Enclomiphene Citrate 100x12.5mg

                                        NOT FOR HUMAN CONSUMPTION

Enclomiphene citrate is a selective estrogen receptor modulator (SERM) derived from clomiphene citrate—a compound long used to induce ovulation in women and, off-label, to treat male hypogonadism. Clomiphene itself consists of two stereoisomers: enclomiphene (trans-isomer) and zuclomiphene (cis-isomer). By separating enclomiphene from the mixture, researchers aimed to create a therapy more precisely tailored to stimulate endogenous testosterone production while minimizing estrogenic side effects.

• Chemical Name: (E)-2-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylethanamine citrate

• Classification: Selective Estrogen Receptor Modulator (SERM)

• Common Use: Investigational for treating secondary hypogonadism in men, with an emphasis on preserving fertility.

2. Mechanism of Action

Enclomiphene’s primary action lies in its ability to block estrogen’s negative feedback at the hypothalamic-pituitary-gonadal (HPG) axis:

1. Antagonism at the Hypothalamus

   • Enclomiphene binds to estrogen receptors in the hypothalamus.

   • By blocking estrogen signaling, it reduces the negative feedback loop that would otherwise suppress gonadotropin-releasing hormone (GnRH) release.

2. Upregulation of LH and FSH

   • With diminished negative feedback, the hypothalamus secretes more GnRH, which in turn stimulates the anterior pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

3. Stimulation of Testosterone Production

   • LH prompts the Leydig cells in the testes to synthesize and release endogenous testosterone.

   • FSH supports Sertoli cell function and overall sperm production.

This endogenous approach to increasing testosterone levels contrasts with exogenous testosterone therapy (TRT), which can suppress the HPG axis and reduce sperm production.

3. Potential Clinical Uses

3.1. Secondary (Hypogonadotropic) Hypogonadism

• Definition: A form of low testosterone resulting from inadequate pituitary stimulation.

• Rationale for Enclomiphene:

  • By boosting LH and FSH production, enclomiphene helps restore the body’s ability to produce its own testosterone.

  • Some clinical studies suggest it may improve serum testosterone levels while maintaining or even increasing sperm counts—potentially beneficial for men who wish to retain fertility.

3.2. Fertility Preservation

• Impact on Spermatogenesis: Unlike exogenous testosterone—which can dramatically reduce intratesticular testosterone levels and sperm production—enclomiphene maintains the HPG axis.

• Compared to Clomiphene: Both clomiphene and enclomiphene can preserve or improve fertility markers. However, enclomiphene may present fewer estrogenic side effects, as zuclomiphene (the cis-isomer in clomiphene) can exhibit more prolonged estrogenic action.

3.3. Alternative to Testosterone Replacement Therapy (TRT)

• Advantage: Enclomiphene enhances the body’s own production of testosterone, theoretically avoiding testicular atrophy and other TRT-related drawbacks.

• Limitation: If the cause of hypogonadism is primary (testicular damage or dysfunction), enclomiphene would be less effective because the testes may not respond adequately to elevated LH/FSH.

4. Clinical Efficacy: Key Research Findings

1. Kim et al. (2017), Reproductive Biology and Endocrinology

   • Demonstrated that enclomiphene could increase testosterone levels in men with secondary hypogonadism without substantially reducing sperm counts.

   • Some participants showed normalized testosterone within a short timeframe.

2. Nieschlag (2015), Expert Opinion on Investigational Drugs

   • Provided an overview suggesting enclomiphene might offer a promising alternative to standard TRT, potentially minimizing fertility concerns.

3. Taylor et al. (2018), Andrologia

   • Reviewed enclomiphene’s mechanism and potential clinical outcomes, calling for larger-scale trials to confirm long-term safety and efficacy.

Despite these findings, studies often have small sample sizes, and more robust, long-term research is still required.

5. Common Dosing and Administration (Investigational Context)

Note: No officially approved dosing regimen exists, as enclomiphene is not widely licensed for clinical use.

• Anecdotal/Experimental:

  • Studies often use 12.5–25 mg daily, but protocols vary.

  • Treatment cycles can last from several weeks to a few months, depending on clinical response and hormone monitoring.

• Monitoring:

  • Serum testosterone, LH, FSH, and estradiol are regularly measured.

  • Liver function, lipid profiles, and complete blood count may also be monitored to assess overall safety.

6. Potential Side Effects and Considerations

6.1. Side Effects

• Headaches and Dizziness: Common to many SERMs.

• Mood Changes: Some users report mood swings, irritability, or slight changes in libido.

• Visual Disturbances: Rare cases of blurred vision or sensitivity to light have been noted with clomiphene-like compounds.

• Gastrointestinal Issues: Nausea or mild stomach discomfort.

6.2. Comparisons to Clomiphene

• Reduced Estrogenic Activity: Enclomiphene, being the trans-isomer, may confer less estrogenic “spillover” than mixed-isomer clomiphene. This potentially translates to fewer adverse events like bloating or breast tenderness.

• Equal or Greater Efficacy: Both enclomiphene and clomiphene boost testosterone, but some preliminary data indicates enclomiphene might provide more consistent testosterone elevation.

6.3. Lack of Long-Term Data

• Safety Profile: Human trials are limited, particularly regarding long-term health outcomes.

• Individual Variability: Different baseline hormone levels and genetic factors can influence both efficacy and side effects.

7. Legal and Regulatory Perspective

• FDA Approval: Enclomiphene is not approved by the FDA for routine clinical use. Most enclomiphene products are labeled for research purposes or available through compounding pharmacies under off-label usage, where allowed.

• Sports and Doping: SERMs, including enclomiphene, may be restricted or prohibited in certain athletic competitions (e.g., by WADA, USADA). Athletes should verify the current banned substances list.

8. Summary of Key Advantages and Limitations

Advantages

• Increases endogenous testosterone production.

• May preserve or enhance fertility compared to traditional TRT.

• Potentially fewer estrogenic side effects versus mixed-isomer clomiphene.

Limitations

• Not widely approved by regulatory agencies; lacks comprehensive clinical data.

• May cause headaches, visual changes, mood swings, or other side effects commonly associated with SERMs.

• No established, standardized dosing—reliance on experimental or anecdotal protocols.

References 

1. Kim E.D., et al. (2017). Enclomiphene citrate stimulates testosterone production while preventing oligospermia: A randomized, open-label, proof of concept study. Reproductive Biology and Endocrinology, 15(1), 97.

2. Nieschlag E. (2015). Enclomiphene for the treatment of secondary male hypogonadism. Expert Opinion on Investigational Drugs, 24(10), 1595–1607.

3. Taylor F., et al. (2018). An update on the use of enclomiphene citrate in male hypogonadism. Andrologia, 50(9), e13123.

4. Narula HS, Carlson HE. (2014). Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: Efficacy and treatment cost. Journal of Sexual Medicine, 11(1), 246–255.