IJE Advance Access originally published online on July 1, 2004
International Journal of Epidemiology 2005 34(2):483-485; doi:10.1093/ije/dyh248
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Published by Oxford University Press on behalf of the International Epidemiological Association
Letters to the Editor |
A hypothesis on the sexual behaviour of men who are destined to develop prostate cancer
The Galton Laboratory, University College London, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK
There is general agreement that prostatic cancer (PC) has genetic and environmental determinants. However, the putative susceptibility genes have so far largely evaded identification1 and the environmental factors are also proving difficult to unravel. But for many years, attention has focussed on the possibility of endocrine (particularly androgenic) determinants of one sort or another. The difficulty is that though it is accepted that androgens stimulate PC in vitro and in vivo, direct data on circulating concentrations of steroids are equivocal.2–4 However, men who are destined to develop the cancer reportedly have a statistically significant excess of sons,5 and there are good grounds for supposing that that indicates high androgen levels at the time of conception.6,7 Frequently these conceptions occurred many years before disease onset, so such data suggest that the disease may be associated with prolonged exposure to high androgen levels. Indeed, this exposure may (as will later be mentioned) even precede the patient's birth.
To illuminate the possibility of endocrine involvement, epidemiologists have studied the sexual behaviour of PC patients and controls. This work was summarized in the authoritative review of Bosland.8 The problem to be discussed was specified in the words of this author:
"In comparison with controls, PC patients (1) have an earlier onset of sexual activity in any sense; (2) show a higher sexual drive especially at a young age and (3) have notwithstanding their high sexual drive, a lower frequency of intercourse especially at older ages or have a higher frequency until about 50 years of age, and a lower frequency thereafter."
This curious association of the disease with low coital rates has been confirmed by two recent well-publicized papers.9,10 In this note I wish to offer (what I take to be) a new hypothesis on this matter.
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The possibilities of confounding |
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 Top The possibilities of confounding Sexual abstinence and subsequent...CommentTestingReferences |
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The potential for confounding occurs between two variables when they are both independently associated with a third variable. Thus there is a very general expectation of confounding when epidemiologists test endocrine diseases against behavioural risk factors.11 This is because much human behaviour is dependent on (high or low) concentrations of the same hormones that cause the diseases. I have cited references to substantiate claims that high testosterone levels in men are associated with aggression, criminal violence, impatience, irritability, hostility, lack of frustration tolerance, impetuosity, dissatisfaction with marriage, high number of sexual partners, early age at first intercourse, and especially with sensation-seeking (which itself correlates with smoking, drug use, use of prostitutes, and possibly vasectomy).12 In that note I suggested that these male personality traits would in some cases cause inharmonious domestic arrangements and so (as contrasted with controls) a greater fall in coital rates over time. Thus I suggested an explanation for the significantly high variance of coital rate of PC cases versus controls. In this explanation, low coital frequency is construed as a marker for high sexual drive via externally imposed inhibitions on sexual expression (e.g. by wives being antagonized by other behavioural aspects of husbands with high testosterone levels). In the rest of this note I wish to supplement this explanation with the suggestion that such inhibitions (externally or internally imposed) may also directly cause the cancer. This suspicion has been expressed before,13 but not for the reason to be offered.
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Sexual abstinence and subsequent risk of PC |
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TopThe possibilities of confoundingSexual abstinence and subsequent...CommentTestingReferences |
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It is established that sperm counts decline following ejaculation, and then rise for some days as a concomitant of abstinence.14 The same is reportedly true of prostate specific antigen.15,16 It has recently been reported (apparently for the first time) that the same is true too of circulating testosterone concentrations.17 If this were so, then it is reasonable to wonder whether PC is partially caused (rather than simply marked) by constraints on sexual release (imposed either externally or internally). Internal constraints might be imposed by religious or other sanctions against various forms of sexual outlet. The reason for considering this seriously is that it might explain the curious cohort effect in prostate cancer reported by Barrett.18 This author noted that men born in England & Wales around 1885 had higher mortality from PC than men in neighbouring cohorts in nearly every age group from 40–45 upwards. He found that it was the age of the man that was important, and the cohort into which he was born, rather than the date on which he died. Holman et al.19 reached a similar conclusion on Australian data (as well as confirming Barrett's conclusion on British data). Barrett18 speculated that the cause might have been the use (by men of this cohort) of non-appliance methods of contraception (chiefly coitus interruptus). In contrast, Holman et al.19 were inclined to attribute the cohort effect to lowered sexual activity during the Great Depression. They cited other authors suggesting sexual frustration as a predisposing factor. I agree and further propose (as will now be elaborated) that an upbringing in the stifling sexual ethos of late Victorian Britain may have contributed to such frustration.
