FERTILITÀ E BENESSERE: TRA LINEE GUIDA E REAL LIFE Importanza dei fattori di rischio Eugenio Ventimiglia, M.D. Division of Experimental Oncology/Unit of Urology URI; IRCCS Ospedale San Raffaele Università Vita-Salute San Raffaele, Milan, Italy

I fattori di rischio nell’epidemiologia moderna Fattore di rischio “Un fattore associato a un determinato evento” Causa “Un evento, condizione o caratteristica senza cui la malattia non si verificherebbe” Kenneth J. Rothman - Modern Epidemiology

Infertilità di coppia – cause Olesen et al, Fertil Steril. 2017 Jan;107(1):74-82.e7.

40% Punab et al, Hum Reprod. 2017 Jan;32(1):18-31. 

“Femminizzazione del maschio”, Presa Diretta, Rai 3 2017

Male reproductive health: what do we know Paternal age Delayed fatherhood Significant downward trend in male pubertal timing during the last decades Secular trend of declining testosterone Lifestyle changes Environmental changes What’s being changing during the last decades in the field of male reproductive endocrinology? Salonia A, et al. Int J Androl, 35:125-32, 2012 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728 Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007

Paternal age Paternal age Delayed fatherhood Significant downward trend in male pubertal timing during the last decades Secular trend of declining testosterone Lifestyle changes Environmental changes What’s being changing during the last decades in the field of male reproductive endocrinology? Salonia A, et al. Int J Androl, 35:125-32, 2012 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728 Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007

Male reproductive health: what do we know Age acts prompts a stepwise decline in both general and reproductive health The 34- to 40-year age range appears indicative of the beginning of age-related effects on seminal parameters The likelihood of intercourse resulting in pregnancy declines continuously in men >34 years, regardless of the woman's age What’s being changing during the last decades in the field of male reproductive endocrinology? Stone et al, Fertil Steril 2013;100:952–8. Ford et al, Hum Reprod 2000;15:1703–8.41.

Male reproductive health: what do we know Paternal age Delayed fatherhood Significant downward trend in male pubertal timing during the last decades Secular trend of declining testosterone Lifestyle changes Environmental changes What’s being changing during the last decades in the field of male reproductive endocrinology? Salonia A, et al. Int J Androl, 35:125-32, 2012 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728 Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007

METHODS A cohort of 1283 Caucasian-European men with MFI who consecutively visited one outpatient clinic over a period of only 7 yr was assessed with a self-reported medical history, including age at presentation, educational status, and the number of months of infertility. Data about the age of each patient’s partner were also collected. Patients’ comorbidities were scored with the Charlson Comorbidity Index (CCI). Analysis of variance (ANOVA) tested the paternal age at presentation throughout the 7-yr time frame. Multivariate linear regression analysis tested the association between predictors (partners’ age, length of infertility at first presentation, CCI, and educational status) and patient’s age at presentation. Salonia A, et al. Int J Androl, 35:125-32, 2012

Salonia A, et al. Int J Androl, 35:125-32, 2012

Male reproductive health: what do we know Delayed fatherhood Significant downward trend in male pubertal timing during the last decades Secular trend of declining testosterone Lifestyle changes Environmental changes Salonia A, et al. Int J Androl, 35:125-32, 2012 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728 Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007

Declining age at PHV  secular trend towards earlier sexual maturation of Danish children born between 1930 and 1969 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728.

This decline was associated with the coincident increase in BMI Estimated mean age at onset of puberty has declined significantly during the last 15 years This decline was associated with the coincident increase in BMI Sørensen et al, Journal of Clinical Endocrinology and Metabolism 2010 95 263–270.

Male reproductive health: what do we know Delayed fatherhood Significant downward trend in male pubertal timing during the last decades Secular trend of declining testosterone Lifestyle changes Environmental changes Salonia A, et al. Int J Androl, 35:125-32, 2012 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728 Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007

Secular trend of declining testosterone 1.0%/year tT levels decline over the period 1987–2004 was observed in the US Age-independent secular change in tT levels in Denmark during 1982-2001, partially explained by the secular increase in BMI. Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007

Male reproductive health: what do we know Delayed fatherhood Significant downward trend in male pubertal timing during the last decades Secular trend of declining testosterone Lifestyle changes Environmental changes Salonia A, et al. Int J Androl, 35:125-32, 2012 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728 Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007

Lifestyle changes EMAS study (35% to 39% in the US has MetS!) 25.9% With metabolic syndrome W/o metabolic syndrome 25.9% 74.1% (35% to 39% in the US has MetS!) NutrMetabCardiovasc Dis 2005; 15 :250–4 Corona G, et al., J Sex Med , 7:1362-80, 2010

Male reproductive health: what do we know Delayed fatherhood Significant downward trend in male pubertal timing during the last decades Secular trend of declining testosterone Lifestyle changes Environmental changes Salonia A, et al. Int J Androl, 35:125-32, 2012 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728 Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007

Environmental changes Exposure to air pollutants (PM10, PM2.5, CO, NOx) was also negatively associated with the level of testosterone  The evidence supporting an effect of air pollution on DNA fragmentation is weak but suggestive, on sperm motility is limited and probably inexistent, on lower sperm count is inconclusive, and on sperm morphology is very suggestive Lafuente et al, Fertil Steril. 2016 Sep 15;106(4):880-96 Radwan et al, Ann Hum Biol. 2016;43(1):50-6

Male reproductive health: risk factors General lack of consensus Worrying temporal trends Open road for treatment and lifestyle changes Salonia A, et al. Int J Androl, 35:125-32, 2012 Aksglaede et al, PLoS One. 2008 Jul 16;3(7):e2728 Travison et al, J Clin Endocrinol Metab 92: 196–202, 2007 Andersson et al, J Clin Endocrinol Metab 92: 4696–4705, 2007