Enclomiphene Can Lower IGF-1 Levels
Yes, enclomiphene (clomiphene) can significantly lower Insulin-like Growth Factor-1 (IGF-1) levels in patients taking it for hypogonadism. The most recent research evidence demonstrates this effect clearly.
Evidence for IGF-1 Reduction
Research from the Journal of the Endocrine Society (2025) found that:
- 75% of hypogonadal men treated with clomiphene exhibited a decrease in serum IGF-1 levels 1
- 10% of patients experienced a clinically significant decrease in IGF-1 (>2 standard deviations below age- and sex-matched mean values) 1
- This reduction was statistically significant (P < .01) 1
Earlier research from 2013 also confirmed that:
- Both transdermal testosterone and enclomiphene citrate decreased IGF-1 levels (p<0.05) 2
- The suppression of IGF-1 was greater in the enclomiphene citrate groups compared to testosterone gel 2
Mechanism of Action
The mechanism behind this effect appears to be related to enclomiphene's action as a selective estrogen receptor modulator (SERM):
- Enclomiphene stimulates pituitary-derived gonadotropins to generate sex steroids including estrogen 1
- Estrogen activates SOCS-3, which can inhibit growth hormone-directed JAK/STAT signaling 1
- This inhibition leads to reduced serum IGF-1 levels 1
Clinical Implications
This IGF-1 lowering effect has several important clinical implications:
- Potential for clinically significant reductions in IGF-1 that could impact health outcomes
- Need for monitoring IGF-1 levels in patients on enclomiphene therapy
- Possible symptoms of growth hormone deficiency in some patients
Monitoring Recommendations
Based on the evidence, patients on enclomiphene therapy should have:
- Baseline IGF-1 measurement before starting therapy
- Interval monitoring of serum IGF-1 levels during treatment 1
- Assessment for symptoms of growth hormone deficiency 1
- Consideration of IGF-1 levels when evaluating overall treatment efficacy
Comparison to Other Treatments
While both testosterone gel and enclomiphene lower IGF-1, research shows:
- Enclomiphene causes greater suppression of IGF-1 than testosterone gel 2
- Enclomiphene increases LH and FSH, while testosterone suppresses these hormones 2
- Enclomiphene maintains or improves sperm counts, unlike testosterone 3
Conclusion
The evidence clearly demonstrates that enclomiphene therapy can lower IGF-1 levels, with some patients experiencing clinically significant reductions. This effect should be considered when prescribing enclomiphene, particularly for patients who may already have borderline low IGF-1 levels or symptoms of growth hormone deficiency.