Testosterone Therapy of Little Benefit in Men with Type 2 Diabetes

New research shows that testosterone therapy does not significantly improve erectile function or lessen mild to moderate aging male symptoms in obese patients with type 2 diabetes mellitus.

New research finds that testosterone therapy does not significantly improve erectile function or lessen mild to moderate aging male symptoms in obese patients with type-2 diabetes (T2D).

The study, which will appear in The Journal of Clinical Endocrinology & Metabolism, randomized 88 such men with moderate reductions in total testosterone (levels below 12.0 nmol/L [346 ng/dl]) between 40 weeks of placebo or intramuscular testosterone undecanoate.

Total testosterone levels and other biochemical parameters were measured in early morning blood samples collected from fasting patients at 0, 18 and 40 weeks. Constitutional and sexual symptoms were assessed using two self-administered questionnaires at 0, 18 and 40 weeks.

Testosterone levels increased as expected in the treatment group (+5.9 nmol/L [170 ng/dl] on average) but not in the placebo group. Patient responses to the Aging Male Symptoms (AMS) and International Index of Erectile Function abridged version 5 (IIEF-5) questionnaires, however, indicated no benefit from testosterone therapy.

“The fact that testosterone treatment did not lead to a substantial symptomatic improvement is consistent with the possibility, supported by observational studies, that constitutional and sexual symptoms in this population may be a consequence of co-morbidities rather than due to mild hypotestosteronemia,” the study authors wrote.

“In support of this, the presence of self-reported depression, but not baseline testosterone levels, was associated with worse aging male symptoms. Similarly, the presence of microvascular diabetic complications, but not testosterone levels, was associated with worse erectile function.”

The AMS has 17 questions designed to assess health-related quality of life in three areas: somato-vegetative (7 questions), psychological (5 questions) and sexual (5 questions. Questions ask about symptoms, which subjects answer on a 5-point scale (1= no symptoms; 5 = severe symptoms). Total scores thus range from 17 (no symptoms) to 85 (uniformly severe symptoms).

Overall, scores worsened for both the placebo and testosterone groups. The median total score rose from 32 to 44 for men in the testosterone group and from 35 to 41 for men in the placebo group. The mean adjusted difference in change over 40 weeks across the testosterone and placebo groups in AMS total score was — 0.9 (95% CI, -4.1 to 2.2, P = .67).

The IIEF-5 questionnaire has five questions, all focused on erectile function and each scored from 1 to 5. In this questionnaire, higher scores indicate better health. Total scores of 1 to 7 indicate severe erectile dysfunction while scores of 22 to 25 indicate no dysfunction.

Overall, IIEF-5 scores moved only slightly during the trial. The median score in the testosterone group began at 18 and fell to 16. The median score in the placebo group began at 17 and rose to 19.

Compared to placebo, erectile function in men assigned to testosterone was reduced (MAD in IIEF-5, —2.0; 95% CI, –3.4, – 0.6; P = .02). However, there was no significant change in IIEF-5 score if men receiving testosterone and placebo were analyzed separately against baseline.

“The negative findings of this RCT do not rule out the possibility that testosterone treatment may lead to a symptomatic improvement to aging obese men with T2D, but they make it unlikely that a substantial, clinically meaningful response occurs in such men,” wrote the study authors, who added that testosterone might have significant effects on other metrics.