# Cardiovascular and metabolic outcomes of GH replacement therapy in adults with GH deficiency – gender gaps

**Authors:** Angelo Milioto, Daniela Esposito, Gudmundur Johannsson, Oskar Ragnarsson

PMC · DOI: 10.1007/s11102-026-01646-0 · 2026-02-20

## TL;DR

This review examines how growth hormone replacement therapy affects cardiovascular and metabolic health in adults with growth hormone deficiency, highlighting differences between men and women.

## Contribution

The paper specifically highlights gender differences in the outcomes of GH replacement therapy and their potential hormonal basis.

## Key findings

- Women with GH deficiency have higher morbidity and mortality than men.
- GH replacement therapy improves outcomes but is less effective in women.
- Differences may stem from interactions between sex steroids and the somatotroph axis.

## Abstract

Adult growth hormone (GH) deficiency is associated with increased body fat mass, abdominal obesity, dyslipidaemia, reduced exercise capacity, impaired cardiac function, reduced self-reported well-being, impaired quality of life, as well as increased morbidity. Randomised controlled trials and cohort studies, together with meta-analyses, have shown improved outcome in adult patients with hypopituitarism receiving GH, with a reassuring safety profile. Women with GH deficiency and hypopituitarism have greater morbidity and mortality than men, particularly in relation to metabolic and cardiovascular outcome. The response to GH replacement is also less favourable in women than in men. The reason for these differences in women and men with hypopituitarism is not entirely clear, but is likely related to the interaction between sex steroid and the somatotroph axis. In this narrative review we summarize the burden of GH deficiency in adults with hypopituitarism, and the impact of GH replacement, with focus on differences among women and men.

## Linked entities

- **Diseases:** hypopituitarism (MONDO:0005152)

## Full-text entities

- **Genes:** LDLR (low density lipoprotein receptor) [NCBI Gene 3949] {aka LDLCQ2}, LCAT (lecithin-cholesterol acyltransferase) [NCBI Gene 3931], GGH (gamma-glutamyl hydrolase) [NCBI Gene 8836] {aka GATD10, GH}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, GHR (growth hormone receptor) [NCBI Gene 2690] {aka GHBP, GHIP}, CETP (cholesteryl ester transfer protein) [NCBI Gene 1071] {aka BPIFF, HDLCQ10}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}, GHRH (growth hormone releasing hormone) [NCBI Gene 2691] {aka GHRF, GRF, INN}, SOCS2 (suppressor of cytokine signaling 2) [NCBI Gene 8835] {aka CIS2, Cish2, SOCS-2, SSI-2, SSI2, STATI2}
- **Diseases:** Adult growth hormone (GH) deficiency (MESH:C537404), impaired myocardial performance (MESH:D009202), overweight (MESH:D050177), stroke (MESH:D020521), diastolic dysfunction (MESH:D018487), hypothalamic-pituitary disorder (MESH:D007029), Obesity (MESH:D009765), NASH (MESH:D005235), GH deficiency (MESH:D006432), disorders (MESH:D009358), hypogonadism (MESH:D007006), metabolic abnormalities (MESH:D008659), dyslipidemia (MESH:D050171), inflammatory (MESH:D007249), abnormal body composition (MESH:C564221), traumatic brain injury (MESH:D000070642), pituitary adenomas (MESH:D010911), NAFLD (MESH:D065626), sexual dysfunction (MESH:D012735), diabetes (MESH:D003920), adrenal insufficiency (MESH:D000309), impaired cardiac function (MESH:D006331), reduction in lean body mass (MESH:D013851), androgen deficiency (MESH:D014770), infectious diseases (MESH:D003141), abdominal obesity (MESH:D056128), cardiovascular abnormalities (MESH:D018376), GH deficiency (MESH:D004393), hypopituitarism (MESH:D007018), hypertension (MESH:D006973), arterial stiffness (MESH:C566112), quality of life (MESH:D003643), Impaired lipid metabolism (MESH:D052439), atherogenic (MESH:D050197), deficiency of each pituitary axis (MESH:C566610), anterior pituitary hormone deficits (MESH:D010900), multiple pituitary hormone deficiencies (MESH:C580003), insulin resistance (MESH:D007333), Cardiovascular comorbidities (MESH:D002318)
- **Chemicals:** free fatty acids (MESH:D005230), Testosterone (MESH:D013739), water (MESH:D014867), nitric oxide (MESH:D009569), cholesterol (MESH:D002784), TG (MESH:D014280), lipid (MESH:D008055), steroid (MESH:D013256), glucose (MESH:D005947), ethinyl estradiol (MESH:D004997), sodium (MESH:D012964), TC (-), macimorelin (MESH:C582727), arginine (MESH:D001120)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12923456/full.md

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Source: https://tomesphere.com/paper/PMC12923456