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Comment |
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It may be difficult for people born in the last 50 years to imagine sexual life before the invention of contraceptive appliances. Artifacts (which now seem amusing or quaint) were part of the fabric of society. Wooden piano legs were fashioned into folds (or covered with fabric) to avoid disturbing the sensitivities of the public: serious medical text-books documented the dangers of masturbation. The fear of prosecution (or ostracism) prevented novelists from portraying more than the merest hint of sexual events: and the existing personal writings of Dickens, Gladstone, and the Pre-Raphaelites all reveal contorted attitudes towards women and girls. Late Victorian Britain publicly engaged in vigorous economic expansion: but this was accompanied (perhaps even fuelled?) by private sexual repression and inhibition—all chillingly presided over by the still-grieving Queen. Long (non-consummated) engagements were commonplace. Before World War II divorce was rare in Britain, so many highly sexed men were locked in marriage with unrelenting wives. In short, one does not have to be an enthusiast for DH Lawrence to suspect that—at least in some sections of society—the overt sexual expression of those brought up in late Victorian Britain was at a lower ebb than that of people reared previously or subsequently.
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Testing |
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TopThe possibilities of confoundingSexual abstinence and subsequent...CommentTestingReferences |
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- The study on the time relationships between ejaculation, abstinence, and testosterone levels reported by Jiang et al.17 should be replicated.
- The excess of sons among the offspring of PC patients needs to be confirmed. So it would be useful if further data were accumulated on the offspring sex ratio of these men. (Such data presumably lie untapped in cancer registries.)
- It has been suggested that PC may be a consequence of intrauterine exposure to high maternal levels of testosterone.20 If this were so, then cases would ex hypothesi have an excess of brothers among their unaffected sibs. Such a form of argument has been used to substantiate the claim that polydactyly is at least partially caused by high intrauterine levels of testosterone.21 So it would be useful to know the sex ratio of the unaffected sibs of cases of PC.
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References |
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1 Schaid DJ. The complex genetic epidemiology of prostate cancer. Hum Mol Genet 2004;13(Spec.No.1):R103–21.
2 Andersson SO, Adami HO, Bergstrom R, Wide L. Serum pituitary and sex steroid hormone levels in the etiology of prostate cancer—a population-based case-control study. Br J Cancer 1993; 68:97–102.[Web of Science][Medline]
3 Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ. Prospective study of sex hormone levels and risk of prostate cancer. J Nat Cancer Inst 1996; 88:1118–26.
4 Stattin P, Lumme S, Tenkanen L et al. High levels of circulating testosterone are not associated with increased prostate cancer risk. Int J Cancer 2004; 108:418–24.[CrossRef][Web of Science][Medline]
5 James WH. The hypothesized hormonal control of human sex ratio at birth – an update. J Theor Biol 1990; 143:555–64.[Web of Science][Medline]
6 James WH. Evidence that mammalian sex ratios are partially controlled by parental hormone levels at the time of conception. J Theor Biol 1996; 180:271–86.[CrossRef][Web of Science][Medline]
7 James WH. Further evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. Hum Reprod 2004; 19:1250–6.
8 Bosland MC. The etiopathogenesis of prostatic cancer with special reference to environmental factors. Adv Cancer Res 1988; 51:1–106.[Web of Science][Medline]
9 Leitzmann MF, Platz EA, Stampfer MJ, Willett WC, Giovannucci E. Ejaculate frequency and the subsequent risk of prostate cancer. J Am Med Assoc 2004; 291:1578–86.
10 Giles GG, Severi G, English DR et al. Sexual factors and prostate cancer. B J U Internat 2003; 92:211–16
11 James WH. Hypothesis: gonadal hormones act as confounders in epidemiological studies of the associations between some behavioural risk factors and some pathological conditions. J Theor Biol 2001; 209:97–102.[CrossRef][Web of Science][Medline]
12 James WH. Prostatic cancer, coital rates, vasectomy and testosterone. J Biosoc Sci 1994; 26:269–72.[Web of Science][Medline]
13 Rotkin ID. Studies in the epidemiology of prostatic cancer: expanded sampling. Cancer Treatment Rep 1977; 61:173–80.[Web of Science][Medline]
14 Sauer MV, Zefer KB, Buster JB, Sokol RZ. Effect of abstinence on sperm motility in normal men. Am J Obstet Gynecol 1988; 158:604–07[Web of Science][Medline]
15 Guay AT, Perez JB, Fitaihi WA, Vereb M. Testosterone treatment in hypogonadal men : prostate specific antigen level and risk of prostate cancer. Endocrine Practice 2000; 6:132–38.
16 Stenner J, Holthaus K, Mackenzie SH, Crawford ED. The effect of ejaculation on prostate-specific antigen in a prostate cancer-screening population. Urology 1998; 51:455–59.[CrossRef][Web of Science][Medline]
17 Jiang M, Xin J, Zou Q, Shen JW. A research on the relationship between ejaculation and serum testosterone in men. J Zheijiang Univ Sci 2003; 4:236–40.
18 Barrett JC. Cohort mortality and prostate cancer. J Biosoc Sci 1980; 12:341–44.[Web of Science][Medline]
19 Holman CDJ, James IR, Segal MR, Armstrong BK. Recent trends in mortality from prostate cancer in male populations of Australia and England & Wales. Br J Cancer 1981; 44:340–48.[Web of Science][Medline]
20 Ross RK, Henderson BE. Do diet and androgens alter prostate cancer risk via a common etiological pathway? J Nat Cancer Inst 1994; 86:252–54.
21 James WH. Hypothesis : one cause of polydactyly. J Theor Biol 1998; 192:1–2.[CrossRef][Web of Science][Medline]
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