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50
Wet Heat as a Reversible Gonadotoxin
Clinical Urology
International Braz J Urol Vol. 33 (1): 50-57, January - February, 2007
Wet Heat Exposure: A Potentially Reversible Cause of Low
Semen Quality in Infertile Men
Shai Shefi, Phiroz E. Tarapore, Thomas J. Walsh, Mary Croughan, Paul J. Turek
Departments of Urology (SS, PET, TJW, PJT), Obstetrics, Gynecology and Reproductive Science
(MC, PJT), and Epidemiology and Biostatistics (MC), University of California San Francisco, San
Francisco, California, USA
ABSTRACT
Objective: To evaluate the recovery of semen quality in a cohort of infertile men after known hyperthermic exposure to hot
tubs, hot baths or whirlpool baths.
Materials and Methods: A consecutive cohort of infertile men had a history remarkable for wet heat exposure in the forms
of hot tubs, Jacuzzi or hot baths. Clinical characteristics and exposure parameters were assessed before exposure was
discontinued, and semen parameters analyzed before and after discontinuation of hyperthermic exposure. A significant
seminal response to withdrawal of hyperthermia was defined as ≥ 200% increase in the total motile sperm count (TMC =
volume x concentration x motile fraction) during follow-up after cessation of wet heat exposure.
Results: Eleven infertile men (mean age 36.5 years, range 31-44) exposed to hyperthermia were evaluated pre and post-
exposure. Five patients (45%) responded favorably to cessation of heat exposure and had a mean increase in total motile
sperm counts of 491%. This increase was largely the result of a statistically significant increase in sperm motility from a
mean of 12% at baseline to 34% post-intervention (p = 0.02). Among non-responders, a smoking history revealed a mean
of 5.6 pack-years, compared to 0.11 pack-years among responders. The prevalence of varicoceles was similar in both
cohorts.
Conclusions: The toxic effect of hyperthermia on semen quality may be reversible in some infertile men. We observed that
the seminal response to exposure elimination varies biologically among individuals and can be profound in magnitude.
Among non-responders, other risk factors that could explain a lack of response to elimination of hyperthermia should be
considered.
Key words: male infertility; induced hyperthermia; semen; analysis; spermatogenesis
Int Braz J Urol. 2007; 33: 50-7
INTRODUCTION
Spermatogenesis is sensitive to a variety of
chemical and physical stressors. Testicular hyperther-
mia has been known to have a deleterious effect on
male fertility since the time of Hippocrates and is a
well-recognized cause of impaired sperm production
(1). Its detrimental effect has been demonstrated in
both animal models and in humans (2-4). Whether
due to endogenous (such as high fevers) or exogenous
stimuli, heat decreases sperm concentration, impairs
motility, and reduces the number of morphologically
normal sperm (5-8). This effect is striking enough that
the effect of laptop computers on scrotal hyperther-
51
Wet Heat as a Reversible Gonadotoxin
mia has recently been reported and the use of heat
exposure as a male contraceptive has been studied
(9,10). In contrast to the well described detrimental
effects of dry heat on spermatogenesis, the conse-
quences of wet heat exposure are relatively undefined.
Our working hypothesis is that the effects of wet heat
on spermatogenesis are similar to that from dry heat.
The only published study to examine the ef-
fects of wet heat exposure on human fertility was
performed by Rock and Robinson in 1965. In this
study, the authors exposed 20 oligospermic men to
wet heat (43-45°C) with a bottle warmer held between
the thighs for 30 minutes on 6 alternating days. They
noted a decline in sperm production that was followed
by improvement in seminal parameters with cessa-
tion of the exposure, however the details of semen
quality before and after exposure were not provided
by the authors (11). The effects of more common ex-
posures to wet heat, such as with hot tubs, Jacuzzis,
or hot baths have not been addressed in the literature.
The data provided by Rock and Robinson, as
well as the well-defined association between dry heat
exposure and impaired spermatogenesis led us to
study the effect of total-body wet heat exposure in
human males. We asked whether withdrawal of ex-
posure in men with poor semen quality and a history
of wet heat exposure could lead to an improvement
in semen quality. We retrospectively compared se-
men quality before and after cessation of wet heat
exposure, and also performed an interval analysis of
responders and non-responders, looking for factors
that might modulate responsiveness to therapeutic
intervention.
