Sex steroid levels in women with hypopituitarism: A case-controlled observational study

Catharina Olivius; Kerstin Landin-Wilhelmsen; Claes Ohlsson; Matti Poutanen; Penelope Trimpou; Daniel S Olsson; Gudmundur Johannsson; Åsa Tivesten

doi:10.1210/clinem/dgae197

Sex steroid levels in women with hypopituitarism: A case-controlled observational study

J Clin Endocrinol Metab. 2024 Apr 4:dgae197. doi: 10.1210/clinem/dgae197. Online ahead of print.

Authors

Catharina Olivius^{1

2}, Kerstin Landin-Wilhelmsen^{3

4}, Claes Ohlsson^{3

5

6}, Matti Poutanen^{3

5

7}, Penelope Trimpou^{3

4}, Daniel S Olsson^{3

4

8}, Gudmundur Johannsson^{3

4}, Åsa Tivesten^{1

4}

Affiliations

¹ Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Department of Medicine, Hospital of Halland, Kungsbacka, Sweden.
³ Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Endocrinology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
⁵ Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
⁷ Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.
⁸ Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

PMID: 38570732
DOI: 10.1210/clinem/dgae197

Abstract

Context: Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped.

Objective: To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay.

Methods: Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started growth hormone replacement 1995-2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay.

Results: Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone and estradiol showed similar patterns. Women with HH and adrenocorticotropic hormone (ACTH) deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency.

Conclusion: This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement.

Keywords: Androgens; Estrogens; Hypogonadotropic hypogonadism; Hypopituitarism; Mass Spectrometry; Women.