Safety and Efficacy of Enclomiphene Compared to Clomiphene in Men with Low Testosterone

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madman

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*Our findings show that enclomiphene provides the same magnitude of improvement in testosterone but through safer means, as noted by its lower rate of documented adverse events

*Further research and larger studies are warranted to validate these conclusions and explore additional long-term effects of enclomiphene







Abstract

Introduction


Clomiphene, and its trans isomer enclomiphene, have been used off-label in recent years for hypogonadal men seeking to maintain fertility. Both drugs have become increasingly widespread within andrology clinics; thus, understanding the comparative benefits and risks of these medications are crucial for optimizing treatment decisions and providing improved therapeutic options.
enclomiphene.jpg


Objective

To investigate the longitudinal benefits and risks associated with enclomiphene compared to clomiphene to provide valuable insights for clinicians when making treatment decisions in the management of hypogonadism and male fertility preservation.


Methods

We retrospectively studied patients who had been prescribed clomiphene, and later enclomiphene, at a university hospital within the observation range of 1/1/2021-12/31/2022, encompassing 66 patients. All included patients were prescribed clomiphene prior to switching to enclomiphene. Baseline laboratory values for each patient prior to being prescribed clomiphene were documented, followed by subsequent values for each of these variables in the most recent visit prior to stopping clomiphene as well as any noted adverse effects experienced during this time. Laboratory values and adverse effects were noted for the same patients in their most recent visit while taking enclomiphene. Adverse events were defined by 1) depressive thoughts; 2) weak muscle strength; 3) gynecomastia; 4) mood changes; or 5) agitation as well as changes in estradiol and hematocrit laboratory values. Two-tailed T-Tests were employed using SPSS to analyze the longitudinal impacts of clomiphene and enclomiphene on serum hormone values.


Results

In our cohort, men on clomiphene experienced any adverse events 18.18% of the time, whereas men on enclomiphene experienced any adverse events 3.45% of the time. From our data, men on enclomiphene had statistically lower rates of documented adverse events than the same men on clomiphene, indicating no increased risk on the newer drug; neither treatment yielded any serious adverse events. In looking specifically at hormone-related adverse events, estradiol increased significantly on clomiphene but not on enclomiphene (17.25 versus -0.29 pg/mL; t=4.271, p=.00005). However, there was no difference in change in hematocrit between the two medications (0.10% versus 0.79% increase; t=-1.103, p=.314). On average, testosterone increased 149.33 ng/dL from their baseline scores while on clomiphene and increased 108.55 ng/dL from their clomiphene values while on enclomiphene. When comparing the improvement of testosterone values attributed to clomiphene versus enclomiphene, the change of testosterone levels over time attributed to either medication are not statistically different (t-value = .883; p-value = .379). Lastly, men stayed on clomiphene for an average of 32.92 months before switching to enclomiphene.


Conclusions

Our findings show that enclomiphene provides the same magnitude of improvement in testosterone but through safer means, as noted by its lower rate of documented adverse events. These findings support the use of enclomiphene as a comparable treatment option for hypogonadal men while minimizing the risk of adverse effects. Further research and larger studies are warranted to validate these conclusions and explore additional long-term effects of enclomiphene.
 
Defy Medical TRT clinic doctor
Neither clomiphene or encomiphene worked for me. I got nasty visual side effects from both and suffered anxiety when I had never had that before I tried those drugs
 
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