Nonatherosclerotic vascular changes may also mediate the effect of smoking on
genital function. The vasoconstrictive effects of nicotine in cigarette smohe may impair
the complicated vascular processes involved in erection (Benowitz 198X). This may
be due in part to disturbances of prostaglandin production in the vascular endothelium
or to an enhancement of platelet aggregation noted by several investigators (Nadler.
Velasco. Horton 1983; Alster et al. 1986: Taylor et al. 19X7: Lassila et al. 198X: Jeremy
et al. 1986: FitzGerald. Oates, Nowak 1 Y8X: Chapter 6).

Finally. hormonal effects of cigarette smoking could alter sexual responsiveness and
spermatogenesis. Alterations in the secretion of luteiniring hormone releahing hor-
mone (Moss, Riskind. Dudley 1979) or catecholamine\ (Patra. Sanyo]. Biswas IY79:
Klaiber and Broverman 1988) are two such possibilities. but disturbances in sex
hormones. particularly low testosterone or high estradiol. have been suggested more
often. In general. men who smoke cigarettes have similar or higher testosterone level\
than nonsmokers: thus. it is difficult to associate low testosterone with sexual dysfunc-
tion among men who smoke (Briggs 1973: Shaarawy and Mahmoud 1982: Andersen.
Semczuk. Tabor 1984; Handelsman et al. 1984: Deslypere and Vermeulen 1984;
Vermeulen and Deslypere 1985: Vogt, Heller. Borelli 1986: Barrett-Connor and Khaw
1987; Dai et al. 1988: Lichtenstein et al. 1987; Meikle et al. 19x7: Klaiber and
Broverman   1988).     The   adrenal  androgens   (i.e..   androstenedione.
dehydroepiandrosterone. and dehydroepiandrosterone sulfate) are elevated in male
smokers (Barrett-Connor. Khaw. Yen 1986; Barrett-Connor and Khaw 1987; Dai et al.
1988). Aromatization of these hormones may explain the elevated levels of estradiol
among males who currently smoke (Entrican. Mackie. Douglas 1978: Lindholm et al.
1982; Klaiber, Broverman, Dalen 1984: Barrett-Connor and Khan 1987; Lichtenstein
et al. 1987: Dai et al. 1988; Klaiber and Broverman lYX8). Elevations in circulating
estrogens may interfere with spermatogenesis and sexual behavior (Klaiber and Brover-
man 1988); such an explanation remains speculative.

Several studies have suggested that the estradiol and testosterone levels of former
smokers are comparable with those of never smokers (Deslypere and Vermeulen 1984:
Vogt, Heller, Borelli 1986; Barrett-Connor and Khaw 1987; Lichtenstein et al. 1987).
This observation implies that smoking cessation is likely to reverse any effect mediated
by disturbances of these hormones. Alternatively, former smokers may have had a
lower total dose. Androstenedione and dehydroepiandrosterone sulfate levels may be
modestly higher in former smokers compared with those of never smokers (Barrett-
Connor. Khaw, Yen 1986; Barrett-Connor and Khaw 1987: Lichtenstein et al. 1987).
However, the relevance of these findings to sexual capabilities is unlikely to be
significant. These hormones appear to have little intrinsic potency, and are important
because of their capacity for conversion to more active hormones such as testosterone
and estradiol (Baxter and Tyrrell 1987).

Sexual Activity and Performance

Surveys of the relationship between smokin p and frequency of sexual episodes
(intercourse or masturbation) have generally found smokers to be as sexually active as
nonsmokers. In two studies of elderly men. sexual activity in smokers was comparable /


