The effect of sildenafil citrate on nine non-dysfunctional men was assessed by a post-exposure questionnaire. Almost all (8/9) reported that sildenafil citrate affected their sexual response, but only 6/9 indicated that it affected their erections. The respondents reported increases in sexual desire (6/9), enjoyment of sex (4/9), and penile skin sensitivity (4/9). The effects of sildenafil citrate were still apparent the next day; 8/9 indicated improvement in their sexual functioning then. Seven out of nine reported a diminution of erectile functioning occurring since adolescence; 6/9 reported improvement with sildenafil citrate. Sexual functioning may be enhanced with sildenafil citrate in non-dysfunctional men.
 
 

There is concern, at least in the popular press, that drugs used in the treatment of erectile dysfunction will be misused by non-dysfunctional men. There is no research to document what the consequences of this misuse will be. A review of the literature found only one study, Aversa et al. (2000), concerning the effect of these drugs on non-dysfunctional men. The present open label exploratory study assesses the effects of sildenafil citrate on middle-aged men without any history of sexual dysfunction.

Sildenafil citrate is a specific phosphodiesterase type 5 (PDE5) enzyme inhibitor, which is predominately localized to the corpus cavernous. Erotic stimulation causes the release of nitric oxide (NO) which acts to increase cyclic guanosine monophosphate (cGMP). The cGMP effects penile smooth muscle relaxation, which leads to tumescence. PDE5 degrades cGMP resulting in detumescence. Sildenafil citrate thus acts to maintain higher intracavernosal levels of cGMP thereby facilitating erection (Goldstein et al., 1998).

While most experts agree that erectile capacity decreases with age (Feldman, Goldstein, Hatzichristou, Krane & McKinlay, 1994; Gentili & Mulligan, 1998; Masters & Johnson, 1966; Mulligan & Moss, 1991), it is not known if these changes are permanent or modifiable. A concise and unambiguous definition of erectile dysfunction does not exist; there is no clear demarcation between normal effects of aging and erectile dysfunction. In reality, the patient diagnoses himself by reporting significant erectile difficulty; other individuals with a similar level of impairment may not find this functioning problematic. The clinical evaluation (history, physical examination, laboratory and other testing) does not establish the diagnosis; it only suggests treatable cause(s), or infers an organic versus psychogenic etiology. Even when the etiology is successfully identified, the specific treatment instituted often has no relationship to the causal element.

Method

A fortuitous sample of nine men, average age 49 (range 41-57), was recruited; all were physicians or sexologists personally known to the author. Potential subjects were eliminated for general poor health, nitrate use, any history of sexual dysfunction or cardiac disease. Informed consent was obtained from 20 subjects, who then received five 50 mg tablets of Viagra™ (sildenafil citrate) with standard instructions on its use. After experiencing five sildenafil influenced erections, the subjects completed a retrospective anonymous questionnaire.

If a subject reported more than a rare incidence of any sexual dysfunction in his life, that questionnaire was discarded; three were actually discarded. Thus 60% of the potential subjects completed the study; 45% were included in the analysis.

Results

The respondents compared their sexual functioning now, without sildenafil citrate, to their adolescence. The respondents judged the firmness of their erections now to be unchanged by 5/9 and softer by 4/9. The duration of their erections now was shorter by 5/9 and unchanged by 4/9. The participants judged the length of time between erections as longer now by 6/9 and "no change" by 3/9. Of all nine respondents, seven reported one or more of these "aging" effects.

Of the four respondents who reported their erections were softer now than in adolescence, three reported that sildenafil citrate improved the firmness, length and thickness of their erections. Though, only 2/4 reported that it decreased their fears of not being able to maintain erections. Of those who reported the duration of their erections was shorter now than in their adolescence, 3/5 indicated their erections lasted longer with sildenafil citrate.

The results depicted in Table 1 indicate the predominant response to most items was no change. Though 8/9 respondents reported some effect, only 6/9 reported the drug affected their erections. More than half the respondents indicated a change from their usual functioning, with increased sexual desire and decreased time between erections. Ease in reaching orgasm and intensity of orgasm had mixed responses, with reports of both increases and decreases. Firmness, erection length and thickness, enjoyment of sex, and penile skin sensitivity, tended to increase with sildenafil citrate use. Fear of erectile difficulties tended to be less than usual.

The sexual effects were still apparent the day after sildenafil citrate use; 8/9 reported improvement on at least one of four measures. Getting an erection was easier for 5/9 and was unchanged in 4/9. Penile sensitivity increased and the overall enjoyment of sex also improved for 5/9 and was unchanged in 4/9. Maintaining an erection was judged easier for 6/9 and unchanged in 3/9. If given unlimited access to sildenafil citrate, 7/9 indicated that they would use it sometimes, and one each indicated on special occasions and rarely. No one wished to use it more frequently.

Discussion

The present study used a small convenience sample and an open label protocol. Replication of these data in a larger double-blind placebo controlled study is necessary. The present study involved "middle-aged" men. Erectile dysfunction is more common as men age (Feldman et al., 1994), but is not rare in younger men (Laumann, Paik, & Rosen, 1999); future studies should include men of all ages.

Aversa et al. (2000) in a placebo controlled, double blind study, found that sildenafil citrate markedly decreased the post-ejaculatory refractory period in normal men aged 28-37. This was measured by requiring the men to self-stimulate after ejaculation until another erection was obtained. While an excellent laboratory technique, it is not necessarily reflective of how men behave "in the field." The other erectile function parameters were all measured by sonography. Aversa et al. (2000) appropriately conclude that the NO/cGMP pathway is maximally activated in young normal males and further stimulation is unlikely to effect improvements in erection.

