Oral 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

Recovery of Male Reproductive Function Following Prolonged Injectable Testosterone Undecanoate Treatment (#24)

Nandini Shankara Narayana 1 , Reena Desai 2 , Ann Conway 1 , Bronwyn GA Stuckey 3 , Warwick Inder 4 , Mathis Grossmann 5 , Bu B Yeap 6 , Robert McLachlan 7 , Lam P Ly 1 2 , Karen Bracken 8 , Gary A Wittert 9 , David J Handelsman 1 2
  1. Andrology, Concord Repatriation General Hospital, Concord, NSW
  2. Andrology, ANZAC Research Institute, Concord, NSW, Australia
  3. Department of Endocrinology and Diabetes, Keogh Institute for Medical Research, Sir Charles Gairdner Hospital and University of Western Australia, Perth, Western Australia, Australia
  4. Department of Endocrinology , Princess Alexandra Hospital and University of Queensland, , Brisbane, Queensland, Australia
  5. Department of Endocrinology , The Austin Hospital and University of Melbourne, Melbourne, Victoria, Australia
  6. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Medical School, University of Western Australia, , Perth, Western Australia, Australia
  7. Endocrinology and Metabolism, Clinical Andrology , Hudson Institute of Medical Research, Melbourne, Victoria, Australia
  8. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  9. Freemasons Foundation Centre for Men’s Health, University of Adelaide, Adelaide, South Australia, Australia

Background: Exogenous androgen treatment suppresses the hypothalamo-pituitary testicular (HPT) axis causing reduced serum LH, FSH and testosterone (T). The Runoff Study [after Testosterone for Diabetes Mellitus (T4DM) Study] investigated the rate and extent of reproductive hormone recovery after 2 years of regular T undecanoate (TU) injections.

Methods: T4DM participants without pathological hypogonadism (n=1007) were randomised to TU or placebo (P) injections every 3 months for 2 years with 303 subsequently entering the Runoff study at 12 weeks after last injection. Before T4DM study unblinding, they provided blood samples and validated sexual function questionnaires (PDQ, IIEF-15) at entry, 6, 12, 18, 24, 40 and 52 weeks later.  Serum steroid profile (T, DHT, E2, E1) was measured batchwise by LCMS and serum LH, FSH and SHBG by immunoassays.

Results: Runoff study participants in both groups were similar and no different from all T4DM participants. As expected, at Runoff study entry serum T was higher in TU-treated men but at all timepoints from 12 weeks onwards serum T and SHBG remained consistently 11% and 12%, respectively, lower in TU treated than in P treated men. Similarly, at Runoff entry sexual function scores were higher in TU-treated men but subsequently no different from P-treated men. Mean serum LH and FSH recovered gradually to reach mean baseline levels at 36 weeks after last injection with the median time to recover to their own pre-treatment baseline of 52.7 weeks (serum LH) and 51.1 weeks (serum FSH) after last injection.

Conclusion: After stopping 2 years of standard dose TU treatment in men without pathological hypogonadism, HPT function recovers slowly, taking 9 to >12 months since last dose, but is eventually complete. Persisting mild, proportionate reduction in serum SHBG and T reflect lasting effects of androgen treatment on hepatic SHBG secretion, but not androgen deficiency.