Objective: To study the role of the GnRH analogue Triptorelin in the assessment of the hypothalamic-pituitary-gonadal axis, in guiding therapy for infertility and identifying hypogonadic patients with recovery potential (functional hypothalamic dysfunction and idiopathic hypogonadotropic hypogonadism).
Methods: Dynamic testing using subcutaneous injection of 100 μg Triptorelin was performed in 29 adults (11 women) with hypogonadotropic hypogonadism (HH). Blood samples were collected for baseline measurements of FSH, LH and estradiol/ testosterone; gonadotropins after 4 hours, and sex steroids after 24 hours.
Results: After excluding patients on hormone replacement therapy (HRT, n=9), the subjects were divided in two groups: HH of probable pituitary (Pit, n=11) and hypothalamic origin (Ht, n= 9), based on clinical and imaging criteria. The Pit group showed a blunt response to the GnRH test (FSH: 1.01±0.72 mUI/ml to 2.29±2.06, P=0.026; LH: 0.29±0.11 mUI/ml to 0.84±0.87 mUI/ml, P=0.057), while gonadotropins increased significantly in the Ht group (FSH: from 3.01±1.49 UI/l to 18.42±12.97 UI/l, P=0.004; LH: from 1.53±1.36 UI/l to 23.65±20.27 UI/l, P=0.009); the sex steroid response was not significant for either group (P=NS). The response to GnRH was higher for the hypothalamic than the pituitary group for both LH (P=0.01) and FSH (P=0.006). While the individual FSH responses overlapped, a cutoff of 2.99 UI/l for stimulated LH had a sensitivity of 88.9% and a specificity of 100% in identifying patients with hypothalamic hypogonadism (LH > 2.99 UI/l). The results were confirmed after including patients on HRT, with a cutoff of 6.93 UI/l for stimulated LH having a sensitivity of 75% and a specificity of 100%.
Conclusion: GnRH analogue testing can help shed light on the etiology of HH, with reasonable sensitivity even in patients already on HRT.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.