with that of nonsmokers (Tjitouras. Martin, Harman IYX?: Diokno. Brown. Herzog
1990): in a cross-sectional study of younger men. no difference\ were indicated (Vogt.
Heller. Borelli lY86). Adolescent smohers are more sexually active than nonsmokers
(Russell I97 I: Malcolm and Shephard 197X ). In contrast. Cendron and Vallery-Mas-
son (IY71 ). in study,ing 70 men older than age 45. found that those who reported
smoking between ages 25 to 40 al\o reported being less sexually active at those ages
than those who denied smoking. Ovrerall. it appean that the relation between current
cigarette smoking and the level of male sexual activity is not very strong. Among
younger males. personality differences between smokers and nonsmokers may
dominate any adverse physiologic effects (Russell 197 I ).
If. as the aforementioned studies suggest, current smokers (or ever smokers) are
similar in sexual habits to never smokers, then no differences would be expected for
former smokers. Vogt, Heller. and Borelli (19X6) evaluated 239 healthy male volun-
teers aged 19 to 30 without genital abnormalities or diseases and taking no medications.
The study results indicated that the 36 former smokers among them were comparable
with both never smokers and current smokers in sexual activity (Vogt. Heller. Borelli
1986).
Impotence. the inability to maintain an erection sufficient for intercourse. has been
more extensively investigated in relation to smoking. Among treated hypertensives
aged 40 to 64. cigarette smoker3 were more likely to report impotence. although the
differences were modest and not statistically significant (Biihler et al. IYXX). A
statistically significant association was reported among men undergoing radiation
therapy for prostatic cancer (Goldstein et al. 1983). However. in both studies. poten-
tially important covariates. such as alcohol intake and age. M#ere not considered. Two
other studies of men undergoing impotence evaluation indicated a high prev*alence ot
smoking and suggested an association between smoking with impotence (Virag.
Bouilly. Frydman 1985: Condra et al. IYXh). Unfortunately. neither study included a
sexually functional control group. and both studie\ based their conclusions on ques-
tionable comparisons ot`the smohing rate in their clinic patients with that of the general
population. Vopt. Heller. and Borelli (1986) studied a group of young volunteers
vvithout selecting for impotence. These investigators found that smokers reported more
difficulties with decrea& libido and erection than nonsmokers (Vogt. Heller. Borelli
19X6). This analysis did not consider former smokers separately.
An acute effect ofsmohing on sexual performance is suggested by a study of smokers
monitored while viewing erotic films (Gilbert. Hagen. D'.Agostino IYX6). The succes-
sive smoking of 2 cigarette\ high in nicotine content significantly impaired the rate of
penile diameter change compared with that observed after smoking I cigarette or eating
candy. Hovvever. the clinical relevance ofthese oh\enation\ is unhnoan hecauke franh
impotence has not studied.
An important clinical measurement in the evaluation of impotence is the PBI. v.hich
indicates the \y stolic blood pressure in the penis div,ided by systolic blood pres\urc in
the arm. A low \,alue i\ considered to be ev idcnce of compromise of the penile blood
apply. a factor v+ hich may interfere v+ ith erection. Several \tudie\ of men undergoing
evaluation of impotence reported an association between smohing and Ioh PBI (Jacobs
et al. IYX3: Condra et al. 1986: Bornman and Du Ples\i\ lYX6: DePulma et al. IYX7).


Among impotent diabetics, evidence of nocturnal erections wJas found less in smokers
compared with nonsmokers. thus suggesting an increased risk of vascular compromise
in smokers (Takahashi and Hirata 1988). However. other studies of impotent men have
not reported differences between smokers and nonsmokers in vascular measurements
(Wabrek et al. 1983; Virag, Bouilly. Frydman 1985: Kaiser et al. 1988). Most of these
investigations did not consider covariates such as alcohol use, although one study
suggested that smoking in isolation had little effect and that an association of smoking
with an abnormal PBI may be due to the association of smohing with other arterial rish
factors (Virag. Bouilly, Frydman 1985).

In many of the studies relating smoking and impotence. the investigators did not
distinquish nonsmokers as ex-smokers or never smokers. However. two investigations
considered former smokers separately (Table 15). Wabrek and associates (1983)
studied I20 men who were referred to a hospital-based erectile dysfunction program.
The percentage of former smokers vvas approximately the same among men with
impaired, borderline. and normal PBI. Condra and colleagues ( 1986) reported on I78
patients also referred for impotence. Former smokers were not separated for analysis.
but this study suggests that the PBI for ex-smokers is more normal than in current
smokers (Condraet al. lY86). However. neither study considered important covariates.
such as age and alcohol use (Wabrek et al. 1983: Condra et al. 1986).

