Hypogonadism: cardiometabolism and gonadal function in men

Abstract

Hypogonadism is a relatively rare condition in men, which increases in frequency as men age, but also as they become less active and gain weight. In the past 20 years, developing knowledge on the relationship between hypogonadism and cardiovascular and cerebrovascular health and on aspects of metabolic health has become clearer. The relationship between hypogonadism and specific endocrine abnormalities of spermatogenesis is much longer established. Long- and short-term testosterone replacement therapies have well-recognised effects on cardiovascular and cerebrovascular health and on aspects of metabolic health. This leads to a sense of safety when it comes to considering these options as ways of managing the recognised symptoms of hypogonadism and the hidden adverse findings. That confidence has yet to be proven by long-term randomised controlled studies. The use of exogenous gonadotrophins to raise endogenous testosterone levels is a cost-efficient method of achieving spermatogenesis but is not suitable for long-term testosterone maintenance therapy.

Keywords

Gonadotrophins / testosterone / cardiovascular health / hypogonadism / hypogonadotropic hypogonadism

References

[1] Saad F,Doros G,Haider A.Long-term treatment with testosterone undecanoate injections in men with hypogonadism alleviates erectile dysfunction and reduces risk of major adverse cardiovascular events, prostate cancer, and mortality.Aging Male2020;23:81-92

[2] Cappelleri JC,Smith MD,Osterloh IH.Diagnostic evaluation of the erectile function domain of the international index of erectile function.Urology1999;54:346-51

[3] Yafi FA,Albersen M.Erectile dysfunction.Nat Rev Dis Primers2016;2:16003 PMCID:PMC5027992

[4] Traish AM,Haider KS,Saad F.Long-term testosterone therapy improves cardiometabolic function and reduces risk of cardiovascular disease in men with hypogonadism: a real-life observational registry study setting comparing treated and untreated (control) groups.J Cardiovasc Pharmacol Ther2017;22:414-33 PMCID:PMC5555449

[5] Yeap BB. Androgens and cardiovascular disease in men. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279151/ [Last accessed on 18 Mar 2024]

[6] Elagizi A,Lavie CJ.Testosterone and cardiovascular health.Mayo Clin Proc2018;93:83-100.

[7] Mann A,König CS.Testosterone replacement therapy: association with mortality in high-risk patient subgroups.Andrology2023;Online ahead of print:

[8] Mårin P,Gustafsson C.Androgen treatment of abdominally obese men.Obes Res1993;1:245-51.

[9] Jarvis TR,Kaplan SA.Testosterone and benign prostatic hyperplasia.Asian J Androl2015;17:212-6. PMCID:PMC4650459

[10] Thirumalai A.Epidemiology of male hypogonadism.Endocrinol Metab Clin North Am2022;51:1-27. PMCID:PMC9136962

[11] Mulligan T,Zuraw QC,McWhirter C.Prevalence of hypogonadism in males aged at least 45 years: the HIM study.Int J Clin Pract2006;60:762-9

[12] Trussell JC,Kiltz RJ.Defining hypogonadism in male partners of couples with unexplained infertility.Can J Urol2020;27:10306-11.

[13] Berg WT.Hypogonadism and metabolic syndrome: review and update.Curr Opin Endocrinol Diabetes Obes2020;27:404-10

[14] Lin L,Xiao K,Zhou L.Genetically elevated bioavailable testosterone level was associated with the occurrence of benign prostatic hyperplasia.J Endocrinol Invest2023;46:2095-102

[15] Hull MG,Kelly NJ.Population study of causes, treatment, and outcome of infertility.Br Med J1985;291:1693-7. PMCID:PMC1418755

[16] Snick HK,Evers JL.The spontaneous pregnancy prognosis in untreated subfertile couples: the Walcheren primary care study.Hum Reprod1997;12:1582-8.

[17] Morris G,Theodorou E.Effect of paternal age on outcomes in assisted reproductive technology cycles: systematic review and meta-analysis.2020;1:16-34.

[18] Buchanan JF.Drug-induced infertility.Drug Intell Clin Pharm1984;18:122-32.

[19] Cocuzza M,Pagani R.The epidemiology and etiology of azoospermia.Clinics2013;68 Suppl 1:15-26 PMCID:PMC3583160

[20] Bieth E,Mieusset R.Genetics of the congenital absence of the vas deferens.Hum Genet2021;140:59-76 PMCID:PMC7864840

[21] Leaver RB.Male infertility: an overview of causes and treatment options.Br J Nurs2016;25:S35-40

[22] Dhindsa S,Jenkins T.High prevalence of subnormal testosterone in obese adolescent males: reversal with bariatric surgery.Eur J Endocrinol2022;186:319-27

[23] Minhas S,Boeri L.EAU Working Group on Male Sexual and Reproductive HealthEuropean association of urology guidelines on male sexual and reproductive health: 2021 update on male infertility.Eur Urol2021;80:603-20

[24] Esteves SC,Roque M.Outcome of varicocele repair in men with nonobstructive azoospermia: systematic review and meta-analysis.Asian J Androl2016;18:246-53 PMCID:PMC4770494

[25] Kirby EW,Rajanahally S,Coward RM.Undergoing varicocele repair before assisted reproduction improves pregnancy rate and live birth rate in azoospermic and oligospermic men with a varicocele: a systematic review and meta-analysis.Fertil Steril2016;106:1338-43

[26] Morris GC,Cahill DJ.Induction of spermatogenesis in men with hypogonadotropic hypogonadism.J Assist Reprod Genet2021;38:803-7 PMCID:PMC8079531

[27] Morris G.Fertility treatments for men with hypogonadotropic hypogonadism.J Cancer Biol2021;2:44-50.

[28] Sohan K,Stegmann M.Local reaction to S.C. injections of a recombinant gonadotrophin preparation possibly related to the osmolality of the reconstituted solution.Hum Reprod1999;14:1921

[29] Holt-Kentwell A.Induction of spermatogenesis in men with hypogonadotrophic hypogonadism - is treatment available in UK fertility clinics?.BJOG An International Journal of Obstetrics and Gynaecology2019;126:209

[30] Wittert GA,Grossmann M.274-OR: effect of testosterone treatment on type 2 diabetes incidence in high-risk men enrolled in a lifestyle program: a two-year randomized placebo-controlled trial.Diabetes2020;69:274-OR.