MATERIALS AND METHODS
Over a 3-year period, infertile men with ex-
posure to wet heat were identified in a single, univer-
sity-based, male infertility practice. Inclusion crite-
ria were wet heat exposure, defined as the immersion
of the body in a hot tub, heated Jacuzzi, or bath at a
temperature warmer than body temperature, for ≥ 30
minutes per week during ≥ 3 months prior to presen-
tation. All female partners were concurrently assessed
for reproductive issues. Patients were excluded if they
had received any medical or surgical infertility treat-
ment within 1 year of study intake, and if a diagnosis
of co-existing female factor infertility was made.
Because patient data was decoded of all protected
health information, a waiver was obtained from the
Committee on Human Research for this study.
All subjects underwent a complete history and
physical examination by a single specialist (PJT).
Information regarding the type, frequency, duration/
episode and overall length of exposure to wet heat
was collected during this visit. Counseling regarding
the cessation of wet heat exposure was given during
the initial visit. We attempted to obtain 2 semen
samples for analysis at baseline (during exposure), <
3 months after intervention, and between 3-6 months
after intervention in all patients. Semen was collected
by masturbation after 2 to 3 days of abstinence and
processed within 1 hour of ejaculation. All semen
analyses were performed in a single andrology labo-
ratory by the same technician, and assessed accord-
ing to World Health Organization guidelines (12).
Motility was reported as the sum of A + B patterns
(12). A positive response to discontinuation of heat
exposure was defined as an increase in total motile
count (TMC = ejaculate volume x sperm concentra-
tion x fraction of motile sperm) > 200% during fol-
low-up. This cutoff was selected to be above the natu-
ral variability in semen parameters within an indi-
vidual: sperm volume, concentration and motility have
been shown to vary by 59%, 54% and 96%, respec-
tively, in a single individual with time (13). Statisti-
cal analysis was performed using two-tailed, paired
“t” test to compare pre- and post-intervention semi-
nal parameters. Probability values < 0.05 were con-
sidered significant.
RESULTS
Patient Characteristics
Table-1 outlines the demographic and clini-
cal characteristics of the 11 eligible study subjects.
Mean patient age was 36.5 years, and mean partner
age was 34.6 years. Couples had been trying to con-
ceive for an average of 2.6 years (range 0 - 15 years)
prior to evaluation. Nine patients (82%) had an evi-
52
Wet Heat as a Reversible Gonadotoxin
dence of infertility, defined as failure to conceive after
one year of unprotected sexual intercourse. The mean
exposure duration was 149 minutes per week (range
60 - 315), with a mean total duration of hyperthermic
exposure of 2.9 years (range 0.75 - 10). Five subjects
were exposed to hot baths, 4 to both hot baths and hot
tubs, and 2 to Jacuzzi. Three of the 11 subjects had a
significant smoking history (> 6 pack-years). Five oth-
ers were only occasional smokers (< 1 pack-years).
Complete pre-intervention semen parameters among
study subjects are given in Table-2. Patients had an
average of 1.6 ± 0.6 and 2.5 ± 1.7 semen analyses per-
formed prior to cessation of exposure and following
cessation, respectively. Nine men (82%) had TMC <
20 x 106 (mean 5 x 106). The other 2 men had TMC’s
of 34 x 106 and 117.6 x 106 sperm.
Response to Cessation of Wet Heat Exposure
Semen analyses for each subject were
categorized into baseline (during exposure), 0 to 3
months post-intervention, and > 3 months post-
intervention. Multiple semen analyses within a given
period were averaged for each individual during that
period. Sperm parameters before and after
discontinuation of exposure are listed in Table-3.
TMC values and response to intervention status are
shown in Table-4. Mean follow-up of the study cohort
was 7 months (range 2-16). Amongst the entire cohort,
improvement in TMC did not reach statistical
significance (p = 0.89). Overall, 44.5 % (95% CI
16.7,76.7) of men showed > 200% increase in total
motile sperm count after discontinuation of wet heat
Table 1 – Characteristics of the study group.
Characteristic Mean ± SD Range
Patient age (yr) 036.5 ± 4.5 31 - 44
Partner age (yr) 034.6 ± 6.4 22 - 42
Time attempting (yr) 002.6 ± 4.3 00 - 15
Exposure (min/week) 148.6 ± 82.3 60 - 315
Exposure history (yr) 002.9 ± 3.3 0.75 - 10
R-testis volume (mL) 016.9 ± 3.7 10 - 20
L-testis volume (mL) 017.0 ± 4.9 08 - 25
Smoking (pack-year) 003.1 ± 5.5 00 - 15
Testicular volume was determined using Prader orchidometer.
Characteristic Mean ± SD Range
Ejaculate volume (mL) 3.3 ± 1.3 1.3 - 5.3
Sperm concentration (x 106/mL) 15.8 ± 16.0 0.2 - 42.5
Sperm motility (%) 23.8 ± 20.6 0.0 - 70
Total motile sperm count (x 106) 17.9 ± 34.5 0.0 - 118
Table 2 – Seminal parameters before intervention.
