PO:16:241 | Prevalence and associated factors of premature ovarian insufficiency in women with systemic lupus erythematosus: the role of human herpesviruses HHV-7 and HHV-8

Margherita Rizzo¹, Francesca Ruffilli¹, Silvia Beltrami², Daria Bortolotti², Roberta Rizzo², Carlo Garaffoni¹, Ettore Silvagni¹, Marcello Govoni¹, Alessandra Bortoluzzi¹ | ¹UOC Reumatologia, Dipartimento di Scienze Mediche, Università di Ferrara e Azienda Ospedaliero-Universitaria S. Anna, Ferrara; ²Dipartimento di Scienze Chimiche, Farmaceutiche e Agrarie, Ferrara Italy

Background. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects women of reproductive age. Fertility may be impaired by intrinsic factors, such as disease activity, flares, and organ damage, as well as by extrinsic factors, including treatment-related effects. Premature ovarian insufficiency (POI), a condition characterized by reduced reproductive potential, represents a significant issue in SLE. Anti-Müllerian hormone (AMH), produced by ovarian follicles, is a reliable indicator of ovarian reserve, while elevated follicle-stimulating hormone (FSH) levels associated with 4–6 months of amenorrhea or oligomenorrhea remain the gold standard for POI diagnosis. The aim of this study was to assess the prevalence of POI in a monocentric cohort of women with SLE and to examine its association with clinical, immunological, therapeutic features, and viral serologies.

Materials and Methods. We included women aged 18–45 years with a diagnosis of SLE according to the 1997 ACR, 2012 SLICC, and/or 2019 EULAR criteria, treated with hydroxychloroquine and/or conventional or biologic immunosuppressants, excluding cyclophosphamide (CYC), and enrolled between 2014 and 2023. Data collected through a secure electronic system included medical history, disease characteristics and activity (SLEDAI-2K, PGA), treatments, and hormonal profile (LH, FSH, prolactin, progesterone, and AMH). Viral serologies included HHV-6, -7, and -8. Categorical variables were expressed as frequencies and percentages, and continuous variables as mean ± standard deviation (SD). POI was defined as AMH <1 ng/mL or FSH >40 IU/L.

Results. Seventy-nine women with SLE were enrolled (Table 1). POI defined by AMH <1 ng/mL was observed in 53.1% of patients, while 30.4% met the criteria based on FSH >40 IU/L. No statistically significant differences were found in disease activity, autoimmune serological profile, clinical manifestations, or treatments between patients with and without POI, regardless of the definition used. Patients with POI had higher exposure to CYC and higher cumulative doses, although without statistical significance. Regarding viral serologies (Table 2), the seroprevalence of anti-HHV-7 IgG and IgM and anti-HHV-8 IgM was significantly associated with POI defined by FSH values.

Conclusions. Our study suggests a possible role of human herpesviruses HHV-7 and HHV-8 in the impairment of female fertility in patients with SLE. The involvement of HHVs in reproductive dysfunction, conception difficulties, and spontaneous abortion—mainly linked to HHV-6, but also to HHV-7 and HHV-8—has been described in the literature. The observed results support the hypothesis of a potential impact of these viruses on ovarian function and follicular reserve, providing a novel perspective on the viral contribution to reproductive impairment.