madman
Super Moderator
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).
Evidence summary
*Alone or in combination with hCG, clomiphene citrate is effective
*CC and testosterone gel is comparable; testosterone injection is better
*Enclomiphene citrate demonstrates improvement in hormone levels
*With EC, testosterone remains elevated after treatment cessation
*There were no major adverse effects, even after 3+ years of treatment
Recommendations from others
Current American Urological Association and Canadian Urological Association Guidelines note that while a greater study on nontraditional testosterone therapies is needed, both organizations support the 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 the 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.
Evidence summary
*Alone or in combination with hCG, clomiphene citrate is effective
*CC and testosterone gel is comparable; testosterone injection is better
*Enclomiphene citrate demonstrates improvement in hormone levels
*With EC, testosterone remains elevated after treatment cessation
*There were no major adverse effects, even after 3+ years of treatment
Recommendations from others
Current American Urological Association and Canadian Urological Association Guidelines note that while a greater study on nontraditional testosterone therapies is needed, both organizations support the 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 the 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.
