What is the difference between enclomiphene and clomiphene (clomiphene citrate) in fertility treatment?

Enclomiphene vs Clomiphene in Fertility Treatment

Enclomiphene is the more effective trans-isomer of clomiphene citrate that increases testosterone, FSH, and LH while significantly improving total motile sperm count, making it superior to standard clomiphene for male fertility treatment. 1

Chemical Composition and Structure

Clomiphene citrate is a mixture of two geometric isomers:

• Enclomiphene (trans-isomer): Makes up 50-70% of clomiphene citrate 2, 3
• Zuclomiphene (cis-isomer): Makes up 30-50% of clomiphene citrate 2, 3

Key Differences Between Enclomiphene and Clomiphene

Pharmacokinetics

• Half-life:
  • Enclomiphene: Short half-life (24 hours) 4
  • Zuclomiphene: Accumulates in the body across consecutive treatment cycles 5

Hormonal Effects

• Enclomiphene:

  • More potent at increasing testosterone levels 6
  • More effective at stimulating FSH and LH production 1
  • Acts primarily as an estrogen receptor antagonist at the hypothalamus 4

• Clomiphene (mixed isomers):

  • Less consistent hormonal response due to mixed isomer effects 6
  • Zuclomiphene component may contribute to side effects without therapeutic benefit 6

Clinical Efficacy

Male Fertility

• Enclomiphene:

  • Significantly increases total motile sperm count (TMSC) 1
  • More effective at raising gonadotropin levels 1
  • Maintains fertility while treating hypogonadism 6

• Clomiphene (mixed isomers):

  • Increases testosterone but less impact on TMSC 1
  • Recommended by AUA and ASRM for male infertility treatment, particularly in hypogonadotropic states 7

Female Fertility

• Both are used for ovulation induction in anovulatory women 8
• Clomiphene citrate is first-line treatment for normally estrogenized, anovulatory women (WHO group II) 8

Clinical Applications

Male Fertility Treatment

• Enclomiphene appears superior for:
  • Treating hypogonadism while preserving fertility 6
  • Improving sperm parameters, particularly total motile sperm count 1

Female Fertility Treatment

• Both can be used for ovulation induction
• Clomiphene citrate (100 mg per day for 5 days) is an acceptable alternative to gonadotrophins for ovulation induction with lower multiple birth rates 9

Important Clinical Considerations

• Monitoring: Regular hormone level monitoring is necessary during treatment 7
• Duration: For anovulatory women, treatment should be at least 6 cycles before considering more complex methods, with a maximum of 12 cycles 8
• Contraindications:
  • Should not be used concurrently with finasteride during fertility treatment 7
  • Avoid exogenous testosterone therapy in males interested in fertility as it inhibits spermatogenesis 7

Emerging Evidence

The most recent evidence (2023) suggests that enclomiphene may be more effective than standard clomiphene for male fertility treatment, with greater improvements in gonadotropin levels and total motile sperm count 1. This represents a significant advancement in our understanding of these medications' comparative efficacy.