Efficacy and security of gonadotropin treatment in adolescents with congenital hypogonadotropic hypogonadism

Laura Sayol-Torres; Judith González; Núria Gonzalez; Ariadna Campos; Eduard Mogas; Diego Yeste; Maria Clemente

Objective: To describe efficacy and security of treatment protocol with gonadotropins in adolescents with hypogonadotropic hypogonadism (HH).

Methods: Prospective study of patients with HH who received hGH and rhFSH in puberty. HH diagnosed during first months of life or in adolescence (testicular volume<4cc in >16 year-old with FSH<1.2UI/L, testosterone<40ng/dL and GnRH-test with LH-peak<6UI/L)

Treatment protocol: First phase: rFSH 75IU/twice-weekly during 2-4 months. Second phase*: rFSH 75-150IU/twice-weekly + hCG 250IU/twice-weekly during 6-12 months. Third phase*: rFSH 150IU/thrice-weekly + hCG at increasing doses (500IU/thrice-weekly during 6-12 months, 1000IU/thrice-weekly during 6 months, 1500IU/thrice-weekly during 6 months, adult doses 1500-2500IU). *hCG and rhFSH doses adjusted according to testosterone and inhibin-B levels respectively.

Efficacy:• Testicular volume(TV): mean of both testicles(mL) • Testosterone and inhibin-B levels. • Spermiogarm in phase 3 (OMS2010). •Adult height (AH) Z-score and Δadult-height-mean parental height (MillennialsGrowth2018).

Security: Blood count, biochemistry and hormonal analysis performed periodically. BMD at onset and end.

Results: 6 patients described in Table 1. Patients 1 and 4 began pubertal induction with intramuscular testosterone and afterwards, received gonadotropin treatment. The rest, started and completed pubertal induction with gonadotropins presenting normal pubertal development.

Table 1: Parameters in patients that underwent treatment with rhFSH-HCG
Patient	Etiology (age at diagnosis)	Age at onset(years)	Basal TV (mL) mean*	Basal InhibinB (pg/mL)	Basal testosterone (ng/dL)	Duration (years)	Final TV (mL) mean*	Final InhibinB (pg/mL)	AH (cm)	Z-score ΔH- mean parental H	Spermiogram Nº performance, count and mobility
1	Acquired Idiopathic intracranial hypertension(15 years)	16.6	4.5	23.8	<10	3.6	20	188	172	+0.12	3rd: 100x10E6/mL, 24% progressively mobile, 2% normal
2	Congenital panhypopituitarism (Neonatal)	12.7	2 (inguinal)	25	<7	4.4	7 (scrotal)	105	167	0.6	1st: Azoospermia
3	Kallmann (Neonatal)	14.7	2	20	18	3.4	7	112	146	0.4	1st, 2nd: Azoospermia
4	Acquired Craneofaringioma (14 years)	17.3	3	58	<10	0.8	8	143	185	0	Without result
5	Congenital panhypopituitarism (Neonatal)	14.9	2	31.2	<7	4	7	77	175	1.4	1st: azoospermia 2nd: 0.34x10E6/mL, 83% no-mobility
6	Kallmann (Neonatal)	12.1	1.5 (inguinal)	20.7	39	5.5	9	104	161.6	-0.4	1º: 1.06 X10E6/mL 37% mobile, 14% progressively mobile 63% immobile
*Prader-orchidometer

Conclusions:• Gonadotropin treatment is secure for pubertal induction. • Testicular volume was increased, although limitedly in severe forms. • Spermatogenic response was scant/null in congenital forms with cryptorchidism (except in one patient). • Clinical parameters (onset and severity of gonadotropin deficiency) may predict treatment response. • Low sample-number limits this study; further research is needed.

ESPE Abstracts

RFC6.5