Two recent investigations considered the effect of smoking cessation on impotence.
Forsberg and colleagues (1979) noted that two smoking men who were impotent
improved their functioning after smoking cessation at the same time that measures of
penile blood flow improved. However. it is not clear how these two men were selected
for this study. and control subjects were lacking. Elist. Jarman. and Edson (1984)
reported on the treatment of 60 impotent men. Twenty nonsmoker\ were treated with
the vasodilator isoxsuprine. and 40 smokers were either advised to stop smoking or
advised to stop smoking and also given isoxsuprine. There was no mention of
randomization. and there was no untreated control group. Similar proportions im-
proved whether given isoxsuprine. convinced to stop smoking. or both (Elist. Jarman.
Edson 1984).

Animal data have not elucidated the relation between smoking and either sexual
activity or impotence. Soulairac and Soulairac (1972) studied the sexual activity of
male rats given either a 0.6 mg/kg or a 1.2 mg/kg dose of nicotine subcutaneously. The
sexual activity of the rats after the nicotine administration was compared with that
before treatment. Sexual activity was markedly increased with the 0.6 mg/kg dose. and
at 1.2 mg/kg there was trembling and twitching and no sexual behavior for 2 to 3 hours.
In contrast, exposure to smoke from 1 cigarette has been shown to interfere with the
physiology of erection in male dogs (Juenemann et al. 1987).

In summary, the level of sexual activity does not appear to be affected by cigarette
smoking. Cigarette smoking may be associated with impaired male sexual perfor-
mance. Among impotent men, smokers are more likely to have an underlying vascular
problem. These associations have been more commonly noted in groups already at high
risk of impotence. such as hypertensives and diabetics. However. these associations
have not been consistently observed, and the positive findings may be due to the
association of smoking with other factors such as alcohol use. Moreover. because the

303


TABLE IS.-Sexual performance among male former smokers

studies of PBI are generated entirel) in referral populations. it i\ unclear if these finding\
can be generalired. Because of limited and uncontrolled data. no conclusion\ can be
drawn regarding WYLI~I performance or PBI among former makers.

Sperm Densit- and Qualit>

Measul-ements of sperm den\it!. mr)rpholog . and motilif arc commonI>, uxd
assessmcntk of sperm qualit! (Roger\ and Ru\\ell IYX7 I. O\er 20 \tudie\ hare dealt
with the relation of cigarette \mohing to sperm den\it!,. motility. and morpholog>
(Vicxian lY6Xa: Schirren and Gt'! 1960: Cm~phcll md Harrison lY7Y: Vogel. Braver-
man. Klaiber lY7Y: Stehhun IYXO: Nebe and Schirrcn IYXO: EVXII\ t't al. I98 I: Godfre!
19X1: Roclrisuc/-Rigau. Smith. Steinherger IYXI: Shaaraw! and hlahmoud IYX2:
Buiatti et al. I YX4: Andervx. Semc/uh. Tabor I YX4: Norden\on. Xbrams\on. Ducheh
19X3: Handcl\man et al. IYX-I: Hoda\ et al. IYX5: Kulihausk. Bluustein. Ahlin IYXS:
Ablin IYXh: Rantala and Ko\himie\ lYX7: Vast. Heller. Borelli lYX6: Klaiber et al.
lYX7: Dihshit. Buch. Jlansuri lYX7: Sxrrunen et al. IYX7: Klaiberand Bro\erman IYXX:
Svaranen et al. I9XY: Rui. Oldereid. Purvi\ IYXY: klar\hburn. Sloan. Hammond IYXY:
Oldereid et al. I YXY). Table I6 `rummari/es the finding\ of those studie\ that reported
mean values for maker\ and nonsmohcrx In mo\t \tudie\. men smohing cigarette\
had lower sperm Jen\it>. although many ofthe\e \tudie\ indicated differences that \+ere
not \tati\tically riynificant. The \moher\' a\`erage sperm density uxs at lea\t X0 percent
that of the nonsmohers. In ~\cral studies sperm morphology or motility L\;LS impaired


