 pmol/L (31.7 pg/mL; p < 0.001) in total and free testosterone levels respectively. This was accompanied by parallel increases in serum DHT (0.17 nmol/L; 4.9 ng/dL; p < 0.001) and oestradiol (14 pmol/L; 3.7 pg/mL; p < 0.001) and significant suppression of luteinizing hormone (change ?1.3 units/L; p = 0.003) levels, suggesting a direct effect at the testicular level. Androstenedione and oestrone increased by 1.3 nmol/L (38 ng/dL; p = 0.011) and 10.7 pmol/L (2.9 pg/mL; p = 0.012), respectively, supporting a possible effect of sildenafil on adrenal steroidogenesis.

In conclusion, sildenafil administration was associated with increased testosterone levels likely ascribable to a direct effect on the testis.

 

[bickel29]

There is definitely some pretty stiff evidence that this would benefit the AAS user. Kind of hard to ignore this study. This could provide a nice little boost during PCT.

 

[foreveryoung]

is there a downside to being on Viagra and Cialis every day for many years?

 

[Michael Scally MD]

is there a downside to being on Viagra and Cialis every day for many years?

I do not know of any. In this case, the thought is short-term to restore testes function.

Any thoughts on the MOA?

 

[youngBuilder]

The study mentions that they determined a direct affect on the testicular level, since witnessing a suppression of LH.

Don't we want to stimulate the pituitary (LH production) as well as the testes? Would this slow LH recovery despite TT recovery being accelerated?

Or am I thinking too much...?

 

[Pericles]

There is definitely some pretty stiff evidence that this would benefit the AAS user. Kind of hard to ignore this study. This could provide a nice little boost during PCT.

I see watcha did there......

 

[CensoredBoardsSuck]

There is definitely some pretty stiff evidence that this would benefit the AAS user. Kind of hard to ignore this study. This could provide a nice little boost during PCT.

Indeed. Let's hope Sildenafil is UP for the challenge and is able to RISE to the occasion. A TOOL like this would be too big to ignore.

 

[CensoredBoardsSuck]

Any thoughts on the MOA?

Am J Physiol Endocrinol Metab. 2010 Oct;299(4)
Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway.
Sildenafil treatment in vivo s... [Am J Physiol Endocrinol Metab. 2010] - PubMed - NCBI
Andric SA, Janjic MM, Stojkov NJ, Kostic TS.

Abstract

Sildenafil citrate (Viagra), a cGMP-selective phosphodiesterase (PDE) inhibitor, is widely used to treat erectile dysfunction and pulmonary arterial hypertension. In contrast to its well established action on erectile dysfunction, little is known on the action of sildenafil on cGMP/cAMP signaling and testicular steroidogenesis. This study was designed to assess the effects of prolonged sildenafil treatment on NO synthase-dependent signaling and steroidogenic function of rat Leydig cells. Male adult rats were treated with Viagra (1.25 mg/kg body wt) daily for 30 days. In our studies, serum testosterone and ex vivo testosterone production significantly increased in sildenafil-treated animals. Human chorionic gonadotropin-stimulated testosterone production and cAMP accumulation were also significantly higher in Leydig cells obtained from sildenafil-treated rats. The expression of soluble guanylyl cyclase (GUCY1) subunits (Gucy1a1, Gucy1b1) significantly increased; cAMP-specific Pde4a, cGMP-specific Pde6c, and dual Pde1c and Nos2 were inhibited and expression of Nos3, protein kinase G1 (Pkg1), and Pde5 remained unchanged. Treatment of purified Leydig cells with NO donor caused a dose-dependent increase in both testosterone and cGMP production. Testosterone and cGMP production was significantly higher in Leydig cells obtained from sildenafil-treated animals. The stimulatory effect of NO donor was significantly enhanced by saturating concentrations of hCG in both Leydig cells obtained from control and sildenafil-treated animals. Occurrence of mature steroidogenic acute regulatory protein also increased in sildenafil treated animals in accord with increased cAMP and cGMP production. In summary, inhibition of PDE activity during prolonged sildenafil treatment increased serum testosterone level and Leydig cells' steroidogenic capacity by coordinated stimulatory action on cAMP and cGMP signaling pathway.




