Testicular growth and sperm detection rates following combined hcg and rfsh therapy in adolescents with congenital and acquired hypogonadotropic hypogonadism

Hasan Karakas; gurkan Tarcın; Hande Turan; Abdurrahman Guney; Haşlak Gokce Velioğlu; Mert Ucar; Ilayda Altun; Cakir Aydilek Dagdeviren; Elvan Bayramoğlu; Olcay Evliyaoglu

doi:10.1530/endoabs.110.P1075

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Endocrine Abstracts (2025) 110 P1075 | DOI: 10.1530/endoabs.110.P1075

ECEESPE2025 Poster Presentations Reproductive and Developmental Endocrinology (93 abstracts)

Testicular growth and sperm detection rates following combined hcg and rfsh therapy in adolescents with congenital and acquired hypogonadotropic hypogonadism

Hasan Karakas ¹ , gürkan Tarçın ¹ , Hande Turan ¹ , Abdurrahman Güney ¹ , Gökçe Velioğlu Haşlak ¹ , Mert Uçar ¹ , Ilayda Altun ¹ , Aydilek Dagdeviren Cakir ¹ , Elvan Bayramoğlu ¹ & Olcay Evliyaoglu ¹

Author affiliations

¹Istanbul University-Cerrahpasa Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, Istanbul, Türkiye

JOINT1844

Introduction: While testosterone monotherapy has traditionally been used in adolescents with hypogonadotropic hypogonadism (HH), there has been growing experience with hCG and rFSH therapies. Unlike testosterone monotherapy, these treatments offer a more physiological approach and enhance fertility potential. This study aims to present our treatment protocol and outcomes.

Method: This retrospective study included adolescent males who received combined rFSH and hCG therapy between 2018-2025. In all cases, 2-month rFSH regimen at 75 IU/day (Dwyer protocol) was followed by low-dose rFSH and hCG, gradually increased every 3–6 months up to 150 IU rFSH and 3000 IU hCG twice weekly (Sato et al., 2015). After the Dwyer protocol, testosterone therapy was also initiated at 25 mg monthly and increased to 125 mg every 6 months. Testicular volumes were recorded quarterly, and semen analysis was performed after the third year.

Results: Twenty-one patients (15 congenital, 6 acquired) were included. Two genetically confirmed congenital cases with LH >5 IU/l but no pubertal progression were classified as partial HH. The mean age at treatment initiation was 16.6±2.1 years (13.1–19.8), and the median treatment duration was 32.8 months (12–82). Congenital cases included 3 with Kallmann syndrome and 12 with non-Kallmann HH, while acquired cases comprised 5 with craniopharyngioma and 1 with prior radiotherapy for nasopharyngeal carcinoma. Table 1 shows the increase in testicular volume from baseline in cases with an 18-month follow-up. In partial HH cases, a dramatic increase was notable at 18 months. In acquired HH cases, the increase became more pronounced compared to complete congenital cases from the 12th month. In the third-year semen analysis, sperm was detected in both partial congenital HH cases. The sperm detection rates in complete congenital and acquired cases were comparable (2/4 vs. 2/3, P = 0.658).

Table 1. Increase in testicular volume during treatment.
		ΔTesticular volume (mL) from baseline
	6th month	12th month	18th month
Complete congenital (n = 11)	1±0.6	1.8±0.6	3.1±1.3
Acquired (n = 6)	1.6±0.9	3.6±2	5.8±2.4
p	0.216	0.027	0.036
Partial congenital (n = 2)	1.2±0.7	3.5±3	9±5

Conclusion: Combined therapy effectively increases testicular volume and, based on semen analysis, improves fertility potential in both congenital and acquired HH cases. Given the lack of evidence for adverse effects of testosterone at priming doses on testicular development, low-dose testosterone alongside conventional therapy may enhance bone mineral density and secondary sexual characteristics earlier, making treatment responses more visible and improving adherence. Further clinical experience will contribute to establishing an optimal protocol.