See commentary " Acute nicotine effects on sexual function in men. See other articles in PMC that cite the published article. Abstract Introduction Chronic nicotine treatment has deleterious effects on vascular functioning and catecholamine modulation, which may compromise erectile functioning. Evidence that long-term cigarette smoking is an independent risk factor for introducing impotence is robust.
However, limited studies have focused on the acute effects of smoking on physiological sexual response, and none have investigated the deleterious effects of isolated nicotine on human sexual arousal. Consequently, pathophysiological underpinnings of tobacco-induced—and particularly, nicotine-induced—erectile dysfunction are not well understood.
Aim To provide the first empirical examination of the acute effects of isolated nicotine on sexual arousal in nonsmoking men. Methods Twenty-eight sexually functional heterosexual men mean age 21 years , each with less than direct exposures to nicotine, participated in a double-blind, randomized, placebo-controlled, crossover trial. Participants received either Nicorette polacrilex gum SmithKline Beecham Consumer Healthcare, Pittsburgh, PA, USA 6 mg; approximately equivalent to smoking one high-yield cigarette or placebo gum, matched for appearance, taste, and consistency, approximately 40 minutes prior to viewing an erotic film.
Main Outcome Measures Physiological circumferential change via penile plethysmography and subjective continuous self-report sexual responses to erotic stimuli were examined, as well as changes in mood. This occurred in 16 of 20 men with valid physiological recordings. Conclusions Isolated nicotine can significantly attenuate physiological sexual arousal in healthy nonsmoking men.
These findings have implications for elucidating physiological mechanisms responsible for the effects of nicotine on sexual dysfunction, and for assisting public health policy in considering the deleterious effects of nicotine on sexual health. Nicotine, Male Sexual Arousal, Penile Plethysmography Introduction The link between long-term cigarette smoking and erectile dysfunction ED is robust and indicates that cigarette smoking is an independent risk factor for introducing vasculogenic impotence [ 1 — 3 ].
Large cross-sectional [ 4 — 8 ] and longitudinal [ 9 ] epidemiological studies suggest that smokers are about 1. Pathophysiological underpinnings of chronic tobacco-induced ED have not been clearly delineated; however, these mechanisms are ultimately expressed as vascular phenomena [ 11 ]. Cigarette smoking decreases penile arterial inflow [ 12 ] and disrupts veno-occlusive mechanisms [ 13 ], resulting in a deficiency of genital vasoengorgement. These disruptions are mediated by a deregulation in endothelium smooth muscle relaxation [ 14 ].
Biochemical processes underlying erection physiology may also be affected by chronic smoking. Nitric oxide NO produced within penile endothelial cells has been identified as the principal neurotransmitter mediating erection [ 15 , 16 ].
Free radicals and other compounds within cigarettes may decrease the synthesis of NO directly, or indirectly by targeting precursors, resulting in decreased penile blood inflow [ 17 ].
This may have significant long-term effects on erectile functioning. Few studies have focused on the acute effects of smoking on physiological sexual response. One animal study [ 2 ] reported impaired genital arterial inflow and impaired venous restriction in dogs after 7—12 minutes of acute smoke exposure. To date, there has only been one experimental study involving the acute effects of smoking on human sexual arousal. Gilbert and colleagues [ 18 ] tested 42 male smokers who were randomly assigned to nicotine, placebo, or wait-list conditions.
Participants who smoked three 0. In the first evaluation of the short-term effects of smoking cessation on physiological sexual arousal, Sighinolfi and associates [ 19 ] demonstrated a significant improvement in penile blood flow within 24—36 hours of smoking discontinuation. How this improvement in penile hemodynamics compares to that of nonsmokers was not investigated.
Experimental studies examining acute and reversible effects of tobacco inhalation on physiological sexual arousal help to elucidate underlying physiological mechanisms that may be responsible for introducing ED.
However, there are several additional factors that, if addressed, would enhance our understanding of the phenomenon. First, because cigarettes contain over 4, active pharmacological constituents, the primary element or group of interacting compounds responsible for the deleterious effects of smoking on sexual response remains unclear.
