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Human chorionic gonadotropin (hCG) for Improved Virility without Negative Behavioral Changes in Hypogonadotropic Hypogonadic Adolescent Males with Prader-Willi Syndrome

8 August 2015


Background: Prader-Willi Syndrome (PWS) is a rare genetic, metabolic disorder affecting both males and females equally. Along with compulsive and gluttonous eating, affected youth also suffer from varying degrees of mental retardation and decreased sexual development. Being physically underdeveloped as compared to their peers may make children suffering from PWS more self-conscious, and more likely to suffer from behavior disturbances. Studies have shown some positive response to exogenous administration of human chorionic gonadotropin (hCG) in the stimulation of sex hormones as well as development of secondary sex characteristics. Traditional treatment with testosterone has led to increased aggression, and exacerbation of PWS behavioral disturbances. hCG has been shown to improve virility in male patients, without the negative behavioral effects seen in testosterone treatment. To this point, only case studies and anecdotal evidence have been available. Could the lives of youth suffering from this disorder be improved with carefully timed administration of hCG?

Methods: An exhaustive search of the literature was conducted using Medline/OVID, NCBI/PubMed, Web of Science, and CINAHL using the key words: Prader-Willi Syndrome, and hCG. Relevant articles were assessed for quality using GRADE. There are no currently registered NIH clinical trials involving the treatment of hypogonadic peripubertal PWS patients with hCG.

Results: Two studies met inclusion criteria for this systematic review. Two clinical follow-up studies involving 6 study subjects treated with hCG injections demonstrated improved sexual maturity (as evidenced by improved testicular volume and secondary sex characteristics) and hormonal normalization with no significantly concerning behavioral changes.

Conclusion: hCG has been shown to improve secondary sex characteristics and hormonal levels without negative behavioral changes in peripubertal male patients when managed by a pediatric endocrinologist. More research is needed to determine comparisons with other existing and potential treatments, including depo-testosterone, etc. Improved studies (including RCTs) and study designs could also further improvements in the management of PWS-hypogonadism. Challenges include the global rarity of the disease, and finding enough subjects to provide adequate study populations.


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