Table 3 – Semen parameters at baseline, 0-3 months post-intervention, and more than 3 months post-intervention.
01 3.0 03.0 34 2.4 14.9 24 1.8 12.0 44
02 5.3 10.5 17 3.5 18.0 62 - - -
03 4.4 00.7 23 4.5 00.7 15 1.8 01.5 7
04 4.0 42.0 70 2.5 63.0 55 - - -
05 1.7 00.2 00 0.8 01.0 23 - - -
06 4.2 09.5 37 6.0 07.0 23 4.6 09.0 32
07 2.0 42.5 40 0-0- - 1.0 21.0 40
08 2.5 13.0 09 3.5 21.0 03 - - -
09 4.8 09.0 24 4.5 05.0 26 5.5 05.4 21
10 3.4 08.9 02 3.3 15.0 36 3.6 19.0 19
11 1.3 35.0 07 1.3 14.0 04 2.1 32.4 22
Pt.
No Volume
(mL) Concentration
(x 106/mL) Motility
(%) Volume
(mL) Concentration
(x 106/mL) Motility
(%) Volume
(mL) Concentration
(x 106/mL) Motility
(%)
Baseline 0-3 months 3+ months
53
Wet Heat as a Reversible Gonadotoxin
exposure and were considered responders to
intervention.
Among responders, the mean increase in
TMC was 491% (range 221-873), excluding an outlier
whose TMC improved from zero to 200,000 sperm.
Responders’ TMC before and after intervention are
illustrated in Figure-1. The seminal response in the
responding cohort showed increases in sperm
concentration, but largely the result of increases in
sperm motility. Although the increase in TMC
increase did not reach statistical significance (p =
0.07) among responders, a subset analysis showed a
mean increase of 22% in sperm motility, which was
statistically significant (p = 0.02). Among responders,
one patient had a TMC increase from 0 to 0.2 million
sperm, two patients had post-intervention TMC’s of
9.3 and 10.7 x 106, while two more had a TMC’s of >
20 x 106 sperm. There was no significant difference
in the length of follow-up among study responders
and non-responders.
Figure 1 – Mean total motile count (TMC) in responders cohort for baseline and > 3 months post-intervention. Bars represent standard
deviation.
Table 4 – TMC (x 106) at baseline, 0-3 months post-intervention, and > 3 months post-intervention.
TMC = total motile sperm count, % change: based on last available data compared to baseline for each individual. Response was
defined as an increase of TMC
≥
200%.
3+ monthsPt. No.
01
02
03
04
05
06
07
080
09
100
11
Baseline 0-3 months Change (%) Responder
02.9
009.5
000.6
117.6
000
014.4
034
0002.9
10.4
0001.1
003.2
10.1
39.1
00.7
86.6
0.2
09.7
-
1.8
5.9
17.8
0.7
09.3
-
00.2
0 -
-
13.2
08.4
-
5.5
10.7
21.1
+ 221
+ 312
- 67
- 26
+ ∞
- 8
- 72
- 38
- 47
+ 873
+ 559
Yes
Yes
No
No
Yes
No
No
No
No
Yes
Yes
54
Wet Heat as a Reversible Gonadotoxin
Factors that could explain a response or lack
of response to the intervention were examined in both
cohorts. Tobacco use emerged as a possible
differentiating factor. Among 6 non-responders, 5
were chronic tobacco users with a significant smoking
history (mean 5.6 pack-years), compared with 3
occasional smokers in the responder group, whose
mean tobacco consumption was 0.11 pack-years. The
prevalence of varicoceles was similar in responders
and non-responders (4/5 and 4/6 patients,
respectively). No other potential gonadotoxic factors
were identified in the study cohort.
COMMENTS
The removal of wet heat exposure resulted
in improvement in semen quality in nearly one-half
of subjects studied. The improvement was largely the
results of increases in sperm motility, and appeared
to persist beyond 3 months, although a continuous
improvement was not observed in all subjects. The
extra-abdominal position of the scrotum and the
proximity of the pampiniform venous plexus to the
testicular arteries contribute to the efficient dissipation
and transfer of heat away from the testes and resultant
lower testicular temperature (8). However, in the
presence of extreme elevation of extra-testicular
temperature, as when immersed in hot liquid, these
same characteristics make the scrotum particularly
susceptible to deleterious thermal effect. It is therefore
not surprising that semen quality might be susceptible
to the effects of wet hyperthermia.