Experimental evidence indicates that chronic nicotine treatment has deleterious effects on modulating the release of epinephrine and norepinephrine [ 5 ], which may compromise erectile functioning. A study examining the direct link between acute nicotine intake and sexual arousal in bovines revealed a significant reduction in erectile response [ 20 ].
Investigating how nicotine affects human sexual response remains unknown. Second, because of underlying vascular degeneration caused by cigarette smoking [ 21 ], it is unknown whether the acute effects of tobacco smoke differentially affect long-term smokers compared to nonsmokers. Additionally, no studies have investigated the acute effects of nicotine with respect to subjective sexual arousal.
Aim The present investigation was designed to provide the first empirical examination of the acute effects of isolated nicotine on sexual arousal in nonsmoking men measured both subjectively and physiologically. Twenty-eight sexually functional men participated in two counterbalanced conditions in which they received either placebo or nicotine gum 6 mg , approximately 40 minutes prior to viewing an erotic film.
Continuous sexual responses to the erotic film stimuli were measured subjectively using a hand-controlled device, and physiologically using penile plethysmography. Methods Participants Sexually functional heterosexual men were recruited from an undergraduate psychology subject pool, as well as via local community and university advertisements. During an initial telephone interview, potential participants were given a detailed description of the experiment and were told that they would receive nicotine during one of the experimental sessions.
Entry criteria included people who were between the ages of 18 and 30, and reported no more than direct exposures to nicotine during their lifetime e. Exclusion criteria were as follows: Study Design and Procedure The study consisted of two counterbalanced experimental conditions, nicotine and placebo, to which eligible participants were randomly assigned. Participants and researchers were blind to condition allocation. The participants were scheduled at approximately the same time during both conditions i.
All participants were asked to abstain from caffeine and alcohol, and to refrain from engaging in sexual intercourse for 24 hours prior to each experimental condition. Because rapid ingestion of salivary byproducts of nicotine gum may cause stomach irritation, the participants were asked to refrain from eating and drinking with the exception of water for 2 hours prior to the experimental conditions.
During the experimental conditions, the participants were given either nicotine 6 mg or placebo, both administered double-blind in gum form. The participants were asked to continually repeat a pattern of chewing for approximately 5 seconds, and placing the gum between the tooth surface and the inner part of the cheek surface for approximately 60 seconds to allow buccal absorption of nicotine. The participants were tested individually while seated in a comfortable armchair within a dimly lit private testing room with a television monitor approximately 10 feet away.
Prior to drug administration, the participants completed questionnaires assessing their demographics, mood, sexual orientation, sexual experience, and sexual functioning, and had their heart rates and systolic and diastolic blood pressures monitored twice using an automatic inflation digital blood pressure and pulse monitor. Thirty minutes after drug administration, the participants completed another mood questionnaire, and had their heart rates and systolic and diastolic blood pressures remonitored to assess placebo- or nicotine-induced mood and cardiovascular effects.
The half-hour waiting period following the administration of nicotine or placebo was used to ensure that nicotine had reached its peak plasma nicotine levels. Following the half-hour waiting period, the participants were instructed on how to fit the penile plethysmograph. After privately fitting the genital gauge themselves, a 5-minute adaptation recording was taken to assess baseline arousal.
Following the adaptation period, the participants were randomized to view one of two In both sequences, the erotic films depicted a heterosexual couple engaging in consensual petting 1. The participants were instructed to continuously monitor their level of subjective sexual arousal by moving a computer mouse positioned on an adjacent table. Pilot testing established that the erotic films induced equivalent genital and self-reported increases in sexual arousal.
The three segments relax, neutral, and erotic within each film sequence were always presented in the same order, and the two sequences were counterbalanced across participants. After assessment of sexual arousal, the participants removed the gum and completed questionnaires assessing any adverse effects, and were asked which drug they believed they were administered.
