Perspectives in Urology: Point-Counterpoint Archives

Testosterone Update on Oral Products

Posted by T. Mike Hsiech, MD, MBA | Jun 2023

T. Mike Hsieh, MD, MBA, provides an update on available oral testosterone treatments, beginning by explaining that oral testosterone is a large and growing market and outlining the development testosterone therapy over recent decades. Dr. Hsieh hones in on the three therapies most recently approved by the U.S. Food and Drug Administration (FDA), all of which are oral testosterone therapies (Jatenzo, Tlando, and Kyzatrex).

He cites a study of Oral Testosterone Undecanoate in Hypogonadal Men, which led to the approval of Jatenzo. Dr. Hsieh then addresses Tlando, and explains the study behind its approval, which found the treatment’s efficacy was 80 percent, exceeding the FDA threshold of 75 percent. He then addresses Kyzatrex, a gelatin capsule that uses a SEDDS formulation (phytosterol esters that form microemulsions in gastrointestinal fluids, allowing oral dosing of poorly-soluble drugs). As far as clinical efficacy, Kyzatrex well exceeded the FDA threshold, with 96 percent of patients achieving testosterone levels in the therapeutic range after 90 days of treatment.

Dr. Hsieh explains that, unlike Jatenzo, Tlando and Kyzatrex do not need to be taken with a high-fat meal. With all three medications, blood pressure increase is a possible side effect (though the data on hypertension was more favorable in the Kyzatrex study), and all these treatments carry FDA warnings to that effect.

Dr. Hsieh concludes that there is a wide variety of commercially available testosterone options on the market, with new oral formulations with favorable safety profiles representing exciting new options for patients. He reiterates that blood pressure should always be monitored in patients on oral testosterone.

Recurrent UTIs in Women: Ask the Guideline

Posted by Jennifer T. Anger, MD, MPH | Jun 2023

Jennifer Anger, MD, MPH, discusses American Urological Association (AUA) guidelines regarding recurrent urinary tract infections (rUTIS) in women. She begins by discussing antimicrobial stewardship and the consideration of collateral damage, explaining antimicrobial resistance among uropathogens has increased dramatically in the past 20 years.

Dr. Anger characterizes the index patient for the 2019 rUTI guideline as an otherwise healthy adult female with an uncomplicated, culture-proven rUTI associated with acute-onset symptoms. She summarizes guideline highlights, including the recommendation that clinicians obtain a complete patient history and perform a pelvic examination in women presenting with rUTIs. Additionally, clinicians should obtain urinalysis, urine culture, and sensitivity with each symptomatic acute cystitis episode prior to initiating treatment for rUTIs.

Dr. Anger outlines first-line therapy (nitrofurantoin, TMP-SMX, and fosfomycin) and explains clinicians should use as short a duration of antibiotics as reasonable for rUTI patients with an acute cystitis episode. For patients with urine cultures resistant to oral antibiotics, clinicians may treat with culture-directed parenteral antibiotics for as short a course as reasonable.

Dr. Anger discusses use, dosing, and duration of prophylactic antibiotics and points out that clinicians may offer cranberry prophylaxis for rUTIs, but explains that studies are lacking in this area. Clinicians should repeat urine culture to guide further management when UTI symptoms persist following antimicrobial therapy.

In peri- and post-menopausal women with rUTIs, clinicians should consider vaginal estrogen therapy to reduce the risk of recurrence. Dr. Anger then highlights the 2022 UTI Guideline Update and explains randomized, controlled trials that contributed evidence to this amendment report.

Role of Circulating Tumor DNA and Adjuvant Therapy in Urothelial Carcinoma

Posted by Tyler F. Stewart, MD | Jun 2023

Tyler F. Stewart, MD, discusses the groundbreaking role of circulating tumor DNA (ctDNA) in adjuvant therapy for urothelial carcinoma, highlighting its potential to revolutionize cancer treatment. ctDNA, a fragmented DNA shed by cells into the bloodstream, holds immense promise in identifying minimal residual disease and predicting patient outcomes.

Dr. Stewart emphasizes the significance of ctDNA as a biomarker and its successful application in various cancer types, including colorectal and bladder cancer. He presents studies showcasing the prognostic value of ctDNA monitoring throughout the treatment course, revealing its ability to accurately predict disease recurrence. The assay DNA methodologies, such as digital PCR and targeted capture NGS, offer remarkable sensitivity and customization to individual patients.

Dr. Stewart explores the potential of ctDNA as a predictive marker for perioperative systemic therapy, which could aid in identifying patients who would benefit most from adjuvant therapy. He highlights the positive outcomes observed in ctDNA-positive patients receiving adjuvant atezolizumab, leading to improved disease-free survival and overall survival rates.

Ongoing clinical trials, such as TOMBOLA and ImVigor011, further explore the integration of ctDNA as an essential biomarker in the management of muscle invasive bladder cancer. The extensive research on ultrasensitive ctDNA assays, novel ctDNA assays, and the use of urinary biomarkers for disease monitoring adds to the growing body of evidence supporting the clinical utility of ctDNA in cancer care.

Hormone Replacement Therapy in Menopause

Posted by Maria Uloko, MD | Jun 2023

Maria Uloko, MD delves into the complexities and clinical considerations of hormone replacement therapy (HRT) in menopause.

Primer on Testosterone Therapy for Women: Treatment of HSDD

Posted by Maria Uloko, MD | Jun 2023

Maria Uloko, MD, discusses testosterone therapy for women with hypoactive sexual desire disorder (HSDD). She explains that people with HSDD have higher rates of impaired body image, low self-confidence and self-worth, relationship stress, depression and anxiety, and increased healthcare costs.

Dr. Uloko shares the Basson Model of Sexual Motivation and emphasizes there is no “quick fix” for low libido. Dr. Uloko advocates a biopsychosocial approach that incorporates the biological, psychological, and social aspects that can affect HSDD. She explains the importance of patient education and therapy as well as medication treatments like flibanserin and testosterone.

Dr. Uloko emphasizes that testosterone is not FDA-approved for women, and it remains challenging to dose women appropriately. She cites studies that conclude testosterone, either alone or in concert with estrogen therapy, can be effective and safe for the treatment of HSDD. Dr. Uloko states that symptomatic improvement takes approximately 12 weeks, and treatment should be discontinued if no improvement occurs within six months.

Dr. Uloko then concludes that HSDD is a common but multifactorial condition for women with significant detriment to quality of life. She re-emphasizes the importance of a biopsychosocial approach to diagnosis and treatment that may include treatment with testosterone therapy.