J Sex Med. 2012 Oct;9(10):2534-43.
Transient rise of serum testosterone level after single sildenafil treatment of adult male rats.
Transient rise of serum testosterone level after s... [J Sex Med. 2012] - PubMed - NCBI
Janjic MM, Stojkov NJ, Bjelic MM, Mihajlovic AI, Andric SA, Kostic TS.

Abstract

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors have been established in therapy for a variety of physiological disorders including erectile dysfunction. Despite its popularity and wide usage in erectile dysfunction treatment, the short-term effect of PDE5 inhibition on Leydig cell functionality and testosterone dynamics is missing.

AIM: This study was designed to assess the acute in vivo effects of sildenafil citrate (Viagra) treatment on testosterone production.

METHODS: Male adult rats were given sildenafil (1.25 mg/kg BW) per os, and testosterone production were analyzed 30, 60, 120, and 180 minutes after treatment. Additionally, in vitro effect of sildenafil extract on Leydig cell steroidogenesis was estimated.

MAIN OUTCOME MEASURES: The formation of testicular interstitial fluid (TIF), and testosterone, cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) content was followed. Occurrence and phosphorylation of mature steroidogenic acute regulatory protein (StAR) and interaction with protein kinase G 1 (PRKG1) were assessed by immunoprecipitation and Western blot.

RESULTS: Serum testosterone was increased 60 and 120 minutes after sildenafil treatment. In 60 minutes, TIF volume was doubled and stayed increased till the end of the experimental period. cGMP and testosterone content in TIF were increased 30 minutes after treatment, and cAMP decreased in 60 minutes. Further, sildenafil-induced stimulation of testosterone production was abolished by ex vivo addition of PRKG1 inhibitor but not by protein kinase A inhibitor. Sildenafil treatment increased the level of phosphorylated and total StAR protein. Moreover, co-immunoprecipitation of StAR and PRKG1 was increased following sildenafil treatment suggesting the active role of this kinase in initiation of testosterone synthesis. Additionally, sildenafil extract applied in vitro on primary Leydig cell culture increased cGMP accumulation and testosterone production in time- and dose-dependent manner without effect on cAMP level.

CONCLUSION: Acute sildenafil treatment enlarged TIF volume but also stimulated testosterone production which may be significant considering the positive testosterone effect in regulation of sexual activity.




Int J Exp Pathol. 2009 Aug;90(4):454-62.
Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion.
Chronic treatment with sildenafil stimulate... [Int J Exp Pathol. 2009] - PubMed - NCBI
Saraiva KL, Silva AK, Wanderley MI, De Araújo AA, De Souza JR, Peixoto CA.

Abstract

The phosphodiesterase type 5 (PDE5) inhibitor, Sildenafil, is a novel, oral treatment approach for pulmonary hypertension. As Leydig cells present PDE5, this study was conducted to investigate the effects of the chronic treatment with Sildenafil (25 mg/kg) on male Swiss Webster mice steroidogenesis. After a 4-week long experimental design, Leydig cells were analysed by morphological and immunocytochemical procedures. Serum testosterone was assayed by radioimmunoassay. Leydig cells presented noteworthy ultrastructural alterations, such as a vesicular smooth endoplasmic reticulum, large vacuoles scattered through the cytoplasm, enlarged mitochondria with discontinue cristaes and whorle membranes with vesicles at the periphery, which are typical characteristics of an activated steroid-secreting cell. Important immunocytochemical labelling for steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage enzyme and testosterone were detected in isolated Leydig cells. In addition, Sildenafil-treated mice showed significant increased levels of total testosterone. The results obtained in the present study are consistent with the hypothesis that the accumulation of cyclic guanosine monophosphate by PDE5 inhibition could be involved in the androgen biosynthesis stimulation. Important clinical implications of hormonal disorders should be taken into account for patients with pulmonary hypertension.

 

[Pericles]

Indeed. Let's hope Sildenafil is UP for the challenge and is able to RISE to the occasion. A TOOL like this would be too big to ignore.

I give this post a 7.2.

 

[JackC4]

Nice I have a 5yr cialis surplus

 

[Pericles]

Nice I have a 5yr cialis surplus

Mine is about 2 years. What I need is a pill to get my wife interested in sex w/ me.[)]

 

[Michael Scally MD]

Based on animal studies by Andric et al., it is possible that steroidogenic acute regulatory protein and protein kinase G1 upregulation may be mechanistically involved.

