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. 2025 Jul 14:17:1759720X251354898.
doi: 10.1177/1759720X251354898. eCollection 2025.

Menopause in systemic sclerosis: the impact on clinical presentation in a multicenter cross-sectional analysis from the National Registry of the Italian Society for Rheumatology (SPRING-SIR)

Martina Orlandi  1 , Dilia Giuggioli  1 , Clodoveo Ferri  1   2 , Rossella De Angelis  3 , Valeria Riccieri  4 , Fabio Cacciapaglia  5 , Silvia Laura Bosello  6 , Veronica Codullo  7   8 , Gianluigi Bajocchi  9 , Lorenzo Dagna  10 , Corrado Campochiaro  10 , Giacomo De Luca  9   10 , Giovanni Zanframundo  7   8 , Rosario Foti  11 , Giovanna Cuomo  12 , Alarico Ariani  13 , Edoardo Rosato  14 , Francesco Girelli  15 , Elisabetta Zanatta  11   16 , Ilaria Cavazzana  17   18 , Francesca Ingegnoli  19 , Maria De Santis, Giuseppe Murdaca  20 , Giuseppina Abignano  21 , Giorgio Petitti  22 , Alessandra Della Rossa  23 , Maurizio Caminiti  24 , Anna Maria Iuliano  25 , Giovanni Ciano  26 , Lorenzo Beretta  27 , Gianluca Bagnato  28 , Ennio Lubrano  29 , Ilenia De Andres  30 , Alessandro Giollo  31 , Marta Saracco  32 , Cecilia Agnes  33 , Edoardo Cipolletta  3 , Federica Lumetti  1 , Amelia Spinella  1 , Luca Magnani, Elisa Visalli, Carlo Iandoli  9   12 , Antonietta Gigante  14 , Greta Pellegrino  34 , Erika Pigatto  35 , Maria Grazia Lazzaroni  17   18 , Franco Franceschini  17   18 , Elena Generali  36 , Gianna Mennillo  21 , Simone Barsotti  23 , Giuseppa Pagano Mariano  24 , Federica Furini  37 , Licia Vultaggio  37 , Simone Parisi  38 , Clara Lisa Peroni  38 , Gerolamo Bianchi  39 , Enrico Fusaro  38 , Gian Domenico Sebastiani  25 , Marcello Govoni  37 , Salvatore D'Angelo  21 , Franco Cozzi  35 , Andrea Doria  34 , Carlo Salvarani  9 , Florenzo Iannone  5 , Serena Guiducci  40 , Silvia Bellando-Randone  40 , Marco Matucci-Cerinic  10 , Cosimo Bruni  41   42
Affiliations

Menopause in systemic sclerosis: the impact on clinical presentation in a multicenter cross-sectional analysis from the National Registry of the Italian Society for Rheumatology (SPRING-SIR)

Martina Orlandi et al. Ther Adv Musculoskelet Dis. .

Abstract

Background: Hormonal changes in menopause might interact with the presentation of underlying autoimmune diseases, such as systemic sclerosis (SSc).

Objectives: Our study aimed to evaluate the association of (1) current menopausal status, (2) early menopause, and (3) disease onset during fertile or post-menopausal age on SSc clinical phenotype in a large SSc cohort from the Italian Systemic sclerosis Progression INvestiGation (SPRING-SIR) registry.

Design: Female SSc patients from the SPRING-SIR registry, fulfilling the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 classification criteria, with data on SSc disease onset, menopausal status, and menopausal age, were eligible. SSc onset was categorized as pre-menopausal if SSc onset happened >1 year before menopause or as post-menopausal onset if it occurred >1 year after menopause. An early menopause was defined by a menopausal age <45 years.

Methods: Descriptive statistics and regression models were built to test the association between current menopausal status, pre-menopausal disease onset, and early menopause with SSc-related features.

Results: At baseline, 1157/1538 (75%) patients were in menopause, 632 (50.4%) had a pre-menopausal SSc onset, and 130 (14.4%) reported an early menopause. Post-menopausal patients had more frequent limited cutaneous SSc, anti-centromere antibody positivity, interstitial lung disease, and gastrointestinal manifestations. Pre-menopausal onset cases showed more frequent diffuse cutaneous involvement and peripheral vasculopathy. Patients with early menopause had more frequent peripheral vasculopathy and interstitial lung disease, being early menopause an independent risk factor for digital ulcers and lower diffusing capacity of the lung for carbon monoxide.

Conclusion: Current post-menopausal status and early menopause may impact SSc presentation, being associated with vascular and gastrointestinal manifestations. Menopausal status and age should therefore be thoroughly addressed, aiming at better disease management.

Keywords: early menopause; menopausal status; menopause; systemic sclerosis.

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Figures

The patient was from the SPRING SSc registry of the Italian Society of Rheumatology
Figure 1.
Flow chart of patient selection process. SPRING-SIR, SSc registry of the Italian Society of Rheumatology; SSc, systemic sclerosis.
“Multivariable regression models testing post-menopausal status as a predictor for SSc-related clinical features: (a) presence of gastric symptoms; (b) presence of diffuse cutaneous subset; (c) value of diffusion capacity of the lung for carbon monoxide (DLco); (d) presence of digital ulcers; (e) value of sPAP; (f) presence of ILD; (g) presence of digital pitting scars; and (h) value of LVEF.”
Figure 2.
Multivariable regression models testing post-menopausal status as a predictor for SSc-related clinical features: (a) presence of gastric symptoms; (b) presence of diffuse cutaneous subset; (c) value of diffusion capacity of the lung for carbon monoxide (DLco); (d) presence of digital ulcers; (e) value of sPAP; (f) presence of ILD; (g) presence of digital pitting scars; and (h) value of LVEF. ATA, anti-Scl-70 antibodies; FVC, forced vital capacity; ILD, interstitial lung disease; LVEF, left ventricular ejection fraction; OR, odds ratio; sPAP, systolic pulmonary artery pressure; SSc, systemic sclerosis.
This figure depicts multivariable regression models examining the impact of early menopause on systemic sclerosis (SSc)-related clinical features, including digital ulcers, interstitial lung disease, FVC, and DLco, using statistical odds ratios (OR) and 1-SD thresholds.
Figure 3.
Multivariable regression models testing early menopause as a predictor for SSc-related clinical features: (a) presence of digital ulcers; (b) presence of interstitial lung disease; (c) value of FVC; and (d) value of DLco. ATA, anti-Scl-70 antibodies; DLco, diffusing capacity of the lung for carbon monoxide; FVC, forced vital capacity; ILD, interstitial lung disease; NVC, nailfold video capillaroscopy; OR, odds ratio; sPAP, systolic pulmonary artery pressure; SSc, systemic sclerosis.
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