The deleterious effect of dry heat on semen
quality and, by extrapolation, male fertility, has been
recognized medically for decades, and to the traditional
medicine community for millennia. Carlsen et al., in
examining the effect of febrile illness on semen quality,
demonstrated a dose-response relationship between the
number of days with fever and sperm concentration
(8). Similarly, Mieusset & Bujan examined mild
testicular heating (about 1°C) as a form of
contraception, an idea originally conceived of by
Robinson et al. (14,15). Both studies found that sperm
concentration rebounded to baseline in 12 to 18 months
following cessation of increased testicular
temperatures. None of these studies, however, were
designed to replicate the frequent, significant wet
hyperthermia that is the fate of the habitual hot-tuber,
thus forming the rationale for this study.
In reviewing our data on the recovery of
semen quality in infertile males following the
cessation of wet heat exposure, we found that there
were two distinct groups of patients: those that
responded to intervention and those that did not.
Among responders, improvements in semen quality
were witnessed well beyond the 3 month period
typically ascribed to a single cycle of spermatogenesis.
This finding is entirely consistent with the time course
of recovery noted after varicocele repair and exposure
to other gonadotoxins (16). Interestingly, the semen
analysis parameter that exhibited the largest change
among responders was sperm motility, and this
increase reached statistical significance after
intervention. This suggests that heat-induced motility
dysfunction may be the parameter most vulnerable to
wet hyperthermic exposure. Although statistical
significance was not achieved in the overall increase
in TMC after intervention, the changes observed could
be considered clinically significant, as more men
could qualify for IUI instead of IVF for infertility
treatment following intervention. Given that
intrauterine insemination (IUI) can be considered for
low semen quality in men with TMC > 8-10 x 106
sperm, the number of men who would qualify for IUI
in the responder group increased from 1/5 pre-
intervention to 4/5 post-intervention. Two of the
responders had TMC > 20 x 106 after intervention
and were advised to consider unprotected intercourse
before IUI. This “shift of care” to less intensive forms
of assisted reproduction has also been described for
varicocele repair (16). We acknowledge that even
statistically significant changes in semen parameters
are always problematic to assess, given the naturally
high intra-individual variability of semen parameters
in both fertile and infertile men. However, the
potential clinical value of these changes must also be
considered, as we have outlined.
Careful analysis of non-responders suggests
that chronic tobacco use was more common among
non-responders, suggesting that it may complicate the
recovery from wet heat exposure. This finding is
hardly surprising, considering that tobacco use is a
55
Wet Heat as a Reversible Gonadotoxin
well established, independent risk factor for poor
semen quality (17-19). It is interesting to speculate
whether the concomitant exposure to tobacco and wet
heat may act synergistically to prevent early and rapid
recovery of semen quality.
It is interesting that two responders
demonstrated subtle declines in TMC following the
3-month time interval. This lack of continuous
improvement suggests that peak improvements in
TMC may be time-limited and could involve other,
less well-described physiological responses. It may
also suggest that a timeline for therapy be offered to
affected patients, to avoid prolonged follow-up
without obvious benefit.
Because this is a small study, the results
should be confirmed in a larger series of patients.
Given the complexity of factors underlying male
infertility, including currently uncharacterized factors,
more accurate results will only be generalizable with
a larger study. We plan further follow-up on the
patients in this study to assess conception after
elimination of hyperthermia.
CONCLUSIONS
This study addressed the relatively
unsubstantiated issue of wet heat exposure as a factor
in male infertility. We demonstrated that infertile men
who are frequently exposed to wet heat in the form of
hot tubs, Jacuzzis, or hot baths, may realize a marked
increase in semen quality following cessation of
exposure. The response persists for more than 3 months,
and is driven mostly by the increase in sperm motility.
CONFLICT OF INTEREST
None declared.
ACKNOWLEDGEMENT
Doctor Shai Shefi is Recipient of fellowship
from The American Physicians Fellowship for
Medicine in Israel
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6. Procope BJ: Effect of repeated increase of body
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7. Saikhun J, Kitiyanant Y, Vanadurongwan V,
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assisted sperm analysis. Int J Androl. 1998; 21: 358-63.
8. Carlsen E, Andersson AM, Petersen JH, Skakkebaek
NE: History of febrile illness and variation in semen
quality. Hum Reprod. 2003; 18: 2089-92.
9. Sheynkin Y, Jung M, Yoo P, Schulsinger D, Komaroff
E: Increase in scrotal temperature in laptop computer
users. Hum Reprod. 2005; 20: 452-5.
10. Kandeel FR, Swerdloff RS: Role of temperature in
regulation of spermatogenesis and the use of heating
as a method for contraception. Fertil Steril. 1988; 49:
1-23.
