Abstract and Introduction
Background and Objective: Previous studies indicated that the treatment of male hypogonadism can be beneficial for intraoperative and postsurgical outcomes. In this study, we aimed to determine the impact of male hypogonadism on urologic surgeries. We provided an overview of the key studies in the field with the focus on the outcomes of urologic surgeries in hypogonadal men with/without testosterone replacement therapy (TRT).
Methods: We performed a literature review in PubMed and Google Scholar databases for the most relevant articles pertaining to the outlined topics without placing any limitations on publication years or study designs. We included full-text English articles published in peer reviewed journals between January 1970 and March 2022.
Key Content and Findings: Androgen deficiency is a common finding after major urologic surgeries. Although guidelines recommend against TRT in men with prostate carcinoma, recent investigations showed no association between TRT and disease progression and recurrence. Indeed, recent evidence suggested that low androgen levels could be related to high grade prostate carcinoma and increased risk of upgrading from low to high grade disease. Investigations on the application of TRT in benign prostatic hyperplasia (BPH) patients also revealed contrasting results. While some studies suggested higher rates of prostate-related events in men who received TRT, others showed that TRT could alleviate urinary symptoms in hypogonadal men with BPH. Decreased testosterone level is commonly seen in bladder cancer patients. The treatment of perioperative androgen deficiency can reduce postoperative morbidities and lower the risk of recurrence in these patients. Low testosterone levels are observed in approximately half of the men who undergo artificial urinary sphincter (AUS) placement and can increase the risk of complications.
Conclusions: The role of testosterone treatment in patients with urologic diseases such as prostate carcinoma and BPH is controversial. Further investigations are needed to determine the impact of hypogonadism and TRT on the outcomes of urologic surgeries in patients with androgen deficiency.
Male hypogonadism is defined as decreased serum testosterone levels (total testosterone <300 ng/dL equivalent to 10.41 nmol/L) in the presence of symptoms and/or signs of androgen deficiency. It affects 5–10% of men above 30 years old and its prevalence increases with age.[2,3] Several studies have reported a physiologic age-dependent decline of nearly 1–2% per year in total and free testosterone concentrations in men after the age of 30 years.[4–6] The incidence rate of male hypogonadism is estimated as 481,000 new cases per year in the United States (US) men. American Urological Association (AUA) guidelines recommend male hormone profile assessment in male patients with signs and symptoms of testosterone deficiency such as decreased bone mineral density, loss of muscular mass, erectile dysfunction (ED), decreased libido, fatigue, and mood changes. There exist several challenges for diagnosis of hypogonadism. Although most patients become symptomatic at total testosterone levels below 300 ng/dL, studies have shown that there are no universal serum testosterone levels associated with hypogonadism symptoms forcing specialists to rely more on patient-reported symptoms than blood test values. Serum testosterone level is also fluctuating over the course of the day and from day-to-day. Previous investigations determined that approximately 15% of healthy men can have low testosterone at any hour of the day. Measurement of testosterone concentration widely depends on the process and protocol utilized by the laboratory. There are several methods to measure total testosterone concentrations including radioimmunoassay, immunometric assays, and liquid chromatography–tandem mass spectrometry (LC-MS/MS). These methods are associated with considerable interassay variations.[3,10] LC-MS/MS generally provides higher specificity, sensitivity, and precision especially in low-range levels compared with other methods. Nonetheless, this technique is costly and is available to a limited number of care facilities. Therefore, the most commonly utilized methods to measure testosterone in non-reference hospitals and commercial laboratories are enzyme immunoassays. Serum total testosterone comprises unbound and protein-bound testosterone. Most of the serum testosterone is bound to sex hormone-binding globulin (SHBG) and albumin, and only 2–4% of the circulating testosterone is considered as unbound or free. Previous investigations revealed that men with low free testosterone levels are affected with testosterone deficiency symptoms regardless of their total testosterone levels. While total testosterone concentration is usually affected by conditions that modestly increase or decrease SHBG, free testosterone levels usually remain within the normal range limits in such conditions. Guidelines recommend measuring free testosterone concentration when total testosterone is mildly above or below the reference ranges.[2,3] Free testosterone is mainly calculated upon accurate measurement of total testosterone, SHBG, and albumin using different available formulas based on the binding characteristics of testosterone to SHBG and albumin.[3,13]
Low testosterone levels cause a wide range of pathophysiologic changes in various body systems. It is associated with increased risk of insulin resistance and metabolic syndrome.[14,15] It has been demonstrated that long-term uncorrected testosterone deficiency is closely related to poor general health, hypercholesterolemia, and anemia.[16,17] Furthermore, male hypogonadism can independently increase the risk of cardiovascular diseases and all-cause mortalities.[18–20] Disease-specific investigations demonstrated that male hypogonadism is associated with higher mortality rates in patients with cardiovascular, respiratory and renal diseases, type 2 diabetes and malignancies.[21,22] Also, male hypogonadism can increase postoperative complication rates and total costs of care after various orthopedic surgeries.[23,24]
Testosterone replacement therapy (TRT) is extensively used to treat men with androgen deficiency and symptoms of hypogonadism. The main goals of TRT are to restore and maintain sexual function and body composition, in addition to improving mood, general health, and quality of life.[14,15,17] Previous investigations demonstrated the benefits of preoperative testosterone administration, even at higher than physiological levels, to minimize postoperative adverse outcomes and improve recovery following major surgeries.[26,27] Studies have also shown that low free testosterone concentration is associated with increased mortality rates after major surgeries.
To the best of our knowledge, no study has reviewed the role of androgen deficiency and TRT in urologic diseases and their surgical outcomes. In this narrative review, we aimed to determine the impact of male hypogonadism on urologic surgeries. We provide an overview of the key studies in the field with the focus on the outcomes of urologic surgeries in hypogonadal men with/without TRT. We present the following article in accordance with the Narrative Review reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-22-308/rc).
Transl Androl Urol. 2022;11(7):1045-1062. © 2022 AME Publishing Company