Enclomiphene Citrate vs. Clomiphene

What is Enclomiphene Citrate?

Enclomiphene citrate (brand name Androxal®), (E)-2-(p-(2-chloro-1,2-diphenylvinyl)phenoxy)triethylamine is an oral, non-steroidal estrogen receptor antagonist (SERM) that promotes testicular testosterone production by occupying estrogen receptors in the hypothalamus, thereby preventing negative feedback. Enclomiphene is thought to compete with estrogen for estrogen receptor binding sites, limiting suppression of gonadotropin release. In women, this leads to ovulation, and in men, it raises testosterone levels by increasing LH and FSH levels.

What is Clomiphene?

Clomiphene is a nonsteroidal ovulatory stimulant. It is suggested that it interacts with estrogen-receptor-containing tissues by competing with estrogen-receptor-binding sites, which then delays the replenishment of estrogen receptors in cells. It also has estrogenic and antiestrogenic properties that aid in the initiation of ovulation with no apparent progestational, androgenic and antiandrogenic effects.

How does it compare to Clomiphene?

• Unique Mechanism - Unlike other treatments, Enclomiphene Citrate does not directly replace testosterone. Instead, it stimulates the bodys natural production by targeting the brain. It blocks estrogen receptors in the hypothalamus, essentially tricking the body into thinking testosterone levels are low. This triggers the release of hormones that ultimately boost testosterone production in the testes. Unlike testosterone replacement therapy, which can carry risks like transference risk, having excessively high testosterone levels, and reducing sperm production and testicular function, enclomiphene avoids these complications.
• Proven Effectiveness - Studies show substantial increases in testosterone levels after Enclomiphene Citrate treatment, even in obese men where traditional methods often fail to preserve sperm count.
• Advantages over Clomiphene - Compared to older medications, Enclomiphene Citrate has several benefits:
  • Stronger and More Targeted - It is more potent in stimulating testosterone production while causing fewer estrogen-related side effects.
  • Maintains Balanced Hormones - It does not decrease estrogen, ensuring a healthier hormonal balance.
• Promising Future - Clinical research suggests Enclomiphene Citrate could be a valuable tool for managing testosterone deficiency and potentially improving fertility.

How can a patient get this medication?

Enclomiphene is not FDA approved to be mass-produced, but it can legally be prepared by a compounding pharmacy with a prescription from a prescriber. Since 2022, there has been much discussion about making enclomiphene more readily available for patients, specifically male patients who struggle with low testosterone levels. As of 2023, it was officially decided to not include enclomiphene of the FDA Bulk list and it can only be obtained via compounding pharmacies. Patients can acquire enclomiphene from most compounding pharmacies across the U.S. with a valid prescription from their healthcare provider.

Compounding is the option to get Enclomiphene citrate

Dosing/Formulation

Enclomiphene can be compounded at any strength as recommended by the prescribing doctor. Enclomiphene comes in compounded oral capsules.

Warning/Precautions

This medication should not be taken if you are allergic to enclomiphene or any ingredients contained in this drug. Currently, enclomiphene has no serious interactions with other drugs.

What should patients on Enclomiphene know?

Enclomiphene is associated with an increased risk of blood clots. Some mild and often temporary side effects include headache, hot flush, and nausea.

Some benefits may include:

• Fertility - Improves sperm quality and quantity, potentially restoring fertility.
• Safety - May be safer than other options due to its unique mechanism.
• Other potential benefits - Anti-aging effects, gynecomastia treatment.

References:

• 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.
• 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.
• (Clomiphene). In: Merative Micromedex® DRUGDEX® (electronic version). Merative Healthcare Solutions/EBSCO Information Services, Greenwood Village, Colorado; Cambridge, Massachusetts, USA. Available at: https://www-dynamed-com.ezproxy.sju.edu (cited: January 5, 2024)
• https://www.maximustribe.com/resources/is-enclomiphene-fda-approved
• https://www.liebertpub.com/doi/abs/10.1089/jomh.2014.0006?casa_token=G6wa_JcdJ9IAAAAA%3A9bcti720b_VtlEDNYr5-GGdysw3hEa6xpvJTKLTwRc0_KOtX-nkDn632TWDQRyEYkLq1zI55qbqtum4p&journalCode=jomh
• https://www.fda.gov/media/159043/download
• https://www.rxlist.com/enclomiphene/generic-drug.htm
• https://www.kiwidrug.com/general-health/androxal/
• https://www.gavinpublishers.com/article/view/successful-management-of-secondary-hypogonadism-with-enclomiphene-citrate--a-case-report-highlighting-advantages-over-clomid-and-other-aromatase-inhibitors-#:~:text=Firstly%2C%20enclomiphene%20citrate%20is%20the,minimizing%20estrogen%2Drelated%20side%20effects.