11. Rock J, Robinson D: Effect of induced intrascrotal
hyperthermia on testicular function in man. Am J Obstet
Gynecol. 1965; 93: 793-801.
12. WHO Laboratory Manual for the Examination of the
Human Semen and Sperm-Cervical Mucus Interaction.
Fourth edition. Cambridge, Cambridge University
Press. 1999.
13. Mallidis C, Howard EJ, Baker HW: Variation of semen
quality in normal men. Int J Androl. 1991; 14: 99-107.
14. Mieusset R, Bujan L: The potential of mild testicular
heating as a safe, effective and reversible contraceptive
method for men. Int J Androl. 1994; 17: 186-91.
15. Robinson D, Rock J, Menkin MF: Control of human
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Wet Heat as a Reversible Gonadotoxin
spermatogenesis by induced changes of intrascrotal
temperature. JAMA. 1968; 204: 290-7.
16. Cayan S, Erdemir F, Ozbey I, Turek PJ, Kadioglu A,
Tellaloglu S: Can varicocelectomy significantly change
the way couples use assisted reproductive
technologies? J Urol. 2002; 167: 1749-52.
17. Hull MG, North K, Taylor H, Farrow A, Ford WC:
Delayed conception and active and passive smoking.
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18. Vine MF: Smoking and male reproduction: a review.
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Accepted after revision:
October 18, 2006
Correspondence address:
Dr. Paul J Turek
Department of Urology, UCSF
1600 Divisidero St, Rm A633
San Francisco, CA, 94143-1695, USA
E-mail: pturek@urology.ucsf.edu
EDITORIAL COMMENT
Numerous factors can elevate scrotal
temperature either by whole body or local scrotal
heating. Scrotal hyperthermia was found in men with
febrile illness, retractile testes, occupations associated
with high temperature exposure, hot bath and sauna
users, men wearing tight jockey shorts, car drivers,
and laptop computer users. Multiple human studies
have confirmed deleterious effect of increased scrotal
temperature on sperm quantity and quality.
The authors investigate a less defined effect
of total body wet heat exposure (hot tub, heated
Jacuzzi or bath) on spermatogenesis. While studied
population is very small and most results are not
statistically significant, this article presents evidence
of occasional reversibility of negative thermal effect
and improvement of total motile sperm count and
motility after cessation of heat exposure within the
predictable interval of 3 months. However, time to
maximum effect and durability of improvement also
remain unclear due to a short follow-up period.
Despite significant limitations the study is
noteworthy since it emphasizes important but
frequently omitted details in the evaluation and
management of the infertile men: 1) It is necessary to
ask patients about habitual and occupational heat
exposure, 2) It is worthwhile to recommend cessation
of confirmed frequent heat exposure and repeat semen
analysis within 3 month interval. Improved sperm
quantity and quality in select patients may “upgrade”
their treatment from IVF to IUI or, possibly, from IUI
to natural pregnancy.
Finally, since such improvement, its
magnitude and durability are not predictable, watchful
waiting approach has to be exercise within strictly
defined and limited time which will not delay other
recommended treatment options.
Dr. Yefim R. Sheynkin
Associate Professor of Clinical Urology
State University of New York at Stony Brook
Stony Brook, New York, USA
E-mail: ysheynkin@notes.cc.sunysb.edu
57
Wet Heat as a Reversible Gonadotoxin
REPLY BY AUTHORS
Although talked about for decades, the
detrimental effect of hot tubs, Jacuzzis and hot baths
on semen quality and male fertility has never been
formally investigated, and forms the rationale for this
study. As a result, we now have actual evidence to
show patients that these recreational activities are a
real risk factor for male subfertility. In addition, these
activities can be comfortably added to that list of
lifestyle recommendations and “things to avoid” as
men attempt to conceive.
We believe that the finding of significantly
improved semen quality in almost half of study
patients is certainly evidence of an exposure effect
that is more than just “occasional,” as suggested
above. And let us examine the clinical impact of this
finding bit closer. How could the ability of a simple
lifestyle maneuver that can “shift the care” from
higher (IVF-ICSI) to lower and less expensive forms
of assisted reproduction (IUI) not have the potential
for enormous clinical impact given the cost of treating
human subfertility? Just ask patients!
What we also find provocative is the
discussion of possible clinical features that might
impair the response to wet heat elimination (i.e.
varicocele and tobacco use). Given the complexity
of factors underlying male infertility, including
currently uncharacterized issues, we agree that
stronger, more generalizable statements regarding this
particular exposure and its effect on male infertility
can only be made with a larger study.