The present study relied on self-report, looked at different aspects of male sexual response and studied older men (aged 41-57). Surprisingly, only 4/9 subjects reported the finding of a subjectively decreased refractory period. The other measures used in the present study were not included in the Aversa et al. (2000) study.

The "length of time between erections" item is a crude attempt to measure the effect of sildenafil citrate on the refractory period. Masters and Johnson (1966) described the refractory period as the decreased ability of a man to respond physiologically after orgasm. They also described a "secondary refractory period" (p. 252) seen in older men, as an inability to attain another erection after an initial erection was lost. The classical refractory period follows orgasm and is part of the resolution phase; the secondary refractory period occurs in the excitement phase prior to orgasm. The complaint of an inability to maintain an erection may reflect the individual's experience of the secondary refractory period. Masters and Johnson (1966) suggested that this phenomenon was rare in men under 60 years of age, but there is no reason to assume that a specific age has any special significance.

The fear of being unable to attain an erection once lost may cause some individuals to truncate the excitement phase of the sexual interaction. His partner or the sex therapist may interpret this as goal-oriented sex, phallocentric sex, a failure to consider the partner's level of sexual excitement or a loss of the playfulness in the sexual interaction. Sildenafil citrate may assist an individual or couple in extending the excitement phase or prolonging the sexual interaction. It may restore the man's confidence in obtaining an erection and allow the couple to address other concerns in their sexual interactions.

While there are concerns about the appropriateness of using pharmaceuticals to enhance sexual functioning, data concerning the long-term consequences do not exist. As individuals age it is not uncommon to treat a diminution in bodily function with drugs (e.g. laxatives for constipation, antacids for dyspepsia, analgesics for joint pain). While any drug can be misused and problems ensue, limitations on the use of the drug should be based upon known dangers.

In the present study, even among men who do not report any sexual dysfunction, most recognize improvement with sildenafil citrate. It is noteworthy that among those who acknowledged diminution of their erectile capacity since adolescence, not all improved. Sildenafil citrate is clearly not an effective treatment for all sexual dysfunctions or effects of aging. There is at least anecdotal evidence that the drug can ameliorate other sexual difficulties(Shen, Urosevich, & Clayton, 1999). Further research is needed to delineate all the effects of sildenafil citrate on men (and women) with and without sexual dysfunction.

Sildenafil citrate has a half-life of approximately four hours (Morales, Gingell, Collins, Wicker, & Osterloh, 1998), so it is somewhat surprising to see a pronounced effect the next day (12-24 hours later). This observation suggests that inhibiting PDE5 may not be the only sexual effect of the drug on "normal" men. Other modes of action may be responsible, either psychogenic or different physiological mechanisms. Sildenafil citrate may have other active metabolites with different half-lives or may persist longer in other body compartments. One should not discount the possibility that a period of sexual functioning without difficulty will reinstitute the individual's own "normal" sexual pattern.

The present study suggests that sildenafil citrate enhances sexual performance or ameliorates an unacknowledged decrease in sexual functioning. Sildenafil citrate may reverse some "aging" effects. Sildenafil citrate may have other sexual effects not recognized in a clinical sample.

Acknowledgements

Dr. Peggy Kleinplatz's assistance in the preparation of the manuscript is greatly appreciated.
 

References

Aversa A., Mazzilli F., Rossi T., Delfino M., Isidori A.M., & Fabbri A. (2000). Effects of sildenafil (Viagra) administration on seminal parameters and post-ejaculatory refractory time in normal males. Hum Reprod, Jan;15(1): 131-134.

Feldman H.A., Goldstein I., Hatzichristou D.G., Krane R.J., & McKinlay J.B. (1994). Impotence and its medical and psychosocial correlates: Results of the Massachusetts male aging study. J Urol, 151: 54-61.

Gentili A., & Mulligan T. (1998). Sexual dysfunction in older adults. Clinics in Geriatric Medicine, 14: 383-393.

Goldstein I., Lue T.F., Padma-Nathan H., Rosen R.C., Steers W.D., & Wicker P.A. (1998). Oral sildenafil in the treatment of erectile dysfunction. NEJM, 338(20): 1397-1404.

Laumann E.O., Paik A., & Rosen R.C. (1999). Sexual dysfunction in the United States: Prevalence and predictors. JAMA 281: 537-544.

Masters W.H., & Johnson V.E. (1966). Human sexual response. Boston: Little, Brown and Company.

Morales, A., Gingell, C., Collins, M., Wicker, P.A., & Osterloh, I.H. (1998). Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. Int J Impot Res. 1998 Jun;10(2):69-74.

Mulligan T., & Moss C.R. (1991) Sexuality and aging in male veterans: A cross-sectional study of interest, ability, and activity. Arch Sex Behav. 20: 17-25.

Shen W.W., Urosevich Z., & Clayton D.O. (1999). Sildenafil in the treatment of female sexual dysfunction induced by selective serotonin reuptake inhibitors. J Reprod Med. 44: 535-542.
 
 
 
 

Table 1. Effects of Sildenafil Citrate

n=9 men, number of men (%)
 

Item	much less	less	no change	more	much more
Sexual desire			3(33)	6(67)
Tendency to premature ejaculation		1(11)	8(89)
Length of time between erections	1(11)	4(44)	3(33)	1(1)
Firmness of erection			5(56)	3(33)	1(11)
Length and thickness of erection			5(56)	3(33)	1(11)
Ease in reaching orgasm		1(11)	7(78)	1(11)
Intensity of orgasm		2(22)	5(56)	2(22)
Enjoyment of sex			5(56)	4(44)
Fear of erectile dysfunction	3(33)	1(11)	5(56)
Penile skin sensitivity			5(56)	4(44)