Table Info

Table 2.

Baseline, study end AMSS values and ∆AMSS broken down into the somatic, psychological, and sexual subscales

AMSS startified by subscales (somatic, psychological and sexual)	P	TU
Somatic subscale (Q1–5, Q9, and Q10) (7–35)
Median (IQR) baseline AMSS, n	17 (13, 21), n = 44	19 (15, 24), n = 38
Median (IQR) AMSS 30-week	15 (11, 20)	16.5 (14, 22)
Median (IQR) ∆AMSS	–1 (–3, 1)	–2 (–4, 1)
p (sign-rank)	0.0048	0.017
Psychological subscale (Q6–8, Q11, and Q13) (5–25)
Median (IQR) baseline AMSS, n	9 (6, 11), n = 45	10 (8, 14), n = 35
Median (IQR) AMSS 30-week	8 (6, 11)	9 (7, 12)
Median (IQR) ∆AMSS	–1 (–2, 1)	–1 (–3, 0)
p (sign-rank)	0.23	0.0039
Sexual subscale (Q12, Q14–17) (5–25)
Median (IQR) baseline AMSS, n	12 (10, 17), n = 45	15 (11, 18.5), n = 36
Median (IQR) AMSS 30-week	13 (9, 16)	13 (9, 16)
Median (IQR) ∆AMSS	0 (–2, 1)	–2 (–4.5, –0.5)
p (sign-rank)	0.66	0.0011

p < 0.05 is considered significant. ∆AMSS: changes in ageing male symptom scale; IQR: interquartile range; P: placebo; Q: questionnaire; TU: testosterone undecanoate

Declarations

Acknowledgments

We acknowledge the contributions of Drs Nigel Cole, Mithun Bhartia, Jesse Raju, David Kennedy, and Peter Wilkinson for their role in conceiving, designing, data collection, statistical analysis, and preparing the original publications from the BLAST Study dataset. We would also like to thank the Primary Care Practices and the patients who took part in the study.

Author contributions

PR: Conceptualization, Writing—original draft, Writing—review & editing. MZ and CSK: Writing—original draft. JM: Writing—original draft, Visualization. SR: Conceptualization, Writing—original draft, Writing—review & editing, Visualization. GH: Conceptualization, Writing—original draft. All authors have read and agreed to the published version of the manuscript.

Conflicts of interest

The author declares that there are no conflicts of interest.

Ethical approval

BLAST study obtained ethics approval from the Multi centre UK Research Ethics Committee (08/H1208/30).

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

The datasets that support the findings of this study are available from Professor Sudarshan Ramachandran upon reasonable request.

Funding

The practice expenses (BLAST RCT) of the research are supported by a grant from Bayer plc [BSP-SOP-040]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors did not receive any support from any organization for the submitted work. No funding was received to assist with the preparation of this manuscript.

Copyright

References

Hackett G, Kirby M, Rees RW, Jones TH, Muneer A, Livingston M, et al. The British Society for Sexual Medicine Guidelines on Male Adult Testosterone Deficiency, with Statements for Practice. World J Mens Health. 2023;41:508–37. [DOI] [PubMed] [PMC]

Antonio L, Wu FCW, Moors H, Matheï C, Huhtaniemi IT, Rastrelli G, et al.; EMAS Study Group. Erectile dysfunction predicts mortality in middle-aged and older men independent of their sex steroid status. Age Ageing. 2022;51:afac094. [DOI] [PubMed]

Kapoor D, Aldred H, Clark S, Channer KS, Jones TH. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity. Diabetes Care. 2007;30:911–7. [DOI] [PubMed]

Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S. EAU Guidelines on Male Hypogonadism [Internet]. European Association of Urology; c2019 [cited 2023 Dec 12]. Available from: https://d56bochluxqnz.cloudfront.net/media/EAU-Guidelines-on-Male-Hypogonadism-2019v2.pdf

Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Lessons From the Testosterone Trials. Endocr Rev. 2018;39:369–86. [DOI] [PubMed] [PMC]

Zitzmann M. Testosterone, mood, behaviour and quality of life. Andrology. 2020;8:1598–605. [DOI] [PubMed]

Lunenfeld B, Mskhalaya G, Kalinchenko S, Tishova Y. Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism in men – a suggested update. Aging Male. 2013;16:143–50. [DOI] [PubMed]

Heinemann LAJ, Saad F, Zimmermann T, Novak A, Myon E, Badia X, et al. The Aging Males’ Symptoms (AMS) scale: update and compilation of international versions. Health Qual Life Outcomes. 2003;1:15. [DOI] [PubMed] [PMC]

Akehi Y, Tanabe M, Yano H, Takashi Y, Kawanami D, Nomiyama T, et al. A simple questionnaire for the detection of testosterone deficiency in men with late-onset hypogonadism. Endocr J. 2022;69:1303–12. [DOI] [PubMed]

10.

Lunenfeld B, Mskhalaya G, Zitzmann M, Arver S, Kalinchenko S, Tishova Y, et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male. 2015;18:5–15. [DOI] [PubMed] [PMC]

11.

