Over the last decades publications have highlighted the decline of serum testosterone (T) levels in aging men, termed late onset hypogonadism (LOH). Rather than chronological age per se, obesity, but also impaired general health, are the more common causes of low T in aging men. It is clear now that the decline of serum T with aging is not an academic question but has important implications for elderly men.
Severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality, to which both the level of T and the presence of sexual symptoms contribute independently. A recent review literature on the risk factors, comorbidities, and consequences of LOH demonstrated that advanced age, obesity, a diagnosis of metabolic syndrome, and a poor general health status were predictors of LOH. Low levels of T may have important long-term negative health consequences. Of the European Male Ageing Study more than 50% of subjects with LOH reported the presence of one or more common morbidities. Overall, hypertension (29%), obesity (24%), and heart diseases (16%) were the most prevalent conditions. Particularly, sexual symptoms might indicate LOH. In one study an inverse relationship between an increasing number of sexual symptoms and a decreasing T level was observed.
T treatment has a number of beneficial effects particularly on weight, fat distribution and metabolic factors. T might be a powerful tool in weight reduction and its associated benefits.
In the present study we analyzed whether the age of subjects receiving T for the treatment of LOH matters for the beneficial effects of T administration. An equally important question was whether potential side effects of T administration were more severe in elderly men.
In a cumulative registry study 561 hypogonadal (T ≤ 12.1 nmol/L ), mainly elderly men, from two urology offices, seeking urological consultation, followed observational registry studies. 450 men were <65 years of age (mean 56.10 ± 6.29) (group Y(oung) and 111 > 65 years (mean 68.45 +/- 2.91 (group O(ld). All men received treatment with parenteral T undecanoate 1000 mg (Nebido®, Bayer Pharma, Berlin, Germany), administered at baseline and 6 weeks and thereafter every 12 weeks for up to at least 72 months.
Over the 6 years there was a progressive decrease of body weight and waist circumference. Mean weight (kg) decreased from 102.52±15.56 to 90.15±9.69 in Group Y and from 102.83±15.64 to 95.35±9.03 in Group O. The mean change from baseline was 14.78±0.35 kg in Group Y and 15.14±0.71 kg in Group O. Percent change from baseline was -13.56±7.56% in Group Y and -13.28±7.14% in Group O. Waist circumference (cm) decreased from 106.54±9.03 to 98.26±7.1 in Group Y and from 108.95±10.75 to 100.72±9.45 in Group O. The mean change from baseline was 9.34±0.2 cm in Group Y and 10.45±0.47 cm in Group O.
Similar decreases of total cholesterol, low density lipoprotein, and triglycerides and increases of high density lipoproteins were noted in group Y and group O.
In Group Y the International Index of erectile function-EF (IIEF-EF) improved from 14.94±7.34 at baseline to 19.23±5.94 after 1 year, with slight improvements over the first 5 years and sustained thereafter. Similarly, in group O: IIEF-EF improved from 11.87±7.58 at baseline to 16.79±6.35 after 1 year, and to 20.16±7.11 at 5 years, and 22.12±6.41 at 6 years. The mean change from baseline was 8.53±0.26 in Group Y and 8.12±0.59 in Group O.
Prostate volume increased in group Y from 26.77±9.4 to 31.58±10.9 ml (p<0.0001), in group O from 33.85±8.66 to 39.95±7.6 ml (p<0.0001)
PSA (ng/ml) increased in Group Y from 1.33±0.91 to 1.65±0.83 (p<0.0001) by 0.36±0.02, in Group O from 1.44±0.98 to 1.88±0.84 (p<0.0001) by 0.38±0.05.
International Prostate Symptoms Score improved in Group Y from 7.74±5 to 3.89±3.12 (p<0.0001), in Group O from 10.7±4.07 to 4.63±2.63 (p<0.0001). These changes were statistically significant vs. previous year for all six years in Group Y and the first five years in Group O and were then maintained throughout the observation period.
Post voiding residue declined in group Y from 34.87±23.12 to 16.72±6.74 ml (p<0.0001), in group O from 41.46±23.48 to 18.84±5.75 ml (p<0.0001).
Prostate cancer occurred in 12 men: 7 men in group Y (1.6%) and 4 men in group O (3.6%). The incidence per 10,000 patient years was 27.1 in the younger and 54.6 in the older group.
During the entire observation time, no cases of major adverse cardiovascular events occurred.
We concluded that the benefits of restoring serum T in men with LOH were not different between men >65 years of age, and younger men. Beneficial effects on lipids and other metabolic factors, on psychological and sexual functioning progressed over the first 24-42 months and were sustained. There were no indications that side effects were more severe in elderly men. The effects on prostate, urinary functions and hematocrit were within safe margins. No increase in cardiovascular problems was noted. Therefore, age in itself need not be a contra-indication to T treatment of elderly men with LOH, but older men may need more surveillance.
Written by:
Saad F, Yassin A, Haider A, Doros G, Gooren L
Global Medical Affairs Andrology, Bayer Pharma AG, Berlin, Germany; Gulf Medical University School of Medicine, Ajman, UAE; Gulf Medical University School of Medicine, Ajman, UAE; Institute for Urology and Andrology, Norderstedt, Germany; Dresden International University, Dresden, Germany; Private Urology Practice, Bremerhaven, Germany; Department of Epidemiology and Statistics, Boston University School of Public Health, Boston, MA, USA; Department of Internal Medicine, Endocrine Section, VU medical Center, Amsterdam, The Netherlands.