in smokers compared with nonsmokers. but this was a less consistent findincg. Few
studies have considered the spermatic chromosomal characteristics of smokers com-
pared with nonsmokers. Nordenson. Abramsson. and Ducheh ( 1983) found smokers
to have more chromosome breaks than nonsmokers. but Oldereid and couorkers ( I YXY)
reported no difference5 in DNA condensation as assessed by flow cytometr\`.
Although differences in mean values of any of these measurements suggest an effect
of smoking. the most relevant parameter may be the percentage of smokers and
nonsmokers who exhibit deficiencies in sperm densit). morpholog\,. or motility.
Several researchers have investigated the relative risk ofa/oospermia (no sperm in the
ejaculate) or oligospermia (reduced number of sperm) in smokers versus nonsmokers
or never smokers (Table 17). Although the ranpe of relative rishs is uide. there is a
clear pattern of increased risk among smokers. However. the clinical significance ot
oligospermia is uncertain. Most studies have used one cjvculate per man. although the
within-man coefficient of variation can be a\ much a\ 60 percent (Schenker et al. 1 YXX ).
The available information suggests that current smohins is related to IOU sperm
density. However. these data are limited. Many studies investigated men visiting
infertility clinics. limiting generalization. Moreover. if male makers with poor sperm
quality are most likely to attend these clinics. selection biases may distort the results.
Also. many of these studies were relatively informal. Few of the studies accounted for
potentially confounding factors such as alcohol use and age. Less than half of the
studies documented that a period of sexual abstinence was required for subjects before
giving the sperm sample, and few of the studies anstyLed multiple semen specimens as
some authorities recommend (Zaneveld and Jeyendran 1988). Most studies have a
small number of subjects. and their statistical pouer is limited for this reason. In come
of the studies. it is not clear whether former smokers u'ere included in the smoker or
nonsmoker group.
A few studies investigated ex-smokers (Table IX). One M;IS a case-control stud!, of
male infertility in Italy (Buiatti et al. 1984). The cases were a/.oospermic or oiigosper-
mic men being treated for infertility at the University of Florence. Controls were
University outpatients who had normal sperm counts.  There were no significant
differences between smoking categories in the percentage of men with Iov. sperm
counts.  Vogt. Heller. and Borelli (1986) e\,aluated 139 male volunteers. Among
former smokers (those who had smoked for at least I year and those who had stopped
smoking for at least 1 year). percent normal spermatozoa. percent young forms. percent
old forms. and percent degenerate forms were comparable with those of never smokers.
Stekhun ( 1980) reported that 42 percent of former smokers had oligospermia compared
with I8 percent of never smokers. Schirren and Gel ( 1969) reported that three men
with low sperm density and motility showed substantial increases in these parameters
3 to 6 months after smoking cessation. However. there w'erc no control\ defined in this
analysis. Because of the limitations of the four studies. no conclusions are possible
regarding the effects of smoking cessation on sperm quality in humans.
Animal studies have not been particularly informative. In some studies. rodent\ that
were heavily exposed to nicotine or cigarette smoke demonstrated testicular atroph!,.
but this has not been a general finding (Larson. Haag. Silvette I96 I ; Larson and Silycttc
IY6X: Dontenuill et al. lY73b: Essenbq. Fagan. Maler\tein lY.5 I: Thienes IYhO:


TABLE 16.-Sperm quality among smokers and nonsmokers

Vtcfian
I IYhXa,

Vogel. Broverman.
Klather
I IY7YI

Nebe and Schlrren
I 19x0)

Evatx er al
(1981)

Spira et 31.
(I')XI)

Rodrtguw-Rteau.
Smith. Stetnkryzr
(19x7)

Andrr\ett. Semcuh
Tahor ( I 0X-l I

Handel\man
et 31. (IYXI)

Kulihaukt\.
Blaustem.
Ahlin i 1985)

Rantala and
Kokimie\
(10X7)

Vogt. Heller. Borellt

lnlerttltt! clmtc
(71175 1

Volttntwr~
1 `O/2 I

Inferttltt\ cltmc (Xhili7,

Semen donor\ (7 I12 3 /

Frrttltt) clmic (1351107,

Volunteer\

0.x7







O.ho"




