Addition of recombinant follicle-stimulating hormone to human chorionic gonadotropin treatment in adolescents and young adults with hypogonadotropic hypogonadism promotes normal testicular growth…

Adding recombinant follicle-stimulating hormone to human chorionic gonadotropin treatment protocols in adolescent/young adult men with hypogonadotropic hypogonadism results in normal testicular growth and may hasten induction of spermatogenesis.

Margaret Zacharin, M.B.B.S., Matthew A. Sabin, Ph.D., Veena V. Nair, M.D., Preeti Dagabdhao, M.D.

Volume 98, Issue 4, Pages 836-842, October 2012


To assess effects on spermatogenesis of adding recombinant FSH (rFSH) to HCG treatment protocols for adolescent/young adult males with hypogonadotrophic hypogonadism (HH).

Observational descriptive study.

Outpatient clinics in Australia and India.

19 males with Hypogonadotrophic Hypogonadism (age 14.5–31 years).

Treatment with either HCG treatment alone (n=9; Group 1) or in combination with rFSH (n=10; Group 2), over 6-9 months.

Main Outcome Measures:
Combined testicular volume (CTV), and testosterone, Inhibin B, semen/urine analysis at 6 – 9 months.

There were no differences between groups for baseline variables or changes in CTV with treatment. Despite this, evidence of spermatogenesis was present in all Group 2 patients by 9 months [range 0.2 to 15×10653 /ml] compared with 3/9 patients in Group 1 [range 0 to <1x10654 /ml]; p=0.003. Whole group and subgroup analyses did not demonstrate significant correlations between age at onset of treatment and either CTV or sperm count. Conclusions:
Addition of rFSH to HCG treatment protocols in adolescent/young adult HH males results in normal testicular growth and may hasten induction of spermatogenesis.

  • José Martínez-Jabaloyas

    Hypogonadotropic hypogonadism is a treatable form of infertility. This entity is not a frequent condition and it is difficult to design adequate clinical trials to know what is the best form of management of these patients during adolescence to assure an adequate
    testicular development. So this excellent work indicates the importance of both
    gonadotropins in testicular maturation in men. Fertility recovery after testosterone
    discontinuation and gonadotropins therapy is, sometimes, difficult. So, it could be interesting to know if patients treated with HCG and FSH during adolescence will have a better chance for recovering the fertility in his adult life after stopping testosterone
    replacement and adding gonadotropins.

  • Juan Giles

    I find the present manuscript interesting for the
    reader, as it provides important data about the effect of addition rFSH to hCG
    treatment in adolescent and young and adults with HH. Although it has
    limitations of an observational study and the entire Indian
    cohort was allocated to hCG alone (authors clarify this point in the

    Another remarkable aspect is suggestion that early
    induction of spermatogenesis may reduce the time required for appearance of
    sperm and future conception and also may reduce the need prolonged cycles of gonadotropin
    treatment in adult life.

  • khwang

    The authors present an observational study of adolescent and young adult males with hypogonadotropic hypogonadism (HH) who are treated with either hCG alone or hCG and recombinant FSH. The authors found that spermatogenesis was present in 10/10 males treated with hCG + rFSH, as opposed to only 3/9 patients treated with hCG alone. While an area that is fairly well established in HH adults, the study focuses on treating adolescents. The next step in this work is to determine whether early introduction of gonadotrophins is responsible for this effect, or if prolonged periods of exogenous testosterone therapy have an adverse effect on future spermatogenic potential.

  • eykko

    Retrospective study comparing 2 groups of men/boys with hypogonadotropic hypogonadism (HH) treated with HCG only (Group 1 – 9 males) and HCG + recombinant FSH (Group 2 – 10 males). Although the groups were small and 1/3 and 1/2 of the groups respectively had previous testosterone replacement therapy in the past, Group 2 males had improved combined testicular volume and much more improved return of spermatogenesis. This demonstrates that HCG alone may not be enough to stimulate adequate spermatogenesis even with normalization of serum testosterone levels. Something to keep in mind as we treat men with HH in our fertility clinics. A prospective double blinded randomized controlled study would be very helpful for the future.

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