From the Guidelines
Enclomiphene is not recommended as a first-line treatment for ovulation induction in women with polycystic ovary syndrome (PCOS) due to the lack of direct evidence supporting its use in this context, and instead, clomiphene citrate is the preferred treatment option as recommended by the American College of Obstetricians and Gynecologists (ACOG) 1. The ACOG guidelines suggest that clomiphene citrate is effective in inducing ovulation in about 80 percent of women with PCOS, with half of these patients conceiving 1. Key points to consider when treating women with PCOS include:
- Weight control and regular exercise as the initial treatment approach
- Use of clomiphene citrate as the primary medication for ovulation induction
- Consideration of low-dose gonadotropin therapy if clomiphene treatment fails, due to its ability to induce monofollicular development with a lower risk of ovarian hyperstimulation 1 While enclomiphene may have potential benefits in certain contexts, its use in women with PCOS is not supported by the available evidence, and therefore, it is not recommended as a treatment option for ovulation induction in this population.
From the FDA Drug Label
Clomiphene citrate is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)] containing between 30% and 50% of the cis-isomer. The trans-isomer of clomiphene citrate is known as enclomiphene.
- Enclomiphene is a component of clomiphene citrate, which is a mixture of two geometric isomers: cis (zuclomiphene) and trans (enclomiphene) 2 3.
From the Research
Enclomiphene Overview
- Enclomiphene citrate is a non-steroidal estrogen receptor antagonist used to treat secondary male hypogonadism 4.
- It is the trans isomer of clomiphene citrate, which has been used off-label for many years to treat secondary male hypogonadism, particularly in the setting of male infertility 4.
Efficacy of Enclomiphene
- Enclomiphene citrate has been shown to increase serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters 4, 5.
- A retrospective study found that enclomiphene citrate (EC) and clomiphene citrate (CC) are effective treatments in increasing total testosterone without negatively affecting spermatogenesis, with EC demonstrating a more significant increase in gonadotropin levels and total motile sperm count (TMSC) 6.
Comparison with Clomiphene Citrate
- Clomiphene citrate is a mixture of both the cis-isomer (zuclomiphene) and the trans-isomer (enclomiphene), with the literature suggesting that most of the beneficial effects of clomiphene are due to the trans-isomer enclomiphene 5.
- A study comparing the effects of CC and EC on serum testosterone levels and semen parameters found that EC had a statistically significant increase in FSH and LH, and a significant increase in TMSC, whereas CC did not 6.
Treatment of Hypogonadism
- Enclomiphene citrate is an alternative treatment option for hypogonadal men who wish to maintain fertility, as it increases testosterone levels without suppressing the hypothalamic-pituitary-gonadal axis 4, 5.
- Testosterone replacement therapy is known to suppress the hypothalamic-pituitary-gonadal axis, resulting in suppressed spermatogenesis, making enclomiphene citrate a viable option for young hypogonadal men who desire children in the future 7.