Systemic sclerosis and female reproductive health over lifespan: A systematic review and meta-analysis

Systemic sclerosis (SSc) is a rare chronic autoimmune disease that may adversely affect reproductive health. Female SSc patients often face reproductive health challenges. This study aims to systematically assess the impact of SSc on female reproductive health outcomes across the lifespan through a systematic review and meta-analysis.

We conducted a thorough search of PubMed, Cochrane, Embase, and Web of Science for relevant studies. Data extraction and quality assessment were performed by two reviewers. Meta-analysis was carried out using Review Manager 5.4 and STATA 18 software, with bias risk evaluated using the Newcastle-Ottawa Scale (NOS). The outcomes assessed primarily included reproductive hormones, pregnancy outcomes, and sexual function.

A total of 27 studies were included based on the inclusion criteria. The meta-analysis revealed that female SSc patients had higher levels of prolactin (PRL), luteinizing hormone (LH), and estradiol (E2) compared to healthy controls (PRL: MD = 11.07, 95% CI: 5.72-16.43, P < 0.0001, I² = 97%; LH: MD = 3.06, 95% CI: 1.17-4.96, P = 0.002, I² = 61%; E2: MD = 18.43, 95% CI: 1.69-35.18, P = 0.03, I² = 89%), while testosterone (T) levels were lower (MD = -0.32, 95% CI: -0.54 --0.11, P = 0.003, I² = 90%). SSc patients had a higher risk of cesarean section, intrauterine growth restriction (IUGR), low birth weight (LBW), and preterm birth (cesarean: RR = 1.72, 95% CI: 1.24-2.39, P = 0.001, I² = 92%; IUGR: RR = 3.01, 95% CI: 1.52-5.99, P = 0.002, I² = 0%; LBW: RR = 4.89, 95% CI: 2.52-9.51, P < 0.00001, I² = 0%; preterm birth: RR = 2.80, 95% CI: 1.91-4.12, P < 0.0001, I² = 77%). Additionally, SSc patients exhibited lower total sexual function scores and a higher prevalence of sexual dysfunction (total sexual function scores: MD = -7.07, 95% CI: -9.65--4.49, P < 0.00001, I² = 75%; prevalence of sexual dysfunction: OR = 5.48, 95% CI: 2.89-10.39, P < 0.00001, I² = 72%).

Women with SSc are more likely to experience reproductive hormone imbalances, increased pregnancy risks, and sexual dysfunction. These findings highlight the need for enhanced clinical awareness and standardized interventions, with a focus on integrating reproductive health management for female SSc patients.