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Altered reproductive hormone profiles in systemic lupus erythematosus - A systematic review and meta-analysis
Alexandru-Marian Constantin1, Nora Mărginean1, Ana-Maria Constantinescu2
1Department of Internal Medicine, Carol Davila University of Medicine and Pharmacy, Lupu 37, Sector 2, 020021 Bucharest, Romania; Departments of Internal Medicine, Rheumatology and Neurology, Clinical Hospital Colentina, Stefan cel Mare 19-21, Sector 2, 020125 Bucharest, Romania.
Background:
Systemic lupus erythematosus (SLE) shows a marked female predominance during reproductive years, possibly suggesting hormonal factors in its pathogenesis. However, evidence regarding reproductive hormone alterations in SLE remains inconsistent.
Objectives:
To systematically review studies assessing reproductive hormone levels in adult SLE patients compared with healthy controls and across disease activity states.
Methods:
Following PRISMA guidelines and a pre-registered protocol (PROSPERO CRD42024544730), PubMed and Scopus were searched (May 2024). Eligible observational studies reported estradiol, testosterone, progesterone, prolactin, FSH, LH, DHEA-S, DHEA or androstenedione in SLE patients versus controls or by disease activity. Random-effects meta-analyses were conducted.
Results:
Eighty-three studies were included (5389 individuals for SLE vs. controls; 2067 for active vs. inactive SLE). Prolactin was consistently higher in SLE (MD 8.07 ng/mL; 95% CI 4.69-11.45; p < 0.001) and even more during flare (MD 5.83 ng/mL; 95% CI 3.88-7.78; p < 0.001). Estradiol showed non-significant overall elevations but was significantly higher in women with active disease (MD 8.55 pg/mL; 95% CI 1.37-15.73; p = 0.03). DHEA-S was found to be significantly lower in SLE (MD -1.00 μg/mL; 95% CI -1.5 to -0.50; p = 0.002) but too few studies evaluated its dynamics during flares. FSH and LH were significantly higher in men with SLE. Other hormones were inconsistent. Only three small heterogeneous studies evaluated hormonal changes during flares.
Conclusions:
Prolactin excess and androgen deficiency are consistent features of SLE, particularly in women, while elevated gonadotropins are mainly seen in men. Estradiol is higher during active disease but other data are inconsistent. Longitudinal studies are limited, with prolactin the only hormone consistently linked to disease activity and full hormonal profiles during flares are largely unstudied.