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Prior testosterone replacement therapy may impact spermatogenic response to combined gonadotropin therapy in severe congenital hypogonadotropic hypogonadism

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Abstract

Objective

To study the effect of prior testosterone replacement therapy (TRT) on the spermatogenic response to combined gonadotropin therapy (CGT) in severe and partial phenotype congenital hypogonadotropic hypogonadism (CHH) patients.

Design

Retrospective cohort study.

Setting

Tertiary care center.

Patients

Patients of CHH without (n = 17) and with prior TRT (n = 18) were subdivided into severe and partial groups, based on mean testicular volume ≤ 3 cc and > 3 cc respectively.

Intervention

Participants were treated with hMG at a dose of 75–150 U 3/week and gradually escalating doses of hCG until maximum dose (2000 U 3/week or 5000 U 2/week) or serum total testosterone of ≥ 3.5 ng/ml was reached.

Main outcome measures

Final mean TV, trough serum testosterone (T), sperm concentration

Results

Thirty-five patients (20 severe, baseline mean TV of 3.6 ± 2.7 ml) were started on CGT at 24.8 ± 6.1 years. The median duration of prior TRT was 38 (IQR 10–63.75) months in the exposed group. After 33 ± 12 months, final mean TV was 8.9 ± 5.5 ml, 86% achieved serum testosterone > 3.5 ng/ml and 70% achieved spermatogenesis [median 5 (0–12.6) million/ml]. Patients without prior TRT had significantly higher peak sperm count than those with prior- TRT (median 9 vs 0.05 million/ml, p = 0.004). This effect of prior TRT was more pronounced in severe phenotype patients (median 7 vs 0 million/ml, p = 0.01).

Conclusion

Prior-TRT may interfere with spermatogenic response to CGT in CHH patients, especially in those with a severe phenotype.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Funding

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Authors and Affiliations

  1. Department of Endocrinology, Seth GS Medical College & KEM Hospital, 103, 1st floor, OPD Building, KEM Hospital Campus, Parel, Mumbai, Maharashtra, 40012, India

    Ravikumar Shah, Virendra Patil, Anurag R. Lila, Brijesh Krishnappa, Manjeetkaur Sehemby, Sanjeet Kumar Jaiswal, Swati Ramteke-Jadhav, Nalini Shah & Tushar Bandgar

  2. Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Center, Bangalore, Karnataka, India

    Vijaya Sarathi

  3. Department of Endocrinology, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia

    Margaret Zacharin

  4. Department of Preventive & Social Medicine, Seth GS Medical College & KEM Hospital, Parel, Mumbai, India

    Pratap L. Jadhav

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  1. Ravikumar Shah
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  2. Virendra Patil
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Corresponding author

Correspondence to Anurag R. Lila.

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Shah, R., Patil, V., Sarathi, V. et al. Prior testosterone replacement therapy may impact spermatogenic response to combined gonadotropin therapy in severe congenital hypogonadotropic hypogonadism. Pituitary 24, 326–333 (2021). https://doi.org/10.1007/s11102-020-01111-6

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  • DOI: https://doi.org/10.1007/s11102-020-01111-6

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