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Long-Term Use Of Enclomiphene: Safety, Side Effects, And Monitoring

Enclomiphene offers a hopeful alternative to testosterone replacement treatment (TRT) for males with low testosterone levels, with the advantages of reduced severe side effects and the preservation of fertility. Although preliminary research indicate that it is well-tolerated and efficacious in the short term, there is a scarcity of extensive study on its long-term usage and direct comparisons with clomiphene citrate.1 Continuous monitoring and more inquiry are necessary to completely demonstrate its long-term safety and effectiveness.

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Enclomiphene is a prescription drug used to treat low testosterone levels (hypogonadism) in men. It is an alternative to testosterone replacement therapy (TRT) that is free of many of the drawbacks associated with TRT, such as reduced fertility/sperm production, serious side effects that can increase your risk of heart attack or stroke, make certain pre-existing conditions like congestive heart failure and sleep apnea worse, or shrink your testicles.

Today, we will explore what is currently known about long-term enclomiphene use, including safety, side effects, and monitoring. However, before we begin, it is important to note that there are very limited studies on this subject. Most current projections are based on a related drug called clomiphene citrate.

Safety of Long-Term Enclomiphene Use

A 2016 study published in Expert Opinion on Pharmacotherapy reported that enclomiphene was being used to treat secondary male hypogonadism because enclomiphene is well-tolerated and does not cause as many adverse effects as TRT.2

The study points out that it is unknown if enclomiphene is superior to clomiphene for treating secondary male hypogonadism because the two medications have not been directly compared to one another.

If future research finds that both clomiphene and enclomiphene are equally effective in treating secondary male hypogonadism, clomiphene may be recognized as the best option of the three medications due to its lower cost.

man holding his head in pain

A 2019 study published in the Journal of Urology looked at the long-term safety and efficacy of using clomiphene citrate to treat hypogonadism (low testosterone levels) in men.3 There were a total of 400 patients in the study. Two hundred eighty patients were treated with clomiphene citrate for less than three years, and 120 were treated with it for longer than three years.

Of the men who received treatment for more than three years, 88 percent reached normal testosterone levels, 77 percent noticed improvement in symptoms, and eight percent experienced side effects. There were no significant differences in results between patients treated for more than three years and patients treated for three or fewer years. The study concluded that clomiphene citrate causes few side effects and is safe and effective in treating male hypogonadism long-term.

Side Effects of Long-Term Enclomiphene Use

The long-term effects of enclomiphene are still ongoing, though some side effects over a 3-year period are known. Clomiphene, which includes enclomiphene as an ingredient, has been studied more extensively, so healthcare professionals often consider the side effects of clomiphene as well.

The known side effects of enclomiphene include:

  • Increased libido
  • Acne
  • Dizziness and headaches
  • Mood changes, including irritability or aggression
  • Hot flashes and night sweats
  • Fatigue
  • Breast tenderness or gynecomastia (resulting from high estradiol)

You should keep your doctor informed of any side effects you experience while using enclomiphene. In studies, enclomiphene is overall well-tolerated, and side effect symptoms were minor. Keeping your doctor advised of side effects and how they develop can help your doctor determine whether your prescription needs to be adjusted or if you should switch to an alternative therapy.

Enclomiphene is not the right answer for everyone. Your doctor should conduct a health evaluation of your current overall health, medications you are taking, and family health history to determine whether enclomiphene is the safest, most effective way to address your health concerns. Those with a history of cardiovascular issues or pituitary adenoma may not be good candidates for an enclomiphene prescription.

Monitoring of Long-Term Enclomiphene Use

While clinical trials and studies have so far shown enclomiphene to be safe, more research is needed on the long-term effects of this medication. Your doctor will need to monitor your condition while taking enclomiphene to ensure the treatment is working well for you and to prevent and treat side effects. If you are looking for a doctor to consult regarding enclomiphene treatments, availability and accessibility are important factors to consider.


Enclomiphene is a prescription medication that restores normal testosterone levels in men with low testosterone levels. Unlike TRT, enclomiphene does not cause many serious side effects or decrease or stop sperm production and fertility. Although enclomiphene seems promising, more research is needed about the effectiveness and safety of use longer than three years.

If you want to conceive while you are treating low testosterone levels, talk to your doctor to learn if enclomiphene is right for you. You may be able to switch from TRT to enclomiphene if you are already taking TRT and are concerned about the side effects or fertility issues associated with TRT.

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[1] Wiehle R, Cunningham GR, Pitteloud N, Wike J, Hsu K, Fontenot GK, Rosner M, Dwyer A, Podolski J. Testosterone Restoration by Enclomiphene Citrate in Men with Secondary Hypogonadism: Pharmacodynamics and Pharmacokinetics. BJU Int. 2013 Jul 12;112(8):1188–200. doi: 10.1111/bju.12363. Epub ahead of print. PMID: 23875626; PMCID: PMC4155868.;

[2] Rodriguez KM, Pastuszak AW, Lipshultz LI. Enclomiphene citrate for the treatment of secondary male hypogonadism. Expert Opin Pharmacother. 2016 Aug;17(11):1561-7. doi: 10.1080/14656566.2016.1204294. Epub 2016 Jul 4. PMID: 27337642; PMCID: PMC5009465.;

[3] Krzastek SC, Sharma D, Abdullah N, Sultan M, Machen GL, Wenzel JL, Ells A, Chen X, Kavoussi M, Costabile RA, Smith RP, Kavoussi PK. Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism. J Urol. 2019 Nov;202(5):1029-1035. doi: 10.1097/JU.0000000000000396. Epub 2019 Oct 9. PMID: 31216250.;