Time-course of biological effects of testosterone replacement therapy
Wheel 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.1 The 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 replacement 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:

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
Decreases in low-density lipoprotein (LDL) cholesterol may be slower, occurring after 3–12 months, with a maximum reached after 24 months
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 replacement therapy.

What is known
The goal of testosterone replacement therapy (TRT) 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 TRT 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 TRT. 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 TRT appear at different rates (Figure). Although the full benefits of TRT 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 TRT 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 TRT and in counselling the patient on when an effect can be expected and when its maximum has been reached.

1. 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.
2. 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.
3. Buvat J, Maggi M, Gooren L, et al. Endocrine aspects of male sexual dysfunctions. J Sex Med 2010;7(4 Pt 2):1627-1656.

This Research News article reviews an open-access article available in full from the European Journal of Endocrinology at: [url]http://eje-online.org/content/165/5/675.long[/url]. 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.