I .Ol









(1.75"



0.X6



O.Y5





O.Y3



O.YY





0 67



0.43"





(I.40




0.x IJ

1).40








lS







O.Y7"







0.Y-t





O.YJ



0.') I"



I (WI




0 h4"



I .07





0 YX



I .ot)





0.0x





I .Ol

I) 77







0.x7"

O.Y.7~'



O.Y)i



I .(Hl




O.h7"



LOX




0.03"



0.7x"





O.Y5





0,YY

Smohrr\ and
non\moLrr~
marched on qxm
den\tl)

OItgoqwrmtc* men
omttted
(<I x IOh/mLI

Ol~foqxrtt~~c~ men
umttted (<I x
I Oh/"lL 1

(1986)         152/l%))

406


TABLE 16.-Continued

Reference

Study population      Ratto of mea\ure among

   (number of     \moker\ to that among non\moher\

non\moker4numhrrof   Sperm   "4 Normal  `4 Motile
    smoker\ I      denwy    sperm    sperm      Comment\

Saaranrn
et al. (IYX7)

Klaiher et al
t lYX7)

Dth\hit. Buch.    lnfertllltj clinic
Man\urI ( I YX7,    t2XXi7lY)

Klaiber and
Broverman ( IYXX)

Saarllnen Cl al.
i 1 YXY)

Volunteers
I'll",
- --


Semen donor\
and fertile men (32/2X I

Mar\hhum. Sloan.
Hammond ( IYXY)

Infenilityclintc
12Y41152,

Rul. Oldereid.
Pur\l\(lYXY)

Infertilq clm~c
( 2031 I47 1

infertillt? clime
(61131 I

InfertIlity clmx
( I I O/.54)

Patd volunteer\ iYO/hOb

Male\ from mterttle
couple\ t4W I,

0.x I



0.77"



0.5?



O.Yh



l1.U



0.x.3



O.YZ



1.17



I.13

I .oU



O.YX



0 Y-I



O.Y4



I 02



0 4



O.YY



I .os



I Oh

0.97



O.XY"

o.xo'l

I 01

0 Y?

I .Ol

0.Y-l

O.Y)h

I.12

Thompson et al. lY73: Patra. Sanyal. Bi\uah 1979: Bi\L\a and Patra 19x1 ). Some
5tudk have noted a disturbance of spermatogrnr~is. ;I decrea\t` in the interstitium. or
a dectruction of the seminiferous epithelium (Lar~n. Haag. Silvette 1961: Larson and
Silvette 1%X: Es\enberg. Fagan. Malerstein lY.5 I : VicAan IY6Xb: Wyrobrch and
Bruce 1975: Bihwas and Patra 19x1: Alwuchi et al. lYX6: El-Salad t`t al. 19x7). The
result> may depend on the duration and dose ofexpo~re. a\ well :I\ on the age\ at u hich
exposure take\ place. Morco\,er. the relevance to humal> of the large don\ yi\cn to
the animals k uncc`rtain. None ofthehe investigation\ considcrcd \pt'rmatogenc\is at'ter
exposure ended: thu4. feu conclusion\ may he draun rt,`
                         ~vrding the t'i'fcct of ct's\ation
ofcspo~re even within the limitation\ of lhe animal \Iuclie\.


TABLE 17.~-Estimated relative risk of azoospermia or oligospermia among
       smokers versus nonsmokers or never smokers

Reference

Study population
  tnumher of
  non\moher\,
number of \moher\)

Contra\t

Estimated
relattve rthk tn
\moher\

Comments

Schirren and Ge)  Andrology clmlc
(IYhYl        lsxo/ll77l

Campbell and    Fertility clmic
Harrlwn t I Y7Y I   (I 19/13-i,


Stehhun       Uot stated (?3/1051
I IYXII)

Rodrtg~r/-Rtyu. Frrtilitk cllnlc
Smith. Stetnherger t 101/5X1

I lYX21

Buwtl et 31.     Fertillt\ cltmc
(14X-I)     ,xo;l.G~

Andrr\en.
Srmc/uh.
T`lhor~ IYX1,

,Ahiln 1 IQXh)

l'og. Heller.
B~Wlll (14X6)

