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Association of aging and obesity with decreased 17-hydroxyprogesterone, a serum biomarker of intratesticular testosterone

Abstract

Obesity’s negative association with serum testosterone can be explained by either decreasing luteinizing hormone (LH) production from the pituitary gland and/or directly impacting intratesticular testosterone production. We hypothesize that obesity will negatively impact intratesticular testosterone levels when compared to those of non-obese men. We performed a cross-sectional analysis of men with symptoms of testosterone deficiency and male infertility between July 2018 and April 2020 to evaluate the association between body mass index (BMI) and age with intratesticular testosterone (using serum 17-hydroxyprogesterone (17-OHP) as a biomarker), and between BMI with LH. Univariable and multiple linear regression analysis were performed using confounding variables to predict 17-OHP and testosterone. A total of 340 men were selected. Median age was 38 [33–44] years, BMI 27.8 [25.4–31.1] kg/m2, serum testosterone 363 [256.3–469.6] ng/dl, 17-OHP 60.5 [39.3–85.8] ng/dl, and LH 4.2 [2.8–5.7] mIU/ml. Older and obese men had lower testosterone compared to younger and non-obese men. Interestingly, increasing age and higher BMI were associated with lower 17-OHP (p < 0.001). Contrarily, age and BMI were not associated with LH levels (p = 0.478). In conclusion, obesity and aging negatively affected 17-OHP independent of LH, suggesting a possible direct effect on testicular function, rather than a secondary effect from a decline in pituitary signaling.

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Fig. 1: Scatter graph showing the correlation of 17-OHP with age (a), BMI (b), and LH (c).
Fig. 2: Scatter graph showing the correlation of LH (a) and Testosterone (b) with BMI.

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References

  1. The Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/products/databriefs/db360.htm. Accessed 26 Apr 2020.

  2. Allen NE, Appleby PN, Davey GK, Key TJ. Lifestyle and nutritional determinants of bioavailable androgens and related hormones in British men. Cancer Causes Control. 2002;13:353–63.

    Article  Google Scholar 

  3. Lokeshwar SD, Patel P, Fantus RJ, Halpern J, Chang C, Kargi AY, et al. Decline in serum testosterone levels among adolescent and young adult men in the USA. Eur Urol Focus. 2020. https://doi.org/10.1016/j.euf.2020.02.006.

  4. Jensen TK, Andersson AM, Jørgensen N, Andersen AG, Carlsen E, Petersen JH, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril. 2004;82:863–70.

    Article  CAS  Google Scholar 

  5. Svartberg J, von Mühlen D, Sundsfjord J, Jorde R. Waist circumference and testosterone levels in community dwelling men. The Tromsø Study. Eur J Epidemiol. 2004;19:657–63.

    Article  CAS  Google Scholar 

  6. Glass AR, Swerdloff RS, Bray GA, Dahms WT, Atkinson RL. Low serum testosterone and sex-hormone-binding-globulin in massively obese men. J Clin Endocrinol Metab. 1977;45:1211–9.

    Article  CAS  Google Scholar 

  7. Zumoff B, Strain GW, Miller LK, Rosner W, Senie R, Seres DS, et al. Plasma free and non sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity. J Clin Endocrinol Metab. 1990;71:929–31.

    Article  CAS  Google Scholar 

  8. Pasquali R, Casimirri F, Cantobelli S, Melchionda N, Morselli Labate AM, Fabbri R, et al. Effect of obesity and body fat distribution on sex hormones and insulin in men. Metabolism. 1991;40:101–4.

    Article  CAS  Google Scholar 

  9. Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006;154:899–906.

    Article  CAS  Google Scholar 

  10. Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes. J Sex Med. 2013;10:1612–27.

    Article  CAS  Google Scholar 

  11. Lima TFN, Patel P, Blachman-Braun R, Madhusoodanan V, Ramasamy R. Serum 17-hydroxyprogesterone is a potential biomarker for evaluating intratesticular testosterone. J Urol. 2020. 101097JU0000000000001016.

  12. Patel A, Patel P, Bitran J, Ramasamy R. Can serum 17-hydroxyprogesterone and insulin-like factor 3 be used as a marker for evaluation of intratesticular testosterone? Transl Androl Urol. 2019;8:S58–63.

    Article  Google Scholar 

  13. Amory JK, Coviello AD, Page ST, Anawalt BD, Matsumoto AM, Bremner WJ. Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in gonadotropin-suppressed normal men receiving various dosages of human chorionic gonadotropin. Fertil Steril. 2008;89:380–6.

    Article  CAS  Google Scholar 

  14. Chen H, Ge RS, Zirkin BR. Leydig cells: from stem cells to aging. Mol Cell Endocrinol. 2009;306:9–16.

    Article  CAS  Google Scholar 

  15. The Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/adult/defining.html. Accessed 26 Apr 2020.

  16. Kort HI. Impact of body mass index values on sperm quantity and quality. J Androl. 2006;27:450–2.

    Article  Google Scholar 

  17. Khodamoradi K, Parmar M, Khosravizadeh Z, Kuchakulla M, Manoharan M, Arora H. The role of leptin and obesity on male infertility. Curr Opin Urol. 2020;30:334–9.

    Article  Google Scholar 

  18. Katib A. Mechanisms linking obesity with male infertility. Cent European J Urol. 2015;68. https://doi.org/10.5173/ceju.2015.01.435.

  19. Zirkin BR, Santulli R, Awoniyi CA, Ewing LL. Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology. 1989;124:3043.

    Article  CAS  Google Scholar 

  20. Jarow JP, Kirkland J, Koritnik DR, Cefalu WT. Effect of obesity and fertility status on sex steroid levels in men. Urology. 1993;42:171–4.

    Article  CAS  Google Scholar 

  21. Tenover J. Declining testicular function in aging men. Int J Impot Res. 2003;15:S3–8.

    Article  CAS  Google Scholar 

  22. Sallmén M, Sandler DP, Hoppin JA, Blair A, Baird DD. Reduced fertility among overweight and obese men. Epidemiology. 2006;17:520–3. https://doi.org/10.1097/01.ede.0000229953.76862.e5.

    Article  PubMed  Google Scholar 

  23. Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999;84:3673–80.

    CAS  PubMed  Google Scholar 

  24. Fui MN, Dupuis P, Grossmann M. Lowered testosterone in male obesity: mechanisms, morbidity and management. Asian J Androl. 2014;16:223–31.

    Article  CAS  Google Scholar 

  25. Paduch DA, Brannigan RE, Fuchs EF, Kim ED, Marmar JL, Sandlow JI. The laboratory diagnosis of testosterone deficiency. Urology. 2014;83:980.

    Article  Google Scholar 

  26. Blanchette S, Marceau P, Biron S, Brochu G, Tchernof A. Circulating progesterone and obesity in men. Horm Metab Res. 2006;38:330–5.

    Article  CAS  Google Scholar 

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Lima, T.F.N., Frech, F.S., Blachman-Braun, R. et al. Association of aging and obesity with decreased 17-hydroxyprogesterone, a serum biomarker of intratesticular testosterone. Int J Impot Res 34, 44–49 (2022). https://doi.org/10.1038/s41443-020-00358-8

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