Actually you've heard Carl and me talk about the purported testosterone boosting effects of sildenafil aka Viagra on the Science Round Up in the past, but Mr. Spitzer and his colleagues from the Greenfield Health Center are the first to prove the potency of the testosterone response in male subjects who received "an optimized dose" (more on that later) of sildenafil, as well as its "direct action on the testes" in a controlled larger-scale trial (Spitzer. 2013).
More than just "spitz" (engl. "horny")
The data Matthew Spitzer et al. analyzed came from the Testosterone and Erectile Dysfunction Trial in the course of which 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 received starting doses of
- 25mg sildenafil, if they were on an alpha-blocker
- 50mg sildenafil, if they never used sildenafil before, and
- 100mg sildenafil, if they were viagra veterans
|Figure 1: Changes of testosterone and other hormones rel. to baseline level (Spitzer. 2013)|
The latter, i.e. the reduced luteinizing hormone levels are what actually suggests that we are dealing with a direct effect at the testicular level and not some weird hyptohalamic feedback. A centrally mediated in crease in testosterone production would after all have gone hand in hand with in- not decreases in luteinizing hormone concentration.
Minimal changes in adrenal hormones
With small, but noticeable increases in 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), Spitzer et al. cannot exclude that the sildenafil induced phosphodiesterase-5 inhibition did also affect the adrenal glands - or, to be precise, "late adrenal androgen synthesis" (Spitzer. 2013):
While the exact mechanism that's responsible for the androstenedione increases must still be determined, it is, as previously mentioned, almost certain that the increase in testosterone levels was mediated by direct effects on the steroidigenic leydig cells in the testes. They are the ones that respond to the luteinizing hormone signalling from the brain have been reported to respond directly to PDE-5 inhibitors in previous studies by Andric et al. from 2007 & 2010, as well as Janjic et al. from 2012.
This could explain the increase in serum androstenedione levels in our participants. However, an increase in 17,20-lyase activity should also result in an increase in DHEAS levels, which was not observed. Further investigation is needed to study the effect of sildenafil on adrenal androgens." (Spitzer. 2013)
More sex = more testosterone?
Whether and to which extend the increase in testosterone has also been indirectly promoted by increases in sexual activity, which have been previously reported to lead to increases in testsosterone levels after successful treatment of erectile dysfunction (Aversa. 2013) remains to be seen. The data from the study at hand does at least not support this notion, because a "greater sexual activity did not predict greater change in serum total testosterone" (Spitzer. 2013).
Other studies have associated greater sexual arousal with acute increases in LH and subsequent increases in testosterone production (LaFerla. 1978; Rowland.1987). With decreasing not increasing LH levels being one of the main findings of the study at hand, it is however more or less impossible that the increased sexual desire was the horse, not the cart in the sildenafil-related increases in testosterone levels Spitzer et al. observed in their 140 borderline to full-blown hypogonadal man.
- 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 Oct;299(4):E544-50.
- Aversa A, Jannini EA, Maggi M, Lenzi A. Effects of testosterone replacement on response to sildenafil citrate. Ann Intern Med. 2013 Apr 2;158(7):569-70.
- 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 Oct;9(10):2534-43.
- LaFerla JJ, Anderson DL, Schalch DS. Psychoendocrine response to sexual arousal in human males. Psychosom Med. 1978 Mar;40(2):166-72.
- Rowland DL, Heiman JR, Gladue BA, Hatch JP, Doering CH, Weiler SJ. Endocrine, psychological and genital response to sexual arousal in men. Psychoneuroendocrinology. 1987;12(2):149-58.
- 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. 2013 Nov;1(6):913-8.