Andric SA, Janjic MM, Stojkov NJ, Kostic TS. Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway. Am J Physiol Endocrinol Metab 2010;299(4):E544-50. http://ajpendo.physiology.org/content/299/4/E544.long (Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway | Endocrinology and Metabolism)

Sildenafil citrate (Viagra), a cGMP-selective phosphodiesterase (PDE) inhibitor, is widely used to treat erectile dysfunction and pulmonary arterial hypertension. In contrast to its well established action on erectile dysfunction, little is known on the action of sildenafil on cGMP/cAMP signaling and testicular steroidogenesis.

This study was designed to assess the effects of prolonged sildenafil treatment on NO synthase-dependent signaling and steroidogenic function of rat Leydig cells.

Male adult rats were treated with Viagra (1.25 mg/kg body wt) daily for 30 days. In our studies, serum testosterone and ex vivo testosterone production significantly increased in sildenafil-treated animals. Human chorionic gonadotropin-stimulated testosterone production and cAMP accumulation were also significantly higher in Leydig cells obtained from sildenafil-treated rats. The expression of soluble guanylyl cyclase (GUCY1) subunits (Gucy1a1, Gucy1b1) significantly increased; cAMP-specific Pde4a, cGMP-specific Pde6c, and dual Pde1c and Nos2 were inhibited and expression of Nos3, protein kinase G1 (Pkg1), and Pde5 remained unchanged.

Treatment of purified Leydig cells with NO donor caused a dose-dependent increase in both testosterone and cGMP production. Testosterone and cGMP production was significantly higher in Leydig cells obtained from sildenafil-treated animals. The stimulatory effect of NO donor was significantly enhanced by saturating concentrations of hCG in both Leydig cells obtained from control and sildenafil-treated animals. Occurrence of mature steroidogenic acute regulatory protein also increased in sildenafil treated animals in accord with increased cAMP and cGMP production.

In summary, inhibition of PDE activity during prolonged sildenafil treatment increased serum testosterone level and Leydig cells' steroidogenic capacity by coordinated stimulatory action on cAMP and cGMP signaling pathway.

 

[Michael Scally MD]

Janjic MM, Stojkov NJ, Bjelic MM, Mihajlovic AI, Andric SA, Kostic TS. Transient rise of serum testosterone level after single sildenafil treatment of adult male rats. J Sex Med 2012;9(10):2534-43. Transient Rise of Serum Testosterone Level after Single Sildenafil Treatment of Adult Male Rats - Janjic - 2012 - The Journal of Sexual Medicine - Wiley Online Library

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors have been established in therapy for a variety of physiological disorders including erectile dysfunction. Despite its popularity and wide usage in erectile dysfunction treatment, the short-term effect of PDE5 inhibition on Leydig cell functionality and testosterone dynamics is missing. AIM: This study was designed to assess the acute in vivo effects of sildenafil citrate (Viagra) treatment on testosterone production.

METHODS: Male adult rats were given sildenafil (1.25 mg/kg BW) per os, and testosterone production were analyzed 30, 60, 120, and 180 minutes after treatment. Additionally, in vitro effect of sildenafil extract on Leydig cell steroidogenesis was estimated.

MAIN OUTCOME MEASURES: The formation of testicular interstitial fluid (TIF), and testosterone, cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) content was followed. Occurrence and phosphorylation of mature steroidogenic acute regulatory protein (StAR) and interaction with protein kinase G 1 (PRKG1) were assessed by immunoprecipitation and Western blot.

RESULTS: Serum testosterone was increased 60 and 120 minutes after sildenafil treatment. In 60 minutes, TIF volume was doubled and stayed increased till the end of the experimental period. cGMP and testosterone content in TIF were increased 30 minutes after treatment, and cAMP decreased in 60 minutes. Further, sildenafil-induced stimulation of testosterone production was abolished by ex vivo addition of PRKG1 inhibitor but not by protein kinase A inhibitor. Sildenafil treatment increased the level of phosphorylated and total StAR protein. Moreover, co-immunoprecipitation of StAR and PRKG1 was increased following sildenafil treatment suggesting the active role of this kinase in initiation of testosterone synthesis. Additionally, sildenafil extract applied in vitro on primary Leydig cell culture increased cGMP accumulation and testosterone production in time- and dose-dependent manner without effect on cAMP level.

