Time-course of biological effects of testosterone therapy

16 April 2012

Onset of effects of testosterone treatment and time span until maximum effects are achieved. Saad F, Aversa A, Isidori AM, et al. Eur J Endocrinol 2011;165(5):675-685.

This article reviewed the published literature of studies analyzing the effects of testosterone administration in hypogonadal men to estimate the onset or time-dependency effects of testosterone.1The analysis consisted of studies performed with testosterone (including testosterone esters and dihydrotestosterone preparations, independent of delivery method) where:

  • the use of an active treatment group was compared with a matched placebo or control group
  • a description of the time course of the effect of active treatment was included, and
  • randomization, adherence to protocol and single/double-blind study design was reported.

Only full articles published in peer-reviewed medical journals were included.

KEY POINTS

Time-course of effects of testosterone therapy in hypogonadal men (see Figure):1

  • Effects on libido, sexual desire, sexual thoughts and satisfaction with sexual life manifest after 3 weeks and plateau at 6 weeks
  • Changes in erections and ejaculations, sexual performance and satisfaction with erections usually achieved within 3–6 months
  • Effects on quality of life evident within 3–4 weeks and continue to develop for up to 18 months
  • Effects on depressive mood noted after 3–6 weeks but may reach a maximum only after 18–30 weeks
  • The time course for improvements in lipids varies:
    1. Decreases in total cholesterol and triglycerides appear as quickly as after 4 weeks, but more commonly after 3 months or longer; a maximum may be reached after 12 months
    2. Decreases in low-density lipoprotein (LDL) cholesterol may be slower, occurring after 3–12 months, with a maximum reached after 24 months
    3. Increases in high-density lipoprotein (HDL) cholesterol may occur after 3–12 months, with further improvement for 12–24 months
  • Effects on glycaemic control become evident after 3–12 months, although insulin sensitivity may improve within a few days
  • Changes in fat mass, lean body mass, and muscle strength occur within 12–16 weeks and stabilize at 6–12 months, with marginal further improvements possible over years
  • Effects on bone mineral density are detectable after 6 months and continue for at least 36 months
  • Effects on inflammatory factors and endothelial markers noted within 3–12 weeks
  • Stimulatory effects on erythropoiesis are dose-dependent and apparent at 3 months, peaking at 9−12 months
  • Prostate-specific antigen (PSA) and prostate volume marginally rise, plateauing at 12 months; further increases may be related to aging rather than testosterone therapy.

What is known

The goal of testosterone  therapy in hypogonadal men is to safely restore testosterone to normal physiological levels to alleviate symptoms associated with testosterone deficiency and to improve health, well-being and quality of life.2,3 The profound physical and/or mental changes in the patient undergoing testosterone therapy make the management of hypogonadism rewarding and satisfying for patient and physician alike.1 An understanding of when the effects of testosterone can and should be expected is useful to the attending physician and of interest to the patient. Furthermore, information on the time-course of the biological effects of testosterone is relevant for the design of clinical trials of testosterone therapy. However, while the spectrum of effects of testosterone is well documented, the same level of attention has not been given to the time course for the onset of treatment effects and the time span required for the achievement of full expression.

It is clear that the effects of testosterone therapy appear at different rates (Figure). Although the full benefits of testosterone therapy may not appear until after the first year of treatment, improvements in libido, erectile function, mood, depression and quality of life typically occur earlier. This is also true for changes in PSA and haematocrit. Finally, the studies selected for the present analysis provided testosterone treatment that delivered adequate doses and delivery of testosterone. The use of sub-optimal therapeutic regimens or the inappropriate use of testosterone therapy in eugonadal men or those with biochemical hypogonadism in the absence of clinical symptoms are likely to show different time courses of effects.

What this article adds

This comprehensive review provides a basis for a better understanding of the physiology of testosterone action, and is a resource informing the monitoring of the effects of testosterone therapy and in counselling the patient on when an effect can be expected and when its maximum has been reached.

visual display of when the effects of testosterone treatment can be expected to occur.

Click here for the Testosterone Effects Tool – a visual display of when the effects of testosterone treatment can be expected to occur.

References

  • Saad F, Aversa A, Isidori AM, et al. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol 2011;165(5):675-685. Return to content
  • Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95(6):2536- 2559. Return to content
  • Buvat J, Maggi M, Gooren L, et al. Endocrine aspects of male sexual dysfunctions. J Sex Med 2010;7(4 Pt 2):1627-1656. Return to content

This Research News article reviews an open-access article available in full from the European Journal of Endocrinology at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188848/pdf/EJE110221.pdf. The original article may be referred to for additional detail and supporting references for the statements summarised in this article, which are too numerous to cite in full.