Morley JE, 3rd HMP, Kevorkian RT, Patrick P. Comparison of screening questionnaires for the diagnosis of hypogonadism. Maturitas. 2006;53:424–9. [DOI] [PubMed]

12.

Elliott J, Kelly SE, Millar AC, Peterson J, Chen L, Johnston A, et al. Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis. BMJ Open. 2017;7:e015284.. [DOI] [PubMed] [PMC]

13.

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. [DOI] [PubMed]

14.

Stern AF. The hospital anxiety and depression scale. Occup Med (Lond). 2014;64:393–4. [DOI] [PubMed]

15.

Behre HM, Tammela TLJ, Arver S, Tolrá JR, Bonifacio V, Lamche M, et al. A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up. Aging Male. 2012;15:198–207. [DOI] [PubMed]

16.

Lee C, Jiang J, Chen Y, Chu C, Hsu S, Chen C, et al. The “Aging Males’ Symptoms” (AMS) Scale assesses depression and anxiety. Aging Male. 2013;16:97–101. [DOI] [PubMed]

17.

Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale: An updated literature review. J Psychosom Res. 2002;52:69–77. [DOI] [PubMed]

18.

Borst SE, Yarrow JF, Fernandez C, Conover CF, Ye F, Meuleman JR, et al. Cognitive effects of testosterone and finasteride administration in older hypogonadal men. Clin Interv Aging. 2014;9:1327–33. [DOI] [PubMed] [PMC]

19.

Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry. 2003;160:105–11. [DOI] [PubMed]

20.

Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al.; Testosterone Trials Investigators. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016;374:611–24. [DOI] [PubMed] [PMC]

21.

Giltay EJ, Tishova YA, Mskhalaya GJ, Gooren LJG, Saad F, Kalinchenko SY. Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome. J Sex Med. 2010;7:2572–82. [DOI] [PubMed]

22.

Walther A, Breidenstein J, Miller R. Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2019;76:31–40. [DOI] [PubMed] [PMC]

23.

Hudson J, Cruickshank M, Quinton R, Aucott L, Wu F, Grossmann M, et al. Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis. Lancet Healthy Longev. 2023;4:e561–72. [DOI] [PubMed]

24.

Messerli FH, Bangalore S, Schmieder RE. Wilder’s principle: pre-treatment value determines post-treatment response. Eur Heart J. 2015;36:576–9. [DOI] [PubMed]

25.

Chantzaras A, Yfantopoulos J. Association between medication adherence and health-related quality of life of patients with diabetes. Hormones (Athens). 2022;21:691–705. [DOI] [PubMed] [PMC]

26.

Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, et al.; Blast Study Group. The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study). Int J Clin Pract. 2014;68:203–15. [DOI] [PubMed]

27.

Hackett G, Cole N, Saghir A, Jones P, Strange RC, Ramachandran S. Testosterone undecanoate improves sexual function in men with type 2 diabetes and severe hypogonadism: results from a 30-week randomized placebo-controlled study. BJU Int. 2016;118:804–13. [DOI] [PubMed]

28.

Hackett G, Cole N, Saghir A, Jones P, Strange RC, Ramachandran S. Testosterone replacement therapy: improved sexual desire and erectile function in men with type 2 diabetes following a 30-week randomized placebo-controlled study. Andrology. 2017;5:905–13. [DOI] [PubMed]

29.

Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536–59. [DOI] [PubMed]

30.

Ramachandran S, König CS, Hackett G, Livingston M, Strange RC. Managing clinical heterogeneity: An argument for benefit-based action limits. J Eng Sci Med Diagn Ther. 2018;1:034701. [DOI]

31.

Uchmanowicz B, Chudiak A, Mazur G. The influence of quality of life on the level of adherence to therapeutic recommendations among elderly hypertensive patients. Patient Prefer Adherence. 2018;12:2593–603. [DOI] [PubMed] [PMC]

32.

Gusmai Lde F, Novato Tde S, Nogueira Lde S. A influência da qualidade de vida na adesão ao tratamento do paciente diabético: revisão sistemática [The influence of quality of life in treatment adherence of diabetic patients: a systematic review]. Rev Esc Enferm USP. 2015;49:839–46. Portuguese. [DOI] [PubMed]

33.

Korenman SG, Grotts JF, Bell DS, Elashoff DA. Depression in Nonclassical Hypogonadism in Young Men. J Endocr Soc. 2018;2:1306–13. [DOI] [PubMed] [PMC]

34.

Indirli R, Lanzi V, Arosio M, Mantovani G, Ferrante E. The association of hypogonadism with depression and its treatments. Front Endocrinol (Lausanne). 2023;14:1198437. [DOI] [PubMed] [PMC]

35.

Zitzmann M, Nieschlag E. Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab. 2007;92:3844–53. [DOI] [PubMed]

36.

Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJG, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf). 2010;73:602–12. [DOI] [PubMed]