CONCLUSION: Acute sildenafil treatment enlarged TIF volume but also stimulated testosterone production which may be significant considering the positive testosterone effect in regulation of sexual activity.

 

[CensoredBoardsSuck]

Based on animal studies by Andric et al., it is possible that steroidogenic acute regulatory protein and protein kinase G1 upregulation may be mechanistically involved.

Andric SA, Janjic MM, Stojkov NJ, Kostic TS. Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway. Am J Physiol Endocrinol Metab 2010;299(4):E544-50. http://ajpendo.physiology.org/content/299/4/E544.long (Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway | Endocrinology and Metabolism)

Sildenafil citrate (Viagra), a cGMP-selective phosphodiesterase (PDE) inhibitor, is widely used to treat erectile dysfunction and pulmonary arterial hypertension. In contrast to its well established action on erectile dysfunction, little is known on the action of sildenafil on cGMP/cAMP signaling and testicular steroidogenesis.

This study was designed to assess the effects of prolonged sildenafil treatment on NO synthase-dependent signaling and steroidogenic function of rat Leydig cells.

Male adult rats were treated with Viagra (1.25 mg/kg body wt) daily for 30 days. In our studies, serum testosterone and ex vivo testosterone production significantly increased in sildenafil-treated animals. Human chorionic gonadotropin-stimulated testosterone production and cAMP accumulation were also significantly higher in Leydig cells obtained from sildenafil-treated rats. The expression of soluble guanylyl cyclase (GUCY1) subunits (Gucy1a1, Gucy1b1) significantly increased; cAMP-specific Pde4a, cGMP-specific Pde6c, and dual Pde1c and Nos2 were inhibited and expression of Nos3, protein kinase G1 (Pkg1), and Pde5 remained unchanged.

Treatment of purified Leydig cells with NO donor caused a dose-dependent increase in both testosterone and cGMP production. Testosterone and cGMP production was significantly higher in Leydig cells obtained from sildenafil-treated animals. The stimulatory effect of NO donor was significantly enhanced by saturating concentrations of hCG in both Leydig cells obtained from control and sildenafil-treated animals. Occurrence of mature steroidogenic acute regulatory protein also increased in sildenafil treated animals in accord with increased cAMP and cGMP production.

In summary, inhibition of PDE activity during prolonged sildenafil treatment increased serum testosterone level and Leydig cells' steroidogenic capacity by coordinated stimulatory action on cAMP and cGMP signaling pathway.

There seems to be quite a bit of animal research that confirms sildenafil's effect on testosterone. I posted this and another one by Janjic/Andric a few posts back along with a study by Saraiva et al that seems to confirm Andric's findings re cGMP. Interesting topic.

 

[Michael Scally MD]

There seems to be quite a bit of animal research that confirms sildenafil's effect on testosterone. I posted this and another one by Janjic/Andric a few posts back along with a study by Saraiva et al that seems to confirm Andric's findings re cGMP. Interesting topic.

My Bad! Apologies.

 

[CensoredBoardsSuck]

My Bad! Apologies.

Oh, don't worry about that - I've done it myself.

I find this thread interesting and it got me thinking, which can be a bad thing sometimes.

It's been my understanding that one of the areas where PDE5 inhibitors aren't supposed to be effective is improving sexual desire and a lack of desire is common with some men or during episodes of depression and even more distressing when it occurs as a side effect of certain antidepressants. However, I've heard anecdotal reports of PDE5 inhibitors giving a boost to desire.

After reading these studies, I'm wondering if the boost in TT could be responsible for these anecdotal reports. The increase isn't huge but could it be enough? One of the studies I posted reported an increase in testosterone levels within 60 - 120 minutes following a single sildenafil administration in rats. The human study you posted found a ~100ng/dL increase in testosterone, but after 3–7 weeks. I assume the increase wouldn't be as great following a single administration, but I wonder if it's enough to acutely affect the CNS and increase desire. Anyway, I'm speculating and getting off topic.

