Sex Differences in Long-Term Safety and Tolerability of GH Replacement Therapy in GH Deficient Adults

Tessa N.A. Slagboom, Christa C. van Bunderen, Aart Jan van der Lely, Madeleine L. Drent

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CONTEXT: Previous studies report that outcomes of growth hormone (GH) replacement therapy (GHRT) might be less beneficial in growth hormone deficient (GHD) women compared with men. OBJECTIVE: This study investigated possible contributing factors regarding this previously found sex difference. METHODS: This retrospective cohort study, conducted at a nationwide outpatient clinic (the Dutch National Registry of GH Treatment in Adults), included Dutch adult GHD men (n = 1335) and women (n = 1251) treated with GHRT. The patients' baseline characteristics, details of GHRT, and the tolerability and long-term safety of GHRT were measured. RESULTS: During treatment, sensitivity analysis showed that insulin-like growth factor-1 (IGF-1) SD scores remained subnormal more often in women (P < 0.001), while scores above normal were more frequent in men (P < 0.001). Women reported more adverse events (P < 0.001), especially symptoms related to fluid retention, and more often needed a dose reduction or temporary stop of GHRT (P = 0.001). In percentages, both sexes equally discontinued GHRT, as was also true for the risk in developing type 2 diabetes mellitus, benign neoplasms, and tumor recurrence. The risk of developing malignant neoplasms was higher in men (P = 0.012). CONCLUSION: Data obtained from the Dutch National Registry of GH Treatment in Adults indicate that GHD women might be treated suboptimally, reflected as lower IGF-1 status and lower GHRT tolerability, leading to more frequent changes in treatment regimen but not discontinuation of GHRT. Regarding long-term safety, we found a higher risk for development of malignancies in GHD men.

Original languageEnglish
Pages (from-to)e415-e424
JournalThe Journal of clinical endocrinology and metabolism
Issue number7
Publication statusPublished - 1 Jul 2023

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© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].


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