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Replacement with sex steroids in hypopituitary men and women: implications for gender differences in morbidities and mortality

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Hypopituitarism is a heterogenous disorder characterised by a deficiency in one or more anterior pituitary hormones. There are marked sex disparities in the morbidity and mortality experienced by patients with hypopituitarism. In women with hypopituitarism, the prevalence of many cardiovascular risk factors, myocardial infarction, stroke and mortality are significantly elevated compared to the general population, however in men, they approach that of the general population. The hypothalamic-pituitary-gonadal axis (HPG) is the most sexually dimorphic pituitary hormone axis. Gonadotropin deficiency is caused by a deficiency of either hypothalamic gonadotropin-releasing hormone (GnRH) or pituitary gonadotropins, namely follicle-stimulating hormone (FSH) and luteinising hormone (LH). HPG axis dysfunction results in oestrogen and testosterone deficiency in women and men, respectively. Replacement of deficient sex hormones is the mainstay of treatment in individuals not seeking fertility. Oestrogen and testosterone replacement in women and men, respectively, have numerous beneficial health impacts. These benefits include improved body composition, enhanced insulin sensitivity, improved atherogenic lipid profiles and increased bone mineral density. Oestrogen replacement in women also reduces the risk of developing type 2 diabetes mellitus. When women and men are considered together, untreated gonadotropin deficiency is independently associated with an increased mortality risk. However, treatment with sex hormone replacement reduces the mortality risk comparable to those with an intact gonadal axis. The reasons for the sex disparities in mortality remain poorly understood. Potential explanations include the reversal of women's natural survival advantage over men, premature loss of oestrogen's cardioprotective effect, less aggressive cardiovascular risk factor modification and inadequate oestrogen replacement in women with gonadotropin deficiency. Regrettably, historical inertia and unfounded concerns about the safety of oestrogen replacement in women of reproductive age have impeded the treatment of gonadotropin deficiency. 

Funding

Emerging Clinician Scientist Award from the Health Research Board, Ireland. (Grant number: ECSA-2020-001)

Charitable Infirmary Charitable Trust, Ireland

Open Access funding provided by the IReL Consortium

History

Data Availability Statement

No datasets were generated or analysed during the current study.

Comments

The original article is available at https://link.springer.com/

Published Citation

Donald DM, McDonnell T, O'Reilly MW, Sherlock M. Replacement with sex steroids in hypopituitary men and women: implications for gender differences in morbidities and mortality. Rev Endocr Metab Disord. 2024;25(5):839-854.

Publication Date

7 October 2024

PubMed ID

39370498

Department/Unit

  • Beaumont Hospital
  • Medicine

Publisher

Springer Nature

Version

  • Published Version (Version of Record)