What is the role of gonadotropin-releasing hormone (GnRH) in the treatment of cryptorchidism?

Updated: Dec 17, 2020
  • Author: Joel M Sumfest, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

Agonistic analogs of GnRH such as nafarelin or buserelin stimulate the release of the pituitary gonadotropins, LH and FSH, temporarily increasing gonadal steroidogenesis. Repeated dosing abolishes the stimulatory effect on the pituitary gland, and twice-daily administration decreases secretion of gonadal steroids by 4 weeks. GnRH is available as a nasal spray but is approved for the treatment of cryptorchidism only in Europe.

The interpretation of results is tainted by multiple treatment strategies. Success rates in uncontrolled studies range from 13-78%, while better-controlled investigations resulted in rates of 6-38%. Rajfer et al conducted a randomized double-blind study comparing hCG at 3300 IU per week for 4 weeks with GnRH spray at 200 mcg 6 times per day for 4 weeks. Descent into the scrotum occurred in 6% of the hCG group and in 19% of the GnRH group. [49]

Several authors have recommended combined GnRH and hCG hormonal treatment.

Lala et al administered LHRH at 1.2 mg/d for 4 weeks. Those who did not respond also received hCG at 500 IU 3 times per week for 3 weeks. After combined treatment, 38% of testes descended. [54]

Bica and Hadziselimovic treated patients with a low dose of buserelin (20 mcg) as a daily spray for 28 days, followed by hCG in those in whom treatment failed. Approximately 26% of the testes descended with the spray alone, and hCG increased the descent rate to 37%. [55] Hadziselimovic advocated initial treatment with GnRH spray at 400 mcg tid into each nostril for 4 weeks, followed by salvage treatment in those in whom treatment failed, with hCG at 1500 IU/week for 3 weeks. The success rate of 56% with GnRH was increased to 65% with the addition of hCG. [56]

The recognized adverse effects of increased androgens, including increased penile or testicular size, scrotal erythema, or erections, seem to be less with GnRH than with hCG.

Initial treatment with GnRH may deserve some consideration because it is administered as a spray rather than an injection. Even in 20% of patients, it may aid descent in more distal testes, make intra-abdominal testes palpable, or help differentiate retractile from true undescended testes.

In summary, hormonal treatment yields an overall efficacy rate of less than 20% for undescended testes. The decision to use hormonal treatment depends on the pretreatment location of the testis.

Treatment with GnRH has also been used as an adjunct to orchiopexy, to increase fertility. A meta-analysis and systematic review by Chua et al found evidence suggesting that a subset of boys with cryptorchidism may benefit in that respect. However, the characteristics of cryptorchidism patients who would will clearly benefit from GnRH treatment have not been identified. [57]  European guidelines note that there is no consensus on hormonal treatment for testicular descent but suggest offering endocrine treatment for bilateral undescended testes, to possibly improve further fertility potential. [58]


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