Long-term effects of testosterone therapy in hypogonadal men with type 2 diabetes

Description

Prof. Saad presents new data from two ongoing long-term registry studies of testosterone therapy in patients with hypogonadism attending urological practices. One report showed a strong correlation between obesity and type 2 diabetes; the prevalence of type 2 diabetes was found to be 33% in men with class I obesity (BMI 30-34.9), raising to 55% in men with class III obesity (BMI >40).

Another report of a registry study which included routine measurement of HbA1c from the very start has provided very intriguing data. It showed that among 505 patients with hypogonadism the prevalence of prediabetes, which is defined as HbA1c between 5.7 – 6.4%, is as high as 50%, while the prevalence of type 2 diabetes is 29%. Hence, around 80% of hypogonadal men – the large majority - have impaired glucose metabolism.

In one registry, out of 311 men (38.6%) with type 2 diabetes and hypogonadism (total testosterone ≤12.1 nmol/L), 141 men opted for testosterone therapy and received testosterone undecanoate injections 1000 mg every 12 weeks (T-group) for up to 10 years, while the remaining 170 men who opted against testosterone therapy served as controls. In the testosterone therapy group, total testosterone levels increased to 18 nmol/L, while in the control group testosterone levels declined to 8 nmol/L. In testosterone treated men HbA1c declined from 9% to 5.3%, while in the control group it increased from 7.9% to 11.5%. This was accompanied with corresponding changes in insulin resistance (HOMA-IR) and insulin medication requirement. After 10 years of testosterone therapy, 91% had reached the HbA1c target of 7% and 80% had reached the HbA1c target of 6.5%. None of the men in the control group reached either target. This was reflected in corresponding changes in body weight; testosterone treated men had lost 19% of initial body weight while men in the control group had gained 5%. This study also analysed “hard clinical outcomes”. In the testosterone group, 8 men (5.7%) died and 7 men (5%) were diagnosed with prostate cancer. No myocardial infarction or stroke occurred. In contrast, in the control group, 41 men (24.1%) died, 17 (10%) men were diagnosed with prostate cancer, and 47 myocardial infarctions and 37 strokes occurred.

The reduction in mortality and protection against myocardial infarction and stroke was reflected in the Framingham risk score, which was reduced in the testosterone group, and as expected, increased in the control group. Regarding prostate cancer, not only was prostate cancer incidence reduced by half in the testosterone group, but the prostate cancer cases were diagnosed during the first 1.5 years of testosterone therapy. This suggests that those men had occult prostate cancer present before the start of the study.

An unexpected and surprising result was that some men in the testosterone group experienced remission of type 2 diabetes. Remission is defined as HbA1c at or below 6.5% without diabetic medications. This was also reported in a case-study of an obese man; for more information, see “Remission of type 2 diabetes in a hypogonadal man after long-term testosterone therapy

In the registry study, when data up to end of 2017 were analysed, 16% (16 of 133) hypogonadal men receiving long-term testosterone therapy had achieved remission of their type 2 diabetes. It is notable that remission was also seen in some men who were not obese. During the first 5 months of 2018, another 15 patients were taken off their anti-diabetic medication and the remission rate increased to 22% (16+15 = 31 patients).

The ADA (American Diabetes Association) has acknowledged the importance of testosterone by adding to the 2018 revision of the standards of medical care in diabetes the recommendation to measure testosterone levels in men with diabetes who have signs and symptoms of hypogonadism.

In summary:

  • Impaired glucose metabolism may be an important feature of hypogonadism.
  • Adequate long-term testosterone therapy in hypogonadal men with type 2 diabetes results in sustained improvement of glycemic control.
  • Long-term testosterone therapy may result in remission of type 2 diabetes.
  • Duration of treatment and medication adherence are of crucial importance.
  • Many studies have shown that testosterone treatment may reduce mortality and major adverse cardiovascular events but further larger studies are needed.
  • Many studies have also shown that testosterone treatment does not increase prostate cancer risk.

UPDATE June 2020:

In a recently published 11-year follow-up of these patients, 34.3% of men who had been treated with testosterone undecanoate injections achieved type 2 diabetes remission.1


 

Speakers

Prof. h.c. Dr. Farid Saad

Prof. h.c. Dr. Farid Saad
Medical Affairs Andrology, Bayer AG, Berlin, Germany,
Gulf Medical University, Research Department, Ajman, United Arab Emirates,
Hang Tuah University, Men’s Health Reproduction Study Center, Surabaya, Indonesia

References

  • Haider KS, Haider A, Saad F, et al. Remission of type 2 diabetes following long-term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11-year data from a real-world registry study. Diabetes, obesity & metabolism. 2020. Return to content