Are SERMs safe and effective for the treatment of hypogonadism in men?
EVIDENCE-BASED ANSWER:
YES. For both normal-weight and obese men with low testosterone levels and hypogonadal symptoms, selective estrogen receptor modulators (SERMs), such as clomiphene citrate (CC) and enclomiphene citrate (EC), appear to be effective and safe for improving serum testosterone levels (strength of recommendation [SOR]: C, disease-oriented outcomes from randomized controlled trials [RCTs] and cohort studies). Studies also show that symptom improvement is comparable to that with exogenous testosterone replacement and similar to eugonadal men (SOR: B, patient-oriented outcomes from retrospective cohort studies).
Finally, the percentage of men reporting adverse effects did not significantly differ between groups: 9% in the ≤ 3 years group and 8% in the > 3 years group (P = .85). The most common adverse effects reported in order of frequency were mood changes, blurred vision, breast tenderness, hypertension, hematocrit changes, and flushing. No major adverse events (eg, myocardial infarction, cerebrovascular accident, venous thromboembolism, suicidal behavior) were reported in any patients.
Of note, although measured estrogen levels at the end of treatment were similar for both groups (54.8 pg/mL in the ≤ 3 years group vs 54.6 pg/mL in the > 3 years group), 37% of patients treated for > 3 years did receive anastrozole treatment for hyperestrogenism compared to 15% in the ≤ 3 years group (P = .05). The authors caution, though, that due to only 20% of the cohort patients having data on pre- and post-treatment estradiol levels, the study was likely underpowered to detect true differences among subgroups.
Recommendations from others
Current American Urological Association and Canadian Urological Association Guidelines note that while greater study on nontraditional testosterone therapies is needed, both organizations support use of SERMs, especially in hypogonadal men who are interested in fertility preservation, as increases in endogenous serum testosterone production do not impact fertility potential, unlike exogenous hormonal replacement.6,7 Additionally, men with low or low-normal serum LH levels may also be good candidates for the use of SERMs for management of testosterone deficiency.
Editor’s takeaway
Laboratory data (disease oriented) consistently shows that SERMs effectively increase testosterone levels to those comparable with testosterone gels. SERMs resulted in higher semen counts and maintained LH and FSH levels, but there were instances of hyperestrogenism. Data on longer-term benefits and adverse effects of both SERMs and testosterone supplementation are still needed.