The time from ingestion of nicotine or placebo to the onset of the erotic film was approximately 40 minutes minute waiting period, 1-minute plethysmograph fitting, 5-minute baseline, 1-minute display of the word relax, and 3-minute neutral film. This device consisted of a computer optical mouse mounted on a wooden track divided into seven equally spaced intervals, where 0 indicated neutral, and 1—7 reflected increasingly higher levels of feeling sexually aroused.
The participants were instructed to continuously rate their subjective sexual arousal throughout the duration of the film presentation. The IIEF is a item measure assessing five-factor analytically derived areas of male sexual functioning: Participants were excluded from analysis if they reported an erectile function score of less than This cutoff value has been demonstrated to have a sensitivity of 0.
Mood Changes in mood were evaluated with a short version of the Profile of Mood States POMS-SF [ 31 ], which is a item self-report questionnaire assessing areas of tension six items , depression eight items , anger seven items , fatigue five items , confusion five items , and vigor six items.
Scores were summed within all six factors, and a total mood disturbance score was obtained by summing the scores with vigor weighed negatively on the six primary mood factors and adding 24 range 0— Higher scores reflect greater mood disturbance. Adverse Effects The participants were administered a item questionnaire developed in our laboratory that assessed any adverse effects attributed to either placebo or nicotine administration.
Scores were summed within the two factors. Main Physiological Outcome Measures Sexual Arousal Male genital arousal was assessed via penile circumferential change using a mercury-in-rubber strain gauge D. Penile tumescence is considered the most sensitive index of sexual arousal and the most reliable measure of physiological response [ 32 ].
Gauges were calibrated over six 5-mm steps between sessions to check for reliability [ 33 ]. Heart rates during the film sequence presentations were extracted from the penile plethysmography signal. Because differences in individual penis size cause differential circumferential changes during sexual arousal, physiological sexual responses were standardized within participants by converting all data points to percentage of full erection PFE [ 35 ].
Because not all participants demonstrate discernable genital arousal patterns to sexual stimuli, their physiological data were removed from analyses if the minimum response to sexual stimuli did not exceed their response to the neutral stimulus by at least 3 mm within the placebo condition.
The physiological exclusion criterion is similar to that used by other researchers [ 36 , 37 ] and yielded the exclusion of eight participants, which is typical of circumferential measurement of erectile response [ 38 ]. The exclusion of nonre-sponders was particularly important in order to distinguish nicotine-induced physiological attenuation from idiosyncratic nonresponding otherwise not due to nicotine administration.
Heart rates during the film presentation were averaged across the neutral and erotic films, yielding a total of four heart rate measures one prior to drug administration, one 30 minutes after drug administration, and two during the film sequence for each participant per experimental condition. Difference scores in mood for all six factor scores, as well as the total mood score, were computed by subtracting the baseline before nicotine or placebo administration from the measure taken 30 minutes after administration of nicotine or placebo.
PFE was the only variable that violated the normality assumption, and therefore was square root transformed. Paired sample t-tests were used on PFE, CSA, and heart rate scores between and within the nicotine and placebo conditions during the neutral and erotic film presentations, on heart rate, and systolic and diastolic blood pressure scores prior to and 30 minutes after either nicotine or placebo administration, and on subjective ratings of mood tension, depression, anger, fatigue, confusion, vigor, total mood disturbance score , and on both potential and bogus nicotine adverse effects, between the placebo and nicotine conditions.
All analyses were performed using SPSS statistical software version Results Sample Characteristics Of the 61 men who completed the initial telephone screening, 11 reported being uninterested in participating, 10 were ineligible, and 10 did not show for their appointments. Thirty men met the initial entry criteria and later completed the two experimental sessions.
Of these participants, data on two men were excluded from analyses because they did not meet the IIEF cutoff score criterion. The participants reported a mean of 7. Forty-six percent reported being in a steady relationship, of which two reported being married.
Because of reported ethnic differences in sexual activity [ 39 ], ethnic demographics were collected by having participants self-report on racial background categories defined by the investigators. No participants reported medical conditions of any kind, three reported currently taking medications antihistamines, acne medications , and one participant reported a psychiatric condition attention-deficit hyperactivity disorder. Characteristics of the participant sample are presented in Table 1.