By: Dr. Geoffrey Modest
There have been a couple of articles on testosterone:
1. Article in j clin endocrinology and metabolism on testosterone therapy for men with type 2 diabetes (T2D) and low testosterone levels (see doi: 10.1210/jc.2014-1872). 88 men aged 35-70 (ave age 62) with A1c <8.5%, total testosterone (TT) < 346 ng/dl (they specifically were looking for men with low normal testosterone levels, and excluded those with TT < 144), with mild to moderate “aging male symptoms” and erectile dysfunction, randomized to 40 weeks of IM testosterone undecanoate 1000 mg or placebo, assessing their AMS (aging male symptoms score, a validated 17-item scale to assess 3 domains: somatovegetative, psychological, and sexual), as well as sexual desire and erectile function. This analysis was a secondary one; with the primary study finding in these men that testosterone injections did not lead to any change in glucose metabolism (insulin resistance or glycemic control) or visceral adiposity (for that study see: Diabetes Care 2014;37:2098–2107). Results of current analysis:
–Testosterone injections did in fact increase TT levels
–No difference in the AMS score with testosterone injections
–No difference in sexual desire (interestingly, those on IM testosterone actually had reduced erectile function)
–Although the utility of free testosterone levels is debated, they found that 72% of the men had low free testosterone and there was no difference in results for them vs.. those with low TT
–Symptoms overall were worse at baseline if men were depressed or if had micro vascular complications (neither of these correlated with TT levels)
–The authors are careful to note that their conclusions do not apply to symptomatic men with unequivocally low testosterone levels, and that their results for men with less severe androgen deficiency were somewhat at odds with some other studies
Note: 30-50% of aging, obese men with T2D have low TT, though the vast majority has only mildly decreased TT (as in this study). In observational studies, 55-70% of those with low TT levels have symptoms of androgen deficiency, but 50-55% of those with normal TT had similar symptoms. So, I think this study is relevant to us because it highlights the importance (and high prevalence) of depression as a likely cause of sexual dysfunction, and the lack of significant efficacy of testosterone therapy. The data for clinical benefit of testosterone therapy in older men is very mixed, with best data for improving libido, though no significant change in erectile function or sexual satisfaction. As a result, the Institute of Medicine’s committee on testosterone concluded that there is insufficient evidence to recommend that testosterone treatment of older men have any well-established benefit. The number of testosterone prescriptions has increased dramatically in the last several years — this study reinforces the lack of real utility for testosterone replacement therapy for the majority of men (with the exception of those with profound TT deficiency, eg a man with symptoms consistent with testosterone deficiency — eg decreased libido, mood, osteoporosis, energy plus a TT level measured between8-10AM and less than 300 ng/dL, and this test should be repeated/confirmed 2x more before giving meds since there are significant daily variations in TT). And there are real risks to testosterone therapy.
2. The Endocrine Society came out with a clinical practice guideline for androgen therapy in women (see doi: 10.1210/jc.2014-2260). They basically recommend:
–Do not diagnose androgen deficiency in healthy women because of lack of well-defined syndrome and lack of data correlating symptoms with androgen levels. And don’t use testosterone routinely in those with hypopituitarism, adrenal insufficiency, etc.
–Do not use testosterone therapy for infertility; sexual dysfunction (other than “hypoactive sexual desire syndrome”, which studies suggest may respond to short term testosterone therapy, though endogenous testosterone levels do not predict response to therapy even in this “syndrome”); cognitive, cardiovascular, metabolic, or bone health; or general well-being
–Not use dehydroepiandrosterone
–AND, none of these testosterone preparations are available in the US for women, women frequently develop very high serum testosterone levels on therapy, and long-term safety data are lacking (though it seems that the testosterone equivalent doses for women is about 10% of those used in men).