A new study in Sweden suggests that late puberty among boys protects against developing prostate cancer later in life. According to the researchers, the association paves the way for understanding the underlying biological mechanisms.
According to a large registry study in Sweden, the results of which have been published in Cancers, the risk of developing prostate cancer is linked to pubertal timing: the later puberty starts, the less risk boys seem to have of developing prostate cancer 30–40 years later. The first author, Jimmy Célind, is a paediatrician at the Department of Paediatrics, Institute of Clinical Studies, Sahlgrenska Academy, University of Gothenburg, Sweden.
“The study shows that late pubertal timing among boys is a protective factor for prostate cancer – especially the clinically important high-risk or metastatic types. This finding could provide new opportunities to reveal the underlying biological mechanisms,” explains Jimmy Célind.
The results support a longstanding hypothesis that men’s risk of developing prostate cancer is strongly associated with the number of years of exposure to adult levels of sex hormones – a period determined by the timing of the pubertal growth spurt in boys. This is a milestone, since researchers have been trying for years to confirm the hypothesis based on men’s self-reported pubertal timing – but these statements were unreliable and the results have therefore been inconclusive.
Research groups around the world have therefore strived to discover a new and more objective marker for pubertal timing among boys that is independent of men’s own memory. Jimmy Célind and colleagues have managed to discover this by figuring out how old boys were at the pubertal growth spurt, which objectively assesses pubertal timing. This final spurt is closely linked to pubertal markers such as voice break and genital and testicular growth.
“We used the height development among the men in the study to determine when the growth velocity peaked, indicating pubertal timing,” says Jimmy Célind.
1.4 million person-years of follow-up
Jimmy Célind and colleagues calculated how old 31,971 men were when they had their maximum pubertal growth spurt based on height measurements recorded continually by the nurses at their respective schools in Sweden while they grew up. The researchers then linked these with the men who developed prostate cancer during their lifetime according to registries for diseases and causes of death. The follow-up was initiated at 20 years of age, and during 1.4 million person-years of follow-up, the researchers found 1759 cases of prostate cancer, of which 449 were especially aggressive.
This enabled the researchers to determine both the timing of the pubertal growth spurt and when prostate cancer developed. They also assessed the risk of developing prostate cancer. Late puberty was associated with a lower risk, or a protective factor for prostate cancer, especially for the most aggressive and metastatic types.
Jimmy Célind says that one challenge in investigating and treating prostate cancer is that the diagnoses range widely.
Although it may be clinically relevant to treat men based on many prostate-specific antigen (PSA) values, ascertaining whether prostate cancer requires treatment is difficult. Treatment can cause significant problems, such as incontinence or impotence. The results of this study could provide new knowledge that may lead to better diagnosis and treatment,” explains Jimmy Célind.
The identification of early life-risk and protective factors for prostate cancer provides opportunities to reveal the underlying biological mechanisms for its origins. Future studies should clarify whether the duration of exposure to adult sex hormone levels in the body actually influences the risk of cancer or whether there is another cause. The current studies are insufficient to document that the association is causal.
Another explanation for the results, according to Jimmy Célind, may be that the men with late pubertal timing are biologically equipped with variations in their testosterone signalling systems that affect both the onset of puberty and the risk of prostate cancer.
“Many factors can come into play other than the duration of major hormonal influences. Some studies suggest that the total amount of testosterone is not crucial but the free amount circulating around the body is,” says Jimmy Célind.
As researchers better understand the origins of prostate cancer, they may be able to determine whether specific types of cells can be used early in men’s lives as a marker for whether they will develop prostate cancer later in life.
Good markers for the start of puberty
This is not the first time researchers have tried to confirm or disprove the hypothesis that pubertal timing affects the risk of prostate cancer. However, the evidence so far has been inconclusive, possibly because previous studies have been based on men’s self-reports of when they remembered reaching puberty – which can be uncertain since men have to try to remember events several decades ago. Since men’s puberty cannot be defined by an equivalent landmark event such as menstruation among women, this does not as clearly imprint memory.
“The female counterpart to prostate cancer is breast cancer, which is known to be associated with the duration of how long women are affected by the major influence of female sex hormones and thus also the onset of puberty. And since this is directly linked to the first menstruation, which women can often clearly remember, the association is much easier to study among women,” explains Jimmy Célind, who concludes:
“Men’s pubertal timing lacks distinct markers that are easily available retrospectively and are sufficiently reliable. The association between objectively assessed pubertal timing and the risk of prostate cancer has therefore not been studied as thoroughly. Our study suggests that the timing of the end of the growth spurt in men is an excellent marker.”