There are few systematic studies of the relationship between blood testosterone concentrations and the symptoms of overt androgen deficiency. Because most testosterone preparations are relatively short-term, the rapid changes in blood testosterone concentrations they cause make it difficult to define any testosterone threshold. By contrast, subdermal testosterone implants provide stable blood testosterone concentrations over days to weeks, while gradually declining to baseline over 5-7 months. Hence, this provides an opportunity to define a blood testosterone threshold for androgen deficiency symptoms by observing androgen-deficient men as their familiar androgen deficiency symptoms return as testosterone pellets slowly dissolve. Among 52 androgen-deficient men who underwent 260 implantations over 5 yr, at the time of return of androgen deficiency symptoms the blood total and free testosterone concentrations were highly reproducible within individuals (F = 0.8, P = 0.49 and F = 1.4, 0.24, respectively) but varied markedly between men (F = 167 and F = 138, both P < 0.001), indicating that each person had a consistent testosterone threshold for androgen deficiency symptoms that differed markedly between individuals. The most reported symptoms of androgen deficiency were lack of energy, lack of motivation, and reduced libido. The symptomatic threshold was significantly lower in men with secondary hypogonadism compared with men with primary or mixed hypogonadism (total, 9.7 +/- 0.5 nmol/liter vs. 11.7 +/- 0.4 nmol/liter and 10.2 +/- 0.3 nmol/liter, P = 0.006; free, 146 +/- 10 pmol/liter vs. 165 +/- 6 pmol/liter and 211 +/- 18 pmol/liter, P = 0.002) but was not affected by the underlying cause of hypogonadism or by specific symptoms of any severity. Despite a wide range in individual thresholds for androgen deficiency symptoms, the mean blood testosterone threshold corresponded to the lower end of the eugonadal reference range for young men. The implications of these observations for the development of more specific quality-of-life measures, as well as for other potential androgen deficiency states such as chronic diseases and aging, remain to be determined.

The 5/4 h MT definition was the most inclusive, but combination with the 10/24 h definition appeared to identify a clinically important patient cohort.

Objective: Androgen deficiency (AD) leads to bone loss and contributes to osteoporotic fractures in men. Although low bone mineral density (BMD) in AD men is improved by testosterone replacement, the responses vary between individuals but the determinants of this variability are not well defined. Design and methods: Retrospective review of dual energy X-ray absorptiometry (DEXA) of the lumbar spine and proximal femur in men with established AD requiring regular androgen replacement therapy (ART). After a DEXA scan all men were treated with testosterone implants (800 mg, , 6 month intervals). Patients were classified as having a congenital, childhood, or post-pubertal onset, as well as according to the adequacy of treatment prior to their first DEXA scan as untreated, partially treated or well treated. Results: Men with AD requiring regular ART (n ¼ 169, aged 46.3^1.1 years, range 22 -84 years) underwent a DEXA scan prior to being treated with testosterone implants (800 mg, ,6 month intervals). In cross-sectional analysis at the time of the first DEXA scan untreated men (n ¼ 24) had significantly reduced age-adjusted BMD at all four sites (L1 -L4, femoral neck, Ward's triangle and trochanter). Well-treated men (n ¼ 77) had significantly better age-adjusted BMD at all four sites compared with those who were partially treated (n ¼ 66) or untreated (n ¼ 24) with their ageadjusted BMD being normalized. In a longitudinal assessment of men (n ¼ 60) who had two or more serial DEXA scans, at the second DEXA scan after a median of 3 years, men who were previously partially treated (n ¼ 19) or untreated (n ¼ 11) had proportionately greater improvements in BMD, significantly for Ward's triangle (P ¼ 0.025) and the trochanter (P ¼ 0.044) compared with men (n ¼ 30) previously well treated. Conclusions: The present study demonstrates a positive relationship between adequacy of testosterone replacement and BMD in men with overt organic AD. Additionally, the BMD of well-treated AD men approximates that of age-matched non-AD controls. The greatest BMD gains are made by those who have been either untreated or partially treated, and optimal treatment over time (median 3 years) normalizes BMD to the level expected for healthy men of the same age.European Journal of Endocrinology 152 881-886

Four weeks of treatment with testosterone or nandrolone had no beneficial or adverse effects compared with placebo on cardiac function in healthy young men.

The pellet washing procedure used during implantation does not reduce the subsequent extrusion rate. The higher rate of both primary and secondary adverse events in this prospective study compared with the previous retrospective survey may reflect either more rigorous follow-up or a secular trend.

Testosterone pellet implants release testosterone at a steady rate of 1.3 mg/200 mg implant/day (95% CI). The duration of action is about 6 months in an uncomplicated cycle with timing of return shortened by extrusions only in the 3.6% of procedures followed by multiple extrusions. No other patient or procedural features influenced duration of action. Among men with an intact hypothalamo-pituitary unit, plasma gonadotropins are more sensitive than blood total or free testosterone to reduced testosterone delivery following an extrusion.

We conclude that the hip site has a higher extrusion rate than the standard abdominal wall site but that track geometry does not increase the risk of extrusion. Neither implantation site, nor track geometry influenced either other adverse effects or the pharmacokinetics or pharmacodynamics of testosterone pellet implants.

The prostate strongly expresses type 2 5 alpha-reductase, which avidly converts on entry most testosterone (T) to 5 alpha-dihydrotestosterone (DHT). However, the quantitative contribution of the prostate to blood DHT is uncertain. We evaluated prostatic contribution to blood DHT by comparing the blood DHT concentrations in androgen-deficient patients with or without a prostate while they were receiving standard dose of T replacement. Androgen-deficient males (ADM) and female to male (F2M) transsexuals were studied in 2 centers, with both groups receiving either testosterone ester injections (250 mg mixed T esters) every 1 wk (Amsterdam) or 800 mg subdermal T implantation (Sydney). Among 39 Dutch patients, F2M (n = 21) were younger and smaller in physique than ADM (n = 18). One week (+/-1 d) after an injection, plasma DHT concentrations were 1.6 +/- 0.2 (F2M) vs. 1.4 +/- 0.2 (ADM) nmol/liter (P = 0.47), but the postinjection time interval to blood sampling was shorter in F2M (5.9 +/- 0.4 vs. 7.2 +/- 0.3 d; P = 0.01). Covariance adjustment for time since last injection, age, and physique did not change the lack of significant difference in postinjection plasma DHT concentration. The rapid and wide excursions in plasma T concentrations after an im T ester injection make the timing of blood sampling critical. To remove confounding by this variable, the experiment was repeated at a second site in similar patients, but using a depot T that achieves steady-state delivery for prolonged periods. Among 29 Australian patients, before and 1 month after subdermal implantation of 800 mg T, plasma DHT concentrations were not significantly different between groups [F2M, 1.1 +/- 0.1 (n = 14); ADM, 1.3 +/- 0.1 (n = 15); P = 0.28]. Correction for covariates, including age, height, weight, body surface area, and body mass index, did not influence the lack of significant difference between treated groups. As both modes of T administration yielded similar plasma DHT concentrations regardless of the presence of a prostate, this study indicates that the normal human prostate is not a major contributor to circulating blood DHT concentrations.