FenlIlt> clonic
lX61l-l7)

uot \tatwi
1 I .7S/`2iX,


Volunteer\
1.53150,

A/oo\permta:
\moher\ v\. nonhmohrrs

Oligoywmia: \mohen
\ `1. non\mohers

Ollgo\permta: current
\mohrr\ ~5. nexer
\mokrr\

OItgo\permta:
I<20 x IOh/mLI:
current smokers VI.
non\mohrr\

Oligoyxrmta
(<?O x IOh/mL):
\mohrr\ ~5.
non\moker\

.A/oo\permta: current
\moher\ x \. nonvnokerx

ollgo\permla
(<JO x IO'/mL):
\moher\ v\ non\mohrr\

Ollao\permiu (<I x
IO'jmLj: current
\moher\ \ 5. nr\cr
rmoher\

.A~ooqxrni~a:
current \mohcr\ \ \.
nt3zr \mohrr\

I .17

I.'


I .h'l

Oligoywmia not
defined
Aroospermic men
omitted

3.2"

Oligoyxrmia not
defined

0.`)






I .o






co,'




2.Yd

I.?






77


TABLE 17.-Continued

Reference

Study population
  tnumber of
non\moLer\l
number of smoker\)

Contra5r

Ewmated
rrlatlvr rt\k in
smohers

Klaiber et al.
lIYX7)
(continued)

Fertility clime    Oligo\permia I<20 x       I .5
without varicocele  10h/mL): current
(35/30)          \moher\ v\. neber
             \moher5

Dthshit. Buch.   Fertility clinic    Olleo\pernlla (GO *       I.2
Manwrt (1987)   (2lY/?XX)     IO5mL,: current
                         \moker\ v\. never
                         smoher\
                  .A/oo\pertnia: current       I I
                         moherh Y\. neker
                         hmohrr\

TABLE l&-Sperm quality among former smokers

Reference     Study population

Findings

Comment\

Schtrren and Gey  Andrology      Smoking cessation improved sperm      No control
(1069)       patients       density and motility in 3 smokers
Stekhun (1980)    Not stated       Former smokers had RR of 2.3 for     Oligo\permia not
                   oligospermia                  defined

Buiatti et al.     Male partners of    No difference between current, former.
( 1984)       infertile couples    and never smoker\ in prevalence of
                    azoo-/oligospermia
Vogt. Heller.    Healthy volunteers   No difference between current. former.    No consrderation
Borelli ( 1986)              and never smokers In rperm          of covariate\
                    morphology

NOTE: RR=relatwe ri\h


CONCLUSIONS

I. Women who stop smoking before becoming pregnant have infants of the same
birthweight as those born to never smokers.

2. Pregnant smokers who stop smoking at any time up to the 30th week of gestation
have infants with higher birthweight than do women who smoke throughout
pregnancy. Quitting in the first .? to 3 months of pregnancy and abstaining
throughout the remainder of pregnancy protect the fetus from the adverse effects of
smoking on birthweight.

3. Evidence from two intervention trials suggests that reducing daily cigarette con-
sumption without quitting has little or no benefit for birthweight.
4. Recent estimates of the prevalence of smoking during pregnancy. combined with an
estimate ofthe relative risk of low birthweight outcome in smokers, suggest that I7
to 26 percent of low birthweight births could be prevented by eliminating smoking
during pregnancy: in groups with a high prevalence of smoking (e.g.. women with
less than a high school education) ,29 to 31 percent of low birthweight births might
be prevjented by elimination of cigarette smoking during pregnancy.
5. Approximately 30 percent of women who are cigarette smokers quit after recogni-
tion of pregnancy. with greater proportions quitting among married women and
especially among women with higher levels of educational attainment.
6. Smoking causes women to have natural menopause I to 7 years early. Former
smokers have an age at natural menopause similar to that of nev'er smokers.

II0


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        CHAPTER 9
SMOKING, SMOKING CESSATION, AND
OTHER NONMALIGNANT DISEASES