BTW, regarding women and Viagra, a psychiatrist friend told me an amusing story a few years ago about a colleague's female patient who cured her lifelong inability to achieve orgasm by taking her husband's Viagra.... and giving it to her boyfriend.

CBS

 

[ddp7]

Oh, don't worry about that - I've done it myself.

I find this thread interesting and it got me thinking, which can be a bad thing sometimes.

It's been my understanding that one of the areas where PDE5 inhibitors aren't supposed to be effective is improving sexual desire and a lack of desire is common with some men or during episodes of depression and even more distressing when it occurs as a side effect of certain antidepressants. However, I've heard anecdotal reports of PDE5 inhibitors giving a boost to desire.

After reading these studies, I'm wondering if the boost in TT could be responsible for these anecdotal reports. The increase isn't huge but could it be enough? One of the studies I posted reported an increase in testosterone levels within 60 - 120 minutes following a single sildenafil administration in rats. The human study you posted found a ~100ng/dL increase in testosterone, but after 3–7 weeks. I assume the increase wouldn't be as great following a single administration, but I wonder if it's enough to acutely affect the CNS and increase desire. Anyway, I'm speculating and getting off topic.

BTW, regarding women and Viagra, a psychiatrist friend told me an amusing story a few years ago about a colleague's female patient who cured her lifelong inability to achieve orgasm by taking her husband's Viagra.... and giving it to her boyfriend.

CBS

Hey... what the hell is the meaning of this part?

Thanks in advance brother,

DDP

 

[ddp7]

This part, you said:

"by taking her husband's Viagra.... and giving it to her boyfriend".

Use of viagra in the long term...is fagot??? Be explicit buddy, this is a serious thread,

Your egocentric warnings do not work if they are not argued explicitly.Shit buddy, come on, spit it out. Thanks.

 

[ddp7]

Humans..no rats shit

Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing capacity. - PubMed - NCBI

 

[Michael Scally MD]

[Rats] Long-Term Inhibition of PDE5 Ameliorates Aging-Induced Changes in Testis

Long-term in vivo PDE5 inhibition:
· reduces aging-related NO increment & testosterone drop in blood
· reduces aging-increased expression of Leydig cells antiapoptotic & survival kinases
· slow down aging-associated regressive changes in testicular structure

NO-cGMP signaling pathway has been implicated in reduction of testicular steroidogenesis during aging. Here we analyzed the effect of PDE5 inhibition on old testicular phenotype formation. The old phenotype exhibited low testosterone and increased nitrite levels in circulation, increased cGMP accumulation in testicular interstitial fluid (TIF), progressive atrophy of testicular seminiferous tubules and enlargement of interstitial area followed by rise in blood vessel density and slight increase in the number of Leydig cells and macrophages.

Leydig cells have reduced steroidogenic capacity, increased MAP kinases expression (MEK, ERK1/2, JNK) and antiapoptotic PRKG1 and AKT, suggesting increased proliferation/survival and accumulation of senescent Leydig cells in testis.

In 12month-old rats, a long-term treatment with sildenafil (PDE5 inhibitor) normalized testosterone/nitrite levels in circulation and cGMP accumulation in TIF; improved Leydig cell steroidogenic capacity; decreased MEK, ERK1/2 and PRKG1 expression; prevented an increase in the Leydig cells number and atrophy of seminiferous tubules leading to histological appearance of young rat testes.

In 18month-old rats, long-term PDE5 inhibition partially recovered testosterone and nitrite levels in serum; normalized PRKG1 expression without effect on MEK and ERK1/2; and slowed down Leydig cell and macrophage accumulation and regressive tubular changes. Culturing of primary Leydig cells from aged rats in presence of PDE5-inhibitor stimulated steroidogenic and MAPK gene expression.

Taking together, results indicate that cGMP targeting alter both steroidogenesis and signaling pathways associated with cell proliferation/survival. The long-term PDE5 inhibition improves testicular steroidogenesis and slows-down regressive changes in testes during aging.

Sokanovic SJ, Capo I, Medar MM, Andric SA, Kostic TS. Long-term inhibition of PDE5 ameliorates aging-induced changes in rat testis. Experimental gerontology 2018. https://www.sciencedirect.com/science/article/pii/S0531556518301086