Risk of testicular cancer in subfertile men: case-control study
BMJ 1999; 318 doi: https://doi.org/10.1136/bmj.318.7183.559 (Published 27 February 1999) Cite this as: BMJ 1999;318:559
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Dear Editor,
Moller and Skakkebaek have shown an association between male
subfetility and subsequent testicular cancer (1). The authors mainly
addressed the problems of a case-control study. However, as a group, we
feel that certain aspects have been over-looked.
First, 31% of controls did not agree to participate, which is a
significant potential source of selection bias. The authors have given no
indication of whether the non-participants are representative of the main
population. It is possible that this sensitive subject may have
discouraged men with concerns about their fertility.
Our second concern is with other possible confounding factors,
specifically vasectomy and use of barrier contraception. These factors may
be particularly important given that Moller and Skakkebaek's data show
that cases are more likely to have had more than 20 female partners.
Information on vasectomy and contraceptive use could have easily been
obtained by telephone interview.
Moller and Skakkebaek have shown preliminary evidence for the
association between male subfertility and testicular cancer. However,
stronger evidence could be provided by a prospective cohort study, in
which objective measures of fertility, such as sperm counts, could then be
included.
Yours sincerely
Roderick Oakes, Rano Bhadoria, Sarah Schofield and Rachael Smith
Stage three medical students, Department of Epidemiology and Public
Health, The Medical School, University of Newcastle upon Tyne.
We would like to acknowledge the assistance of Dr Paula Whitty.
Competing interests: None.
1 Moller, H. & Skakkebaek, N. E. Risk of testicular cancer in
subfertile men: case-control study. BMJ 1999;318:559-562.
Competing interests: No competing interests
Editor- Moller and Skakebaek1 have confirmed in their excellent paper
the association between male subfertility and subsequent testicular
cancer. We2 and others3,4 have shown that men with malignant disease, and
especially with testicular cancer, have a reduced sperm quality at the
time of diagnosis of their illness. Further deterioration has been
observed due to the damaging effect of chemotoxic agents on
spermatogenesis, which may be temporary or permanent5. However, most of
these patients have sufficient suitable sperm for freezing before starting
the chemotherapy. The Improved survival in recent years of young males
suffering from cancer combined with the recent progress in assisted
reproductive techniques and especially in the field of micromanipulation
and intracytoplasmic sperm injection (ICSI), can secure the fertility
potential of these men. These men, particularly the young ones who have
not completed their family yet, must have the opportunity to freeze semen
samples for their future use. Our results2 indicated that their
probability of fathering their own genetic children is quite high.
Moreover, patients' knowledge that their fertility potential is secured
would help in the emotional battle against the cancer.
We wish to increase the awareness of general practitioners, oncologists,
haematologists and patients themselves to the new opportunities opened to
them in recent years. Our impression, after running a successful sperm
cryopreservation program for the last nine years, is that only small
minority of eligible patients is offered sperm cryopreservation. We call
medical teams treating male cancer patients to refer them before starting
chemotherapy, for semen cryopreservation in tertiary assisted conception
centres, which have the facilities and experience for cryopreservation and
can offer the whole range of appropriate sophisticated assisted
reproductive treatments.
1. Møller H. and Skakkebæk, N.E. Risk of testicular cancer in
subfertile men: case-control Study. BMJ 1999;318:559-562.
2. Lass A., Akagbosu F., Abusheikha N., Hassouneh M. Blayney M. Avery S.
and Brinsden P. A program of semen cryopreservation for patients with
malignant disease: Lessons from eight years experience. Hum Reprod 1998;
11:3256-3261.
3. Meirow D. and Schenker, J.G. Cancer and male infertility. Hum.
Reprod.1995;10:2017-2022.
4. Fossa, S.D., Aass, N., Molne, K. Is routine pre-treatment
cryopreservation of semen worthwhile in the management of patients with
testicular cancer? Br. J. Urol 1989; 64:524-529.
5. Pont, J. and Albrecht. Fertility after chemotherapy for testicular
cancer. Fertil. Steril.1997;68:1-5.
Amir Lass Consultant Gynaecologist
Naim Abusheikha Consultant Gynaecologist
Fidelis Akagbosu Consultant Gynaecologist
Peter Brinsden Medical Director
Competing interests: No competing interests
EDITOR - In their paper (BMJ, 7183, 27 Feb. 1999) Moller and
Skakkebaek conclude that infertility and testicular cancer share
aetiological factors.
No attempt is made to explain what these might be. It is wellknown
that an undescended testis is infertile and is liable to develop
malignancy. Presumably this is because it has not descended into the
cooler environment of the scrotum. Can it be inferred that excess warmth
is an enemy of the testis?
The authors indicate that the incidence of both infertility and
testicular malignancy have increased in recent years. We know that our
ancestors were content to bath no more than about once a week, whereas
many modern men like to relax daily in piping hot baths, especially in
winter. The testis
is being exposed to the increasing use of such hot baths. Could this be
perhaps an aetiological factor?
Godfrey P. Charlewood, FRCS(Ed.), FRCOG
Gynaecologist, retired
Simon's Town, South Africa
Competing interests: No competing interests
Authors' reply
Reply
We appreciate the interest in our work that is expressed in the
electronic letters by G.P. Charlewood, A. Lass and R. Oakes et al. As to
the hypothesis linking testicular cancer to excess warmth and, in
particular, to hot baths, there is little evidence, circumstantial or
direct, to its support. The age-distribution of testicular cancer strongly
suggests that the relevant causes act very early in life. We know of one
population, the Finnish, where the widespread habit of sauna bathing
exposes male genitals to heat. Yet, the rates of testicular cancer
occurrence is lower in Finland than in the other Nordic countries (1).
With regard to semen cryopreservation, we agree with the comments of
A. Lass (2).
Vasectomy is not associated with testicular cancer risk (3), and is
therefore not a potential confounder in the analysis of paternity and
testicular cancer. The interview-based case-control study certainly has
potential sources of error, notably due to differential participation
(selection bias) and differential recall (information bias). The comment
of R. Oakes et al does not convince us that our result is likely to be the
consequence of such biases (see also Discussion). We are currently
analysing data on paternity and testicular cancer from a large follow-up
study based on data from population registers, hereby eliminating the
possible influences of both selection bias and information bias.
Sperm count is not the perfect, "objective" measure of fertility. The
association between measured characteristics in a semen sample and the
fertility potential of the man is not straightforward, and such
characteristics are subject to intra-personal variation from one sample to
the next. We are currently investigating the associations between specific
semen characteristics and subsequent risk of testicular cancer, and we
anticipate that this may shed further light on the observed association
between subfertility and testicular cancer.
Yours sincerely
Henrik Moller and Niels E. Skakkebaek
(1) Møller H. Trends in sex-ratio, testicular cancer and male
reproductive hazards: are they connected? Acta Pathologica, Microbiologica
et Immunologica Scandinavica 1998; 106: 232-9
(2) Petersen PM, Skakkebaek NE, Giwercman A. Gonadal function in men
with testicular cancer. Acta Pathologica, Microbiologica et Immunologica
Scandinavica 1998; 106: 24-36
(3) Møller H, Knudsen LB, Lynge E. Risk of testicular cancer after
vasectomy: cohort study of over 73,000 men. British Medical Journal 1994;
309: 295-9
Competing interests: No competing interests