An update on the role of medical treatment including antioxidant therapy in varicocele

Abstract

Varicocele-associated male infertility has classically been managed using surgery or assisted reproductive techniques. With increasing evidence of oxidative stress as a pathophysiological factor in varicocele-associated infertility, medical therapy especially antioxidants might become a treatment option with lower risks. We reviewed the existing literature on the role of various medical agents in the management of male infertility attributed to varicoceles. Medical therapy is typically evaluated in three different situations such as (a) comparison of two drugs or one drug with placebo, (b) comparison of drugs versus surgery, and (c) comparison of drugs as adjuvant therapy with surgery versus drug therapy alone. Due to heterogeneity of data and lack of well-conducted studies, there is insufficient data to recommend routine use of medical therapy for men with varicocele-associated infertility and surgery remains the treatment of choice. Pregnancy and live birth rates are usually not reported in most studies and mere improvement in sperm parameters or antioxidant capacity is insufficient to support its routine use. Antioxidant therapy is a potential option due to its theoretical benefit, data from preclinical studies, and lack of major side effects. Adjuvant therapy with antioxidants after surgical repair of varicocele may improve the outcome and is a potential area for further research.

Current medical management of endocrine-related male infertility

“…It is thought that varicoceles increase scrotal temperature, reflux of blood blow, and damaged microcirculation, all of which act together to increase germ cell death and produce high amounts of reactive oxygen species leading to impaired fertility. 59 61 Varicocele grade has also been shown to correlate with the degree of oxidative stress. 61 Although surgery is still the standard of care in managing varicoceles, antioxidants could offer a potential low-risk solution in treating varicocele-induced infertility.…”

“… 59 61 Varicocele grade has also been shown to correlate with the degree of oxidative stress. 61 Although surgery is still the standard of care in managing varicoceles, antioxidants could offer a potential low-risk solution in treating varicocele-induced infertility. Due to the heterogeneity of current studies, the lack of larger placebo-controlled studies, and lack of studies using pregnancy as an end point, there is currently insufficient data to recommend the use of antioxidants solely as medical management.…”

“…reported significant improvements of sperm morphology that lasted 4 weeks after the end of treatment when using combination therapy of pentoxifylline (1200 mg per day) + zinc (66 mg per day) + folic acid (5 mg per day) in 36 men with clinical varicoceles. 61 …”

“…Although promising, the value of these results is limited because the study was a short, open labeled, uncontrolled trial. 61 …”

The effect of vitamin E & vitamin B on sperm function in rat varicocele model

“…Recently, oxidative stress-related diseases such as varicocele have become central attention to andrologist due to the attack of ROS and their metabolites to DNA, lipids and proteins, leading to decreased semen quality and eventually infertility. Therefore, antioxidant therapy as one of the treatment options has been considered for these individuals (Asadi, Bahmani, Kheradmand, & Rafieian-Kopaei, 2017;Garg & Kumar, 2016).…”