Cryptozoospermia after treatment with clomiphene citrate following long-term use of intramuscular testosterone undecanoate depot injection (Nebido®)

Abstract Objective To illustrate the importance of treatment duration with intramuscular testosterone undecanoate (Nebido®) for the final spermatogenesis recovery after treatment cessation. Also, to show a subsequent poor efficacy of the selective estrogen receptor modulator (SERM) clomiphene citrate (CC) in treating steroid-induced azoospermia following Nebido® cessation and describe that initial oligozoospermia, existing before starting Nebido®, largely contributes to that treatment outcome. Methodology Setting: Department of Human Reproduction and Department of Endocrinology, Clinical Hospital Center Rijeka, Rijeka, and Department of Endocrinology, Clinical Hospital Center Sestre milosrdnice, Zagreb, Croatia. Patient: A male patient having been diagnosed with primary hypogonadotropic hypogonadism, oligozoospermia and low testosterone (T) level, was treated with intramuscular testosterone undecanoate (TU) depot 1 g (Nebido®) to prevent further progression of testosterone deficiency symptoms (low mood, energy and concentration, fatigue, muscle weakness). Interventions: Stopping Nebido® and treatment with CC 50 mg per day 5 days per week for 3–6 month to recover spermatogenesis. Main outcome measures: T levels and semen analyses. Results Semen analyses did not return to values before taking Nebido® 1 year after cessation nor after 3 months of treatment with CC. Values of T, follicle stimulating hormone (FSH) and luteinizing hormone (LH) dropped even more than before starting Nebido®, after 1 year of cessation. Conclusions Here we describe a case of initially idiopathic gonadal failure with subsequent secondary gonadal failure and infertility resulting from testosterone replacement therapy (TRT) treatment, and poor spermatogenesis recovery outcome of CC used post Nebido® cessation.